Akkermansia muciniphila strain and use thereof

Abstract

The present application relates to the field of microorganisms, in particular to a mucinophilic Akkermansia strain and application thereof, the mucinophilic Akkermansia has a preservation number of CCTCC NO: M 20241304.The mucinophilic Akkermansia AKK-86 of the present application has good effects of promoting iron absorption, improving iron metabolism, and relieving intestinal inflammation.In addition, the mucinophilic Akkermansia of the present application can also promote the production of GLP-1, and has potential application in reducing blood sugar and weight loss products.

Description

Technical Field

[0001] This invention relates to the field of microbiology, and in particular to a myxotropic Akkerman strain and its applications. Background Technology

[0002] Iron deficiency anemia (IDA) is characterized by hemoglobin levels <10.0 g / dL and is associated with learning difficulties, frailty, and an increased risk of complications such as infection and death. According to the World Health Organization, children, adolescents, young women, and pregnant women are most susceptible to this condition. Iron deficiency can also adversely affect the regulation of specific immune systems, such as immune-active cells and their cytokines, thereby impacting inflammation levels.

[0003] For decades, iron fortification of foods has been a common practice. However, the most concerning aspect is the physiological availability of iron from fortified foods. Foods acting as iron carriers must be considered in light of their synergistic effects with iron complexes to enhance absorption and availability. The primary foods used for iron fortification are cereals and dairy products. Cereals, flour, and their derivatives are not ideal carriers due to their high phytic acid content, which reduces iron absorption. Oral iron supplements also help improve the incidence of IDA, but commonly used iron supplements such as ferrous sulfate, sodium EDTA, and ferrous diglycinate can affect the taste of food. Furthermore, excessive iron intake, if not absorbed, can accumulate in the colon, generating free radicals, causing intestinal inflammation, disrupting the gut microbiota, and altering the ratio of protective to pathogenic bacteria.

[0004] Probiotics have gained widespread consumer acceptance due to their safety and beneficial properties. Using probiotics as a carrier in conjunction with iron supplements to treat IDA can improve the bioavailability of iron supplements and enhance treatment efficacy, making it an effective approach.

[0005] Furthermore, probiotics can regulate various metabolic functions, including intestinal barrier homeostasis, glucose homeostasis, and energy absorption. Numerous studies have shown that supplementation with live or pasteurized Akkermansia muciniphila can improve diabetes, enhance intestinal barrier function, and thus improve systemic metabolic status. GLP-1 can stimulate insulin secretion, promoting a reduction in blood glucose levels. Secondly, GLP-1 can inhibit glucagon secretion, thereby reducing the liver's production of glucose. Summary of the Invention

[0006] In view of the shortcomings of the prior art described above, the purpose of this invention is to provide a myxotropic Akkerman strain and its application to solve the problems in the prior art.

[0007] To achieve the above and other related objectives, the present invention provides a *Ackermania* strain that is adsorbent to myxotropes. Akkermansia muciniphilaThe AKK-86 strain has the preservation number CCTCC NO: M 20241304.

[0008] The present invention also provides a microbial agent containing the live Akkermansia AKK-86 and / or its metabiotics.

[0009] The present invention also provides a method for preparing the bacterial agent, comprising: incorporating the *Ackermania* species described above... Akkermansia muciniphila The pure strain of AKK-86 is inoculated into a culture medium and cultured. After the culture is completed, the precipitate is collected by centrifugation, or freeze-dried after adding a protectant to obtain the bacterial agent.

[0010] The present invention also provides the use of Akkermansia myxophilus or its metabiotics in the preparation of iron absorption promoting drugs, iron supplements, hypoglycemic drugs or health products, diabetes prevention products, diabetes treatment products, weight loss products or products for improving intestinal inflammation.

[0011] The present invention also provides an iron supplement, which includes an iron supplement and Akkermansia myxophilus or its postbiotic.

[0012] As described above, the *Ackermannii* strain and its application of the present invention have the following beneficial effects: The *Ackermannii* AKK-86 strain of the present invention effectively promotes iron absorption, improves iron metabolism, and alleviates intestinal inflammation. Furthermore, the *Ackermannii* strain of the present invention can also promote GLP-1 production, showing potential application in lowering fasting blood glucose and in weight-loss products. Attached Figure Description

[0013] Figure 1 The image shows a time-of-flight mass spectrometry (TOF) identification mass spectrum of Akkermansia myxophilus.

