Microbial compositions for the treatment of skin disorders

Abstract

Provided herein are compositions, methods, kits, and devices for the treatment of skin diseases. Also provided herein are isolated and purified bacteria, excipients, carriers, dosage forms, and administration routes for such bacteria. Additionally, provided herein are mixtures of isolated and purified bacteria, excipients, carriers, dosage forms, and administration routes for such mixtures. Also provided herein are conditions for treatment with bacteria and bacterial mixtures. The compositions may be formulated as suspensions, emulsions, creams, lotions, tinctures, gels, foams, powders, ointments, pastes, or oils.

Description

[Technical field]

[0001] cross reference This application claims the benefit of U.S. Provisional Patent Application No. 63 / 278,134, filed November 11, 2021, the entire disclosure of which is incorporated by reference herein.

[0002] Sequence Listing This application contains a Sequence Listing, which has been submitted electronically in XML format and is incorporated by reference in its entirety. The XML copy was created on November 8, 2022, is named ST26_202421-701601, and is 43,284 bytes in size. Summary of the Invention

[0003] Summary of the Invention Disclosed herein is a composition. In some embodiments, the composition comprises a purified bacterial strain, the bacterial strain comprises a first strain comprising a 16s rRNA sequence having at least 97% sequence identity to SEQ ID NO:4; a second strain comprising a 16s rRNA sequence having at least 97% sequence identity to SEQ ID NO:1; and a third strain comprising a 16s rRNA sequence having at least 97% sequence identity to SEQ ID NO:2; (a) the bacterial strain is lyophilized; or (b) the composition is formulated for delivery to the skin. In some embodiments, the first strain comprises a 16s rRNA sequence having at least 97% sequence identity to SEQ ID NO:4 over at least 1000 bases. In some embodiments, the second strain comprises a 16s rRNA sequence having at least 97% sequence identity to SEQ ID NO:1 over at least 1000 bases. In some embodiments, the third strain comprises a 16s rRNA sequence having at least 97% sequence identity to SEQ ID NO:2 over at least 1000 bases. In some embodiments, the first strain further comprises a sequence having at least 95% sequence identity to SEQ ID NO:11, SEQ ID NO:12, or both. In some embodiments, the first strain further comprises a sequence having SEQ ID NO:11, SEQ ID NO:12, or both. In some embodiments, the second strain further comprises a sequence having at least 95% sequence identity to SEQ ID NO:15. In some embodiments, the second strain further comprises a sequence of SEQ ID NO:15. In some embodiments, the third strain further comprises a sequence having at least 95% sequence identity to SEQ ID NO:7, SEQ ID NO:8, or both. In some embodiments, the third strain further comprises a sequence of SEQ ID NO:7, SEQ ID NO:8, or both. In some embodiments, the composition is formulated as a suspension, emulsion, cream, lotion, tincture, gel, foam, powder, ointment, paste, or oil. In some embodiments, the composition further comprises a fourth bacterial strain. In some embodiments, the composition is formulated as at least 10 3In some embodiments, the composition contains 10 colony forming units (cfu) / gram of bacteria. 3 ~10 12 In some embodiments, the composition comprises at least about 10 colony forming units (cfu) / gram of bacteria. In some embodiments, the bacterial strain is grown under aerobic conditions. In some embodiments, the bacterial strain is grown without animal products. In some embodiments, the bacterial strain is grown in tryptic soy broth (TSB). In some embodiments, the composition comprises at least about 10 colony forming units (cfu) / gram of bacteria when stored in a sealed container at 20° C. after 6 months. 4 cfu. In some embodiments, the composition further comprises an excipient. In some embodiments, the composition further comprises a lyoprotectant. In some embodiments, the composition further comprises an emollient. In some embodiments, the composition further comprises, or a salt thereof. In some embodiments, the bacterial strain, when contacted with S. aureus, reduces expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB, and said reduced expression is measured by a fluorescent reporter assay. In some embodiments, the bacterial strain is present in an amount effective to inhibit virulence of S. aureus, as measured by reduced expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB, and said reduced expression is measured by a fluorescent reporter assay.

[0004] In some embodiments, the composition comprises a purified bacterial strain, the bacterial strain comprising a first strain comprising a 16s rRNA sequence having at least 97% sequence identity to SEQ ID NO:5; a second strain comprising a 16s rRNA sequence having at least 97% sequence identity to SEQ ID NO:1; and a third strain comprising a 16s rRNA sequence having at least 97% sequence identity to SEQ ID NO:2; (a) the bacterial strain is lyophilized; or (b) the composition is formulated for delivery to the skin. In some embodiments, the first strain comprises a 16s rRNA sequence having at least 97% sequence identity to SEQ ID NO:5 over at least 1000 bases. In some embodiments, the second strain comprises a 16s rRNA sequence having at least 97% sequence identity to SEQ ID NO:1 over at least 1000 bases. In some embodiments, the third strain comprises a 16s rRNA sequence having at least 97% sequence identity to SEQ ID NO:2 over at least 1000 bases. In some embodiments, the first strain further comprises a sequence having at least 95% sequence identity to SEQ ID NO: 13. In some embodiments, the first strain further comprises having a sequence of SEQ ID NO: 13. In some embodiments, the second strain further comprises a sequence having at least 95% sequence identity to SEQ ID NO: 15. In some embodiments, the second strain further comprises a sequence of SEQ ID NO: 15. In some embodiments, the third strain further comprises a sequence having at least 95% sequence identity to SEQ ID NO: 7, SEQ ID NO: 8, or both. In some embodiments, the third strain further comprises a sequence having SEQ ID NO: 7, SEQ ID NO: 8, or both. In some embodiments, the composition is formulated as a suspension, emulsion, cream, lotion, tincture, gel, foam, powder, ointment, paste, or oil. In some embodiments, the composition further comprises a fourth bacterial strain. In some embodiments, the composition is formulated as at least 10 3 In some embodiments, the composition contains 10 colony forming units (cfu) / gram of bacteria. 3 ~10 12In some embodiments, the composition comprises at least about 10 colony forming units (cfu) / gram of bacteria. In some embodiments, the bacterial strain is grown under aerobic conditions. In some embodiments, the bacterial strain is grown without animal products. In some embodiments, the bacterial strain is grown in tryptic soy broth (TSB). In some embodiments, the composition comprises at least about 10 colony forming units (cfu) / gram of bacteria when stored in a sealed container at 20° C. after 6 months. 4 cfu. In some embodiments, the composition further comprises an excipient. In some embodiments, the composition further comprises a lyoprotectant. In some embodiments, the composition further comprises an emollient. In some embodiments, the composition further comprises, or a salt thereof. In some embodiments, the bacterial strain, when contacted with S. aureus, reduces expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB, and said reduced expression is measured by a fluorescent reporter assay. In some embodiments, the bacterial strain is present in an amount effective to inhibit virulence of S. aureus, as measured by reduced expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB, and said reduced expression is measured by a fluorescent reporter assay.

[0005] In some embodiments, the composition comprises a purified bacterial strain, the bacterial strain comprising a first strain comprising a 16s rRNA sequence having at least 97% sequence identity to SEQ ID NO:5; a second strain comprising a 16s rRNA sequence having at least 97% sequence identity to SEQ ID NO:3; and a third strain comprising a 16s rRNA sequence having at least 97% sequence identity to SEQ ID NO:6; (a) the bacterial strain is lyophilized; or (b) the composition is formulated for delivery to the skin. In some embodiments, the first strain comprises a 16s rRNA sequence having at least 97% sequence identity to SEQ ID NO:5 over at least 1000 bases. In some embodiments, the second strain comprises a 16s rRNA sequence having at least 97% sequence identity to SEQ ID NO:3 over at least 1000 bases. In some embodiments, the third strain comprises a 16s rRNA sequence having at least 97% sequence identity to SEQ ID NO:6 over at least 1000 bases. In some embodiments, the first strain further comprises a sequence having at least 95% sequence identity to SEQ ID NO: 13. In some embodiments, the first strain further comprises having a sequence of SEQ ID NO: 13. In some embodiments, the second strain further comprises a sequence having at least 95% sequence identity to SEQ ID NO: 9, SEQ ID NO: 10, or both. In some embodiments, the second strain further comprises a sequence having SEQ ID NO: 9, SEQ ID NO: 10, or both. In some embodiments, the third strain further comprises a sequence having at least 95% sequence identity to SEQ ID NO: 14. In some embodiments, the third strain further comprises a sequence having SEQ ID NO: 14. In some embodiments, the composition is formulated as a suspension, emulsion, cream, lotion, tincture, gel, foam, powder, ointment, paste, or oil. In some embodiments, the composition further comprises a fourth bacterial strain. In some embodiments, the composition is formulated as at least 10 3 In some embodiments, the composition contains 10 colony forming units (cfu) / gram of bacteria. 3 ~10 12In some embodiments, the composition comprises at least about 10 colony forming units (cfu) / gram of bacteria. In some embodiments, the bacterial strain is grown under aerobic conditions. In some embodiments, the bacterial strain is grown without animal products. In some embodiments, the bacterial strain is grown in tryptic soy broth (TSB). In some embodiments, the composition comprises at least about 10 colony forming units (cfu) / gram of bacteria when stored in a sealed container at 20° C. after 6 months. 4 cfu. In some embodiments, the composition further comprises an excipient. In some embodiments, the composition further comprises a lyoprotectant. In some embodiments, the composition further comprises an emollient. In some embodiments, the composition further comprises, or a salt thereof. In some embodiments, the bacterial strain, when contacted with S. aureus, reduces expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB, and said reduced expression is measured by a fluorescent reporter assay. In some embodiments, the bacterial strain is present in an amount effective to inhibit virulence of S. aureus, as measured by reduced expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB, and said reduced expression is measured by a fluorescent reporter assay.

[0006] In some embodiments, the composition comprises a purified bacterial strain, the bacterial strain comprises at least two of the following bacterial strains: a first strain comprising a 16s rRNA sequence having at least 97% sequence identity to SEQ ID NO:4; a second strain comprising a 16s rRNA sequence having at least 97% sequence identity to SEQ ID NO:1; a third strain comprising a 16s rRNA sequence having at least 97% sequence identity to SEQ ID NO:2; a fourth strain comprising a 16s rRNA sequence having at least 97% sequence identity to SEQ ID NO:5; a fifth strain comprising a 16s rRNA sequence having at least 97% sequence identity to SEQ ID NO:6; and a sixth strain comprising a 16s rRNA sequence having at least 97% sequence identity to SEQ ID NO:3; (a) the at least two bacterial strains are lyophilized; or (b) the composition is formulated for delivery to the skin. In some embodiments, the first strain further comprises a sequence having at least 95% sequence identity to SEQ ID NO:11, SEQ ID NO:12, or both. In some embodiments, the first strain further comprises having a sequence of SEQ ID NO:11, SEQ ID NO:12, or both. In some embodiments, the second strain further comprises a sequence having at least 95% sequence identity to SEQ ID NO:15. In some embodiments, the second strain further comprises a sequence of SEQ ID NO:15. In some embodiments, the third strain further comprises a sequence having at least 95% sequence identity to SEQ ID NO:7, SEQ ID NO:8, or both. In some embodiments, the third strain further comprises a sequence of SEQ ID NO:7, SEQ ID NO:8, or both. In some embodiments, the fourth strain further comprises a sequence having at least 95% sequence identity to SEQ ID NO:13. In some embodiments, the fourth strain further comprises a sequence of SEQ ID NO:13. In some embodiments, the fifth strain further comprises a sequence having at least 95% sequence identity to SEQ ID NO:14. In some embodiments, the fifth strain further comprises a sequence of SEQ ID NO:14. In some embodiments, the sixth strain further comprises a sequence having at least 95% sequence identity to SEQ ID NO:9, SEQ ID NO:10, or both.In some embodiments, the sixth strain further comprises having a sequence of SEQ ID NO:9, SEQ ID NO:10, or both. In some embodiments, the composition is formulated as a suspension, emulsion, cream, lotion, tincture, gel, foam, powder, ointment, paste, or oil. In some embodiments, the first strain comprises a 16s rRNA sequence having at least 97% sequence identity over at least 1000 bases to SEQ ID NO:4. In some embodiments, the second strain comprises a 16s rRNA sequence having at least 97% sequence identity over at least 1000 bases to SEQ ID NO:1. In some embodiments, the third strain comprises a 16s rRNA sequence having at least 97% sequence identity over at least 1000 bases to SEQ ID NO:2. In some embodiments, the fourth strain comprises a 16s rRNA sequence having at least 97% sequence identity over at least 1000 bases to SEQ ID NO:4. In some embodiments, the fifth strain comprises a 16s rRNA sequence having at least 97% sequence identity over at least 1000 bases to SEQ ID NO:1. In some embodiments, the sixth strain comprises a 16s rRNA sequence having at least 97% sequence identity over at least 1000 bases to SEQ ID NO:2. In some embodiments, the bacterial strain comprises a first strain and a second strain. In some embodiments, the bacterial strain comprises a fourth strain and a second strain. In some embodiments, the bacterial strain comprises a fourth strain and a sixth strain. In some embodiments, the bacterial strain comprises a first strain and a third strain. In some embodiments, the bacterial strain comprises a second strain and a third strain. In some embodiments, the bacterial strain comprises a fifth strain and a sixth strain. In some embodiments, the composition comprises at least 10. 3 In some embodiments, the composition contains 10 colony forming units (cfu) / gram of bacteria. 3 ~10 12In some embodiments, the composition comprises at least about 10 colony forming units (cfu) / gram of bacteria. In some embodiments, the bacterial strain is grown under aerobic conditions. In some embodiments, the bacterial strain is grown without animal products. In some embodiments, the bacterial strain is grown in tryptic soy broth (TSB). In some embodiments, the composition comprises at least about 10 colony forming units (cfu) / gram of bacteria when stored in a sealed container at 20° C. after 6 months. 4 cfu. In some embodiments, the composition further comprises an excipient. In some embodiments, the composition further comprises a lyoprotectant. In some embodiments, the composition further comprises an emollient. In some embodiments, the composition further comprises, or a salt thereof. In some embodiments, the bacterial strain, when contacted with S. aureus, reduces expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB, and said reduced expression is measured by a fluorescent reporter assay. In some embodiments, the bacterial strain is present in an amount effective to inhibit virulence of S. aureus, as measured by reduced expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB, and said reduced expression is measured by a fluorescent reporter assay.

[0007] In some embodiments, the composition comprises a purified bacterial strain, the bacterial strain comprises a 16s rRNA sequence having at least 97% sequence identity to SEQ ID NO:4; (a) the bacterial strain is lyophilized; or (b) the composition is formulated for delivery to the skin. In some embodiments, the bacterial strain comprises a 16s rRNA sequence having at least 97% sequence identity to SEQ ID NO:4 over at least 1000 bases. In some embodiments, the bacterial strain further comprises a sequence having at least 95% sequence identity to SEQ ID NO:11, SEQ ID NO:12, or both. In some embodiments, the bacterial strain further comprises a sequence having SEQ ID NO:11, SEQ ID NO:12, or both. In some embodiments, the composition is formulated as a suspension, emulsion, cream, lotion, tincture, gel, foam, powder, ointment, paste, or oil. In some embodiments, the composition further comprises a second bacterial strain. In some embodiments, the composition is formulated as at least 10 3 In some embodiments, the composition contains 10 colony forming units (cfu) / gram of bacteria. 3 ~10 12 In some embodiments, the composition comprises at least about 10 colony forming units (cfu) / gram of bacteria. In some embodiments, the bacterial strain is grown under aerobic conditions. In some embodiments, the bacterial strain is grown without animal products. In some embodiments, the bacterial strain is grown in tryptic soy broth (TSB). In some embodiments, the composition comprises at least about 10 colony forming units (cfu) / gram of bacteria when stored in a sealed container at 20° C. after 6 months. 4cfu. In some embodiments, the composition further comprises an excipient. In some embodiments, the composition further comprises a lyoprotectant. In some embodiments, the composition further comprises an emollient. In some embodiments, the composition further comprises, or a salt thereof. In some embodiments, the bacterial strain, when contacted with S. aureus, reduces expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB, and said reduced expression is measured by a fluorescent reporter assay. In some embodiments, the bacterial strain is present in an amount effective to inhibit virulence of S. aureus, as measured by reduced expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB, and said reduced expression is measured by a fluorescent reporter assay.

[0008] In some embodiments, the composition comprises a purified bacterial strain, the bacterial strain comprises a 16s rRNA sequence having at least 97% sequence identity to SEQ ID NO:1; (a) the bacterial strain is lyophilized; or (b) the composition is formulated for delivery to the skin. In some embodiments, the bacterial strain comprises a 16s rRNA sequence having at least 97% sequence identity to SEQ ID NO:1 over at least 1000 bases. In some embodiments, the bacterial strain further comprises a sequence having at least 95% sequence identity to SEQ ID NO:15. In some embodiments, the bacterial strain further comprises a sequence having SEQ ID NO:15. In some embodiments, the composition is formulated as a suspension, emulsion, cream, lotion, tincture, gel, foam, powder, ointment, paste, or oil. In some embodiments, the composition further comprises a second bacterial strain. In some embodiments, the composition is formulated as at least 10 3 In some embodiments, the composition contains 10 colony forming units (cfu) / gram of bacteria. 3 ~10 12In some embodiments, the composition comprises at least about 10 colony forming units (cfu) / gram of bacteria. In some embodiments, the bacterial strain is grown under aerobic conditions. In some embodiments, the bacterial strain is grown without animal products. In some embodiments, the bacterial strain is grown in tryptic soy broth (TSB). In some embodiments, the composition comprises at least about 10 colony forming units (cfu) / gram of bacteria when stored in a sealed container at 20° C. after 6 months. 4 cfu. In some embodiments, the composition further comprises an excipient. In some embodiments, the composition further comprises a lyoprotectant. In some embodiments, the composition further comprises an emollient. In some embodiments, the composition further comprises, or a salt thereof. In some embodiments, the bacterial strain, when contacted with S. aureus, reduces expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB, and said reduced expression is measured by a fluorescent reporter assay. In some embodiments, the bacterial strain is present in an amount effective to inhibit virulence of S. aureus, as measured by reduced expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB, and said reduced expression is measured by a fluorescent reporter assay.

[0009] In some embodiments, the composition comprises a purified bacterial strain, the bacterial strain comprises a 16s rRNA sequence having at least 97% sequence identity to SEQ ID NO:2; (a) the bacterial strain is lyophilized; or (b) the composition is formulated for delivery to the skin. In some embodiments, the bacterial strain comprises a 16s rRNA sequence having at least 97% sequence identity to SEQ ID NO:2 over at least 1000 bases. In some embodiments, the bacterial strain further comprises a sequence having at least 95% sequence identity to SEQ ID NO:7, SEQ ID NO:8, or both. In some embodiments, the bacterial strain further comprises a sequence having SEQ ID NO:7, SEQ ID NO:8, or both. In some embodiments, the composition is formulated as a suspension, emulsion, cream, lotion, tincture, gel, foam, powder, ointment, paste, or oil. In some embodiments, the composition further comprises a second bacterial strain. In some embodiments, the composition is formulated as at least 10 3 In some embodiments, the composition contains 10 colony forming units (cfu) / gram of bacteria. 3 ~10 12 In some embodiments, the composition comprises at least about 10 colony forming units (cfu) / gram of bacteria. In some embodiments, the bacterial strain is grown under aerobic conditions. In some embodiments, the bacterial strain is grown without animal products. In some embodiments, the bacterial strain is grown in tryptic soy broth (TSB). In some embodiments, the composition comprises at least about 10 colony forming units (cfu) / gram of bacteria when stored in a sealed container at 20° C. after 6 months. 4cfu. In some embodiments, the composition further comprises an excipient. In some embodiments, the composition further comprises a lyoprotectant. In some embodiments, the composition further comprises an emollient. In some embodiments, the composition further comprises, or a salt thereof. In some embodiments, the bacterial strain, when contacted with S. aureus, reduces expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB, and said reduced expression is measured by a fluorescent reporter assay. In some embodiments, the bacterial strain is present in an amount effective to inhibit virulence of S. aureus, as measured by reduced expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB, and said reduced expression is measured by a fluorescent reporter assay.

[0010] In some embodiments, the composition comprises a purified bacterial strain, the bacterial strain comprises a 16s rRNA sequence having at least 97% sequence identity to SEQ ID NO:5; (a) the bacterial strain is lyophilized; or (b) the composition is formulated for delivery to the skin. In some embodiments, the bacterial strain comprises a 16s rRNA sequence having at least 97% sequence identity to SEQ ID NO:5 over at least 1000 bases. In some embodiments, the bacterial strain further comprises a sequence having at least 95% sequence identity to SEQ ID NO:13. In some embodiments, the bacterial strain further comprises a sequence having SEQ ID NO:13. In some embodiments, the composition is formulated as a suspension, emulsion, cream, lotion, tincture, gel, foam, powder, ointment, paste, or oil. In some embodiments, the composition further comprises a second bacterial strain. In some embodiments, the composition is formulated as at least 10 3 In some embodiments, the composition contains 10 colony forming units (cfu) / gram of bacteria. 3 ~10 12In some embodiments, the composition comprises at least about 10 colony forming units (cfu) / gram of bacteria. In some embodiments, the bacterial strain is grown under aerobic conditions. In some embodiments, the bacterial strain is grown without animal products. In some embodiments, the bacterial strain is grown in tryptic soy broth (TSB). In some embodiments, the composition comprises at least about 10 colony forming units (cfu) / gram of bacteria when stored in a sealed container at 20° C. after 6 months. 4 cfu. In some embodiments, the composition further comprises an excipient. In some embodiments, the composition further comprises a lyoprotectant. In some embodiments, the composition further comprises an emollient. In some embodiments, the composition further comprises, or a salt thereof. In some embodiments, the bacterial strain, when contacted with S. aureus, reduces expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB, and said reduced expression is measured by a fluorescent reporter assay. In some embodiments, the bacterial strain is present in an amount effective to inhibit virulence of S. aureus, as measured by reduced expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB, and said reduced expression is measured by a fluorescent reporter assay.

[0011] In some embodiments, the composition comprises a purified bacterial strain, the bacterial strain comprises a 16s rRNA sequence having at least 97% sequence identity to SEQ ID NO:6; (a) the bacterial strain is lyophilized; or (b) the composition is formulated for delivery to the skin. In some embodiments, the bacterial strain comprises a 16s rRNA sequence having at least 97% sequence identity to SEQ ID NO:6 over at least 1000 bases. In some embodiments, the bacterial strain further comprises a sequence having at least 95% sequence identity to SEQ ID NO:14. In some embodiments, the bacterial strain further comprises a sequence having SEQ ID NO:14. In some embodiments, the composition is formulated as a suspension, emulsion, cream, lotion, tincture, gel, foam, powder, ointment, paste, or oil. In some embodiments, the composition further comprises a second bacterial strain. In some embodiments, the composition is formulated as at least 10 3 In some embodiments, the composition contains 10 colony forming units (cfu) / gram of bacteria. 3 ~10 12 In some embodiments, the composition comprises at least about 10 colony forming units (cfu) / gram of bacteria. In some embodiments, the bacterial strain is grown under aerobic conditions. In some embodiments, the bacterial strain is grown without animal products. In some embodiments, the bacterial strain is grown in tryptic soy broth (TSB). In some embodiments, the composition comprises at least about 10 colony forming units (cfu) / gram of bacteria when stored in a sealed container at 20° C. after 6 months. 4cfu. In some embodiments, the composition further comprises an excipient. In some embodiments, the composition further comprises a lyoprotectant. In some embodiments, the composition further comprises an emollient. In some embodiments, the composition further comprises, or a salt thereof. In some embodiments, the bacterial strain, when contacted with S. aureus, reduces expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB, and said reduced expression is measured by a fluorescent reporter assay. In some embodiments, the bacterial strain is present in an amount effective to inhibit virulence of S. aureus, as measured by reduced expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB, and said reduced expression is measured by a fluorescent reporter assay.

