Composition for increasing glutathione concentration in immune cells

Abstract

To provide a composition for increasing glutathione concentration in immune cells. [Solution] A composition for increasing the glutathione concentration in immune cells, which contains lactic acid bacteria that are phagocytosed by immune cells.

Description

[Technical Field]

[0001] This disclosure relates to a composition for increasing glutathione concentration in immune cells. [Background technology]

[0002] Within the body, the immune system breaks down targets such as viruses that invade or develop in the body. The immune system involves a variety of immune cells, including NK cells, killer T cells, helper T cells, and B cells. These cells break down targets by recognizing, presenting, promoting degradation, and remembering antigens.

[0003] Among immune cells, plasmacytoid dendritic cells (pDCs), also known as plasmacytoid dendritic cells, are a type of dendritic cell that constitutes the innate immune system. pDCs are the main producers of the cytokine type I interferon in the body and play an extremely important role in the body's defense. Type I interferon exhibits inhibitory activity against viruses and other pathogens. pDCs are involved in the activation of immune cells such as NK cells, killer T cells, helper T cells, and B cells through the production of type I interferon. In addition, myeloid dendritic cells (mDCs), which are also dendritic cells that constitute the innate immune system, and peripheral blood mononuclear cells (PBMCs), which include NK cells, killer T cells, helper T cells, and B cells that directly play a role in the immune system's defense mechanisms, also contribute greatly to maintaining immune function through antigen presentation and cytokine production.

[0004] Glutathione (GSH) is known to have antioxidant properties and to suppress oxidative stress in cells. Regarding the relationship between glutathione and immune cells, for example, Non-Patent Literature 1 states that a decrease in intracellular glutathione concentration present in pDCs or mDCs leads to the development of CD4 in these immune cells. +It has been disclosed that this can lead to inhibition of T cell proliferation and differentiation, or suppression of inflammatory cytokine production. Furthermore, Non-Patent Document 2 reports that glutathione levels in immune cells are decreased in elderly individuals, and it has been disclosed that this decrease in glutathione levels in immune cells may be involved in the decline of immune function in elderly individuals.

[0005] Previously, it had been reported that certain strains of lactic acid bacteria could increase glutathione levels in specific immune cells (Patent Document 1). However, it remained completely unknown what properties of lactic acid bacteria were responsible for increasing glutathione levels in immune cells. [Prior art documents] [Patent Documents]

[0006] [Patent Document 1] Japanese Patent Publication No. 2007-126399 [Non-patent literature]

[0007] [Non-Patent Document 1] JianpingHu et al., "Lithocholic acid inhibits dendritic cell activation by reducingintracellular glutathione via TGR5 signaling", Int. J. Biol. Sci. 2022,18(11): 4545-4559. [Non-Patent Document 2] LorenaArranz et al., "The glutathione precursor N-acetylcysteine ​​improves immune function in postmenopausal women", Free Radic Biol Med. 2008, 45(9):1252-1262. [Overview of the project] [Problems that the invention aims to solve]

[0008] This disclosure aims to provide a composition for increasing glutathione concentration in immune cells. [Means for solving the problem]

[0009] The inventors have discovered that, among lactic acid bacteria, those that are phagocytosed by immune cells have the effect of increasing the glutathione concentration within immune cells.