[0014] Figure 2 The effect of Akkermansia myxophilus and its postbiotics on ferritin production in Caco-2 cells is shown.

[0015] Figure 3 The effect of Akkermansia myxophilus and its postbiotics on macrophage production of pro-inflammatory factors is shown.

[0016] Figure 4 The effect of Akkermansia myxophilus and its postbiotics on serum iron levels in mice is shown.

[0017] Figure 5 The image shows the effects of Akkermansia myxophilus and its postbiotics on pro-inflammatory and anti-inflammatory factors in mouse serum.

[0018] Figure 6The effect of Akkermansia myxophilus and its postbiotics on GLP-1 production in NCI-H716 cells is shown.

[0019] Figure 7 The effect of Akkermansia myxophilus and its postbiotics on mouse body weight is shown.

[0020] Figure 8 The effect of Akkermansia myxophilus and its postbiotics on fasting blood glucose and serum GLP-1 in mice is shown.

[0021] In the figure, ** indicates that the experimental group is less than 0.01 compared with the control group; *** indicates that the experimental group is less than 0.001 compared with the control group; and different superscript letters (a, b, c, d) indicate that the p is less than 0.05. Detailed Implementation

[0022] This invention first conducted extensive screening through in vitro experiments to promote ferritin synthesis in Caco-2 cells, and discovered some strains that can promote ferritin synthesis in Caco-2 cells, among which Akkermansia myxophilus AKK-86 showed the best effect.

[0023] Based on this, the present invention provides a strain of Akkermansia myxophilus. Akkermansia muciniphila The strain is deposited at the China Center for Type Culture Collection (CCTCC). Strain name: Akkermansia muciniphila AKK-86, accession number: CCTCC NO: M 20241304, accession date: June 19, 2024, accession address: Wuhan University, Wuhan, China.

[0024] The group in which Akkermansia muciniphila AKK-86 was added showed a 428% increase in iron absorption compared to the group in which Akkermansia muciniphila AKK-86 was not added.

[0025] The increase in iron absorption was obtained by the following method:

[0026] Using 50 μM FeCl3 and Caco-2 cells as the control group, the experimental group received 2*10 μM FeCl3 in addition to the control group. 8 Live Akkermansia AKK-86 bacteria (cfu / mL) were co-cultured in both the experimental and control groups for 24 h. After culturing, ferritin levels in Caco-2 cells from both groups were measured, and the increase rate was calculated using the following formula 1):

[0027] Improvement rate = (A0 – A1) / A1 × 100% 1)

[0028] Where: A0 is the intracellular ferritin concentration in the experimental group; A1 is the intracellular ferritin concentration in the control group.

[0029] The present invention also provides a microbial agent containing the live Akkermansia AKK-86 and / or its metabiotics.

[0030] Postbiotics are preparations of non-living microorganisms and / or their components that are beneficial to the health of the host. Postbiotics include microbial cells or cell components that have undergone inactivation treatment (e.g., pasteurization), such as dead cells, cell walls, cell membrane lipids, peptidoglycans, or metabolites (e.g., short-chain fatty acids, vitamins, or bacteriocins).

[0031] The bacterial agent can be a liquid bacterial agent or a solid bacterial agent.

[0032] In some embodiments of the present invention, the microbial agent comprises 2*10 8 CFU / mL or above, or 2*10 8 Akkermansia myxophilus AKK-86 or its equivalent metabiotic at TFU / mL or TFU / g or higher. CFU refers to colony forming units, used to measure viable bacteria, while TFU is the total bacterial count, including both dead and live bacteria.

[0033] The present invention also provides a method for preparing the bacterial agent, comprising the following steps: inoculating a pure strain of Akkermansia muciniphila AKK-86 into a culture medium for culture, centrifuging after culture, collecting the precipitate, or adding a protectant and then freeze-drying to obtain the bacterial agent.

[0034] In some embodiments of the present invention, the culture medium is formulated based on the total volume of the culture medium as follows: tryptone 9-11 g / L, ox heart extract powder 16-19 g / L, sodium chloride 4-6 g / L, glucose 1-3 g / L, disodium hydrogen phosphate 1-4 g / L, and mucin 4-6 g / L.