[0012] In some embodiments, the composition comprises a purified bacterial strain, the bacterial strain comprises a 16s rRNA sequence having at least 97% sequence identity to SEQ ID NO:3; (a) the bacterial strain is lyophilized; or (b) the composition is formulated for delivery to the skin. In some embodiments, the bacterial strain comprises a 16s rRNA sequence having at least 97% sequence identity to SEQ ID NO:3 over at least 1000 bases. In some embodiments, the bacterial strain further comprises a sequence having at least 95% sequence identity to SEQ ID NO:9, SEQ ID NO:10, or both. In some embodiments, the bacterial strain further comprises a sequence having SEQ ID NO:9, SEQ ID NO:10, or both. In some embodiments, the composition is formulated as a suspension, emulsion, cream, lotion, tincture, gel, foam, powder, ointment, paste, or oil. In some embodiments, the composition further comprises a second bacterial strain. In some embodiments, the composition comprises at least 10 bases of a 16s rRNA sequence having at least 97% sequence identity to SEQ ID NO:3. 3 In some embodiments, the composition contains 10 colony forming units (cfu) / gram of bacteria. 3 ~10 12In some embodiments, the composition comprises at least about 10 colony forming units (cfu) / gram of bacteria. In some embodiments, the bacterial strain is grown under aerobic conditions. In some embodiments, the bacterial strain is grown without animal products. In some embodiments, the bacterial strain is grown in tryptic soy broth (TSB). In some embodiments, the composition comprises at least about 10 colony forming units (cfu) / gram of bacteria when stored in a sealed container at 20° C. after 6 months. 4 cfu. In some embodiments, the composition further comprises an excipient. In some embodiments, the composition further comprises a lyoprotectant. In some embodiments, the composition further comprises an emollient. In some embodiments, the composition further comprises, or a salt thereof. In some embodiments, the bacterial strain, when contacted with S. aureus, reduces expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB, where the reduced expression is measured by a fluorescent reporter assay. In some embodiments, the bacterial strain is present in an amount effective to inhibit virulence of S. aureus, as measured by reduced expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB, where the reduced expression is measured by a fluorescent reporter assay.

[0013] Also disclosed herein is a method of administering the composition.In some embodiments, the method comprises administering an amount sufficient to treat a disease selected from the group consisting of atopic dermatitis, seborrheic dermatitis, inflammation, eczema, psoriasis, rosacea, mycosis, dermatophytosis, folliculitis, acne, alopecia, vitiligo, dandruff, chronic wound, skin ulcer, Netherton syndrome, sweat gland abscess, sycosis vulgaris, staphylococcal scalded skin syndrome, impetigo, ecthyma, cellulitis, carbuncle, furuncle, and abscess.In some embodiments, the method comprises administering an amount sufficient to reduce symptoms associated with atopic dermatitis.In some embodiments, the method comprises administering the composition to a subject having a microbiome that is prone to developing eczema prior to administration.In some embodiments, the method comprises administering an amount sufficient to reduce symptoms associated with dry skin.

[0014] Also disclosed herein is a method of administering the above composition. In some embodiments, the method comprises administering an amount sufficient to reduce the incidence of inflammation-related conditions, the inflammation-related conditions comprising itching, rash, redness, pain, swelling, blistering, or desquamation. In some embodiments, the method comprises administering an amount sufficient to suppress the virulence of S. aureus, as measured by a reduction in the expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB, the reduction in expression being measured by a fluorescent reporter assay. In some embodiments, the method of administration is topical administration.

[0015] Also disclosed herein are compositions for use in treating skin conditions (e.g., the compositions disclosed above). Disclosed herein are compositions for use in treating inflammation.

[0016] Also disclosed herein is a method for treating inflammation, comprising topically administering a composition comprising a bacterial strain comprising a 16s rRNA sequence having at least 97% sequence identity to SEQ ID NO:1 to a subject in need thereof, wherein the bacterial strain is purified and the bacterial strain is present in a sufficient amount for treatment of inflammation.

[0017] Also disclosed herein is a method for reducing the growth of Staphylococcus aureus in the skin of a subject, comprising topically administering to the skin of the subject a pharmaceutical composition comprising: a first bacterial strain comprising a 16s rRNA sequence having at least 97% sequence identity to SEQ ID NO:5; a second bacterial strain comprising a 16s rRNA sequence having at least 97% sequence identity to SEQ ID NO:1; and a third bacterial strain comprising a 16s rRNA sequence having at least 97% sequence identity to SEQ ID NO:2, wherein the bacterial strains are purified and the bacterial strains are viable and present in a sufficient amount for the reduction of S. aureus in the skin of a subject in need thereof.

[0018] Also disclosed herein is a method for alleviating symptoms associated with atopic dermatitis, comprising topically administering a composition comprising a bacterial strain comprising a 16s rRNA sequence having at least 97% sequence identity to SEQ ID NO:5 to a subject in need thereof, wherein the bacterial strain is purified and the bacterial strain is present in a sufficient amount for alleviation of symptoms associated with atopic dermatitis.

[0019] Also disclosed herein is a method for reducing the incidence of a condition associated with inflammation, comprising topically administering a composition comprising a first bacterial strain comprising a 16s rRNA sequence having at least 97% sequence identity to SEQ ID NO:1; and a second bacterial strain comprising a 16s rRNA sequence having at least 97% sequence identity to SEQ ID NO:6 to a subject in need thereof, wherein the bacterial strains are purified and the bacterial strains are present in a sufficient amount for reduction of the incidence of a condition associated with inflammation, wherein the condition associated with inflammation comprises itching, rash, redness, pain, swelling, blistering, or scaling.

[0020] Also disclosed herein is a method of administering the above composition. In some embodiments, the method can include administering an amount sufficient to treat a condition selected from the group consisting of pruritus, aesthetic conditions, and body odor. In some embodiments, the aesthetic condition includes the appearance of wrinkles or aging.

[0021] Also disclosed herein is a method for reducing the growth of Staphylococcus aureus on the skin of a subject, comprising topically administering to the skin of the subject a composition comprising a first bacterial strain comprising a 16s rRNA sequence having at least 97% sequence identity to SEQ ID NO:5; a second bacterial strain comprising a 16s rRNA sequence having at least 97% sequence identity to SEQ ID NO:1; and a third bacterial strain comprising a 16s rRNA sequence having at least 97% sequence identity to SEQ ID NO:2, wherein the bacterial strains are purified and the bacterial strains are viable and present in sufficient amounts to improve the appearance of the skin of the subject. In some embodiments, improving the appearance of the skin of the subject comprises reducing wrinkles, reducing lesion size, reducing pore size, reducing pore density, reducing the occurrence of wrinkles, reducing wrinkle depth, reducing age spots, or increasing skin elasticity.

[0022] Incorporation by Reference All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. [Brief description of the drawings]

[0023] The features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings, in which:

[0024] [Figure 1] Figure 1 is a pie chart summarizing the number of strain combinations tested that inhibited different S. aureus genes. Figure 1 shows the percentage of two-strain combinations that inhibit Staphylococcus aureus agr and psmA expression (left) or agr, psmA, and sigB expression (right). Strain combinations that inhibit multiple functions in S. aureus are rare.

[0025] [Diagram 2] Figure 2 is a bar graph plotting the percentage activity of S. aureus gene expression by fluorescent reporters. The X-axis indicates the strains in the combinatorial screening assay. The Y-axis indicates the percentage activity (0-100%) compared to S. aureus monoculture. Figure 2 shows the inhibition of different S. aureus promoter-reporter constructs when the reporter strain of S. aureus is mixed with a single strain, two strains, or three strains of strains jl.83, jl.27, and jl.77.

[0026] [Diagram 3]Figure 3 is a bar graph plotting the percentage activity of S. aureus gene expression by fluorescent reporters. The X-axis indicates the strains in the combinatorial screening assay. The Y-axis indicates the percentage activity (0-100%) compared to S. aureus monoculture. Figure 3 shows the inhibition of different S. aureus promoter-reporter constructs when the reporter strain of S. aureus is mixed with a single strain, two strains, or three strains of strains jl.21, jl.68, and jl.121.

[0027] [Figure 4] Figure 4 is a bar graph plotting the percentage activity of S. aureus gene expression by fluorescent reporters. The X-axis indicates the strains in the combinatorial screening assay. The Y-axis indicates the percentage activity (0-100%) compared to S. aureus monoculture. Figure 4 shows the inhibition of different S. aureus promoter-reporter constructs when the reporter strain of S. aureus is mixed with a single strain, two strains, or three strains of strains jl.27, jl.68, and jl.121.

[0028] [Diagram 5] FIG. 5 is a bar graph plotting the percentage change in fluorescent reporter S. aureus gene expression in a three-strain mixture of jl.83, jl.27, and jl.77 strains compared to S. aureus monocultures under different environmental conditions. The Y-axis shows the percentage change compared to S. aureus monocultures. The X-axis shows the environmental conditions tested. FIG. 5 shows the inhibition of different S. aureus promoter-reporter constructs (agr, psmA, GMK) when the reporter strain of S. aureus is mixed with a three-strain mixture of jl.83, jl.27, and jl.77 strains in the presence of additional environmental conditions (e.g., different nutrients). The data show that the strain combinations retained the inhibitory function of S. aureus across different nutrients.

[0029] [Figure 6]FIG. 6 is a bar graph plotting the percentage change in fluorescent reporter S. aureus gene expression in a three-strain mixture of jl.21, jl.68, and jl.121 strains compared to S. aureus monocultures under different environmental conditions. The Y-axis shows the percentage change compared to S. aureus monocultures. The X-axis shows the environmental conditions tested. FIG. 6 shows the inhibition of different S. aureus promoter-reporter constructs (agr, psmA, GMK) when the reporter strain of S. aureus is mixed with a three-strain mixture of jl.21, jl.68, and jl.121 strains in the presence of additional environmental conditions (e.g., different nutrients). The data show that the strain combinations retained the inhibitory function of S. aureus across different nutrients.

[0030] [Figure 7] FIG. 7 is a bar graph plotting the percentage change in fluorescent reporter S. aureus gene expression in a three-strain mixture of jl.27, jl.68, and jl.121 strains compared to S. aureus monocultures under different environmental conditions. The Y-axis shows the percentage change compared to S. aureus monocultures. The X-axis shows the environmental conditions tested. FIG. 7 shows the inhibition of different S. aureus promoter-reporter constructs (agr, psmA, GMK) when the reporter strain of S. aureus is mixed with a three-strain mixture of jl.27, jl.68, and jl.121 strains in the presence of additional environmental conditions (e.g., different nutrients). The data show that the strain combinations retained the inhibitory function of S. aureus across different nutrients.

[0031] [Figure 8]Figure 8 is a bar graph plotting the percentage activity of fluorescent reporter gene expression in S. aureus under different growth conditions. The Y-axis shows the percentage activity compared to S. aureus monoculture. The X-axis shows the expression of agr (quorum sensing), psmA (toxin production), and GMK (metabolic function) in S. aureus. Figure 8 shows the inhibition of different S. aureus promoter-reporter constructs (agr, psmA, GMK) when the reporter strain of S. aureus is mixed with a three-strain mixture of jl.83, jl.27, and jl.77 in the presence of thiamine. The presence of thiamine enhances the inhibition of S. aureus by the three-strain mixture.

[0032] [Figure 9] Figure 9 is a bar graph plotting the maximum colony forming units (cfu) / ml of isolates in different media. The Y-axis shows the cfu / mL observed across the tested media. The X-axis shows the strains tested and the animal-free medium formulation used for the strains tested. Figure 9 shows the growth of different skin isolates in animal-free medium compared to animal-based medium. The figure shows increased growth for most isolates in animal-free medium.

[0033] [Figure 10] FIG. 10 is a bar graph plotting the percentage of growth of mixed cultures compared to monocultures of S. aureus. The Y-axis shows the effect of growth inhibition (%) by strain combinations. The X-axis shows the growth of different S. aureus strains in the presence of an ensemble (e.g., combination of three strains) or S. aureus strains alone. FIG. 10 shows the inhibition of different S. aureus strains when grown with strains jl.83, jl.27, and jl.77. This figure shows that combining isolates can inhibit the growth of multiple S. aureus isolates.

[0034] [Figure 11] FIG. 11 is a bar graph plotting the percentage of growth of mixed cultures compared to monocultures of S. aureus. The Y-axis shows the effect of growth inhibition (%) by strain combinations. The X-axis shows the growth of different S. aureus strains in the presence of an ensemble (e.g., combination of three strains) or S. aureus strains alone. FIG. 11 shows the inhibition of different S. aureus strains when grown with strains jl.21, jl.68, and jl.121. This figure shows that combining isolates can inhibit the growth of multiple S. aureus isolates.

[0035] [Figure 12] FIG. 12 is a bar graph plotting the percentage of growth of mixed cultures compared to monocultures of S. aureus. The Y-axis shows the effect of growth inhibition (%) by strain combinations. The X-axis shows the growth of different S. aureus strains in the presence of an ensemble (e.g., combination of three strains) or S. aureus strains alone. FIG. 12 shows the inhibition of different S. aureus strains when grown with strains jl.27, jl.68, and jl.121. This figure shows that combining isolates can inhibit the growth of multiple S. aureus isolates.

[0036] [Figure 13] Figure 13 is a data plot of the log2 (co-culture / monoculture) change in gene expression of S. aureus with a fluorescent reporter in different mixtures with jl.27 strains. The Y-axis shows the log2 expression change of the co-culture / S. aureus promoter-reporter monoculture. The X-axis shows the gene promoters tested. Figure 13 shows the inhibition of different S. aureus promoter-reporter constructs when the reporter strain of S. aureus is mixed with a strain combination of jl.27 strains.

[0037] [Figure 14]FIG. 14 is a bar graph plotting the percentage of S. aureus behavior (i.e., expression) of S. aureus genes with the fluorescent reporters agr, psmA, and GMK. Expression of the reporters is plotted relative to expression of S. aureus monocultures. Different strain combinations of jl.121, jl.21, and jl.68 were tested for their ability to reduce gene expression of S. aureus in the presence of up to seven microbial communities. The Y-axis shows the percentage expression of the reporters relative to S. aureus monocultures. The X-axis shows the strain combinations tested. The data show that the triple combination of jl.121, jl.21, and jl.68 typically reduced gene expression more robustly than its subsets (e.g., single strains or combinations of two strains) and was able to reduce gene expression of S. aureus in the presence of additional microorganisms.

[0038] [Figure 15] FIG. 15 is a bar graph plotting the percentage of S. aureus behavior (i.e., expression) of S. aureus genes with the fluorescent reporters agr, psmA, and GMK. Expression of the reporters is plotted relative to expression of S. aureus monocultures. Different strain combinations of jl.121, jl.27, and jl.68 were tested for their ability to reduce gene expression of S. aureus in the presence of up to seven microbial communities. The Y-axis shows the percentage expression of the reporters relative to S. aureus monocultures. The X-axis shows the strain combinations tested. The data show that the triple combination of jl.121, jl.27, and jl.68 strains typically reduced gene expression more robustly than their subsets (e.g., single strains or combinations of two strains) and were able to reduce gene expression of S. aureus in the presence of additional microorganisms.

[0039] [Figure 16]FIG. 16 is a bar graph plotting the percentage of S. aureus behavior (i.e., expression) of S. aureus genes with the fluorescent reporters agr, psmA, and GMK. Expression of the reporters is plotted relative to expression of S. aureus monocultures. Different strain combinations of jl.27, jl.77, and jl.83 were tested for their ability to reduce gene expression of S. aureus in the presence of up to seven microbial communities. The Y-axis shows the percentage expression of the reporters relative to S. aureus monocultures. The X-axis shows the strain combinations tested. The data show that the triple combination of jl.27, jl.77, and jl.83 strains typically reduced gene expression more robustly than their subsets (e.g., single strains or combinations of two strains) and were able to reduce gene expression of S. aureus in the presence of additional microorganisms.

[0040] [Figure 17A] 17A-17B show images of an agar plate containing whole cells of the jl.68 strain plated on a lawn of S. aureus cells. The S. aureus cells contained reporters for expression of agr (quorum sensing) and GMK (metabolism). Expression of agr and GMK was affected by the addition of the jl.68 strain. FIG. 17A shows a zoomed-out picture of the plate. FIG. 17B shows a zoomed-in picture of the plate. [Figure 17B] 17A-17B show images of an agar plate containing whole cells of the jl.68 strain plated on a lawn of S. aureus cells. The S. aureus cells contained reporters for expression of agr (quorum sensing) and GMK (metabolism). Expression of agr and GMK was affected by the addition of the jl.68 strain. FIG. 17A shows a zoomed-out picture of the plate. FIG. 17B shows a zoomed-in picture of the plate.

[0041] [Figure 18A-B]18A-18F show bar graphs showing the expression of S. aureus agr and GMK reporters in S. aureus cells after monoculture or mixing with different bacterial strains, as well as the CFU of S. aureus cells. FIG. 18A shows the CFU of S. aureus and the expression of GMK and agr in monoculture of S. aureus. FIG. 18B shows the CFU of S. aureus and the expression of GMK and agr in 1:1 coculture with S. aureus WT strain (which does not have agr / GMK reporter). FIG. 18C shows the CFU of S. aureus and the expression of GMK and agr in 1:1 coculture with a 3-strain mix of jl.27, jl.68, and jl.77 strains. FIG. 18D shows the CFU of S. aureus and the expression of GMK and agr in 1:1 coculture with a single jl.68 strain. Figure 18E shows the CFU and expression of GMK and agr of S. aureus in cultures using supernatants from a mix of three strains, jl.27, jl.68, and jl.77. Figure 18F shows the CFU and expression of GMK and agr of S. aureus in cultures using supernatants from the jl.68 strain. [Fig. 18C-D]18A-18F show bar graphs showing the expression of S. aureus agr and GMK reporters in S. aureus cells after monoculture or mixing with different bacterial strains, as well as the CFU of S. aureus cells. FIG. 18A shows the CFU of S. aureus and the expression of GMK and agr in monoculture of S. aureus. FIG. 18B shows the CFU of S. aureus and the expression of GMK and agr in 1:1 coculture with S. aureus WT strain (which does not have agr / GMK reporter). FIG. 18C shows the CFU of S. aureus and the expression of GMK and agr in 1:1 coculture with a 3-strain mix of jl.27, jl.68, and jl.77 strains. FIG. 18D shows the CFU of S. aureus and the expression of GMK and agr in 1:1 coculture with a single jl.68 strain. Figure 18E shows the CFU and expression of GMK and agr of S. aureus in cultures using supernatants from a mix of three strains, jl.27, jl.68, and jl.77. Figure 18F shows the CFU and expression of GMK and agr of S. aureus in cultures using supernatants from the jl.68 strain. [Fig. 18E-F]18A-18F show bar graphs showing the expression of S. aureus agr and GMK reporters in S. aureus cells after monoculture or mixing with different bacterial strains, as well as the CFU of S. aureus cells. FIG. 18A shows the CFU of S. aureus and the expression of GMK and agr in monoculture of S. aureus. FIG. 18B shows the CFU of S. aureus and the expression of GMK and agr in 1:1 coculture with S. aureus WT strain (which does not have agr / GMK reporter). FIG. 18C shows the CFU of S. aureus and the expression of GMK and agr in 1:1 coculture with a 3-strain mix of jl.27, jl.68, and jl.77 strains. FIG. 18D shows the CFU of S. aureus and the expression of GMK and agr in 1:1 coculture with a single jl.68 strain. Figure 18E shows the CFU and expression of GMK and agr of S. aureus in cultures using supernatants from a mix of three strains, jl.27, jl.68, and jl.77. Figure 18F shows the CFU and expression of GMK and agr of S. aureus in cultures using supernatants from the jl.68 strain.

[0042] [Figure 19A] Figures 19A-19B show bar graphs showing metabolic and quorum sensing activities in S. aureus cultures of different densities. Supernatant from jl.68 strain (10%) or PBS (control) was added to S. aureus at different concentrations. Figure 19A shows the expression of GMK after the addition of the supernatant. Figure 19B shows the expression of agr after the addition of the supernatant. [Figure 19B] Figures 19A-19B show bar graphs showing metabolic and quorum sensing activities in S. aureus cultures of different densities. Supernatant from jl.68 strain (10%) or PBS (control) was added to S. aureus at different concentrations. Figure 19A shows the expression of GMK after the addition of the supernatant. Figure 19B shows the expression of agr after the addition of the supernatant.

[0043] [Figure 20]Figure 20 shows images of agar plates with different concentrations (0%, 5%, and 10%) of the supernatant from strain jl.68 embedded in TSB agar plates and a 10-fold dilution series of S. aureus plated onto the agar. CFU / ml is the amount of S. aureus present on the plate after incubation. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0044] Detailed Description of the Invention Provided herein are compositions, methods, kits, and devices for the treatment of skin diseases. Further provided herein are (1) mixtures of bacteria, (2) excipients, dosage forms, and routes of administration for such mixtures, and (3) conditions of treatment with such mixtures of bacteria.

[0045] Throughout this disclosure, various embodiments are expressed in range format. It should be understood that the description in range format is for convenience and brevity only and is not to be construed as immutably limiting the scope of any embodiment. Thus, unless the context clearly indicates otherwise, the description of a range should be considered to have specifically disclosed all possible subranges as well as individual numerical values ​​within that range to the tenth of the unit of the lower limit. For example, the description of a range such as 1 to 6 should be considered to have specifically disclosed subranges such as 1 to 3, 1 to 4, 1 to 5, 2 to 4, 2 to 6, 3 to 6, etc., as well as individual values ​​within that range (e.g., 1.1, 2, 2.3, 5, and 5.9). The upper or lower limits of these intervening ranges may be independently included in the smaller ranges and are encompassed within the scope of the invention, subject to any specifically excluded limit of the stated range. Unless the context clearly indicates otherwise, when a stated range includes one or both of the limits, ranges excluding either or both of the included limits are also included.

[0046] The terms used herein are intended only to describe particular examples and are not intended to limit any embodiment. As used herein, the singular forms "a," "an," and "the" are intended to include the plural forms unless the context clearly dictates otherwise. As used herein, the term "and / or" includes any and all combinations of one or more of the associated listed items.

[0047] Unless specifically stated or clear from the context, as used herein, the term "about" in reference to a numerical value or range of numerical values ​​is understood to mean the stated numerical value and + / - 10% of that numerical value, or, for values ​​recited in a range, less than 10% of the recited lower limit and more than 10% of the recited upper limit.

[0048] As used herein, the term "subject" includes human and non-human mammals, including, for example, primates, cows, horses, pigs, sheep, goats, dogs, cats, or rodents that can be colonized by other organisms.

[0049] In some embodiments, compositions are provided herein that include bacteria that have a certain percent identity based on comparison of 16S rRNA bacterial gene sequences, 16S rRNA hypervariable regions, or whole genomes with a reference strain. Typically, comparison of 16S rRNA bacterial gene sequences can be used to identify whether the strain is within the same species or is a different strain by comparing the sequence with known bacterial DNA sequences using NCBI BLAST search. The level of identity for a nucleotide sequence may be determined for at least 20 contiguous nucleotides, at least 30 contiguous nucleotides, at least 40 contiguous nucleotides, at least 50 contiguous nucleotides, at least 60 contiguous nucleotides, at least 100 contiguous nucleotides, at least 200 contiguous nucleotides, at least 300 contiguous nucleotides, at least 400 contiguous nucleotides, at least 500 contiguous nucleotides, at least 600 contiguous nucleotides, at least 700 contiguous nucleotides, at least 800 contiguous nucleotides, at least 900 contiguous nucleotides, at least 1000 contiguous nucleotides, at least 1100 contiguous nucleotides, at least 1200 contiguous nucleotides, at least 1300 contiguous nucleotides, at least 1400 contiguous nucleotides, or at least 1500 contiguous nucleotides. In some embodiments, the level of identity for a nucleotide sequence is determined for the entire sequence searched. The percent identity can be at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% to the 16S rRNA sequence, 16S rRNA V4 region sequence, or entire genome sequence of the reference bacterium.The percent identity may be at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% relative to the sequence of the 16S rRNA:V1 region, V2 region, V3 region, V5 region, V6 region, V7 region, V8 region, or V9 region of the reference bacterium. The percent identity may be at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% relative to the sequence of the reference bacterium.

[0050] As used herein, a substance is "pure" or "substantially pure" if it is substantially free of other components of the sample source from which it is obtained. The terms "purify", "purifying" and "purified" when applied to a bacterium or bacteria can refer to a bacterium that has been separated from at least some components with which it was associated when the bacterium was first produced or produced, or any time period after its first production. A bacterium or bacterial population can be considered purified if it has been separated from or passaged in culture from materials or environments, etc., that contain the bacterium or bacterial population during or after production. A purified bacterium or bacterial population can contain at least up to about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, or more than about 90% of other materials and still be considered purified. A purified bacterium or population of bacteria may be one in which a single strain type is present at at least about 5, 10, 15, 20, 25, 30, 35, 40, 45, 50%, or more of the bacteria present in the composition and still be considered purified.

[0051] bacterial mixture Human skin provides multiple environments for the microbiome. In healthy individuals, both the skin microbiome and the skin host environment are important for maintaining skin health. However, dysbiosis of the skin microbiome and replacement of commensal bacterial species with pathogenic bacterial species can cause disease. To this end, the function and diversity of the skin microbiome can be restored by perturbing the damaged skin microbiome with bacterial isolates from healthy individuals. For example, the repair and / or modification of the damaged microbiome can be used to treat disease. The compositions described herein are used for the treatment of damaged skin microbiome, and the compositions include purified bacterial species. In some embodiments, the bacterial species include at least one, two, or three of the following bacterial species: Bacillus velezensis, Bacillus wiedmannii, Lysinibacillus macrolides, Bacillus amyloliquefaciens, Staphylococcus caprae, and Bacillus tropicus. In some embodiments, the composition comprises at least one, two, or three of the following bacterial species: Bacillus cereus, Staphylococcus epidermidis, Bacillus nakamurai, Bacillus vallismortis, Lysinibacillus boronitolerans, Bacillus paranthracis, Bacillus thuringiensis, Psychrobacillus sp. INOP01, Lysinibacillus sp. FN11, Bacillus sp. Lzh-5, or Staphylococcus capitis. The bacterial species is lyophilized and / or formulated for delivery to the skin. The composition can be formulated as a suspension, emulsion, cream, lotion, tincture, gel, foam, powder, ointment, paste, or oil. Administration of the bacterial species is used to treat skin inflammation, skin disorders (such as atopic dermatitis), or symptoms associated with skin inflammation or skin disorders.

[0052] Further, the compositions described herein are used for the treatment of damaged skin microbiome, and the compositions comprise purified bacterial strains. In some embodiments, the bacterial strains comprise at least one, two, or three of the following bacterial strains: jl.121, jl.21, jl.27, jl.68, jl.83, or jl.77. The bacterial strains are lyophilized and / or formulated for delivery to the skin. The compositions can be formulated as suspensions, emulsions, creams, lotions, tinctures, gels, foams, powders, ointments, pastes, or oils. Administration of the bacterial strains is used to treat skin inflammation, skin disorders (such as atopic dermatitis), or symptoms associated with skin inflammation or skin disorders.

[0053] The bacteria described herein and mixtures of bacteria described herein are used to treat or inhibit, reduce, and / or eliminate pathogenic bacterial colonization or induction of inflammation of the skin. The bacteria described herein and mixtures of bacteria described herein are used to suppress the growth of pathogenic bacteria. The bacteria described herein are used to modulate gene expression in pathogenic microorganisms. The bacteria described herein are used to modulate protein expression in pathogenic microorganisms. The bacteria described herein are isolated from the skin of a healthy individual. In some embodiments, the bacteria described herein are purified. For example, isolates of the bacteria described herein can be purified by one or more passages on agar medium. In some cases, a healthy individual is a subject who does not have one or more skin diseases. In some cases, the bacteria are isolated from the epidermis of the skin. In some cases, the bacteria are isolated from the skin of the feet, legs, arms, torso, hands, groin, armpits, back, neck, head, ears, nose, face, or any area of ​​the body covered with skin. In some embodiments, the bacteria described herein are present in a composition. In some embodiments, the bacteria described herein are administered for the treatment of a disease. In some cases, the compositions described herein are lyophilized. In some cases, the compositions described herein are formulated for delivery to the skin.

[0054] In some embodiments, the composition comprises live bacteria. In some cases, live bacteria include bacteria that retain membrane stability. In some cases, live bacteria include bacteria that can transcribe and translate. In some cases, live bacteria include bacteria that can undergo cell division. In some cases, live bacteria are determined by culture-dependent or culture-independent techniques. In some cases, live bacteria include individual bacteria or groups of bacteria that can obtain colony forming units (cfu) when plated on a stable growth medium. In some embodiments, live and / or dead bacteria are determined by imaging, for example, with live / dead staining. In some cases, a viability PCR based method can be used to determine live bacteria. In some cases, a metabolomic assay is used to determine live bacteria.

[0055] In some embodiments, the bacteria described herein are grown under aerobic conditions. In some cases, the bacteria described herein are grown under anaerobic conditions. In some cases, the bacteria described herein can be obligate aerobes, obligate anaerobes, facultative anaerobes, microaerophiles, or aerotolerant microorganisms and can be grown under any conditions applicable for growth (e.g., 0-40% O2, and / or 0-40% CO2). The bacteria described herein are grown at room temperature or in an incubator. For example, the bacteria described herein can be grown at any temperature conducive to growth. In some examples, the bacteria described herein are grown at about 1°C to 50°C. In some examples, the bacteria described herein are grown at 30°C. In some examples, the bacteria described herein are grown at 37°C. The bacteria described herein are grown in liquid culture or on solid media (such as agar supplemented with nutrients). In some cases, the bacteria are grown in media with or without animal products. In some cases, the bacteria are grown in media without animal products. In some examples, the bacteria are grown in tryptic soy broth (TSB).

[0056] In some cases, the bacteria and / or compositions described herein are stored in a container. In some cases, the container is glass, plastic, metal, or any solid material. In some cases, the container is included in a kit. In some examples, the sealed container containing the bacteria or compositions described herein is stored at about: -80°C, -79°C, -78°C, -77°C, -76°C, -75°C, -74°C, -73°C, -72°C, -71°C, -70°C, -69°C, -68°C, -67°C, -66°C, -65°C, -64°C, -63°C, -62°C, -61°C, -60°C, -59°C, -58°C, -57°C, -56°C, -55°C, -54°C, -53 ... °C, -52°C, -51°C, -50°C, -49°C, -48°C, -47°C, -46°C, -45°C, -44°C, -43°C, -42°C, -41°C, -40°C, -39°C, -38°C, -37°C, -36°C, -35°C, -34°C, -33°C, -32°C, -31°C, -30°C, -29°C, -28°C, -27°C, -26°C, -25°C, -24°C, -23°C, -22°C, -21°C, -20°C, -19°C, -1 8℃, -17℃, -16℃, -15℃, -14℃, -13℃, -12℃, -11℃, -10℃, -9℃, -8℃, -7℃, -6℃, -5℃, -4℃, -3℃, -2℃, -1℃, 0℃, 1℃, 2℃, 3℃, 4℃, 5℃, 6℃, 7℃, 8℃, 9℃, 10℃, 11℃, 12℃, 13℃, 14℃, 15℃, 16℃, 17℃, 18℃, 19℃, 20℃, 21℃, 22℃, 23℃, 24℃, 25℃, 2 When placed at 6°C, 27°C, 28°C, 29°C, 30°C, 31°C, 32°C, 33°C, 34°C, 35°C, 36°C, 37°C, or 38°C, the bacteria may retain greater than about: 0.1%, 1%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 99% culture viability as measured by cfu count after 3 months, 6 months, or 12 months.In some examples, the sealed container containing the bacteria or compositions described herein is incubated at room temperature for about: -80°C, -79°C, -78°C, -77°C, -76°C, -75°C, -74°C, -73°C, -72°C, -71°C, -70°C, -69°C, -68°C, -67°C, -66°C, -65°C, -64°C, -63°C, -62°C, -61°C, -60°C, -59°C, -58°C, -57°C, - 56℃, -55℃, -54℃, -53℃, -52℃, -51℃, -50℃, -49℃, -48℃, -47℃, -46℃, -45℃, -44℃, -43℃, -42℃, -41℃, -40℃, -39℃, -38℃, -37℃, -36℃, -35℃, -34℃, -33℃, -32℃, -31℃, -30℃, -29℃, -28℃, -27℃, -26℃, -25℃ ,-24℃,-23℃,-22℃,-21℃,-20℃,-19℃,-18℃,-17℃,-16℃,-15℃,-14℃,-13℃,-12℃,-11℃,-10℃,-9℃,-8℃,-7℃,-6℃,-5℃,-4℃,-3℃,-2℃,-1℃,0℃,1℃,2℃,3℃,4℃,5℃,6℃,7℃,8℃,9℃,10℃,11℃,12℃,13℃, When placed at 14°C, 15°C, 16°C, 17°C, 18°C, 19°C, 20°C, 21°C, 22°C, 23°C, 24°C, 25°C, 26°C, 27°C, 28°C, 29°C, 30°C, 31°C, 32°C, 33°C, 34°C, 35°C, 36°C, 37°C, or 38°C, the bacteria decreased to about:10 after 3 months, 6 months, or 12 months as measured by cfu count. 3 cfu, approximately 10 4 cfu, approximately 10 5 cfu, approximately 10 6 cfu, approximately 10 7 cfu, approximately 10 8 cfu, approximately 10 9 cfu, approximately 10 10 cfu, approximately 10 11 cfu, approximately 10 12 In some cases, the compositions disclosed herein are stable in a freezer (e.g., from -80°C to about -20°C), a refrigerator (e.g., 4°C), or at room temperature.

[0057] In some embodiments, compositions of bacterial species are provided herein. In some cases, the compositions described herein comprise one or more bacterial species. For example, the compositions described herein comprise two, three, four, five, six, seven, eight, nine, ten, or more bacterial species. In some cases, the compositions described herein comprise one bacterial species. In some cases, the compositions described herein comprise two bacterial species. In some cases, the compositions described herein comprise three bacterial species. In some cases, the compositions described herein comprise four bacterial species. A mixture of bacteria is provided herein that comprises one or more bacterial species of Table 1. In some embodiments, the compositions described herein comprise one, two, three, four, five, six, seven, eight, nine, ten, or more bacterial species in Table 1.

[0058] [Table 1]

[0059] In some cases, the compositions described herein comprise one or more bacterial strains. For example, the compositions described herein comprise two, three, four, five, six, seven, eight, nine, ten, or more bacterial strains. In some cases, the compositions described herein comprise one bacterial strain. In some cases, the compositions described herein comprise two bacterial strains. In some cases, the compositions described herein comprise three bacterial strains. In some cases, the compositions described herein comprise four bacterial strains. Provided herein is a mixture of bacteria comprising one or more bacterial strains of Table 2. In some embodiments, the compositions described herein comprise one, two, three, four, five, six, seven, eight, nine, ten, or more bacterial strains in Table 2.

[0060] [Table 2]

[0061] In some cases, the bacterial strain comprises a jl.83 strain, a jl.27 strain, a jl.77 strain, a jl.68 strain, a jl.121 strain, or a jl.21 strain. In some examples, the bacterial strains herein are identified by 16s rRNA sequences. In some cases, the jl.83 strain comprises a 16s rRNA sequence of SEQ ID NO:4. In some cases, the jl.83 strain comprises a 16s rRNA sequence having at least: 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO:4. In some cases, the jl.27 strain comprises a 16s rRNA sequence of SEQ ID NO:1. In some cases, the jl.27 strain comprises a 16s rRNA sequence having at least: 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO:1. In some cases, the jl.77 strain comprises a 16s rRNA sequence of SEQ ID NO:2. In some cases, the jl.77 strain comprises a 16s rRNA sequence having at least: 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO:2. In some cases, the jl.68 strain comprises a 16s rRNA sequence of SEQ ID NO:5. In some cases, the jl.68 strain comprises a 16s rRNA sequence having at least: 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO:5. In some cases, the jl.121 strain comprises a 16s rRNA sequence of SEQ ID NO:6. In some cases, the jl.121 strain comprises a 16s rRNA sequence having at least: 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO:6. In some cases, the jl.21 strain comprises a 16s rRNA sequence of SEQ ID NO: 3. In some cases, the jl.21 strain comprises a 16s rRNA sequence having at least: 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 3.

[0062] In some cases, the bacterial strain comprises strain jl.19, strain jl.39, strain jl.26, strain jl.116, strain jl.119, or strain jl.45. In some cases, the jl.19 strain comprises a 16s rRNA sequence of SEQ ID NO: 16. In some cases, the jl.19 strain comprises a 16s rRNA sequence having at least: 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 16. In some cases, the jl.39 strain comprises a 16s rRNA sequence of SEQ ID NO: 17. In some cases, the jl.39 strain comprises a 16s rRNA sequence having at least: 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 17. In some cases, the jl.26 strain comprises a 16s rRNA sequence of SEQ ID NO: 18. In some cases, the jl.26 strain comprises a 16s rRNA sequence having at least: 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 18. In some cases, the jl.116 strain comprises a 16s rRNA sequence of SEQ ID NO: 19. In some cases, the jl.116 strain comprises a 16s rRNA sequence having at least: 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 19. In some cases, the jl.119 strain comprises a 16s rRNA sequence of SEQ ID NO: 20. In some cases, the jl.119 strain comprises a 16s rRNA sequence having at least: 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 20. In some cases, the jl.45 strain comprises a 16s rRNA sequence of SEQ ID NO: 21. In some cases, the jl.45 strain comprises a 16s rRNA sequence having at least: 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 21. In some cases, the bacterial strains herein comprise a 16s rRNA sequence having at least: 95%, 96%, 97%, 98%, or 99% sequence identity over at least 500 bases, 600 bases, 700 bases, 800 bases, 900 bases, 1000 bases, or 1100 bases to any one of SEQ ID NOs: 1-6 or 16-21.In some cases, the bacterial strains herein comprise a 16s rRNA sequence having 100% sequence identity over at least 500 bases, 600 bases, 700 bases, 800 bases, 900 bases, 1000 bases, or 1100 bases to any one of SEQ ID NOs:1-6 or 16-21.

[0063] In some examples, the bacterial strains herein are identified by identifier sequences. For example, the identifier sequences are sequences found in genomes and / or accessory genomes (such as plasmids) used to identify bacterial strains. In some cases, the jl.83 strain comprises an identifier sequence of SEQ ID NO:11, SEQ ID NO:12, or both. In some cases, the jl.83 strain comprises an identifier sequence with at least: 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO:11. In some cases, the jl.83 strain comprises an identifier sequence with at least: 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO:12. In some cases, the jl.27 strain comprises an identifier sequence of SEQ ID NO:15. In some cases, the jl.27 strain comprises an identifier sequence having at least: 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 15. In some cases, the jl.77 strain comprises an identifier sequence of SEQ ID NO: 7, SEQ ID NO: 8, or both. In some cases, the jl.77 strain comprises an identifier sequence having at least: 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 7. In some cases, the jl.77 strain comprises an identifier sequence having at least: 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 8. In some cases, the jl.68 strain comprises an identifier sequence of SEQ ID NO: 13. In some cases, the jl.68 strain comprises an identifier sequence having at least: 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 13. In some cases, the jl.121 strain comprises an identifier sequence of SEQ ID NO: 14. In some cases, the jl.121 strain comprises an identifier sequence having at least: 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 14.In some cases, the jl.21 strain comprises an identifier sequence of SEQ ID NO:9, SEQ ID NO:10, or both. In some cases, the jl.21 strain comprises an identifier sequence having at least: 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO:9. In some cases, the jl.21 strain comprises an identifier sequence having at least: 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO:10. In some cases, the bacterial strains herein comprise an identifier sequence having at least: 95%, 96%, 97%, 98%, or 99% sequence identity over at least 500 bases, 600 bases, 700 bases, 800 bases, 900 bases, 1000 bases, 1100 bases, or 1200 bases to any one of SEQ ID NOs: 7-15. In some cases, the bacterial strains herein comprise an identifier sequence having 100% sequence identity over at least 500 bases, 600 bases, 700 bases, 800 bases, 900 bases, 1000 bases, 1100 bases, or 1200 bases to any one of SEQ ID NOs: 7-15.

[0064] In some embodiments, bacteria are provided herein that include a sequence of SEQ ID NO:11, SEQ ID NO:12, or both. In some cases, bacteria are provided herein that include a sequence with at least: 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO:11. In some cases, bacteria are provided herein that include a sequence with at least: 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO:12. In some cases, bacteria are provided herein that include a sequence of SEQ ID NO:15. In some cases, bacteria are provided herein that include a sequence with at least: 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO:15. In some cases, bacteria are provided herein that include a sequence of SEQ ID NO:7, SEQ ID NO:8, or both. In some cases, bacteria are provided herein that include a sequence that has at least: 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO:7. In some cases, bacteria are provided herein that include a sequence that has at least: 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO:8. In some cases, bacteria are provided herein that include a sequence of SEQ ID NO:13. In some cases, bacteria are provided herein that include a sequence that has at least: 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO:13. In some cases, bacteria are provided herein that include a sequence of SEQ ID NO:14. In some cases, provided herein are bacteria that include a sequence having at least: 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 14. In some cases, provided herein are bacteria that include a sequence of SEQ ID NO: 9, SEQ ID NO: 10, or both.In some cases, provided herein are bacteria comprising a sequence having at least: 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 9. In some cases, provided herein are bacteria comprising a sequence having at least: 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 10.

[0065] In some embodiments, the compositions herein can include cell-free components (such as supernatants from any one of the strains listed in Table 2). In some cases, the compositions herein can include cell-free components from any combination of the strains listed in Table 2. In some cases, the compositions herein can include cell-free components from one or more bacterial strains having at least 95%, 96%, 97%, 98%, or 99% sequence identity to any one of SEQ ID NOs: 1-6 or 16-21. In some cases, the compositions herein can include cell-free components from one or more bacterial strains including any one of SEQ ID NOs: 1-6 or 16-21. In some cases, the compositions herein can include cell-free components from a bacterial strain having at least 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 5. In some cases, the compositions herein can include cell-free components from a bacterial strain including SEQ ID NO: 5.

[0066] In some cases, the compositions described herein include one or more bacterial strains and one or more bacterial species. For example, the compositions described herein include two bacterial species and one bacterial strain.

[0067] In some embodiments, the composition comprises two or more bacterial species or strains. In some embodiments, the composition comprises at least two of the following bacterial species: Staphylococcus cohnii, Staphylococcus capitis, Staphylococcus caprae, Bacillus tropicus, Bacillus mycoides, Bacillus wiedmannii, Bacillus mediterraneensis, Bacillus amyloliquefaciens, Bacillus velezensis, Bacillus cereus, Bacillus cecembensis, Kocuria marina, and Lysinibacillus macroides. In some embodiments, the composition comprises at least two of the following bacterial species: Bacillus cereus, Staphylococcus epidermidis, Bacillus nakamurai, Bacillus vallismortis, Lysinibacillus boronitolerans, Bacillus paranthracis, Bacillus thuringiensis, Psychrobacillus sp. INOP01, Lysinibacillus sp. FN11, Bacillus sp. Lzh-5, or Staphylococcus capitis. In some embodiments, the composition comprises at least two of the following bacterial species: Bacillus velezensis, Bacillus wiedmannii, Lysinibacillus macrolides, Bacillus amyloliquefaciens, Staphylococcus caprae, and Bacillus tropicus. In some embodiments, the composition comprises at least two of the following bacterial strains: strain jl.83, strain jl.27, strain jl.77, strain jl.68, strain jl.121, and strain jl.21. In some cases, the composition comprises bacterial strains jl.83 and jl.27. In some cases, the composition comprises bacterial strains jl.68 and jl.27.In some cases, the composition comprises bacterial strains jl.68 and jl.21. In some cases, the composition comprises bacterial strains jl.83 and jl.77. In some cases, the composition comprises bacterial strains jl.27 and jl.121. In some cases, the composition comprises bacterial strains jl.21 and jl.121.

[0068] In some embodiments, the composition comprises three or more bacterial species or strains. In some embodiments, the composition comprises at least three of the following bacterial species: Staphylococcus cohnii, Staphylococcus capitis, Staphylococcus caprae, Bacillus tropicus, Bacillus mycoides, Bacillus wiedmannii, Bacillus mediterraneensis, Bacillus amyloliquefaciens, Bacillus velezensis, Bacillus cereus, Bacillus cecembensis, Kocuria marina, and Lysinibacillus macroides. In some embodiments, the composition comprises at least three of the following bacterial species: Bacillus velezensis, Bacillus wiedmannii, Lysinibacillus macrolides, Bacillus amyloliquefaciens, Staphylococcus caprae, and Bacillus tropicus. In some embodiments, the composition comprises at least three of the following bacterial strains: strain jl.83, strain jl.27, strain jl.77, strain jl.68, strain jl.121, and strain jl.21.

[0069] In some embodiments, the compositions described herein include three bacterial species or strains. In some embodiments, the compositions include the bacterial species Bacillus velezensis, Bacillus wiedmannii, and Lysinibacillus macrolides. In some cases, the compositions include the bacterial strains jl.83, jl.27, and jl.77. In some embodiments, the compositions include the bacterial species Bacillus amyloliquefaciens, Bacillus wiedmannii, and Staphylococcus caprae. In some cases, the compositions include the bacterial strains jl.68, jl.27, and jl.121. In some embodiments, the compositions include the bacterial species Bacillus amyloliquefaciens, Bacillus tropicus, and Staphylococcus caprae. In some cases, the compositions include the bacterial strains jl.68, jl.21, and jl.121. In some embodiments, the compositions include a combination of bacterial species from Table 3. In some embodiments, the composition is a combination of bacterial species from Table 3. In some embodiments, the composition comprises a combination of bacterial strains from Table 4. In some embodiments, the composition is a combination of bacterial strains from Table 4.