[0035] Preferably, based on the total volume of the culture medium, the culture medium formula is as follows: 10 g / L tryptone, 17.5 g / L ox heart extract, 5 g / L sodium chloride, 2 g / L glucose, 2.5 g / L disodium hydrogen phosphate, and 5 g / L mucin.

[0036] In some embodiments of the present invention, the culture temperature is 30~38°C. Specifically, the culture temperature is, for example, 30~33°C, 33~35°C, or 35~38°C.

[0037] In some embodiments of the present invention, the culture method is anaerobic culture. The culture gas composition is, for example, 85-94% N2, 5% H2, and 1-10% CO2.

[0038] In some embodiments of the present invention, the collected bacterial solution is pasteurized to obtain a bacterial agent containing the adjuvant of Akkermansia AKK-86.

[0039] The metabiotic obtained after inactivating the Acetobacter xanthophile Akkermansia AKK-86 has a similar effect to the live bacteria.

[0040] The protective agent is not specifically limited, and may include, for example, skim milk powder, xylooligosaccharides, trehalose, monosodium glutamate, soluble starch, sodium VC salt, etc.

[0041] The present invention also provides the use of Akkermansia myxophilus or its metabiotics in the preparation of iron absorption promoting drugs, iron supplements, hypoglycemic drugs or health products, diabetes prevention products, diabetes treatment products, weight loss products or products for improving intestinal inflammation.

[0042] In some embodiments of the present invention, the Akkermansia myxophilus is Akkermansia myxophilus AKK-86.

[0043] The iron absorption-enhancing product has a higher iron absorption rate compared to products without Akkermansia muciniphilis or its post-biotics.

[0044] The blood sugar-lowering drugs or health products, diabetes prevention products, diabetes treatment products or weight loss products mentioned above can promote GLP-1 secretion.

[0045] The present invention also provides an iron supplement, which includes an iron supplement and Akkermansia myxophilus or its postbiotic.

[0046] The iron supplement is selected from one or more of the following: ferrous sulfate, sodium ethylenediaminetetraferric sulfate, ferrous diglycinate chelate, dextran iron, ferrous fumarate, polysaccharide iron complex, and ferrous succinate.

[0047] The Akkermansia myxophilus is Akkermansia myxophilus AKK-86.

[0048] The iron supplement can improve iron absorption and increase iron bioavailability.

[0049] The iron supplement also includes pharmaceutically acceptable carriers or excipients.

[0050] "Pharmaceutical acceptable" means that when a drug is properly administered to animals or humans, it will not produce adverse, allergic, or other adverse reactions.

[0051] "Pharmaceutical-acceptable carriers or excipients" should be compatible with the active ingredient, meaning they can be miscible with it without significantly reducing the drug's efficacy under normal circumstances. Specific examples of substances that can serve as carriers or excipients include sugars such as lactose, glucose, and sucrose; starches such as corn starch and potato starch; cellulose and its derivatives such as sodium methylcellulose, ethylcellulose, and methylcellulose; tragacanth gum powder; malt; gelatin; talc; solid lubricants such as stearic acid and magnesium stearate; calcium sulfate; vegetable oils such as peanut oil, cottonseed oil, sesame oil, olive oil, corn oil, and cocoa butter; polyols such as propylene glycol, glycerin, sorbitol, mannitol, and polyethylene glycol; alginic acid; emulsifiers such as Tween; wetting agents such as sodium lauryl sulfate; colorants; flavoring agents; tableting agents; stabilizers; antioxidants; preservatives; pyrogen-free water; isotonic salt solutions; and phosphate buffers, etc. These substances are used as needed to help stabilize the formulation or to improve its activity or bioavailability or to produce an acceptable taste or smell when taken orally.

[0052] The dosage form of the iron supplement is not specifically limited, such as oral liquid, lyophilized powder, capsule, tablet, granule or gummies.

[0053] The following specific examples illustrate the implementation of the present invention. Those skilled in the art can easily understand other advantages and effects of the present invention from the content disclosed in this specification. The present invention can also be implemented or applied through other different specific embodiments, and various details in this specification can also be modified or changed based on different viewpoints and applications without departing from the spirit of the present invention.

[0054] Before further describing specific embodiments of the present invention, it should be understood that the scope of protection of the present invention is not limited to the specific embodiments described below; it should also be understood that the terminology used in the embodiments of the present invention is for describing specific embodiments and not for limiting the scope of protection of the present invention; in the specification and claims of the present invention, unless otherwise expressly stated in the text, the singular forms "a", "an" and "this" include the plural forms.

[0055] When numerical ranges are given in the embodiments, it should be understood that, unless otherwise stated in the present invention, both endpoints of each numerical range and any value between the two endpoints may be selected. Unless otherwise defined, all technical and scientific terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art. In addition to the specific methods, apparatus, and materials used in the embodiments, based on the knowledge of the prior art possessed by one of ordinary skill in the art and the description of this invention, any prior art methods, apparatus, and materials similar to or equivalent to those described, apparatus, and materials in the embodiments of this invention may be used to implement the present invention.

[0056] Example 1: Isolation and Identification of Akkermansia myxophilus

[0057] Collect a small amount of fresh stool sample from a healthy 6-year-old child and place it in 5 mL of Green's solution using a sterile sampling spoon. Immediately after sampling, transfer the sample to an anaerobic chamber (gas environment: 80% N2, 10% H2, 10% CO2). Dilute the sample to 10 mL using a 1:10 dilution ratio. -10 0.1 mL of each dilution was spread onto a medium containing mucin (5 g / L) as the sole carbon source and anaerobically cultured for 5 days. After single colonies grew, a small amount of each colony was scraped onto a medium containing mucin for further propagation. The culture was continued until significant turbidity was observed, then stored in cryovials. The remaining single colonies were then identified using time-of-flight mass spectrometry (TOF-MS). The TOF-MS identification mass spectra are shown in the figure below. Figure 1 (Scoring criteria: [9.5, 10.0] species confidence level, possible subspecies; [9.0, 9.5) species confidence level; [6.0, 9.0) genus confidence level; [0.0, 6.0) not confident). After identification, the cryovials obtained from the amplification of a single colony identified as Akkermansia muciniphila were retained, and the other cryovials were discarded.

[0058] Example 2: Effects of live Akkermansia myxophilus bacteria and its postbiotics on ferritin production levels in Caco-2 cells

[0059] The relative iron bioavailability among samples was measured using the Caco-2 cell bioassay established by Glahn R et al. This model uses ferritin in Caco-2 cells as a marker of iron absorption. Ferritin is an intracellular iron storage protein in Caco-2 cells, and its content is directly proportional to the amount of iron absorbed by the cell. By measuring the ferritin content in Caco-2 cells, iron bioavailability can be indirectly assessed.

[0060] The CaCo-2 cell group served as the blank control. CaCo-2 cells were co-cultured with FeCl3 at a final concentration of 50 μM for 24 h, with the FeCl3 group serving as the control group. The experimental groups were supplemented with 2*10... 8 Live Akkermansia muciniphila (AKK), live Lactobacillus rhamnosus (LR), live Lactobacillus casei (LC), or equivalent amounts of each of these probiotics at cfu / mL.

[0061] Ferritin test results as follows Figure 2 As shown, the Fe+AKK live bacteria group and the Fe+AKK post-biotic group showed significantly different ferritin content compared with the control group, and were much higher than those of the live Lactobacillus rhamnosus (LR) and Lactobacillus casei (LC) bacteria and their post-biotic groups. This indicates that the live Akkermansia muciniphilus bacteria and post-biotics are effective in promoting iron absorption.

[0062] Example 3: Effects of live Akkermansia myxophilus bacteria and its post-biotics on the production of pro-inflammatory factors by RAW 264.7 macrophages.

[0063] RAW 264.7 macrophages were cultured at a concentration of 50,000 cells / cm². 2 Inoculated and cultured in RPMI medium for 24 h, then grouped and cultured according to Example 1. After incubation for 3 h, TNF-α and IL-6 were detected. Detection was performed according to the ELISA kit instructions (eBioscience Ltd., Hatfield, UK).

[0064] The results are as follows Figure 3 As shown, compared with the control group, the levels of TNF-α and IL-6 decreased significantly after the addition of live Akkermansia myxotroph or its post-biotic. This indicates that live Akkermansia myxotroph or its post-biotic can inhibit the production of pro-inflammatory factors and alleviate inflammation.