[0070] [Table 3]

[0071] [Table 4-1] [Table 4-2]

[0072] In some embodiments, the compositions described herein comprise one bacterial species or strain. In some embodiments, the compositions comprise a second bacterial species or strain. In some embodiments, the compositions comprise Bacillus velezensis. In some cases, the compositions comprise a jl.83 strain. In some embodiments, the compositions comprise Bacillus wiedmannii. In some cases, the compositions comprise a jl.27 strain. In some embodiments, the compositions comprise Lysinibacillus macroides. In some cases, the compositions comprise a jl.77 strain. In some embodiments, the compositions comprise Bacillus tropicus. In some cases, the compositions comprise a jl.21 strain. In some embodiments, the compositions comprise Bacillus amyloliquefaciens. In some cases, the compositions comprise a jl.68 strain. In some embodiments, the compositions comprise Staphylococcus caprae. In some cases, the compositions comprise a jl.121 strain. In some embodiments, the compositions comprise Staphylococcus cohnii. In some cases, the compositions comprise a jl.19 strain. In some embodiments, the composition comprises Staphylococcus capitis. In some cases, the composition comprises a jl.39 strain. In some embodiments, the composition comprises Bacillus mycoides. In some cases, the composition comprises a jl.26 strain. In some embodiments, the composition comprises Bacillus mediterraneensis. In some cases, the composition comprises Bacillus mediterraneensis jl.44. In some embodiments, the composition comprises Bacillus cereus. In some cases, the composition comprises a jl.116 strain. In some embodiments, the composition comprises Bacillus cecembensis. In some cases, the composition comprises a jl.119 strain. In some embodiments, the composition comprises Kocuria marina. In some cases, the composition comprises a jl.45 strain.

[0073] In some embodiments, the Bacillus velezensis is Bacillus velezensis DSM23117 and is available from the DSMZ-German Collection of Microorganisms and Cell Cultures depository. In some embodiments, the Bacillus wiedmannii is Bacillus wiedmannii DSM102050 and is available from the DSMZ-German Collection of Microorganisms and Cell Cultures depository. In some embodiments, the Lysinibacillus macroides is Lysinibacillus macroides DSM54 and is available from the DSMZ-German Collection of Microorganisms and Cell Cultures depository. In some embodiments, the Bacillus amyloliquefaciens is Bacillus amyloliquefaciens DSM7 and is available from the DSMZ-German Collection of Microorganisms and Cell Cultures depository. In some embodiments, the Staphylococcus caprae is Staphylococcus caprae DSM20608, available from the DSMZ-German Collection of Microorganisms and Cell Cultures depository. In some embodiments, the Bacillus amyloliquefaciens is Bacillus amyloliquefaciens ATCC23350 (Bacillus amyloliquefaciens F IFO15535), available from the ATCC (American Type Culture Collection) depository.In some embodiments, the Bacillus tropicus is Bacillus tropicus ATCC4342 (Bacillus tropicus NRS731), available from the American Type Culture Collection (ATCC) depository.

[0074] In some embodiments, when administered to a subject, the bacterial species or strains described herein can reduce or eliminate the colonization of the skin of pathogenic bacteria, fungi, or viruses. In some cases, the compositions described herein can be used to kill pathogenic bacteria, fungi, or viruses. In some cases, the compositions described herein can be used to inhibit the growth of pathogenic bacteria, fungi, or viruses. In some cases, the compositions described herein can be used to control the growth of pathogenic bacteria, fungi, or viruses. In some cases, the compositions described herein can be used to control the virulence of pathogenic bacteria, fungi, or viruses. In some cases, a composition comprising one or more bacterial species or strains can reduce or eliminate the colonization of the skin of pathogenic bacteria, fungi, or viruses when administered. Skin pathogenic bacteria include, but are not limited to, Staphylococcus sp., Micrococcus sp., Corynebacterium sp., Staphylococcus aureus, Streptococcus pyogenes, Pseudomonas aeruginosa, Pasteurella multocida, Capnocytophaga canimorsus, Bartonella sp., Klebsiella rhinoscleromatis, and Vibrio vulnificus. In some cases, pathogenic bacteria include Gardnerella vaginalis. Pathogenic skin fungi include, but are not limited to, ascomycete dermatophytes, including those in the genera Aspergillus, Trichophyton, Microsporum, and Epidermophyton, and basidiomycete fungi in the genus Malassezia. In some cases, skin pathogenic fungi include Malassezia pachydermatis, Candida albicans, Microsporum canis, and Trichophyton mentagrophytes.Exemplary skin pathogenic viruses include, but are not limited to, Herpes sp., Herpes zoster., Herpes simplex., Molluscum contagiosum, and human papillomavirus. Such reduction of pathogenic bacteria, fungi, or viruses can be in any location of the skin (e.g., the forearm, leg, or stomach of a subject). In some cases, the compositions herein can reduce the toxin production of S. aureus, reduce the hypha formation of fungi (e.g., Candida), reduce the sebum metabolism of Malassezia, or reduce the biofilm formation of Gardnerella.

[0075] Provided herein are compositions comprising the bacterial species and / or bacterial strains described herein in an amount sufficient for modulating gene expression in a pathogenic microorganism or modulating protein expression in a pathogenic microorganism. In some cases, the modulation is an increase in gene expression or protein expression. In some cases, the modulation is a decrease in gene expression or protein expression. In some cases, the composition reduces the expression of a gene or protein from S. aureus or S. pyogenes. Examples of genes for modulation and suppression include, but are not limited to, virulence genes, metabolic genes, transcription genes, translation genes, protein processing genes, protein folding genes, secretion genes, cell division genes, biosynthetic genes, cell wall genes, cell membrane genes, antibiotic resistance genes, and proteins encoded by one of these genes. In some cases, the gene or protein is related to growth, regulation (e.g., virulence regulation, metabolic regulation, or growth regulation), direct virulence (such as toxins, stress, or metabolic conditions). In some cases, the gene is gmk, agr, psmA, sigB, saeR, and / or ccpA. In some cases, the protein is encoded by gmk, agr, psmA, sigB, saeR, and / or ccpA. In some cases, the expression of the gene is measured by a promoter-reporter strain. For example, the promoter of the gene of interest, such as gmk, agr, psmA, sigB, saeR, or ccpA, can be fused to a fluorescent reporter (such as GFP) or luciferase to measure gene expression. Exemplary genes of promoter-reporter S. aureus strains are shown in Table 5. In some cases, gene expression is used to evaluate constitutive metabolic functions, quorum sensing, toxins that damage host tissues, stress response sigma factors, virulence regulation, and / or carbon catabolite repression.In some cases, gene expression is measured by Northern blot, Western blot, promoter-reporter gene, microarray, PCR assay (such as reverse transcription polymerase chain reaction), serial analysis of gene expression (SAGE), next generation sequencing technology (such as RNA Seq), or a combination of these methods. In some cases, protein expression is measured. In some cases, protein expression is measured by Western blot, enzyme-linked immunosorbent assay (ELISA), SDS-PAGE gel, bicinchoninic acid (BCA) assay, or any assay that quantifies protein expression and / or amount.

[0076] [Table 5]

[0077] In some embodiments, the composition comprising the bacterial species and / or strain can further comprise one or more compounds. In some cases, the compound can be an environmental component. In some cases, the compound comprises a carbon source, a nitrogen source, a phosphorus source, a sulfur source, or a metal ion source. In some cases, the compound can have a synergistic effect with the bacterial composition. For example, the compound can enhance the inhibition of S. aureus expression. In some cases, the compound increases the efficacy of the bacterial composition. In some cases, the compound comprises thiamine (vitamin B-1) or a salt thereof. In some cases, the compound comprises acetate, beta-alanine, bicarbonate, biotin, butyrate, caffeine, citrate, creatine, D-cellobiose, D-fructose, D-glucosamine, D-glucose, D-mannitol, D-raffinose, D-sorbitol, D-sucrose, D-trehalose, D-xylose, formate, GlcNAc, glycerol, glycine, L-alanine, L-arabinose. , L-arginine, L-citrulline, L-glutamine, L-hydroxyproline, L-isoleucine, L-leucine, L-methionine, L-ornithine, L-proline, L-serine, L-taurine, L-threonine, L-valine, L-ascorbate, L-lactate, nicotinamine, polysorbate 20, polysorbate 80, propionate, pyruvate, succinate, thiamine, triethanolamine, or urea.

[0078] Route of administration, excipients, dosage, and dosage form In some embodiments, the terms "administer", "administering" and "administration" as used herein can refer to methods that can be used to deliver the compositions described herein to the desired biological site of action. In some cases, delivery includes local administration. In some cases, delivery can include injection, inhalation, catheterization, gastrostomy tube administration, intravenous administration, intraosseous administration, ocular administration, auricular administration, topical administration, transdermal administration, oral administration, rectal administration, nasal administration, vaginal administration, intracavernosal administration, intracerebral administration, transurethral administration, buccal administration, sublingual administration, or combinations thereof. Delivery can include direct application to affected tissue or affected area of ​​the body. Delivery can include parenchymal injection, intrathecal injection, intravenous injection, intracisternal injection, or intracisternal injection. The compositions provided herein can be administered by any method. The method of administration can be by intraarterial injection, intraventricular injection, intracisternal injection, intramuscular injection, intraorbital injection, intraparenchymal injection, intraperitoneal injection, intraspinal injection, intrathecal injection, intravenous injection, intravenous injection, stereotactic injection, subcutaneous injection, epidural injection, or combination thereof. The delivery includes parenteral administration (e.g., intravenous, subcutaneous, intrathecal, intraperitoneal, intramuscular, intravascular, or injection). In some embodiments, the delivery includes nanoparticles, microparticles, virus-like particles, liposomes, exosomes, extracellular vesicles, microneedles, implants, or combinations thereof. In some cases, the delivery is from a device. In some cases, the delivery is by enema, eye drops, nasal spray, spray, ear drops, or any combination thereof. In some cases, the delivery is in the form of a liquid, suspension, emulsion, tablet, pill, pellet, capsule, capsule containing liquid, powder, sustained release formulation, directed release formulation, lyophilisate (freeze-dried / lyophilized), aerosol, spray, granule, powder, or syrup. In some cases, the delivery includes an inhaler, diffuser, nebulizer, or combination thereof.Delivery can include topical administration (such as lotions, creams, patches, films, gels, sprays, drops, liquid formulations, ointments, suspensions, emulsions, tinctures, foams, powders, pastes, or oils) to an external surface such as the skin. In some cases, the subject can administer the composition without supervision. In some cases, the subject can administer the composition under the supervision of a medical professional (e.g., a doctor, a nurse, a physician's assistant, an orderly, a hospice worker, etc.). In some cases, a medical professional can administer the composition. In some cases, the subject can administer the composition.

[0079] In order to facilitate administration, the pharmaceutical compositions described herein may contain one or more pharma- ceutically acceptable excipients.Exemplary pharma-ceutically acceptable excipients include, but are not limited to, diluents, adjuvants, excipients, water, oil (including petroleum oil, animal oil, vegetable oil, natural oil, synthetic oil).Further examples include saline, gum acacia, gelatin, starch paste, talc, keratin, colloidal silica, and urea. Such excipients may include binders (such as ethyl cellulose, carboxymethyl cellulose, microcrystalline cellulose, or gelatin); fillers (such as starch, lactose, or dextrin); disintegrants (such as alginic acid, sodium alginate, Primogel, and corn starch); lubricants (such as magnesium stearate or Sterotex); glidants (such as colloidal silicon dioxide); sweeteners (such as sucrose or saccharin), flavors (such as peppermint, methyl salicylate, or orange flavor), or colorants. Further examples of excipients include polyethylene glycol, cyclodextrin, oil, or any other similar liquid carrier that can be formulated into a capsule. Still further examples of excipients include sterile diluents such as water, saline, physiological saline, Ringer's solution, isotonic sodium chloride, phosphate buffered saline, fixed oils (synthetic mono- or diglycerides), polyethylene glycol, glycerin, cyclodextrin, propylene glycol, or other solvents; antimicrobial agents (such as benzyl alcohol or methylparaben); antioxidants (such as ascorbic acid or sodium bisulfite); chelating agents (such as ethylenediaminetetraacetic acid); buffers (such as acetate, citrate, or phosphate buffers) and agents for adjusting tonicity (such as sodium chloride or dextrose), thickeners, lubricants, and colorants. In some embodiments of the present invention, the pharma- ceutically acceptable carrier comprises a growth medium capable of supporting the growth and / or static existence of the bacteria described herein that are advantageous in the context of the pharmaceutical composition prior to administration of the pharmaceutical composition to a subject.

[0080] In some embodiments, the compositions described herein include a lyoprotectant. In some cases, the compositions described herein include a cryoprotectant. In some embodiments, the compositions can further include an emollient. In some cases, the compositions described herein are freeze-dried or lyophilized. In some cases, the lyoprotectant can include milk, sugar, sucrose, lactose, glucose, trehalose, glycerol, mannitol, sorbitol, glycine, alanine, lysine, polyethylene glycol, dextran, or polyvinylpyrrolidone (PVP).

[0081] A variety of other additives may be included in the composition.

[0082] Non-limiting examples of additives include antioxidants, astringents, fragrances, preservatives, emollients, pigments, dyes, humectants, propellants, and sunscreens, as well as other classes of materials whose presence may be pharmaceutical or otherwise desirable. In some cases, emollients can include moisturizers.

[0083] Non-limiting examples of optional additives include preservatives (such as sorbates); solvents (such as isopropanol and propylene glycol); astringents (such as menthol and ethanol); emollients (such as polyalkylene methyl glucosides); humectants (such as glycerin); emulsifiers (such as glycerol stearate, PEG-100 stearate, polyglyceryl-3 hydroxyluryl ether, and polysorbate 60); sorbitol and other polyhydroxy alcohols (such as polyethylene glycol); sunscreens (methoxyoctyl cinnamate (Parsol MCX) and butyl methoxybenzoylmethane (Parsol 1789); antioxidants (such as ascorbic acid (vitamin C), α-tocopherol (vitamin E), β-tocopherol, γ-tocopherol, δ-tocopherol, ε-tocopherol, ζ1-tocopherol, ζ2-tocopherol, η-tocopherol, and retinol (vitamin THE)); essential oils, ceramides, essential fatty acids, mineral oils, vegetable oils (e.g., soybean oil, palm oil, shea butter liquid fraction, sunflower oil), animal oils (e.g., perhydrosqualene), synthetic oils, silicone oils or waxes (e.g., cyclomethicone and dimethicone), fluorinated oils (usually perfluoropolyethers), fatty alcohols (e.g., cetyl alcohol), and waxes (e.g., beeswax, carnauba wax, and paraffin wax); modifiers of skin feel; and thickeners and structurants (such as expanding clays and crosslinked carboxypolyalkylenes).

[0084] In some cases, the composition comprises a therapeutic agent. In some cases, the therapeutic agent is a drug or a compound. In some cases, the therapeutic agent can comprise a salt of the therapeutic agent. As used herein, the therapeutic agent can also refer to the free base, acid, salt, ester, and mixture of the therapeutic agent. In some cases, the salt can comprise a pharmaceutically acceptable salt. In some cases, the salt comprises HCl salt, ascorbate salt, mandelate salt, aspartate salt, carbonate salt, citrate salt, formate salt, glutamate salt, lactate salt, laurate salt, maleate salt, palmitate salt, or phosphate salt.

[0085] In some embodiments, the administration comprises administration of one or more additional therapeutic agents. In some cases, a second therapeutic agent is administered. In some cases, the second treatment is administered in conjunction with or sequentially with the first treatment. In some cases, the second treatment is administered in parallel with the first treatment. In some cases, the second treatment can enhance the effectiveness of the first treatment. In some cases, the second treatment comprises a single administration with the first treatment. For example, an additional therapeutic agent can be added to the bacterial mixture described herein. In some cases, the second treatment comprises a separate administration from the first treatment. In some cases, the second treatment comprises a cream, a moist dressing, light treatment (e.g., phototherapy), or behavioral modification. In some cases, the second treatment comprises an antibody (such as a human monoclonal antibody). In some cases, the second treatment comprises an antibiotic. In some cases, the second treatment comprises a corticosteroid, a calcineurin inhibitor, pimecrolimus, tacrolimus, crisaborole, doxepin, narrow band ultraviolet B (NBUVB) phototherapy, ultraviolet A1 (UVA1) phototherapy, an antihistamine, diphenhydramine, hydroxyzine, cyproheptadine, fexofenadine, cetirizine, loratadine, cyclosporine, dupilumab, tralokinumab, nemolizumab, an anti-OX40 antibody, a JAK1 / JAK2 inhibitor, a PDE4 inhibitor, upadacitinib, abrocitinib, azathioprine, an emollient, a moisturizer, an interleukin inhibitor, methotrexate, mycophenolate mofetil, or interferon gamma. In some cases, the second treatment comprises a cephalosporin (e.g., cefazolin, cephalothin, and cephalexin), clindamycin, lincomycin, erythromycin, flucloxacillin, dicloxacillin, rifampicin, lincosamide (e.g., clindamycin, lincomycin), cotrimoxazole, linezolid, quinupristin, dalfopristin, trimethoprim, sulfamethoxazole, fusidic acid, penicillin, methicillin, vancomycin, or a salt of any of these.In some examples, the second therapeutic agent or the first therapeutic agent can be administered bucally, enterally, by inhalation, by injection, intramuscularly, intrathecally, intravenously, nasally, ophthalmically, orally, auricularly, rectally, subcutaneously, sublingually, topically, transdermally, or by any method of administration.

[0086] Dosing can include single or multiple administrations of the pharmaceutical composition described herein.Examples include multiple times a day, daily, every other day, 1, 2, 3, 5, 6, or 7 times a week, weekly or less frequently, a single administration, a series of treatments including several treatments on a regular or irregular basis, or multiple administrations over a period of time during which disease or condition is treated.In some cases, dosing can be done daily, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 1 year, 2 years, or as needed. The dosing regimen (including the regularity and mode of administration) may depend on factors including, but not limited to, the subject being treated; the severity of the condition; the mode of administration, the stage of colonization, the amount of pathogenic organisms present, the presence of one or more other conditions (such as pregnancy, infancy, etc.), or the presence of one or more additional diseases. In some cases, the subject is an infant. The infant may be up to 6 months old, up to 12 months old, or up to 24 months old. In some cases, the subject is a minor. The minor may be 2 to 21 years old. In some cases, the minor may be up to 5, 7, 12, 18, or 21 years old. In some cases, the subject is an adult. The adult may be 21 years old or older. In some embodiments, the adult is an older adult (e.g., 65 years old or older).

[0087] The compositions disclosed herein can be administered or applied for a treatment period of at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 1 month, at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, at least 7 months, at least 8 months, at least 9 months, at least 10 months, at least 11 months, at least 12 months, at least 1 year, at least 2 years, at least 3 years, at least 4 years, about 5 years, at least 6 years, at least 7 years, at least 8 years, at least 9 years, at least 10 years, at least 15 years, at least 20 years, or a lifetime. It can be administered repeatedly throughout the subject's lifetime (such as once a month or once a year throughout the subject's lifetime). It can be administered repeatedly throughout a substantial portion of the subject's lifetime (such as once a month or once a year for at least about 1 year, 5 years, 10 years, 15 years, 20 years, 25 years, 30 years, or more).

[0088] The compositions (including pharmaceutical compositions) described herein may contain a single (unit) dose of bacteria. 2 ~about 10 15 The compositions described herein may contain about 10 colony forming units (cfu) of the bacteria, bacterial species, or bacterial strains described herein. 2 ~10 12 cfu, 10 3 ~10 12 cfu, 10 3 ~10 11 cfu, 10 3 ~10 10 cfu, 10 3 ~10 9 cfu, 10 3 ~10 8 cfu, 10 3 ~10 7 cfu, 10 3 ~10 6 cfu, 10 3 ~about 10 5 cfu, 10 3~10 4 cfu, 10 4 ~10 12 cfu, 10 4 ~10 11 cfu, 10 4 ~10 10 cfu, 10 4 ~10 9 cfu, 10 4 ~10 8 cfu, 10 4 ~10 7 cfu, 10 4 ~10 6 cfu, 10 5 ~10 12 cfu, 10 5 ~10 11 cfu, approximately 10 5 ~about 10 10 cfu, 10 6 ~10 12 cfu, 10 7 ~10 12 cfu, 10 8 ~10 12 cfu, 10 9 ~10 12 cfu, 10 10 ~10 12 cfu, 10 11 ~10 12 cfu, or 10 6 ~10 10 cfu of a bacterium, bacterial species, or bacterial strain described herein. In some embodiments, the composition comprises about 10 3 cfu, approximately 10 4 cfu, approximately 10 5 cfu, approximately 10 6 cfu, approximately 10 7 cfu, approximately 10 8 cfu, approximately 10 9 cfu, approximately 10 10 cfu, approximately 10 11 cfu, approximately 10 12 cfu, or about 10 13 cfu of a bacterium, bacterial species, or bacterial strain as described herein.

[0089] The compositions (e.g., pharmaceutical compositions) described herein may be administered in a concentration of 10 per mL. 2 ~1015 The compositions described herein may contain colony forming units (cfu) of the bacteria, bacterial species, or bacterial strains described herein. The compositions described herein may contain about 10 2 ~10 12 cfu, 10 3 ~10 12 cfu, 10 3 ~10 11 cfu, 10 3 ~10 10 cfu, 10 3 ~10 9 cfu, 10 3 ~10 8 cfu, 10 3 ~10 7 cfu, 10 3 ~10 6 cfu, 10 3 ~about 10 5 cfu, 10 3 ~10 4 cfu, 10 4 ~10 12 cfu, 10 4 ~10 11 cfu, 10 4 ~10 10 cfu, 10 4 ~10 9 cfu, 10 4 ~10 8 cfu, 10 4 ~10 7 cfu, 10 4 ~10 6 cfu, 10 5 ~10 12 cfu, 10 5 ~10 11 cfu, 10 5 ~10 10 cfu, 10 6 ~10 12 cfu, 10 7 ~10 12 cfu, 10 8 ~10 12 cfu, 10 9 ~10 12 cfu, 10 10 ~10 12 cfu, 10 11 ~10 12 cfu, or 10 6~10 10 The cfu may include any bacteria, bacterial species, or bacterial strain described herein.

[0090] The compositions (e.g., pharmaceutical compositions) described herein may be administered in amounts of 10 2 ~10 15 The compositions described herein may contain colony forming units (cfu) of the bacteria, bacterial species, or bacterial strains described herein. The compositions described herein may contain about 10 2 ~10 12 cfu, 10 3 ~10 12 cfu, 10 3 ~10 11 cfu, 10 3 ~10 10 cfu, 10 3 ~10 9 cfu, 10 3 ~10 8 cfu, 10 3 ~10 7 cfu, 10 3 ~10 6 cfu, 10 3 ~about 10 5 cfu, 10 3 ~10 4 cfu, 10 4 ~10 12 cfu, 10 4 ~10 11 cfu, 10 4 ~10 10 cfu, 10 4 ~10 9 cfu, 10 4 ~10 8 cfu, 10 4 ~10 7 cfu, 10 4 ~10 6 cfu, 10 5 ~10 12 cfu, 10 5 ~10 11 cfu, 10 5 ~10 10 cfu, 10 6 ~10 12 cfu, 10 7 ~10 12 cfu, 10 8 ~1012 cfu, 10 9 ~10 12 cfu, 10 10 ~10 12 cfu, 10 11 ~10 12 cfu, or 10 6 ~10 10 The cfu may include any bacteria, bacterial species, or bacterial strain described herein.