[0065] Example 4: Effects of Akkermansia myxophilus and its postbiotics on iron absorption in mice

[0066] Forty 3-week-old ICR mice were used in the experiment. Dark and light cycles were alternated every 12 hours, and the ambient temperature was 22±1℃. Intervention began after one week of acclimatization, with free access to water. Mice were randomly divided into five groups: a control group, and experimental groups (IDA group, Fe group, Fe + live bacteria group, and Fe + post-biotic group), with eight mice in each group. The control group was fed an iron-rich diet (45 mg / kg iron) according to the ANI standard throughout the experiment. The experimental groups were fed a low-iron diet (10 mg / kg iron) for four weeks to induce iron deficiency anemia, followed by five weeks of intervention before the experiment ended.

[0067] Intervention method: The control group and IDA group were administered 0.2 mL of normal saline by gavage daily, while the experimental group was administered 0.2 mL of ferrous sulfate solution (containing 2 mg / kg body weight of iron) by gavage; and live Akkermansia myxophilus bacteria (containing 2 × 10⁻⁶ cells / mL). 8 CFU) + ferrous sulfate solution (containing 2 mg / kg body weight of iron) 0.2 mL; Akkermansia myxophilus metabiotic (2 × 10⁻⁶) 8 TFU + ferrous sulfate solution (containing 2 mg / kg body weight of iron) 0.2 mL.

[0068] Before blood collection at the end of the experiment, mice were fasted for 16 hours. 250 μL of blood was collected from the orbital vein and centrifuged at 3000g for 15 min to separate the serum. The iron content and inflammatory factors in the mouse serum were shown in [data missing]. Figure 4 and Figure 5 .

[0069] Depend on Figure 4It was found that serum iron levels decreased in the IDA group compared to the control group. After iron supplementation (Fe group), serum iron levels rebounded significantly, but were still lower than the control group. However, after simultaneous gavage administration of live Akkermansia myxophilus and post-biotics, serum iron levels were comparable to the control group, with no significant difference. This indicates that both live Akkermansia myxophilus and post-biotics can effectively promote iron absorption.

[0070] Depend on Figure 5 It was found that, compared with the IDA group, serum inflammatory factors TNF-α and IL-6 were significantly reduced after iron supplementation. The reduction in TNF-α and IL-6 was even lower after supplementation with live Akkermansia myxophilus or its post-biotic, approaching the levels of the control group. This indicates that Akkermansia myxophilus and its post-biotic can alleviate inflammation while promoting iron absorption.

[0071] Detection method:

[0072] Serum iron levels were measured using Iron Assay (Aibok, Shanghai), following the instructions provided.

[0073] Inflammatory cytokines in serum, namely tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), were detected using an ELISA kit (Sangon Biotech, Shanghai) according to the manufacturer's instructions.

[0074] Example 5: Effect of Akkermansia myxophilus on GLP-1 production by NCI-H716

[0075] GLP-1 secretion was detected using the NCI-H716 (human colorectal adenocarcinoma cell model). Cells were cultured and passaged continuously in DEME medium supplemented with 10% (v / v) fetal bovine serum and 1% penicillin-streptomycin in a humid incubator containing 5% CO2 at 37°C.

[0076] On the day of the experiment, the cells were packed at 3×10 5 Cells were seeded at a concentration of [cells / mL] in collagen-coated 96-well plates and cultured overnight. Cells were then starved for 2 hours in HBSS buffer containing 0.2% BSA, followed by treatment for 2 hours according to different experimental groups. Cell supernatant was then collected for measuring GLP-1 concentration.

[0077] The treatment consisted of three groups: a blank group (no treatment) and experimental groups containing live bacteria of Akkermansia muciniphila (AKK), Lactobacillus rhamnosus (LR), Lactobacillus casei (LC), and Lactobacillus salivarius (LS), along with their postbiotics. The amounts of live bacteria and postbiotics added to each group were the same as in Example 1. GLP-1 detection results are shown in... Figure 6As shown in the figure, the blank group secreted almost no GLP-1, while the experimental group treated with live Akkermansia myxophilus or postbiotics had a much higher GLP-1 content than the blank group and other experimental groups, indicating that live Akkermansia myxophilus AKK86 and its postbiotics can promote GLP-1 secretion.

[0078] The GLP-1 concentration of each sample was determined using a human GLP-1 ELISA kit. The assay method followed the manufacturer's instructions (Elabscience, Wuhan, China).