[0091] The compositions described herein may comprise at least about 0.01 wt.%, at least about 0.05 wt.%, at least about 0.1 wt.%, at least about 0.2 wt.%, at least about 0.3 wt.%, at least about 0.4 wt.%, at least about 0.5 wt.%, at least about 0.6 wt.%, at least about 0.7 wt.%, at least about 0.8 wt.%, at least about 0.9 wt.%, at least about 1.0 wt.%, at least about 1.5 wt.%, at least about 2.0 wt.%, at least about 3.0 wt.%, at least about 4.0 wt.%, at least about 5.0 wt.%, at least about 6.0 wt.%, at least about 7.0 wt.%, at least about 8.0 wt.%, at least about 9.0 wt.%, at least about 10.0 wt.%, at least about 11.0 wt.%, at least about 12.0 wt.%, at least about 13.0 wt.%, at least about 14.0 wt.%, at least about 15.0 wt.%, at least about 16.0 wt.%, at least about 17.0 wt.%, at least about 18.0 wt.%, at least about 19.0 wt.%, at least about 20.0 wt.%, at least about 21.0 wt.%, at least about 22.0 wt.%, at least about 23.0 wt.%, at least about 24.0 wt.%, at least about 25.0 wt.%, at least about 26.0 wt.%, at least about 27.0 wt.%, at least about 28.0 wt.%, at least about 29.0 wt.%, at least about 30.0 wt.%, at least about 31.0 wt.%, at least about 32.0 %, at least about 9.0%, at least about 10.0%, at least about 11.0%, at least about 12.0%, at least about 13.0%, at least about 14.0%, at least about 15.0%, at least about 16.0%, at least about 17.0%, at least about 18.0%, at least about 19.0%, at least about 20.0%, at least about 25.0%, at least about 30.0%, at least about 35.0%, at least about 40.0%, at least about 45.0%, or at least about 50.0% by weight of the bacteria, bacterial species, or bacterial strains described herein. In some embodiments, the composition may comprise from 0.01% to 30% by weight, from about 0.01% to 20% by weight, 0.01% to 5% by weight, 0.1% to 30% by weight, 0.1% to 20% by weight, 0.1% to about 15% by weight, 0.1% to 10% by weight, 0.1% to 5% by weight, 0.2% to 5% by weight, 0.3% to 5% by weight, 0.4% to 5% by weight, 0.5% to 5% by weight, or 1% to 5% by weight of the bacteria, bacterial species, or bacterial strain described herein.

[0092] The compositions (including pharmaceutical compositions) described herein may comprise a ratio of a species in Table 1 to another species in Table 1, a ratio of a strain in Table 2 to another strain in Table 2, or a ratio of a species in Table 1 to a strain in Table 2 (cfu to cfu) of about: 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:20, 1:30, 1:40, 1:50, 1:60, 1:70, 1:80, 1:90, 1:100, 1:200, 1:300, 1:400, 1:500, 1:600, 1:700, 1:800, 1:900, or about 1:1000. The compositions (including pharmaceutical compositions) described herein may comprise a ratio (cfu to cfu) of multiple strains of Bacillus velezensis, Bacillus wiedmannii, Lysinibacillus macrolides, Bacillus amyloliquefaciens, Staphylococcus caprae, and / or Bacillus tropicus of about: 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:20, 1:30, 1:40, 1:50, 1:60, 1:70, 1:80, 1:90, 1:100, 1:200, 1:300, 1:400, 1:500, 1:600, 1:700, 1:800, 1:900, or about 1:1000.

[0093] In some embodiments, the compositions herein comprise formulations. In some cases, the formulations comprise freeze-dried or lyophilized bacteria. In some cases, the formulations comprise reconstituted bacteria. In some cases, individual species or strains are stored in containers such as vials. In some examples, the formulations herein comprise a mixture of bacteria from 2, 3, 4, 5 or more reconstituted vials.

[0094] situation In some embodiments, compositions are provided herein for treating skin conditions or diseases. As described in more detail herein, such conditions or diseases are epidermal, dermal, or subcutaneous tissue (e.g., tissue under the skin). In some cases, the conditions or diseases are stratum corneum, stratum germinativum, stratum spinosum, stratum basale, dermal papilla, sebaceous gland, hair follicle, nerve fiber, arrector pili muscle, dermal papilla, sweat gland, or any combination thereof. Skin can include skin on any surface of the body. For example, skin from the head, arms, legs, torso, stomach, feet, toes, fingers, thumbs, forearms, back, groin, or any area on the body. In some cases, the compositions described include isolated bacteria present in sufficient amount to reduce the incidence of pathogenic bacterial, fungal, or viral colonization. In some cases, the compositions described include isolated bacteria present in sufficient amount to reduce pathogenic bacterial, fungal, or viral gene expression. In some cases, the compositions described herein include isolated bacteria present in sufficient amounts to reduce the metabolism of pathogenic bacteria, fungi, or viruses. In some cases, the compositions described herein include isolated bacteria present in sufficient amounts to reduce the virulence of pathogenic bacteria, fungi, or viruses. In some cases, the disease or condition may be related to bacterial infection. Sources of bacterial infection for treatment with the pharmaceutical compositions described herein include, but are not limited to, S. aureus (methicillin-resistant S. aureus (MRSA) and methicillin-sensitive S. aureus (MSSA)), Gardnerella vaginalis, and Streptococcus pyogenes.

[0095] In some embodiments, a skin condition or disease is treated by administering a composition as described herein. In some cases, treatment can be used with reference to a pharmaceutical or other intervention regimen to obtain an advantageous or desired result in the recipient. An advantageous or desired result includes, but is not limited to, a therapeutic benefit and / or a prophylactic benefit. A therapeutic benefit can refer to the eradication or amelioration of symptoms of the underlying disorder being treated. In some cases, a prophylactic effect can include delaying, preventing, or eliminating the appearance of a disease or condition, delaying or eliminating the onset of symptoms of a disease or condition, or delaying, stopping, or reversing the progression of a disease or condition. In some cases, inflammation is treated by administering a composition as described herein. Skin conditions and diseases for treatment according to administration of a composition as described herein include, but are not limited to, fungal infections, dry skin, itchy skin, dermatophytosis (Tinea spp.), bacterial folliculitis, bacterial infections, inflammatory conditions, or genetic conditions. Skin conditions and diseases for treatment according to administration of a composition as described herein include skin and soft tissue infections. In some cases, administering the compositions described herein includes repairing the microbiome that is prone to developing eczema. For example, the microbiome that is prone to developing eczema can be repaired to a healthy or non-prone microbiome that is not prone to developing eczema. In some cases, the fungal disease includes Malassezia folliculitis, tinea versicolor, cutaneous candidiasis, candidal paronychia. In some cases, the dermatophytosis (Tinea genus) includes tinea capitis (tinea of ​​the scalp), tinea barbae (tinea beard), tinea corporis (tinea corporis), tinea cruris ("jock itch"), tinea pedis ("tinea pedis"), tinea capitis (tinea of ​​the scalp), tinea barbae (tinea beard), tinea corporis (tinea corporis), tinea unguium (onychomycosis), tinea manubrium (hand), tinea facialis (face). In some instances, bacterial infections include S. aureus folliculitis, folliculitis, sycosis vulgaris ("barber's itch"), staphylococcal scalded skin syndrome, impetigo, ecthyma, cellulitis, furuncles, abscesses, furuncles, mastitis, ecthyma, erysipelas, necrotizing fasciitis, secondary skin infections (e.g., secondary skin infections of wounds, dermatitis, scabies, diabetic ulcers, etc.), tropical ulcers, bullous acrodermatitis, streptococcal perianal and / or exonuclear dermatitis.In some cases, the disease or condition includes atopic dermatitis, seborrheic dermatitis, inflammation, eczema, psoriasis, rosacea, mycosis, dermatophytosis, folliculitis, acne, alopecia, vitiligo, dandruff, chronic wounds, skin ulcers, Netherton syndrome, sweat gland abscess, psoriasis vulgaris, staphylococcal scalded skin syndrome, impetigo, ecthyma, cellulitis, carbuncles, furuncles, and abscesses. In some cases, the genetic condition includes Netherton syndrome. In some cases, the inflammatory condition includes atopic dermatitis, contact dermatitis, eczema, pruritus, seborrheic dermatitis, acne (acne vulgaris), psoriasis (psoriasis vulgaris, psoriasis vulgaris), rosacea, sweat gland abscess. In some cases, the skin condition includes aging conditions (such as wrinkles). In some cases, the skin condition includes dandruff, or photodermatitis. In some cases, the skin disease or condition includes eczema, diaper rash, seborrheic dermatitis, blisters, measles, warts, acne, fifth disease, hives, ringworm, a rash from a bacterial or fungal infection (e.g., cutaneous candidiasis), or a rash from an allergic reaction.

[0096] In some embodiments, the compositions described herein are administered to treat a vaginal condition. Vaginal conditions and diseases for treatment according to administration of the compositions described herein can include vulvovaginal candidiasis, recurrent vulvovaginal candidiasis, and bacterial vaginosis.

[0097] In some embodiments, provided herein is a method for preventing or alleviating a skin condition in a subject, comprising topically administering to the subject a composition as described herein. In some cases, the compositions and methods described herein are compositions used to improve cosmetic irregularities. In some cases, the compositions and methods described herein are compositions used to treat a condition selected from the group consisting of pruritis, aesthetic conditions, and body odor. In some cases, the aesthetic condition includes the appearance of wrinkles or aging. In some examples, the aesthetic condition is a cosmetic irregularity. The improvement of cosmetic imperfections may reduce the appearance of fine lines, the depth of fine lines, the appearance of wrinkles, the depth of wrinkles, scaly patches, roughness, acne, scars, irregular pigmentation, sunspots, melasma, solar lentigo, melasma, poikiloderma, actinic keratosis, lentigo maligna, periorbital hyperpigmentation, shine, glare, oily appearance, blistering, peeling, crusting, dryness, or pore size; may improve skin tone, skin firmness, tactile smoothness, suppleness, luster, visual smoothness, or radiance. Furthermore, the improvement of cosmetic imperfections using the compositions or methods described herein may reduce pathogenic bacteria, viruses, or fungi on and / or within the skin of a subject in need of such reduction. In some cases, the compositions and methods described herein improve the barrier function of the skin as measured by transepidermal water loss.The administration (e.g., topical, oral, or rectal) described herein can reduce recurrence, so that further occurrences of cosmetic irregularities of the skin are reduced in number, intensity, or frequency.The administration can increase the duration of relief (such as the length of time between occurrences).In some embodiments, further occurrences of cosmetic irregularities do not occur for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 weeks after application.In some embodiments, further occurrences of cosmetic irregularities do not occur for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 months after topical application.For example, the compositions herein are administered to reduce wrinkles, reduce lesion size, reduce pore size, or reduce pore density. Further provided herein is a method of preventing or alleviating a skin condition in a subject, the skin condition comprising: occurrence of fine lines, wrinkle depth, occurrence of wrinkles, wrinkle depth, nasolabial folds, scaly patches, roughness, acne, scarring, redness, irregular pigmentation, loss of firmness, compromised skin barrier, age spots, sunspots, melasma, photodamage, sun exposure, damage from sun exposure, environmental damage, solar lentigines, melasma, poikiloderma, actinic keratosis, lentigo maligna, periorbital hyperpigmentation, shine, glare, oily appearance, decreased ability of skin to retain moisture, abnormalities in epidermal thickness, compromised dermal-epidermal junction, blistering, peeling, crusting, dryness, pore size, skin tone, skin firmness, skin texture, skin elasticity, tactile smoothness, suppleness, luster, visual smoothness, radiance, or combinations thereof. In some cases, the evaluation of the efficacy of the treatment on skin condition and / or cosmetic irregularities can be clinically graded on the subject's treatment area (e.g., the subject's face) using a 10-point scale (0=none, 0.5-3.5=mild, 4-6.5=moderate, and 7-10=severe). In some cases, the efficacy evaluation can be performed over a period of time (e.g., after each treatment, or weekly, or monthly). All grading evaluations can be performed by the same investigator at each visit or by computerized implementation of an algorithm to ensure consistency of grading. In some cases, the number of wrinkles or the depth of the wrinkles, etc. are measured, which are factors in the clinical score.

[0098] In some embodiments, the symptoms of inflammation are treated by administering the compositions described herein. In some embodiments, the symptoms of skin conditions or diseases are treated by administering the compositions described herein. For example, the compositions can be administered in an amount sufficient to reduce symptoms associated with atopic dermatitis. In some cases, the symptoms include raised bumps, discolored bumps, rashes, pain, itching, scaly skin, rough skin, peeling skin, ulcers, open sores, lesions, dry skin, cracked skin, discolored skin spots, fleshy bumps, warts, skin growths, birthmarks, changes in size or color of birthmarks, loss of skin pigment, or excessive flushing. In some embodiments, the symptoms include itching, rashes, redness, pain, swelling, blistering, or scaling. In some embodiments, the compositions are administered in an amount sufficient to reduce symptoms associated with dry skin. In some cases, the composition is administered in an amount sufficient to reduce the incidence of conditions associated with inflammation (eg, itching, rash, redness, pain, swelling, blistering, or scaling).

[0099] In some embodiments, the method for treating inflammation comprises topically administering a composition comprising Bacillus wiedmannii to a subject in need of the composition. In some cases, the Bacillus wiedmannii is purified and the Bacillus wiedmannii is present in a sufficient amount for treating inflammation. In some embodiments, the method comprises reducing the growth of S. aureus in the skin of a subject in need of reducing the growth of S. aureus in the skin. In some cases, the method comprises topically administering a pharmaceutical composition comprising Bacillus velezensis, Bacillus wiedmannii, and Lysinibacillus macroides to the skin of a subject in need of the composition. In some cases, Bacillus velezensis, Bacillus wiedmannii, and Lysinibacillus macroides are purified, and Bacillus velezensis, Bacillus wiedmannii, and Lysinibacillus macroides are viable and present in sufficient amounts to reduce S. aureus in the skin of a subject in need of reducing S. aureus in the skin. In some embodiments, a method for reducing symptoms associated with atopic dermatitis comprises topically administering a composition comprising Bacillus amyloliquefaciens to a subject in need of topically administering the composition. In some cases, Bacillus amyloliquefaciens is purified, and Bacillus amyloliquefaciens is present in sufficient amounts to reduce symptoms associated with atopic dermatitis. In some embodiments, a method for reducing the incidence of inflammation-related conditions comprises topically administering a composition comprising Bacillus wiedmannii and Staphylococcus caprae to a subject in need of topically administering the composition. In some cases, Bacillus wiedmannii and Staphylococcus caprae have been purified.In some cases, Bacillus wiedmannii and Staphylococcus caprae are present in sufficient amounts to reduce the incidence of inflammation-related conditions. In some cases, inflammation-related conditions include itching, rash, redness, pain, swelling, blistering, or scaling.

[0100] In some embodiments, the method for treating inflammation comprises topically administering a composition comprising the bacterial strain jl.27 to a subject in need of the composition. In some cases, the jl.27 strain is purified and the jl.27 strain is present in a sufficient amount for the treatment of inflammation. In some embodiments, the method comprises reducing the growth of S. aureus in the skin of a subject in need of reducing the growth of S. aureus in the skin. In some cases, the method comprises topically administering a pharmaceutical composition comprising the jl.83 strain, the jl.27 strain, and the jl.77 strain to the skin of a subject in need of the composition. In some cases, the jl.83 strain, the jl.27 strain, and the jl.77 strain are purified and the jl.83 strain, the jl.27 strain, and the jl.77 strain are viable and present in a sufficient amount for the reduction of S. aureus in the skin of a subject in need of the reduction of S. aureus in the skin. In some embodiments, the method for reducing symptoms associated with atopic dermatitis comprises topically administering a composition comprising the jl.68 strain to a subject in need of topical administration of the composition. In some cases, the jl.68 strain is purified, and the jl.68 strain is present in a sufficient amount to reduce symptoms associated with atopic dermatitis. In some embodiments, the method for reducing the incidence of a condition associated with inflammation comprises topically administering a composition comprising the jl.27 strain and the jl.121 strain to a subject in need of topical administration of the composition. In some cases, the jl.27 strain and the jl.121 strain are purified. In some cases, the jl.27 strain and the jl.121 strain are present in a sufficient amount to reduce the incidence of a condition associated with inflammation. In some examples, the condition associated with inflammation comprises itching, rash, redness, pain, swelling, blistering, or scaling.

[0101] kit The pharmaceutical compositions described herein may include kits in which the bacteria described herein (e.g., lyophilized cells) are contained in a first container and one or more pharma- ceutically acceptable excipients (e.g., water or buffer) are contained in a second container. In some embodiments, kits are provided herein, comprising a first container comprising purified, lyophilized bacteria, including Staphylococcus cohnii, Staphylococcus capitis, Staphylococcus caprae, Bacillus tropicus, Bacillus mycoides, Bacillus wiedmannii, Bacillus mediterraneensis, Bacillus amyloliquefaciens, Bacillus velezensis, Bacillus cereus, Bacillus cecembensis, Kocuria marina, Lysinibacillus macrolides, or a mixture thereof; and a second container comprising a pharma-ceutically acceptable excipient. In some embodiments, a kit is provided herein, the kit comprising: a first container comprising purified, lyophilized bacteria including strain jl.83, strain jl.27, strain jl.77, strain jl.68, strain jl.121, strain jl.21, or a mixture thereof; and a second container comprising a pharmaceutically acceptable excipient. In some embodiments, a kit is provided herein, the kit comprising: a first container comprising purified, lyophilized bacteria including strain jl.83, strain jl.27, strain jl.77, strain jl.68, strain jl.121, strain jl.21, or a mixture thereof; and a second container comprising a pharmaceutically acceptable excipient. In some embodiments, a kit is provided herein, the kit including a first container comprising Bacillus amyloliquefaciens, Bacillus wiedmannii, and Staphylococcus caprae; and a second container comprising a pharma- ceutically acceptable excipient.In some embodiments, a kit is provided herein, the kit comprising: a first container comprising purified, lyophilized bacteria, including Bacillus amyloliquefaciens; Bacillus tropicus; and Staphylococcus caprae; and a second container comprising a pharma- ceutically acceptable excipient.

[0102] In some embodiments, a kit is provided herein, the kit comprising a first container comprising purified, lyophilized bacteria comprising strains jl.83, jl.27, and jl.77; and a second container comprising a pharmaceutically acceptable excipient. In some embodiments, a kit is provided herein, the kit comprising a first container comprising purified, lyophilized bacteria comprising strains jl.68, jl.27, and jl.121; and a second container comprising a pharmaceutically acceptable excipient. In some embodiments, a kit is provided herein, the kit comprising a first container comprising purified, lyophilized bacteria comprising strains jl.68, jl.21, and jl.121; and a second container comprising a pharmaceutically acceptable excipient.

[0103] In some embodiments, a kit is provided herein, the kit comprising a first container having at least 10 3 and a second container comprising a pharmaceutically acceptable excipient. In some examples, the kit comprises 1, 2, 3, 4, 5, or more containers, each container comprising a separate strain or species of bacteria. Further provided herein is a kit, wherein the purified lyophilized bacteria is present in a total amount of 10 15 Kits are further provided herein, in which the purified, lyophilized bacteria are present in total amounts up to 10 cfu. 3 ~1012 Present in total cfu.

[0104] Numbered embodiments Several compositions and methods are disclosed herein. Specific exemplary embodiments of these compositions and methods are disclosed below. The following embodiments list non-limiting permutations of the combinations of features disclosed herein. Other permutations of the combinations of features are also contemplated. In particular, each of these numbered embodiments is intended to depend on or relate to any preceding or following numbered embodiment, regardless of the order of listing.

[0105] Embodiment 1. A composition, wherein the composition comprises purified bacterial species, the bacterial species comprising Bacillus velezensis, Bacillus wiedmannii, and Lysinibacillus macroides; (a) the bacterial species is lyophilized; or (b) the composition is formulated for delivery to the skin.

[0106] Embodiment 2. The composition of embodiment 1, wherein the composition is formulated as a suspension, emulsion, cream, lotion, tincture, gel, foam, powder, ointment, paste, or oil.

[0107] Embodiment 3. The composition of embodiment 1, further comprising a fourth bacterial species.

[0108] Embodiment 4. A composition, wherein the composition comprises purified bacterial species, the bacterial species comprising Bacillus amyloliquefaciens; Bacillus wiedmannii; and Staphylococcus caprae; (a) the bacterial species are lyophilized; or (b) the composition is formulated for delivery to the skin.

[0109] Embodiment 5. The composition of embodiment 4, wherein the composition is formulated as a suspension, emulsion, cream, lotion, tincture, gel, foam, powder, ointment, paste, or oil.

[0110] Embodiment 6 The composition of embodiment 4, further comprising a fourth bacterial species.

[0111] Embodiment 7. A composition, wherein the composition comprises purified bacterial species, the bacterial species comprising Bacillus amyloliquefaciens; Bacillus tropicus; and Staphylococcus caprae; (a) the bacterial species are lyophilized; or (b) the composition is formulated for delivery to the skin.

[0112] Embodiment 8. The composition of embodiment 7, wherein the composition is formulated as a suspension, emulsion, cream, lotion, tincture, gel, foam, powder, ointment, paste, or oil.

[0113] Embodiment 9. The composition of embodiment 7, further comprising a fourth bacterial species.

[0114] Embodiment 10. A composition comprising purified bacterial species, the bacterial species comprising at least two of the following bacterial species: Bacillus velezensis, Bacillus wiedmannii, Lysinibacillus macrolides, Bacillus amyloliquefaciens, Staphylococcus caprae, and Bacillus tropicus, wherein (a) the at least two bacterial species are lyophilized; or (b) the composition is formulated for delivery to the skin.

[0115] Embodiment 11. The composition of embodiment 10, wherein the composition is formulated as a suspension, emulsion, cream, lotion, tincture, gel, foam, powder, ointment, paste, or oil.

[0116] Embodiment 12. A composition, wherein the composition comprises a purified bacterial species, the bacterial species comprising Bacillus velezensis; (a) the bacterial species is lyophilized; or (b) the composition is formulated for delivery to the skin.

[0117] Embodiment 13. The composition of embodiment 12, wherein the composition is formulated as a suspension, emulsion, cream, lotion, tincture, gel, foam, powder, ointment, paste, or oil.

[0118] Embodiment 14 The composition of embodiment 12, further comprising a second bacterial species.

[0119] Embodiment 15. A composition, wherein the composition comprises a purified bacterial species, the bacterial species comprising Bacillus wiedmannii; (a) the bacterial species is lyophilized; or (b) the composition is formulated for delivery to the skin.

[0120] Embodiment 16. The composition of embodiment 15, wherein the composition is formulated as a suspension, emulsion, cream, lotion, tincture, gel, foam, powder, ointment, paste, or oil.

[0121] Embodiment 17 The composition of embodiment 15, further comprising a second bacterial species.

[0122] Embodiment 18. A composition, wherein the composition comprises a purified bacterial species, the bacterial species comprising Lysinibacillus macroides; (a) the bacterial species is lyophilized; or (b) the composition is formulated for delivery to the skin.

[0123] Embodiment 19. The composition of embodiment 18, wherein the composition is formulated as a suspension, emulsion, cream, lotion, tincture, gel, foam, powder, ointment, paste, or oil.

[0124] Embodiment 20. The composition of embodiment 18, further comprising a second bacterial species.

[0125] Embodiment 21. A composition, wherein the composition comprises a purified bacterial species, the bacterial species comprising Bacillus tropicus; (a) the bacterial species is lyophilized; or (b) the composition is formulated for delivery to the skin.

[0126] Embodiment 22. The composition of embodiment 21, wherein the composition is formulated as a suspension, emulsion, cream, lotion, tincture, gel, foam, powder, ointment, paste, or oil.

[0127] Embodiment 23 The composition of embodiment 21, further comprising a second bacterial species.

[0128] Embodiment 24. The composition comprises at least 10 3 24. The composition of any one of embodiments 1 to 23, comprising colony forming units (cfu) / gram of bacteria.

[0129] Embodiment 25. The composition comprises 10 3 ~10 12 25. The composition of any one of embodiments 1-24, comprising colony forming units (cfu) / gram of bacteria.

[0130] Embodiment 26. The composition of any one of embodiments 1 to 25, wherein the bacterial species is grown under aerobic conditions.

[0131] Embodiment 27. The composition of any one of embodiments 1 to 26, wherein the bacterial species is grown without animal products.

[0132] Embodiment 28. The composition of any one of embodiments 1 to 27, wherein the bacterial species is grown in tryptic soy broth (TSB).

[0133] Embodiment 29. The composition, when stored in a sealed container at 20° C., produces approximately 10 4 29. The composition of any one of embodiments 1-28, wherein the composition maintains greater than cfu.

[0134] Embodiment 30. The composition of any one of embodiments 1 to 29, further comprising an excipient.

[0135] Embodiment 31. The composition of any one of embodiments 1 to 30, further comprising a lyoprotectant.

[0136] Embodiment 32. The composition of any one of embodiments 1 to 31, further comprising an emollient.

[0137] Embodiment 33. The composition of any one of embodiments 1 to 32, further comprising thiamine or a salt thereof.

[0138] Embodiment 34. The composition of any one of embodiments 1 to 33, wherein the bacterial species, when contacted with S. aureus, reduces expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB, and the reduction in expression is measured by a fluorescent reporter assay.

[0139] Embodiment 35. The composition of any one of embodiments 1 to 33, wherein the bacterial species is present in an amount effective to inhibit virulence of S. aureus as measured by a reduction in expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB, wherein the reduction in expression is measured by a fluorescent reporter assay.

[0140] Embodiment 36. A method of administering a composition according to any one of embodiments 1 to 35, comprising administering an amount sufficient to treat a disease selected from the group consisting of atopic dermatitis, seborrheic dermatitis, inflammation, eczema, psoriasis, rosacea, mycosis, dermatophytosis, folliculitis, acne, alopecia, vitiligo, dandruff, chronic wounds, skin ulcers, Netherton syndrome, sweat gland abscess, sycosis vulgaris, staphylococcal scalded skin syndrome, impetigo, ecthyma, cellulitis, carbuncles, furuncles, and abscesses.

[0141] Embodiment 37. A method of administering a composition according to any one of embodiments 1 to 35, comprising administering an amount sufficient to reduce symptoms associated with atopic dermatitis.

[0142] Embodiment 38. A method of administering a composition according to any one of embodiments 1 to 35, comprising administering said composition to a subject having a microbiome prone to developing eczema prior to said administration.

[0143] Embodiment 39. A method of administering a composition according to any one of embodiments 1 to 35, comprising administering an amount sufficient to alleviate symptoms associated with dry skin.

[0144] Embodiment 40. A method of administering a composition according to any one of embodiments 1 to 35, comprising administering an amount sufficient for a reduction in the incidence of a condition associated with inflammation, said condition associated with inflammation comprising itching, rash, redness, pain, swelling, blistering, or scaling.

[0145] Embodiment 41. A method of administering a composition described in any one of embodiments 1 to 35, comprising administering an amount sufficient to inhibit virulence of S. aureus as measured by a reduction in expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB, wherein the reduction in expression is measured by a fluorescent reporter assay.

[0146] Embodiment 42. A composition according to any one of embodiments 1 to 35 for use in treating a skin condition.

[0147] Embodiment 43. A composition according to any one of embodiments 1 to 35 for use in treating inflammation.

[0148] Embodiment 44. A method for treating inflammation, comprising topically administering a composition comprising Bacillus wiedmannii to a subject in need thereof, wherein the Bacillus wiedmannii is purified and the Bacillus wiedmannii is present in an amount sufficient for treatment of inflammation.

[0149] Embodiment 45. A method for reducing the growth of Staphylococcus aureus in the skin of a subject in need thereof, comprising topically administering to the skin of a subject in need thereof a pharmaceutical composition comprising Bacillus velezensis, Bacillus wiedmannii, and Lysinibacillus macroides, wherein the Bacillus velezensis, Bacillus wiedmannii, and Lysinibacillus macroides are purified, and the Bacillus velezensis, Bacillus wiedmannii, and Lysinibacillus macroides are viable and present in an amount sufficient for the reduction of S. aureus in the skin of a subject in need thereof.

[0150] Embodiment 46. A method for reducing symptoms associated with atopic dermatitis, comprising topically administering a composition comprising Bacillus amyloliquefaciens to a subject in need thereof, wherein the Bacillus amyloliquefaciens is purified and the Bacillus amyloliquefaciens is present in an amount sufficient to reduce symptoms associated with atopic dermatitis.

[0151] Embodiment 47. A method for reducing the incidence of a condition associated with inflammation, comprising topically administering a composition comprising Bacillus wiedmannii and Staphylococcus caprae to a subject in need thereof, wherein the Bacillus wiedmannii and Staphylococcus caprae are purified, and the Bacillus wiedmannii and Staphylococcus caprae are present in an amount sufficient for a reduction in the incidence of a condition associated with inflammation, wherein the condition associated with inflammation comprises itching, rash, redness, pain, swelling, blistering, or scaling.

[0152] Embodiment 48. A method of administering a composition according to any one of embodiments 1 to 35, comprising administering an amount sufficient to treat a condition selected from the group consisting of pruritus, cosmetic conditions, and body odor.

[0153] Embodiment 49. The method of embodiment 48, wherein the aesthetic condition comprises the appearance of wrinkles or aging.

[0154] Overview of the embodiment

[0155] Compositions are disclosed herein. In some embodiments, the compositions comprise purified bacterial species. In some embodiments, the bacterial species comprise Bacillus velezensis; Bacillus wiedmannii; and Lysinibacillus macroides. In some embodiments, (a) the bacterial species is lyophilized; or (b) the composition is formulated for delivery to the skin. In some embodiments, the composition is formulated as a suspension, emulsion, cream, lotion, tincture, gel, foam, powder, ointment, paste, or oil. In some embodiments, the composition can further comprise a fourth bacterial species. In some embodiments, the composition comprises at least 10 3 In some embodiments, the composition contains 10 colony forming units (cfu) / gram of bacteria. 3 ~10 12 In some embodiments, the bacterial species is grown in aerobic conditions. In some embodiments, the bacterial species is grown without animal products. In some embodiments, the bacterial species is grown in tryptic soy broth (TSB). In some embodiments, the composition, when stored in a sealed container at 20° C., has a bacterial yield of about 10 after 6 months as measured by cfu count. 4cfu. In some embodiments, the composition may further comprise an excipient. In some embodiments, the composition may further comprise a lyoprotectant. In some embodiments, the composition may further comprise an emollient. In some embodiments, the composition may further comprise thiamine or a salt thereof. In some embodiments, the bacterial species, when contacted with S. aureus, is capable of reducing expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB. In some embodiments, the reduced expression is measured by a fluorescent reporter assay. In some embodiments, the bacterial species is present in an amount effective to inhibit virulence of S. aureus as measured by reduced expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB. In some embodiments, the reduced expression is measured by a fluorescent reporter assay. Methods of administering the compositions are also disclosed herein. In some embodiments, the method comprises administering an amount sufficient to treat a disease selected from the group consisting of atopic dermatitis, seborrheic dermatitis, inflammation, eczema, psoriasis, rosacea, mycosis, dermatophytosis, folliculitis, acne, alopecia, vitiligo, dandruff, chronic wounds, skin ulcers, Netherton syndrome, sweat gland abscess, sycosis vulgaris, staphylococcal scalded skin syndrome, impetigo, ecthyma, cellulitis, carbuncles, furuncles, and abscesses. In some embodiments, the method comprises administering an amount sufficient to treat a condition selected from the group consisting of pruritus, aesthetic conditions, and body odor. In some embodiments, the aesthetic conditions include wrinkles or the appearance of aging. In some embodiments, the method comprises administering an amount sufficient to reduce symptoms associated with atopic dermatitis. In some embodiments, the method comprises administering the composition to a subject having a microbiome predisposed to developing eczema prior to administration thereof. In some embodiments, the method comprises administering an amount sufficient to reduce symptoms associated with dry skin.In some embodiments, the method comprises administering an amount sufficient to reduce the incidence of a condition associated with inflammation, the condition associated with inflammation comprising itching, rash, redness, pain, swelling, blistering, or scaling. In some embodiments, the method comprises administering an amount sufficient to inhibit virulence of S. aureus as measured by a reduction in expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB. In some embodiments, the reduction in expression is measured by a fluorescent reporter assay. In some embodiments, the composition is for use in treating a skin condition. In some embodiments, the composition is for use in treating inflammation.

[0156] In some embodiments, the composition comprises a purified bacterial species. In some embodiments, the bacterial species comprises Bacillus amyloliquefaciens, Bacillus wiedmannii, and Staphylococcus caprae. In some embodiments, (a) the bacterial species is lyophilized; or (b) the composition is formulated for delivery to the skin. In some embodiments, the composition is formulated as a suspension, emulsion, cream, lotion, tincture, gel, foam, powder, ointment, paste, or oil. In some embodiments, the composition can further comprise a fourth bacterial species. In some embodiments, the composition comprises at least 10 3 In some embodiments, the composition contains 10 colony forming units (cfu) / gram of bacteria. 3 ~10 12 In some embodiments, the bacterial species is grown in aerobic conditions. In some embodiments, the bacterial species is grown without animal products. In some embodiments, the bacterial species is grown in tryptic soy broth (TSB). In some embodiments, the composition, when stored in a sealed container at 20° C., has a bacterial yield of about 10 after 6 months as measured by cfu count. 4cfu. In some embodiments, the composition may further comprise an excipient. In some embodiments, the composition may further comprise a lyoprotectant. In some embodiments, the composition may further comprise an emollient. In some embodiments, the composition may further comprise thiamine or a salt thereof. In some embodiments, the bacterial species, when contacted with S. aureus, is capable of reducing expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB. In some embodiments, the reduced expression is measured by a fluorescent reporter assay. In some embodiments, the bacterial species is present in an amount effective to inhibit virulence of S. aureus as measured by reduced expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB. In some embodiments, the reduced expression is measured by a fluorescent reporter assay. Methods of administering the compositions are also disclosed herein. In some embodiments, the method comprises administering an amount sufficient to treat a disease selected from the group consisting of atopic dermatitis, seborrheic dermatitis, inflammation, eczema, psoriasis, rosacea, mycosis, dermatophytosis, folliculitis, acne, alopecia, vitiligo, dandruff, chronic wounds, skin ulcers, Netherton syndrome, sweat gland abscess, sycosis vulgaris, staphylococcal scalded skin syndrome, impetigo, ecthyma, cellulitis, carbuncles, furuncles, and abscesses. In some embodiments, the method comprises administering an amount sufficient to treat a condition selected from the group consisting of pruritus, aesthetic conditions, and body odor. In some embodiments, the aesthetic conditions include wrinkles or the appearance of aging. In some embodiments, the method comprises administering an amount sufficient to reduce symptoms associated with atopic dermatitis. In some embodiments, the method comprises administering the composition to a subject having a microbiome predisposed to developing eczema prior to administration thereof. In some embodiments, the method comprises administering an amount sufficient to reduce symptoms associated with dry skin.In some embodiments, the method comprises administering an amount sufficient to reduce the incidence of a condition associated with inflammation, the condition associated with inflammation comprising itching, rash, redness, pain, swelling, blistering, or scaling. In some embodiments, the method comprises administering an amount sufficient to inhibit virulence of S. aureus as measured by a reduction in expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB. In some embodiments, the reduction in expression is measured by a fluorescent reporter assay. In some embodiments, the composition is for use in treating a skin condition. In some embodiments, the composition is for use in treating inflammation.

[0157] In some embodiments, the composition comprises a purified bacterial species. In some embodiments, the bacterial species comprises Bacillus amyloliquefaciens, Bacillus tropicus, and Staphylococcus caprae. In some embodiments, (a) the bacterial species is lyophilized; or (b) the composition is formulated for delivery to the skin. In some embodiments, the composition is formulated as a suspension, emulsion, cream, lotion, tincture, gel, foam, powder, ointment, paste, or oil. In some embodiments, the composition can further comprise a fourth bacterial species. In some embodiments, the composition comprises at least 10 3 In some embodiments, the composition contains 10 colony forming units (cfu) / gram of bacteria. 3 ~10 12 In some embodiments, the bacterial species is grown in aerobic conditions. In some embodiments, the bacterial species is grown without animal products. In some embodiments, the bacterial species is grown in tryptic soy broth (TSB). In some embodiments, the composition, when stored in a sealed container at 20° C., has a bacterial yield of about 10 after 6 months as measured by cfu count. 4cfu. In some embodiments, the composition may further comprise an excipient. In some embodiments, the composition may further comprise a lyoprotectant. In some embodiments, the composition may further comprise an emollient. In some embodiments, the composition may further comprise thiamine or a salt thereof. In some embodiments, the bacterial species, when contacted with S. aureus, is capable of reducing expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB. In some embodiments, the reduced expression is measured by a fluorescent reporter assay. In some embodiments, the bacterial species is present in an amount effective to inhibit virulence of S. aureus as measured by reduced expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB. In some embodiments, the reduced expression is measured by a fluorescent reporter assay. Methods of administering the compositions are also disclosed herein. In some embodiments, the method comprises administering an amount sufficient to treat a disease selected from the group consisting of atopic dermatitis, seborrheic dermatitis, inflammation, eczema, psoriasis, rosacea, mycosis, dermatophytosis, folliculitis, acne, alopecia, vitiligo, dandruff, chronic wounds, skin ulcers, Netherton syndrome, sweat gland abscess, sycosis vulgaris, staphylococcal scalded skin syndrome, impetigo, ecthyma, cellulitis, carbuncles, furuncles, and abscesses. In some embodiments, the method comprises administering an amount sufficient to treat a condition selected from the group consisting of pruritus, aesthetic conditions, and body odor. In some embodiments, the aesthetic conditions include wrinkles or the appearance of aging. In some embodiments, the method comprises administering an amount sufficient to reduce symptoms associated with atopic dermatitis. In some embodiments, the method comprises administering the composition to a subject having a microbiome predisposed to developing eczema prior to administration thereof. In some embodiments, the method comprises administering an amount sufficient to reduce symptoms associated with dry skin.In some embodiments, the method comprises administering an amount sufficient to reduce the incidence of a condition associated with inflammation, the condition associated with inflammation comprising itching, rash, redness, pain, swelling, blistering, or scaling. In some embodiments, the method comprises administering an amount sufficient to inhibit virulence of S. aureus as measured by a reduction in expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB. In some embodiments, the reduction in expression is measured by a fluorescent reporter assay. In some embodiments, the composition is for use in treating a skin condition. In some embodiments, the composition is for use in treating inflammation.

[0158] In some embodiments, the composition comprises a purified bacterial species. In some embodiments, the bacterial species comprises at least two of the following bacterial species: Bacillus velezensis, Bacillus wiedmannii, Lysinibacillus macrolides, Bacillus amyloliquefaciens, Staphylococcus caprae, and Bacillus tropicus. In some embodiments, (a) the at least two bacterial species are lyophilized; or (b) the composition is formulated for delivery to the skin. In some embodiments, the composition is formulated as a suspension, emulsion, cream, lotion, tincture, gel, foam, powder, ointment, paste, or oil. In some embodiments, the composition comprises at least 10 3 In some embodiments, the composition contains 10 colony forming units (cfu) / gram of bacteria. 3 ~10 12In some embodiments, the bacterial species is grown in aerobic conditions. In some embodiments, the bacterial species is grown without animal products. In some embodiments, the bacterial species is grown in tryptic soy broth (TSB). In some embodiments, the composition, when stored in a sealed container at 20° C., has a bacterial yield of about 10 after 6 months as measured by cfu count. 4cfu. In some embodiments, the composition may further comprise an excipient. In some embodiments, the composition may further comprise a lyoprotectant. In some embodiments, the composition may further comprise an emollient. In some embodiments, the composition may further comprise thiamine or a salt thereof. In some embodiments, the bacterial species, when contacted with S. aureus, is capable of reducing expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB. In some embodiments, the reduced expression is measured by a fluorescent reporter assay. In some embodiments, the bacterial species is present in an amount effective to inhibit virulence of S. aureus as measured by reduced expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB. In some embodiments, the reduced expression is measured by a fluorescent reporter assay. Methods of administering the compositions are also disclosed herein. In some embodiments, the method comprises administering an amount sufficient to treat a disease selected from the group consisting of atopic dermatitis, seborrheic dermatitis, inflammation, eczema, psoriasis, rosacea, mycosis, dermatophytosis, folliculitis, acne, alopecia, vitiligo, dandruff, chronic wounds, skin ulcers, Netherton syndrome, sweat gland abscess, sycosis vulgaris, staphylococcal scalded skin syndrome, impetigo, ecthyma, cellulitis, carbuncles, furuncles, and abscesses. In some embodiments, the method comprises administering an amount sufficient to treat a condition selected from the group consisting of pruritus, aesthetic conditions, and body odor. In some embodiments, the aesthetic conditions include wrinkles or the appearance of aging. In some embodiments, the method comprises administering an amount sufficient to reduce symptoms associated with atopic dermatitis. In some embodiments, the method comprises administering the composition to a subject having a microbiome predisposed to developing eczema prior to administration thereof. In some embodiments, the method comprises administering an amount sufficient to reduce symptoms associated with dry skin.In some embodiments, the method comprises administering an amount sufficient to reduce the incidence of a condition associated with inflammation, the condition associated with inflammation comprising itching, rash, redness, pain, swelling, blistering, or scaling. In some embodiments, the method comprises administering an amount sufficient to inhibit virulence of S. aureus as measured by a reduction in expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB. In some embodiments, the reduction in expression is measured by a fluorescent reporter assay. In some embodiments, the composition is for use in treating a skin condition. In some embodiments, the composition is for use in treating inflammation.

[0159] In some embodiments, the composition comprises a purified bacterial species. In some embodiments, the bacterial species comprises Bacillus velezensis. In some embodiments, (a) the bacterial species is lyophilized; or (b) the composition is formulated for delivery to the skin. In some embodiments, the composition is formulated as a suspension, emulsion, cream, lotion, tincture, gel, foam, powder, ointment, paste, or oil. In some embodiments, the composition can further comprise a second bacterial species. In some embodiments, the composition comprises at least 10 3 In some embodiments, the composition contains 10 colony forming units (cfu) / gram of bacteria. 3 ~10 12 In some embodiments, the bacterial species is grown in aerobic conditions. In some embodiments, the bacterial species is grown without animal products. In some embodiments, the bacterial species is grown in tryptic soy broth (TSB). In some embodiments, the composition, when stored in a sealed container at 20° C., has a bacterial yield of about 10 after 6 months as measured by cfu count. 4cfu. In some embodiments, the composition may further comprise an excipient. In some embodiments, the composition may further comprise a lyoprotectant. In some embodiments, the composition may further comprise an emollient. In some embodiments, the composition may further comprise thiamine or a salt thereof. In some embodiments, the bacterial species, when contacted with S. aureus, is capable of reducing expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB. In some embodiments, the reduced expression is measured by a fluorescent reporter assay. In some embodiments, the bacterial species is present in an amount effective to inhibit virulence of S. aureus as measured by reduced expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB. In some embodiments, the reduced expression is measured by a fluorescent reporter assay. Methods of administering the compositions are also disclosed herein. In some embodiments, the method comprises administering an amount sufficient to treat a disease selected from the group consisting of atopic dermatitis, seborrheic dermatitis, inflammation, eczema, psoriasis, rosacea, mycosis, dermatophytosis, folliculitis, acne, alopecia, vitiligo, dandruff, chronic wounds, skin ulcers, Netherton syndrome, sweat gland abscess, sycosis vulgaris, staphylococcal scalded skin syndrome, impetigo, ecthyma, cellulitis, carbuncles, furuncles, and abscesses. In some embodiments, the method comprises administering an amount sufficient to treat a condition selected from the group consisting of pruritus, aesthetic conditions, and body odor. In some embodiments, the aesthetic conditions include wrinkles or the appearance of aging. In some embodiments, the method comprises administering an amount sufficient to reduce symptoms associated with atopic dermatitis. In some embodiments, the method comprises administering the composition to a subject having a microbiome predisposed to developing eczema prior to administration thereof. In some embodiments, the method comprises administering an amount sufficient to reduce symptoms associated with dry skin.In some embodiments, the method comprises administering an amount sufficient to reduce the incidence of a condition associated with inflammation, the condition associated with inflammation comprising itching, rash, redness, pain, swelling, blistering, or scaling. In some embodiments, the method comprises administering an amount sufficient to inhibit virulence of S. aureus as measured by a reduction in expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB. In some embodiments, the reduction in expression is measured by a fluorescent reporter assay. In some embodiments, the composition is for use in treating a skin condition. In some embodiments, the composition is for use in treating inflammation.