[0079] Example 6 Effects of Akkermansia myxophilus and its postbiotics on mouse plasma GLP-1

[0080] Thirty-two 6-week-old male C57BL / 6J mice were randomly divided into four groups of eight mice each after one week of acclimatization feeding. The groups were: control group, high-fat, high-sugar diet (HFD) group, HFD + live bacteria group, and HFD + postbiotic group. Dark and light were alternated every 12 hours, and the ambient temperature was 22±1℃.

[0081] Intervention methods: The control group was fed a normal diet and administered 0.2 mL of physiological saline by gavage daily. The HFD group was fed a high-fat, high-sugar diet and administered 0.2 mL of physiological saline by gavage daily. The HFD + live bacteria group was fed a high-fat, high-sugar diet and administered 0.2 mL of bacterial suspension (containing 2 × 10⁶ live Akkermansia myxophilus bacteria) by gavage daily. 8 CFU). The HFD+metogenic group was fed a high-fat, high-sugar diet and was given 0.2 mL of bacterial suspension (containing 2 × 10⁻⁶ Akkermansia muciniphila metabiotics) by gavage daily. 8 TFU). Measure body weight once a week during the feeding period.

[0082] After 14 weeks of feeding, mice were fasted overnight, blood was collected, and they were euthanized by cervical dislocation. Blood glucose and GLP-1 levels in the plasma were measured. Results are shown below. Figure 7 and Figure 8 As shown in the figure, the fasting blood glucose levels in the HFD+ live bacteria group and the HFD+ postbiotic group were significantly lower than those in the HFD group, indicating that supplementation with live Akkermansia myxophilus or its postbiotics can lower blood glucose. Furthermore, the plasma GLP-1 levels in the HFD+ live bacteria group and the HFD+ postbiotic group were significantly higher than those in the HFD group, but not significantly different from the control group, suggesting that supplementation with live Akkermansia myxophilus or its postbiotics can promote intestinal GLP-1 secretion.

[0083] The above embodiments are for illustrating the implementation schemes disclosed in this invention and should not be construed as limiting the invention. Furthermore, various modifications and variations of the methods listed herein will be apparent to those skilled in the art without departing from the scope and spirit of the invention. Although the invention has been specifically described in conjunction with various specific preferred embodiments, it should be understood that the invention should not be limited to these specific embodiments. In fact, various modifications as described above that are obvious to those skilled in the art to obtain the invention should be included within the scope of this invention.

Claims

1. A type of Akkermansia myxophilus ( Akkermansia muciniphila AKK-86 strain, preservation number CCTCC NO: M 20241304.

2. The Akkermansia muciniphila strain of claim 1, Akkermansia muciniphila ) AKK-86 strain, characterized in that, The Akkermansia muciniphila (Akkermansia muciniphila) Akkermansia muciniphila ) AKK-86 can promote the absorption of iron.

3. An inoculant characterized in that, The bacterial agent comprises the mucinophilic Akkermansia of claim 1 or 2 Akkermansia muciniphila ) AKK-86 viable bacteria and / or its postbiotic.

4. The bacterial agent of claim 3, characterized in that, The bacterial agent includes 2*10 8 or more cfu / mL or cfu / g of Akkermansia muciniphila Akkermansia muciniphila (AKK-86) viable bacteria and / or an equivalent amount of postbiotic.

5. Use of Akkermansia muciniphila or a postbiotic thereof in the manufacture of a medicament for promoting iron absorption, a medicament for iron supplementation, a medicament for reducing blood glucose, or a health product; said Akkermansia muciniphila being Akkermansia muciniphila of claim 1 or 2 (AKK-86). Akkermansia muciniphila ) AKK-86.

6. Use according to claim 5, characterized in that, The hypoglycemic drug or health product promotes the production of GLP-1 by intestinal cells through the use of the Akkermansia muciniphila (AKK-86) Akkermansia muciniphila ) 7. An iron supplement medicine, characterized by, The iron supplement and the Akkermansia muciniphila or the postbiotic thereof are included in the iron supplement medicine; the Akkermansia muciniphila is the Akkermansia muciniphila according to claim 1 or 2. Akkermansia muciniphila ) AKK-86.

8. The iron supplement of claim 7, wherein the iron supplement is a tablet. The iron supplement is selected from any one or more of ferrous sulfate, ethylenediaminetetraacetic acid sodium iron, ferrous bis-glycinate chelate, iron dextran, ferrous fumarate, polysaccharide iron complex, ferrous succinate.

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