[0160] In some embodiments, the composition comprises a purified bacterial species. In some embodiments, the bacterial species comprises Bacillus wiedmannii. In some embodiments, (a) the bacterial species is lyophilized; or (b) the composition is formulated for delivery to the skin. In some embodiments, the composition is formulated as a suspension, emulsion, cream, lotion, tincture, gel, foam, powder, ointment, paste, or oil. In some embodiments, the composition can further comprise a second bacterial species. In some embodiments, the composition comprises at least 10 3 In some embodiments, the composition contains 10 colony forming units (cfu) / gram of bacteria. 3 ~10 12 In some embodiments, the bacterial species is grown in aerobic conditions. In some embodiments, the bacterial species is grown without animal products. In some embodiments, the bacterial species is grown in tryptic soy broth (TSB). In some embodiments, the composition, when stored in a sealed container at 20° C., has a bacterial yield of about 10 after 6 months as measured by cfu count. 4cfu. In some embodiments, the composition may further comprise an excipient. In some embodiments, the composition may further comprise a lyoprotectant. In some embodiments, the composition may further comprise an emollient. In some embodiments, the composition may further comprise thiamine or a salt thereof. In some embodiments, the bacterial species, when contacted with S. aureus, is capable of reducing expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB. In some embodiments, the reduced expression is measured by a fluorescent reporter assay. In some embodiments, the bacterial species is present in an amount effective to inhibit virulence of S. aureus as measured by reduced expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB. In some embodiments, the reduced expression is measured by a fluorescent reporter assay. Methods of administering the compositions are also disclosed herein. In some embodiments, the method comprises administering an amount sufficient to treat a disease selected from the group consisting of atopic dermatitis, seborrheic dermatitis, inflammation, eczema, psoriasis, rosacea, mycosis, dermatophytosis, folliculitis, acne, alopecia, vitiligo, dandruff, chronic wounds, skin ulcers, Netherton syndrome, sweat gland abscess, sycosis vulgaris, staphylococcal scalded skin syndrome, impetigo, ecthyma, cellulitis, carbuncles, furuncles, and abscesses. In some embodiments, the method comprises administering an amount sufficient to treat a condition selected from the group consisting of pruritus, aesthetic conditions, and body odor. In some embodiments, the aesthetic conditions include wrinkles or the appearance of aging. In some embodiments, the method comprises administering an amount sufficient to reduce symptoms associated with atopic dermatitis. In some embodiments, the method comprises administering the composition to a subject having a microbiome predisposed to developing eczema prior to administration thereof. In some embodiments, the method comprises administering an amount sufficient to reduce symptoms associated with dry skin.In some embodiments, the method comprises administering an amount sufficient to reduce the incidence of a condition associated with inflammation, the condition associated with inflammation comprising itching, rash, redness, pain, swelling, blistering, or scaling. In some embodiments, the method comprises administering an amount sufficient to inhibit virulence of S. aureus as measured by a reduction in expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB. In some embodiments, the reduction in expression is measured by a fluorescent reporter assay. In some embodiments, the composition is for use in treating a skin condition. In some embodiments, the composition is for use in treating inflammation.

[0161] In some embodiments, the composition comprises a purified bacterial species. In some embodiments, the bacterial species comprises Lysinibacillus macroides. In some cases, (a) the bacterial species is lyophilized; or (b) the composition is formulated for delivery to the skin. In some embodiments, the composition is formulated as a suspension, emulsion, cream, lotion, tincture, gel, foam, powder, ointment, paste, or oil. In some embodiments, the composition can further comprise a second bacterial species. In some embodiments, the composition is at least 10 3 In some embodiments, the composition contains 10 colony forming units (cfu) / gram of bacteria. 3 ~10 12 In some embodiments, the bacterial species is grown in aerobic conditions. In some embodiments, the bacterial species is grown without animal products. In some embodiments, the bacterial species is grown in tryptic soy broth (TSB). In some embodiments, the composition, when stored in a sealed container at 20° C., has a bacterial yield of about 10 after 6 months as measured by cfu count. 4cfu. In some embodiments, the composition may further comprise an excipient. In some embodiments, the composition may further comprise a lyoprotectant. In some embodiments, the composition may further comprise an emollient. In some embodiments, the composition may further comprise thiamine or a salt thereof. In some embodiments, the bacterial species, when contacted with S. aureus, is capable of reducing expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB. In some embodiments, the reduced expression is measured by a fluorescent reporter assay. In some embodiments, the bacterial species is present in an amount effective to inhibit virulence of S. aureus as measured by reduced expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB. In some embodiments, the reduced expression is measured by a fluorescent reporter assay. Methods of administering the compositions are also disclosed herein. In some embodiments, the method comprises administering an amount sufficient to treat a disease selected from the group consisting of atopic dermatitis, seborrheic dermatitis, inflammation, eczema, psoriasis, rosacea, mycosis, dermatophytosis, folliculitis, acne, alopecia, vitiligo, dandruff, chronic wounds, skin ulcers, Netherton syndrome, sweat gland abscess, sycosis vulgaris, staphylococcal scalded skin syndrome, impetigo, ecthyma, cellulitis, carbuncles, furuncles, and abscesses. In some embodiments, the method comprises administering an amount sufficient to treat a condition selected from the group consisting of pruritus, aesthetic conditions, and body odor. In some embodiments, the aesthetic conditions include wrinkles or the appearance of aging. In some embodiments, the method comprises administering an amount sufficient to reduce symptoms associated with atopic dermatitis. In some embodiments, the method comprises administering the composition to a subject having a microbiome predisposed to developing eczema prior to administration thereof. In some embodiments, the method comprises administering an amount sufficient to reduce symptoms associated with dry skin.In some embodiments, the method comprises administering an amount sufficient to reduce the incidence of a condition associated with inflammation, the condition associated with inflammation comprising itching, rash, redness, pain, swelling, blistering, or scaling. In some embodiments, the method comprises administering an amount sufficient to inhibit virulence of S. aureus as measured by a reduction in expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB. In some embodiments, the reduction in expression is measured by a fluorescent reporter assay. In some embodiments, the composition is for use in treating a skin condition. In some embodiments, the composition is for use in treating inflammation.

[0162] In some embodiments, the composition comprises a purified bacterial species. In some embodiments, the bacterial species comprises Bacillus tropicus. In some embodiments, (a) the bacterial species is lyophilized; or (b) the composition is formulated for delivery to the skin. In some embodiments, the composition is formulated as a suspension, emulsion, cream, lotion, tincture, gel, foam, powder, ointment, paste, or oil. In some embodiments, the composition can further comprise a second bacterial species. In some embodiments, the composition comprises at least 10 3 In some embodiments, the composition contains 10 colony forming units (cfu) / gram of bacteria. 3 ~10 12 In some embodiments, the bacterial species is grown in aerobic conditions. In some embodiments, the bacterial species is grown without animal products. In some embodiments, the bacterial species is grown in tryptic soy broth (TSB). In some embodiments, the composition, when stored in a sealed container at 20° C., has a bacterial yield of about 10 after 6 months as measured by cfu count. 4cfu. In some embodiments, the composition may further comprise an excipient. In some embodiments, the composition may further comprise a lyoprotectant. In some embodiments, the composition may further comprise an emollient. In some embodiments, the composition may further comprise thiamine or a salt thereof. In some embodiments, the bacterial species, when contacted with S. aureus, is capable of reducing expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB. In some embodiments, the reduced expression is measured by a fluorescent reporter assay. In some embodiments, the bacterial species is present in an amount effective to inhibit virulence of S. aureus as measured by reduced expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB. In some embodiments, the reduced expression is measured by a fluorescent reporter assay. Methods of administering the compositions are also disclosed herein. In some embodiments, the method comprises administering an amount sufficient to treat a disease selected from the group consisting of atopic dermatitis, seborrheic dermatitis, inflammation, eczema, psoriasis, rosacea, mycosis, dermatophytosis, folliculitis, acne, alopecia, vitiligo, dandruff, chronic wounds, skin ulcers, Netherton syndrome, sweat gland abscess, sycosis vulgaris, staphylococcal scalded skin syndrome, impetigo, ecthyma, cellulitis, carbuncles, furuncles, and abscesses. In some embodiments, the method comprises administering an amount sufficient to treat a condition selected from the group consisting of pruritus, aesthetic conditions, and body odor. In some embodiments, the aesthetic conditions include wrinkles or the appearance of aging. In some embodiments, the method comprises administering an amount sufficient to reduce symptoms associated with atopic dermatitis. In some embodiments, the method comprises administering the composition to a subject having a microbiome predisposed to developing eczema prior to administration thereof. In some embodiments, the method comprises administering an amount sufficient to reduce symptoms associated with dry skin.In some embodiments, the method comprises administering an amount sufficient to reduce the incidence of a condition associated with inflammation, the condition associated with inflammation comprising itching, rash, redness, pain, swelling, blistering, or scaling. In some embodiments, the method comprises administering an amount sufficient to inhibit virulence of S. aureus as measured by a reduction in expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB. In some embodiments, the reduction in expression is measured by a fluorescent reporter assay. In some embodiments, the composition is for use in treating a skin condition. In some embodiments, the composition is for use in treating inflammation.

[0163] Also disclosed herein is a method for treating inflammation, comprising topically administering a composition comprising Bacillus wiedmannii to a subject in need of the composition. In some embodiments, the Bacillus wiedmannii is purified. In some embodiments, the Bacillus wiedmannii is present in an amount sufficient for treating inflammation.

[0164] Also disclosed herein is a method for reducing the growth of Staphylococcus aureus on the skin of a subject in need of such reduction, comprising topically administering a pharmaceutical composition comprising Bacillus velezensis, Bacillus wiedmannii, and Lysinibacillus macroides to the skin of a subject in need of such reduction. In some embodiments, Bacillus velezensis, Bacillus wiedmannii, and Lysinibacillus macroides are purified. In some embodiments, Bacillus velezensis, Bacillus wiedmannii, and Lysinibacillus macroides are viable and present in sufficient amounts for the reduction of S. aureus on the skin of a subject in need of such reduction.

[0165] Also disclosed herein is a method for reducing symptoms associated with atopic dermatitis, comprising topically administering a composition comprising Bacillus amyloliquefaciens to a subject in need thereof. In some embodiments, the Bacillus amyloliquefaciens is purified. In some embodiments, the Bacillus amyloliquefaciens is present in an amount sufficient to reduce symptoms associated with atopic dermatitis.

[0166] Also disclosed herein is a method for reducing the incidence of inflammation-related conditions, comprising topically administering a composition comprising Bacillus wiedmannii and Staphylococcus caprae to a subject in need of the composition. In some embodiments, Bacillus wiedmannii and Staphylococcus caprae are purified. In some embodiments, Bacillus wiedmannii and Staphylococcus caprae are present in an amount sufficient for reducing the incidence of inflammation-related conditions. In some embodiments, inflammation-related conditions include itching, rash, redness, pain, swelling, blistering, or scaling. EXAMPLES

[0167] Example 1: Bacterial strains and screening

[0168] 1750 bacterial isolates were screened from different sites of skin of 20 healthy donors. Of the 1750 strains, 609 were frozen and 180 were selected for initial screening. The 180 strains were identified by 16S full-length sequencing using Sanger sequencing. The reads were trimmed and concatenated. The 16S sequences were compared with the NCBI 16S database by BLAST algorithm and species were identified as the top hits from the database. A minimum threshold was applied to the sequences for quality control. The top 28 strains from the 180 strains in the initial screening were further selected for some experiments. Table 1 shows the species from the top 28 strains selected.

[0169] Strains were screened in an array assay as a global approach to determine the interaction of isolate(s) with strains of S. aureus. Briefly, isolates and S. aureus strains were added to an array assay containing thousands of microwells. Strains were mixed with molecules of different identifying wavelengths, which when mixed generated a unique wavelength code that was read by an imaging device to determine the input. S. aureus strains were promoter / reporter strains used to screen for inhibition of gene expression. The reduction in expression of the promoter / reporter strain when grown with the skin isolate(s) was shown as a reduction in fluorescence compared to the promoter / reporter strain grown alone.

[0170] S. aureus promoter / reporter strains contained a fluorescent reporter under the control of the promoter of a gene of interest. The promoter / reporter strains generated were as follows: strain 1 - agr promoter for quorum sensing induction, strain 2 - psmA promoter for toxins that damage host tissues, strain 3 - saeR promoter for virulence regulation, strain 4 - sigB promoter for stress response sigma factors, strain 5 - ccpA promoter for metabolism (e.g., carbon catabolite repression), and strain 6 - GMK promoter for constitutive metabolic functions.

[0171] In addition to array assays, strains can be tested for gene expression inhibition in a wide variety of assays, such as microtiter plate growth assays, or other liquid culture growth assays. In another example, strains can be screened for gene inhibition on agar plates.

[0172] Example 2: Pairwise assay of bacterial isolates for inhibition of gene expression in S. aureus

[0173] One hundred eighty diverse bacterial isolates from healthy human skin were screened in a pairwise combinatorial screening assay against four S. aureus behavior reporters. S. aureus behavior was measured via a series of plasmid-mediated "promoter-reporter" strains whose fluorescence reports one specific activity. Strain combinations were screened for 10 days in the array assay. Controls were 1) no isolate (which was a monoculture of S. aureus), 2) wild-type S. aureus, and 3) streptomycin as a negative control for eradication of S. aureus. The screen analyzed a reporter for constitutive metabolic function GMK, a reporter for quorum sensing induction agr, a reporter for toxins that damage host tissues psmA, and a reporter for stress response sigma factors sigB. Referring to Figure 1, the left side of Figure 1 shows that among the 180 bacterial isolates screened, only 3.8% of the pairwise combinations inhibited agr and psmA to 3-fold or 12.5% ​​of monoculture levels. Similarly, the right side of Figure 1 shows that among the 180 bacterial isolates screened, only 1.1% of the pairwise combinations inhibited agr, psmA, and sigB to 3-fold or 12.5% ​​of monoculture levels. These data indicate that combinations possessing multiple functions are rare.

[0174] Example 3: Assay of bacterial isolates in triplicate for inhibition of gene expression in S. aureus

[0175] Bacterial isolates from healthy human skin were screened in a three-wise combinatorial screening assay against six S. aureus behavior reporters. S. aureus behavior was measured via a series of plasmid-mediated "promoter-reporter" strains whose fluorescence reports one specific activity. Strain combinations were screened for 4 days in the array assay. The strain mixture conditions were 1) no isolate (which was a monoculture of S. aureus), 2) wild-type S. aureus with isolates, and 3) streptomycin as a negative control for eradication of S. aureus. The screen analyzed expression of a reporter agr for quorum sensing induction, a reporter psmA for toxins damaging host tissues, a reporter saeR for virulence regulation, a reporter sigB for stress response sigma factors, a reporter ccpA for metabolism (e.g., carbon catabolite repression), and a reporter GMK for constitutive metabolic functions.

[0176] Referring to FIG. 2, the Y-axis shows the percentage of activity compared to S. aureus monoculture. The X-axis shows the strains in the combinatorial screening assay. An "X" associated with one or more strains indicates that all individual strains from the top 28 isolates were added to the mixture, and the average from the mixture is shown. For example, jl27+jl77+X data is the average of 26 different triplicate compositions. In another example, jl27+X+X is the average of 351 different compositions. The random community is a community of three isolates randomly selected from the top 28 isolates. The reporters are shown from left to right as follows: agr, psmA, saeR, sigB, ccpA, and GMK. Triple combinations including strains jl.83, jl.27, and jl.77 were effective in suppressing agr (quorum sensing) and psmA (toxin production) in S. aureus; these pairs were still more potent; all three combined yielded the greatest effect. In some conditions, triple combinations including strains jl.83, jl.27, and jl.77 were effective in suppressing saeR, sigB, ccpA, and GMK in S. aureus. All three combined reduced the activity of all reporters to less than 10% activity compared to monocultures. The reduction was unexpected compared to the random community, which only reduced the expression levels of saeR, sigB, ccpA, and GMK to approximately 20%-40% compared to monocultures. The data indicate that strain combinations can be effective in inhibiting gene expression in S. aureus.

[0177] Referring to FIG. 3, the Y-axis shows the percentage of activity compared to S. aureus monoculture. The X-axis shows the strains in the combinatorial screening assay. An "X" associated with one or more strains indicates that all individual strains from the top 28 isolates were added to the mixture, and the average from the mixture is shown. For example, jl21+jl68+X data is the average of 26 different triplicate compositions. In another example, jl21+X+X is the average of 351 different compositions. The random community is a community of three isolates randomly selected from the top 28 isolates. The reporters are shown from left to right as follows: agr, psmA, saeR, sigB, ccpA, and GMK. Triple combinations including strains jl.21, jl.68, and jl.121 were effective in suppressing agr (quorum sensing) and psmA (toxin production) in S. aureus; these pairs were still more potent; all three combined yielded the greatest effect. In some conditions, triple combinations including strains jl.21, jl.68, and jl.121 were effective in suppressing saeR, sigB, ccpA, and GMK in S. aureus. All three combined reduced the activity of all reporters to less than 10% activity compared to monocultures. The reduction was unexpected compared to the random community, which only reduced the expression levels of saeR, sigB, ccpA, and GMK to approximately 20%-40% compared to monocultures. The data indicate that strain combinations can be effective in inhibiting gene expression in S. aureus.

[0178] Referring to FIG. 4, the Y-axis shows the percentage of activity compared to S. aureus monoculture. The X-axis shows the strains in the combinatorial screening assay. An "X" associated with one or more strains indicates that all individual strains from the top 28 isolates were added to the mixture, and the average from the mixture is shown. For example, jl27+jl68+X data is the average of 26 different triplicate compositions. In another example, jl27+X+X is the average of 351 different compositions. The random community is a community of three isolates randomly selected from the top 28 isolates. The reporters are shown from left to right as follows: agr, psmA, saeR, sigB, ccpA, and GMK. Triple combinations including strains jl.27, jl.68, and jl.121 were effective in suppressing agr (quorum sensing) and psmA (toxin production) in S. aureus; these pairs were still more potent; all three combined yielded the greatest effect. In some conditions, triple combinations including strains jl.27, jl.68, and jl.121 were effective in suppressing saeR, sigB, ccpA, and GMK in S. aureus. All three combined reduced the activity of all reporters to less than 10% activity compared to monocultures. The reduction was unexpected compared to the random community, which only reduced the expression levels of saeR, sigB, ccpA, and GMK to approximately 20%-40% compared to monocultures. The data indicate that strain combinations can be effective in inhibiting gene expression in S. aureus.

[0179] Example 4: Assay of gene expression inhibition in S. aureus under different environmental conditions

[0180] Triplicate combinations of strains jl.83, jl.27, jl.77, jl.21, jl.68, and jl.121 were screened to assess the behavior of S. aureus when further environmental components such as nutrients were added to the mixture. The behavior of S. aureus was measured via a series of plasmid-mediated "promoter-reporter" strains whose fluorescence reports one specific activity. Combinations of strains and environmental conditions were screened for one day in the array. The conditions for the strain mixture were 1) S. aureus culture alone, and 2) S. aureus mixed with three skin isolates. The screen analyzed the expression of the reporter agr for quorum sensing induction, the reporter psmA for toxins damaging host tissues, and the reporter GMK for constitutive metabolic functions.

[0181] Referring to Figure 5, the Y-axis shows the percentage change compared to S. aureus monoculture. Monoculture conditions are shown using grey bars, and black bars show conditions where strains jl.83, jl.27, and jl.77 were added to the culture. The X-axis shows the environmental conditions tested. Conditions are shown from left to right: (1) basal medium, then basal medium supplemented with one of the following: (2) acetate, (3) beta-alanine, (4) bicarbonate, (5) biotin, (6) butyrate, (7) caffeine, (8) citrate, (9) creatine, (10) D-cellobiose, (11) D-fructose, (12) D-glucosamine, (13) D-glucose, (14) D-mannitol, (15) D-raffinose, (16) D-sorbitol, (17) D-sucrose, (18) D-trehalose, (19) D-xylose, (20) formate, (21) GlcNAc, (22) glycerol, (23) glycine, (24) L-alanine, (25) L-glucose, (26) L-glucose, (27) L-glucose, (28) L-glucose, (29) L-glucose, (30) L-glucose, (31) L-glucose, (32) L-glucose, (33) L-glucose, (34) L-glucose, (35) L-glucose, (36) L-glucose, (37) L-glucose, (38) L-glucose, (39) L-glucose, (40) L-glucose, (41) L-glucose, (42) L-glucose, (43) L-glucose, (44) L-glucose, (45) L-glucose, (46) L-glucose, (47) L-glucose, (48) L-glucose, (49) L-glucose, (50) L-glucose, (51) L-glucose, (52) L-glucose, 5) L-arabinose, (26) L-arginine, (27) L-citrulline, (28) L-glutamine, (29) L-hydroxyproline, (30) L-isoleucine, (31) L-leucine, (32) L-methionine, (33) L-ornithine, (34) L-proline, (35) L-serine, (36) L-taurine, (37) L-threonine, (38) L-valine, (39) L-ascorbate, (40) L-lactate, (41) nicotinamine, (42) polysorbate 20, (43) polysorbate 80, (44) propionate, (45) pyruvate, (46) succinate, (47) thiamine, (48) triethanolamine, or (49) urea. The data show that strain combinations including strains jl.83, jl.27, and jl.77 were effective in suppressing agr (quorum sensing), psmA (toxin production), and GMK (metabolic function) of S. aureus under all tested environmental conditions, including those that supported the growth of S. aureus.

[0182] Referring to Figure 6, the Y-axis shows the percentage change compared to S. aureus monoculture. Monoculture conditions are shown using grey bars, and black bars show conditions where strains jl.21, jl.68, and jl.121 were added to the culture. The X-axis shows the environmental conditions tested. Conditions are shown from left to right: (1) basal medium, then basal medium supplemented with one of the following: (2) acetate, (3) beta-alanine, (4) bicarbonate, (5) biotin, (6) butyrate, (7) caffeine, (8) citrate, (9) creatine, (10) D-cellobiose, (11) D-fructose, (12) D-glucosamine, (13) D-glucose, (14) D-mannitol, (15) D-raffinose, (16) D-sorbitol, (17) D-sucrose, (18) D-trehalose, (19) D-xylose, (20) formate, (21) GlcNAc, (22) glycerol, (23) glycine, (24) L-alanine, (25) L-glucose, (26) L-glucose, (27) L-glucose, (28) L-glucose, (29) L-glucose, (30) L-glucose, (31) L-glucose, (32) L-glucose, (33) L-glucose, (34) L-glucose, (35) L-glucose, (36) L-glucose, (37) L-glucose, (38) L-glucose, (39) L-glucose, (40) L-glucose, (41) L-glucose, (42) L-glucose, (43) L-glucose, (44) L-glucose, (45) L-glucose, (46) L-glucose, (47) L-glucose, (48) L-glucose, (49) L-glucose, (50) L-glucose, (51) L-glucose, (52) L-glucose, 5) L-arabinose, (26) L-arginine, (27) L-citrulline, (28) L-glutamine, (29) L-hydroxyproline, (30) L-isoleucine, (31) L-leucine, (32) L-methionine, (33) L-ornithine, (34) L-proline, (35) L-serine, (36) L-taurine, (37) L-threonine, (38) L-valine, (39) L-ascorbate, (40) L-lactate, (41) nicotinamine, (42) polysorbate 20, (43) polysorbate 80, (44) propionate, (45) pyruvate, (46) succinate, (47) thiamine, (48) triethanolamine, or (49) urea. In all cases, the strain combinations were able to reduce expression of all three reporters to less than 10% of monoculture levels. The data show that strain combinations including strains jl.21, jl.68, and jl.121 were effective in suppressing agr (quorum sensing), psmA (toxin production), and GMK (metabolic function) in S. aureus under all tested environmental conditions, including conditions that supported the growth of S. aureus. In all cases, the strain combinations were able to reduce expression of all three reporters to less than 10% of monoculture levels.

[0183] Referring to Figure 7, the Y-axis shows the percentage change compared to S. aureus monoculture. Monoculture conditions are shown using grey bars, and black bars show conditions where strains jl.27, jl.68, and jl.121 were added to the culture. The X-axis shows the environmental conditions tested. Conditions are shown from left to right: (1) basal medium, then basal medium supplemented with one of the following: (2) acetate, (3) beta-alanine, (4) bicarbonate, (5) biotin, (6) butyrate, (7) caffeine, (8) citrate, (9) creatine, (10) D-cellobiose, (11) D-fructose, (12) D-glucosamine, (13) D-glucose, (14) D-mannitol, (15) D-raffinose, (16) D-sorbitol, (17) D-sucrose, (18) D-trehalose, (19) D-xylose, (20) formate, (21) GlcNAc, (22) glycerol, (23) glycine, (24) L-alanine, (25) L-glucose, (26) L-glucose, (27) L-glucose, (28) L-glucose, (29) L-glucose, (30) L-glucose, (31) L-glucose, (32) L-glucose, (33) L-glucose, (34) L-glucose, (35) L-glucose, (36) L-glucose, (37) L-glucose, (38) L-glucose, (39) L-glucose, (40) L-glucose, (41) L-glucose, (42) L-glucose, (43) L-glucose, (44) L-glucose, (45) L-glucose, (46) L-glucose, (47) L-glucose, (48) L-glucose, (49) L-glucose, (50) L-glucose, (51) L-glucose, (52) L-glucose, 5) L-arabinose, (26) L-arginine, (27) L-citrulline, (28) L-glutamine, (29) L-hydroxyproline, (30) L-isoleucine, (31) L-leucine, (32) L-methionine, (33) L-ornithine, (34) L-proline, (35) L-serine, (36) L-taurine, (37) L-threonine, (38) L-valine, (39) L-ascorbate, (40) L-lactate, (41) nicotinamine, (42) polysorbate 20, (43) polysorbate 80, (44) propionate, (45) pyruvate, (46) succinate, (47) thiamine, (48) triethanolamine, or (49) urea. In all cases, the strain combinations were able to reduce expression of all three reporters to approximately 50% below monoculture levels. The data show that strain combinations including strains jl.27, jl.68, and jl.121 were effective in suppressing agr (quorum sensing), psmA (toxin production), and GMK (metabolic function) of S. aureus under all tested environmental conditions, including those that supported the growth of S. aureus.

[0184] Example 5: Assay for enhancement of inhibition of gene expression in S. aureus by thiamine

[0185] Strains jl.83, jl.27, and jl.77 were screened in an evaluation of S. aureus behavior when thiamine was added to the mixture. S. aureus behavior was measured via a series of plasmid-mediated "promoter-reporter" strains whose fluorescence reports one specific activity. Combinations of strains and environmental conditions were screened for one day in an array assay. The strain mixture conditions were: (1) S. aureus monoculture, (2) S. aureus monoculture in medium with excess thiamine, (3) S. aureus mixed with strains jl.83, jl.27, and jl.77, and (4) S. aureus mixed with strains jl.83, jl.27, and jl.77 in medium with excess thiamine. In the array assay, the expression of the reporter agr for quorum sensing induction, the reporter psmA for toxins damaging host tissues, and the reporter GMK for constitutive metabolic functions was analyzed. Referring to FIG. 8, the Y-axis shows the percentage of activity compared to S. aureus monoculture. The X-axis shows the expression of agr (quorum sensing), psmA (toxin production), and GMK (metabolic function) of S. aureus. For each gene, the conditions of the three strain mixtures are shown from left to right, the conditions being condition (4), condition (3), and condition (2). The addition of thymine surprisingly showed a synergistic effect in suppressing the expression of agr (quorum sensing) and psmA (toxin production) of S. aureus when added together with strains jl.83, jl.27, and jl.77. For example, agr expression and psmA expression were reduced by more than half in both cases. The data indicate that thymine synergized with the bacterial mixture to increase gene inhibition in S. aureus.

[0186] Example 6: Isolates grown in animal-derived-free media

[0187] Bacterial isolates jl.27, jl.77, jl.83, jl.21, jl.68, and jl.121 were grown under similar conditions in the animal-origin-based medium tryptic soy broth (TSB) and various animal-origin-free media (AFM). The strains were grown for 48 hours after inoculation with the same number of bacteria. With reference to FIG. 9, the Y-axis shows the colony forming units (cfu) / mL observed across the media tested. The X-axis shows the strains tested and the animal-origin-free media formulations used for the strains tested (e.g., AFM-6 for animal-origin-free media formulation 6). The strains tested were strain JL.27 (JL27), strain JL.77 (JL77), strain JL.83 (JL83), strain JL.21 (JL21), strain JL.68 (JL68), and strain JL.121 (JL121). For most strains grown in animal-origin-free media, there was a 10-100-fold improvement in culture cfu / ml after 48 hours. The data indicate that the strains can be cultured in a variety of media and manufactured in animal-origin-free media for the production of compositions, such as pharmaceutical compositions.

[0188] Example 7: Assay of growth inhibition of S. aureus using combinations of bacterial isolates

[0189] Bacterial isolates from the skin of healthy individuals were tested for their ability to inhibit the growth of several S. aureus strains. The strains were grown for 48 hours after inoculation with an equal number of bacteria. With reference to Figures 10, 11, and 12, the Y-axis shows the effect of growth inhibition by strain combinations. The X-axis shows the growth of different S. aureus strains in the presence of an ensemble (e.g., a combination of three strains) or S. aureus strains alone. For the S. aureus strains tested, the ensemble is on the left side of the bar graph, and the S. aureus strains alone are on the right side of the bar graph. Figure 10 tested the ensemble jl27 / jl77 / jl83 (strains jl.27, jl.77, and jl.83), Figure 11 tested the ensemble jl21 / jl68 / jl121 (strains jl.21, jl.68, and jl.121), and Figure 12 tested the ensemble jl27 / jl68 / jl121 (strains jl.27, jl.68, and jl.121). All three tested strain combinations were able to inhibit the growth of different S. aureus strains, suggesting that the strain combinations are effective against a wide variety of S. aureus strains.

[0190] Example 8: Assay of gene expression inhibition in S. aureus with Bacillus wiedmannii alone and in combination with additional strains

[0191] The jl.27 strain was isolated from the skin of a healthy individual and screened in a pairwise combinatorial screening assay against four S. aureus behavior reporters. S. aureus behavior was measured through a series of plasmid-mediated "promoter-reporter" S. aureus strains whose fluorescence reports one specific activity. Strain combinations were screened in an array assay. The strain mixture conditions were 1) self-cross of jl.27 strain, 2) jl.27 strain with a random skin isolate, and 3) jl.27 strain with another isolate that showed inhibition of S. aureus gene expression. The screen analyzed the expression of reporter agr for quorum sensing induction, reporter sigB for stress response sigma factor, reporter psmA for toxins that damage host tissues, and reporter GMK for constitutive metabolic functions. Referring to Figure 13, the Y-axis shows the log2 expression change of co-culture / S. aureus promoter-reporter monoculture. The x-axis indicates the gene promoters tested. The large circles indicate data points for self-crosses (strain jl.27 and strain jl.27). The small black circles indicate strain jl.27 crossed with another isolate that showed inhibition of gene expression in S. aureus. The small light grey circles indicate strain jl.27 with a random skin isolate. The data show that strain jl.27 had a strong inhibitory effect on S. aureus growth, stress, and toxin production. Also, many combinations occurred that strongly inhibited quorum sensing in S. aureus. The data show that strain jl.27 is effective alone or in combination in inhibiting gene expression in S. aureus.

[0192] Example 9: Inhibition of gene expression in S. aureus in the presence of additional microorganisms

[0193] Triplicate combinations, pairwise combinations, and individual strains of strains jl.83, jl.27, jl.77, jl.21, jl.68, and jl.121 were screened in an evaluation of S. aureus behavior in the presence of different microorganisms. Bacterial strains added to the mixtures were randomly selected from 92 strains selected from an initial collection of 609 frozen strains. S. aureus behavior was measured through a series of plasmid-mediated "promoter-reporter" strains whose fluorescence reports one specific activity. The screen analyzed the expression of reporters: agr for quorum sensing induction, psmA for toxins damaging host tissues, and GMK for constitutive metabolic functions. Strain combinations were screened in arrays after one day of growth. The strain mixture conditions were: 1) triplicate combinations with an additional set of four strains, 2) pairwise combinations with an additional set of five strains, and 3) one individual strain with an additional set of six strains. For example, jl121 / jl21 / jl68+4X indicates a test community in which jl.121, jl.21, and jl.68 and up to four additional microorganisms (selected from 89 strains) are present. In another example, jl121 / jl21+5X indicates a test community in which jl.121 and jl.21 and up to five additional microorganisms (selected from 90 strains) are present. In another example, jl121+6X indicates a test community in which jl.121 and up to six additional microorganisms (selected from 91 strains) are present.

[0194] Referring to FIG. 14, the Y-axis shows the percentage expression of the reporter compared to S. aureus monoculture (i.e., monoculture is 100%). The X-axis shows the strain combinations tested. The strains tested were jl.121, jl.21, and jl.68. These strains were tested in different combinations where the strains were randomly selected so that a 7-strain community was formed. The data shows that the strain combinations including jl.121, jl.21, and jl.68 (1) were effective in suppressing agr (quorum sensing), psmA (toxin production), and GMK (metabolic function) of S. aureus; (2) the strain combination (ensemble) still worked strongly even in the presence of other microorganisms, suggesting that the combination works well in the native microbiome; and (3) worked stronger than any subset of the three-species combination when present. For example, the triple combination of strains jl.121, jl.21, and jl.68 was robust to the larger community and more robust than its subsets, as agr expression was reduced to less than about 5%, psmA expression was reduced to less than about 2%, and GMK expression was reduced to less than about 20%.

[0195] Referring to FIG. 15, the percentage expression of the reporters compared to S. aureus monoculture (i.e., monoculture is 100%) is shown. The X-axis shows the strain combinations tested. The strains tested were jl.121, jl.27, and jl.68. These strains were tested in different combinations where the strains were randomly selected so that a 7-strain community was formed. The data shows that the strain combinations including jl.121, jl.27, and jl.68 (1) were effective in suppressing agr (quorum sensing), psmA (toxin production), and GMK (metabolic function) of S. aureus; (2) the strain combination (ensemble) still worked strongly even in the presence of other microorganisms, suggesting that the combination works well in the native microbiome; and (3) worked stronger than any subset of the three-species combination when present. For example, the triple combination of strains jl.121, jl.27, and jl.68 was robust to the larger community and more robust than its subsets, as agr expression was reduced to less than about 5%, psmA expression was reduced to less than about 2%, and GMK expression was reduced to less than about 40%.

[0196] Referring to FIG. 16, the expression percentage of the reporters compared to S. aureus monoculture (i.e., monoculture is 100%) is shown. The x-axis shows the strain combinations tested. The test strains were jl.27, jl.77, and jl.83. These strains were tested in different combinations where the strains were randomly selected so that a 7-strain community was formed. The data shows that the strain combinations including jl.27, jl.77, and jl.83 (1) were effective in suppressing agr (quorum sensing), psmA (toxin production), and GMK (metabolic function) of S. aureus; (2) the strain combination (ensemble) still worked strongly even in the presence of other microorganisms, suggesting that the combination works well in the native microbiome; and (3) worked stronger than any subset of the three-species combination when present. For example, the triple combination of strains jl.27, jl.77, and jl.83 was robust to the larger community and more robust than its subsets, as agr expression was reduced to less than about 2%, psmA expression was reduced to less than about 2%, and GMK expression was reduced to less than about 10%.

[0197] Example 10: Clinical study of skin inflammation

[0198] A female subject diagnosed with skin inflammation is treated with a pharmaceutical composition comprising strains jl.21, jl.68, and jl.121. After administering the pharmaceutical composition for two weeks, the following are observed: amount of pain, amount of redness, amount of swelling, and amount of itching.

[0199] Example 11: Clinical study of atopic dermatitis

[0200] A male subject diagnosed with atopic dermatitis is treated with a pharmaceutical composition comprising strains jl.83, jl.27, and jl.77. After administering the pharmaceutical composition for 3 weeks, the following are observed: amount of dryness, amount of redness, amount of dryness, and amount of peeling.

[0201] Example 12: Sequencing of isolates

[0202] Isolates were subjected to whole genome sequencing and assembly of the generated contigs. Additionally, 16s rRNA gene sequences were sequenced by Sanger sequencing and manually trimmed. 16s rRNA sequences from the isolates are shown in Table 6. Additionally, several identifier sequences were obtained from each isolate assembly for identification. Identifier sequences from the isolates are shown in Table 7. To identify identifier sequences, genome assemblies were evaluated for strain identification sequences. Assemblies were preprocessed by removing 1000bp from each side of each assembly sequence to minimize edge effects, and sequences obtained after harvesting were removed from consideration if their length was less than 10kbp. A series of novel partial sequences were generated by applying sliding windows of several lengths (with 10% overlap across the windows); 5000bp windows with 500bp overlap were used, and 1200bp windows with 120bp overlap were used. The sequences were searched by BLAST from the Nucleotide Collection database (Nucleotide Collection (nt) database) provided by the National Center for Biotechnology Information (NCBI) downloaded on September 17, 2022. Identifier sequences that had BLAST sequence search results with a query coverage greater than or equal to 99% and a sequence identity percentage less than 98% are included in Table 7.

[0203] [Table 6-1] [Table 6-2] [Table 6-3] [Table 6-4] [Table 6-5] [Table 6-6]

[0204] [Table 7-1] [Table 7-2] [Table 7-3] [Table 7-4] [Table 7-5] [Table 7-6] [Table 7-7] [Table 7-8] [Table 7-9] [Table 7-10]

[0205] Example 13: Quorum sensing and metabolic expression of S. aureus on agar plates when mixed with strain jl.68

[0206] S. aureus reporter strains containing GMK promoter-fused GFP reporter or agr promoter-fused GFP reporter were plated on agar plates. Ten microliters of jl.68 strain was plated in the center of the plate. After 24 hours of incubation at 37°C, images of the plates were taken. Figures 17A-B show the expression and growth of S. aureus reporter strains. Reporter expression is shown in the GFP column. S. aureus growth is shown in the bright field column. The images show that jl.68 strain cells retard the growth of S. aureus on the agar plates, suggesting that they affect quorum sensing.

[0207] Example 14: Growth of S. aureus and expression of S. aureus genes after mixing with selected strains and supernatants of selected strains

[0208] S. aureus reporter strains containing GMK promoter-fused GFP reporters or agr promoter-fused GFP reporters were grown in liquid culture under the following conditions: in monoculture, mixed with S. aureus WT (control); mixed with jl.27, jl.68, and jl.77 strains; mixed with jl.68 strain only; mixed with supernatants from jl.27, jl.68, and jl.77 strains; or mixed with supernatants from jl.68 strain only. Expression of GMK and agr was determined after 24 hours of incubation. Expression and CFU levels were compared to PBS control and calculated by (time 24-time 0) / (PBS at time 24-PBS at time 0). Figures 18A-F show CFU, GMK expression, and agr expression in different growth conditions on the X-axis, with levels compared to PBS on the Y-axis. Error bars for "agr" are apparently large because values ​​below zero were set to 0. Figure 18A shows the CFU of S. aureus as well as the expression of GMK and agr in the S. aureus monoculture control. Figure 18B shows 1:1 coculture with ai.15 (S. aureus WT), which increased quorum sensing but had little to no effect on cell viability or metabolism. Figures 18C-D show 1:1 coculture with strains jl.27, jl.68, and jl.77 or jl.68, which decreased cell viability (less than 1% (CFU)). Similarly, quorum sensing (agr-GFP) was reduced to negligible levels (almost 0%) compared to the PBS control, and metabolism (GMK-GFP) was reduced to 5-10% compared to the PBS control. Figures 18E-F show that the supernatants of strains jl.27, jl.68, and jl.77, or strain jl.68, reduced quorum sensing (agr-GFP) (near 0%). Cell viability (CFU) was unaffected, and metabolism (GMK-GFP) was reduced by 5-10% compared to the PBS control. High density S. aureus (10 9In liquid co-cultures with 1000 ng / mL β-lactams, the triple strain combination of JL.27, JL.68, and JL.77 as well as the single JL.68 strain inhibited quorum sensing (AGR) and reduced viability (<1%). Similarly, the supernatant maintained this effect on quorum sensing without reducing viability.

[0209] Example 15: Metabolism and quorum sensing expression of S. aureus after mixing with supernatants of selected strains

[0210] S. aureus reporter strains containing GMK promoter-fused GFP reporter or agr promoter-fused GFP reporter were grown in liquid cultures with increasing starting densities such as 1E4, 1E5, 1E6, 1E7, 1E8, or 1E9 CFU / ml. Liquid cultures were mixed with PBS or 10% (v / v) supernatant from an overnight culture of jl.68 strain. Cultures were grown for 48 hours. Expression levels were compared to the PBS control and calculated by (hour 48-hour 0) / (PBS at hour 48-PBS at hour 0). Figure 19A shows a graph plotting the expression of GMK and Figure 19B shows the expression of agr. The graphs show the activity of GMK or agr over 48 hours compared to the PBS control on the Y-axis. The X-axis shows the initial density of S. aureus at different concentrations. Metabolism (and by extension, quorum sensing) appeared to be stopped in low density cultures of S. aureus (starting at or below 1E6 CFU / mL). Metabolism appeared to be partially restored in medium and higher density S. aureus cultures (20-30% compared to no supernatant), while quorum sensing was only slightly increased (1-3% compared to no supernatant). Results from this experiment may indicate that the supernatant slows metabolism, driving S. aureus into a slower growth regime where it is not quorum sensing, and / or that the supernatant affects quorum sensing, slowing overall metabolic activity.

[0211] Example 16: Growth inhibition of S. aureus after mixing with supernatants of selected strains

[0212] S. aureus containing the agr promoter-fused GFP reporter was plated in 10-fold dilution series on TSB agar plates containing 0% (PBS control), 5%, or 10% (v / v) of the supernatant from strain jl.68. The plates were incubated at 37°C for 18 hours and colonies were counted. Figure 20 shows images of plates containing a dilution series of S. aureus on agar plates containing various percentages of the supernatant from strain jl.68. In the presence of unmodified TSB medium, approximately 6-7 individual colonies in the 10-fold dilution series could be counted as saturated cultures. These were brightly fluorescent, indicating that quorum sensing was operating. In the presence of 5% of strain jl.68 supernatant, the colonies were visually smaller and much less fluorescent, suggesting that growth and quorum sensing were affected. Colony counts were not obviously changed compared to the TSB-only control. At 18 hours, few colonies were visible. In the presence of 10% strain jl.68 supernatant, no countable colonies were present. Residues of plated cultures were present and no fluorescence was detected. Occasionally, colonies appeared in cases of low dilution that overcame the inhibitory effect of the supernatant. Taken together, the data indicate that strain jl.68 supernatant embedded on an agar surface virtually eliminated colony growth and quorum sensing of S. aureus.

[0213] Although preferred embodiments of the present invention are shown and described herein, it will be apparent to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, modifications, and substitutions will occur to those skilled in the art without departing from the present invention. It should be understood that various alternatives to the embodiments of the invention described herein can be used in implementing the present invention. The following claims define the scope of the present invention, and it is intended that methods and structures within the scope of these claims and their equivalents be covered thereby.

Claims

1. A composition comprising: A first bacterial strain that is a Lysinibacillus strain comprising a 16S rRNA gene sequence having at least 98% sequence identity to SEQ ID NO:2; and A second bacterial strain, which is a Bacillus strain comprising a 16S rRNA gene sequence having at least 99% sequence identity to SEQ ID NO:

4.

1. A composition comprising a purified, lyophilized bacterial strain comprising:

2. The composition described in claim 1, wherein the 16S rRNA gene sequence of the first bacterial strain comprises at least 98% sequence identity over at least 1,000 bases to SEQ ID NO:

2.

3. The composition described in claim 1, wherein the 16S rRNA gene sequence of the second bacterial strain comprises at least 99% sequence identity over at least 1,000 bases to SEQ ID NO:

4.

4. The composition described in claim 1, wherein the first bacterial strain further comprises a nucleic acid having a sequence with at least 99% sequence identity to SEQ ID NO:

7.

5. The composition described in claim 1, wherein the second bacterial strain further comprises a nucleic acid having a sequence with at least 99% sequence identity to SEQ ID NO:

11.

6. The composition described in claim 1, wherein the second bacterial strain further comprises a nucleic acid having a sequence with at least 99% sequence identity to SEQ ID NO:

13.

7. The composition described in claim 1, wherein the 16S rRNA gene sequence of the second bacterial strain comprises SEQ ID NO: 4 or SEQ ID NO:

5.

8. The composition of claim 1, further comprising a third bacterial strain, the third bacterial strain being a Bacillus strain.

9. The composition described in claim 8, wherein the 16S rRNA gene sequence of the second bacterial strain comprises SEQ ID NO: 4 and the 16S rRNA gene sequence of the third bacterial strain comprises SEQ ID NO:

5.

10. The composition described in claim 9, wherein the 16S rRNA gene sequence of the first bacterial strain comprises SEQ ID NO: 2, the 16S rRNA gene sequence of the second bacterial strain comprises SEQ ID NO: 4, and the 16S rRNA gene sequence of the third bacterial strain comprises SEQ ID NO:

5.

11. The composition of claim 1, wherein the composition comprises at least 10 3 colony forming units (cfu) of bacteria per gram of the composition.

12. The composition of claim 1, wherein the composition comprises 10 3 to 10 12 colony forming units (cfu) of bacteria per gram of the composition.

13. The composition of claim 1, wherein the bacterial strains are present in a CFU ratio of approximately 1:1 relative to each other.

14. The composition of claim 1, wherein the bacterial strain is cultured under aerobic conditions prior to freeze-drying.

15. The composition of claim 1, wherein the bacterial strain is cultured in an animal product-free medium prior to freeze-drying.

16. The composition of claim 1, further comprising an excipient.

17. The composition of claim 16, wherein the excipient comprises one or more growth medium components.

18. The composition of claim 1, further comprising thiamine or a salt thereof.

19. The composition of claim 1, further comprising sugar.

20. The composition of claim 1, wherein the composition is disposed in a container.

21. The composition of claim 20, wherein the container is a solid material, glass, plastic, or metal.

22. The composition of claim 1, wherein the bacterial strain, when present in an effective amount and in contact with S. aureus, reduces expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB, compared to expression of the at least one of the following genes in S. aureus that is not in contact with the bacterial strain in the effective amount, wherein the reduced expression is measured by a fluorescent reporter assay.

23. The composition of claim 1, wherein the bacterial strain, when present in an effective amount and in contact with S. aureus, suppresses virulence of S. aureus as measured by a decrease in expression of at least one of the following genes in S. aureus: gmk, agr, psma, saeR, ccpA, and SigB compared to the expression of the at least one of the following genes: gmk, agr, psma, saeR, ccpA, and SigB in S. aureus that is not in contact with the bacterial strain in the effective amount, wherein the decrease in expression is measured by a fluorescent reporter assay.

24. The composition of claim 1, wherein the composition is disposed in a vial.

25. The composition of claim 1, wherein the composition comprises the bacterial strains individually in an amount of at least 10 4 to 10 8 colony forming units (CFU) of bacteria per gram of the composition.

26. The composition of any one of claims 1 to 25 for reducing the growth of Staphylococcus aureus in the skin of a subject in need thereof, wherein the composition is topically administered to the skin of the subject, and the composition is in an amount sufficient to reduce S. aureus in the skin of the subject in need thereof.

27. The composition of claim 26, wherein administering the composition is for treating a skin disease or condition.

28. The composition of claim 27, wherein the skin disease or condition comprises a fungal infection, dry skin, itchy skin, dermatophytosis (Tinea spp.), bacterial folliculitis, a bacterial infection, an inflammatory condition, a genetic condition, or a microbiome prone to developing eczema.

29. The composition of claim 26, wherein the composition is administered multiple times a day, every day, for 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 1 year, 2 years, or as needed.

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