[0010] This disclosure relates, for example, to the following: <a1>A composition for increasing the glutathione concentration in immune cells, containing lactic acid bacteria that are phagocytosed by immune cells. <a2>The above immune cells are peripheral blood mononuclear cells. <a1>The composition described above. <a3>The above immune cells are at least one selected from the group consisting of plasmacytoid dendritic cells and myeloid dendritic cells. <a1>or <a2>The composition described above. <a4>The above lactic acid bacteria is at least one species selected from the group consisting of Lactococcus, Bifidobacterium, Lactobacillus, Rimosilactobacillus, Lacticaseibacillus, Pediococcus, and Lactiplantybacillus. <a1> ~ <a3>A composition as described in any one of the following. <a5>The above lactic acid bacteria include Lactococcus lactis, Lactococcus lactis subsp. lactis, Bifidobacterium longum, Bifidobacterium longum subsp. longum, Lactobacillus acidophilus, Lactobacillus helveticus, Limosilactobacillus reuteri, Limosilactobacillus reuteri subsp. reuteri, and Lacticaseibacillus paracasei. Lacticaseibacillus paracasei subsp. paracasei, Lacticaseibacillus casei, Lactobacillus crispatus, Lactobacillus johnsonii, Pediococcus acidilactici, Pediococcus pentosaceus, Lacticaseibacillus rhamnosus, Lactiplantibacillus plantarum It is at least one species selected from the group consisting of Lactiplantibacillus plantarum subsp. plantarum and Lactobacillus plantarum. <a1> ~ <a4>A composition as described in any one of the following. <a6>The above lactic acid bacteria are Lactococcus lactis subsp. lactis JCM 5805, Bifidobacterium longum subsp. longum JCM 11340, Lactobacillus acidophilus JCM 1021, Lactobacillus helveticus JCM 1003, Limosilactobacillus reuteri subsp. reuteri JCM 1112, and Lacticaseibacillus paracasei subsp. paracasei JCM 1053, Lacticaseibacillus casei JCM 1134, Lactobacillus crispatus JCM 1185, Lactobacillus johnsonii JCM 2012, Pediococcus acidilactici JCM 2014, Pediococcus acidilactici JCM 8797, Pediococcus pentosaceus JCM 5890, Lactobacillus acidophilus JCM 1132, Lacticaseibacillus rhamnosus rhamnosus) JCM 1136, Lactiplantibacillus plantarum subsp.It is at least one species selected from the group consisting of Lactobacillus plantarum JCM 1149 and Lactobacillus plantarum L-137. <a1> ~ <a5>A composition as described in any one of the following. <a7>The above lactic acid bacterium is Lactococcus lactis subsp. lactis JCM 5805. <a1> ~ <a6>A composition as described in any one of the following. <a8>For administration or ingestion to subjects whose glutathione concentration in immune cells has decreased, <a1> ~ <a7>A composition as described in any one of the following. <a9>The subjects in whom the glutathione concentration in the immune cells described above decreased were humans aged 40 or older. <a8>The composition described above. <a10>To increase the expression level of the NRF2 protein and / or the mRNA encoding it within the above-mentioned immune cells, <a1> ~ <a9>A composition as described in any one of the following. <a11>The above composition is used for at least one selected from the group consisting of protection of the above immune cells and suppression of the decrease of the above immune cells. <a1> ~ <a10>A composition as described in any one of the following. <a12>The above composition is used for at least one selected from the group consisting of antioxidant and intracellular oxidative stress suppression. <a1> ~ <a11>A composition as described in any one of the following. <a13>At least one composition selected from the group consisting of a composition for protecting immune cells, a composition for suppressing the decrease of immune cells, an antioxidant composition, and a composition for suppressing intracellular oxidative stress, which contains lactic acid bacteria that are phagocytosed by immune cells. <a14>A composition for protecting immune cells and / or a composition for suppressing the reduction of immune cells, which contains lactic acid bacteria that are phagocytosed by immune cells. <a15>An antioxidant composition and / or a composition for suppressing intracellular oxidative stress, containing lactic acid bacteria that are phagocytosed by immune cells. <a16>To increase the expression level of the NRF2 protein and / or the mRNA encoding it within the above-mentioned immune cells, <a13> ~ <a15>A composition as described in any one of the following. <a17>A composition for increasing the expression level of the NRF2 protein and / or the mRNA encoding it of immune cells, comprising lactic acid bacteria that are phagocytosed by immune cells. <a18>The above composition is used to increase the glutathione concentration in the above immune cells. <a13> ~ <a17>A composition as described in any one of the following. <a19>The above immune cells are at least one selected from the group consisting of plasmacytoid dendritic cells and myeloid dendritic cells. <a13> ~ <a18>A composition as described in any one of the following. <a20>The above immune cells are peripheral blood mononuclear cells. <a13> ~ <a19>A composition as described in any one of the following. <a21>The above lactic acid bacteria is at least one species selected from the group consisting of Lactococcus, Bifidobacterium, Lactobacillus, Rimosilactobacillus, Lacticaseibacillus, Pediococcus, and Lactiplantybacillus. <a13> ~ <a20>A composition as described in any one of the following. <a22>The above lactic acid bacteria include Lactococcus lactis, Lactococcus lactis subsp. lactis, Bifidobacterium longum, Bifidobacterium longum subsp. longum, Lactobacillus acidophilus, Lactobacillus helveticus, Limosilactobacillus reuteri, Limosilactobacillus reuteri subsp. reuteri, and Lacticaseibacillus paracasei. Lacticaseibacillus paracasei subsp. paracasei, Lacticaseibacillus casei, Lactobacillus crispatus, Lactobacillus johnsonii, Pediococcus acidilactici, Pediococcus pentosaceus, Lacticaseibacillus rhamnosus, Lactiplantibacillus plantarum It is at least one species selected from the group consisting of Lactiplantibacillus plantarum subsp. plantarum and Lactobacillus plantarum. <a13> ~ <a21>A composition as described in any one of the following. <a23>The above lactic acid bacteria are Lactococcus lactis subsp. lactis JCM 5805, Bifidobacterium longum subsp. longum JCM 11340, Lactobacillus acidophilus JCM 1021, Lactobacillus helveticus JCM 1003, Limosilactobacillus reuteri subsp. reuteri JCM 1112, and Lacticaseibacillus paracasei subsp. paracasei JCM 1053, Lacticaseibacillus casei JCM 1134, Lactobacillus crispatus JCM 1185, Lactobacillus johnsonii JCM 2012, Pediococcus acidilactici JCM 2014, Pediococcus acidilactici JCM 8797, Pediococcus pentosaceus JCM 5890, Lactobacillus acidophilus JCM 1132, Lacticaseibacillus rhamnosus rhamnosus) JCM 1136, Lactiplantibacillus plantarum subsp.It is at least one species selected from the group consisting of Lactobacillus plantarum JCM 1149 and Lactobacillus plantarum L-137. <a13> ~ <a22>A composition as described in any one of the following. <a24>The above lactic acid bacterium is Lactococcus lactis subsp. lactis JCM 5805. <a13> ~ <a23>A composition as described in any one of the following. <a25>For ingestion or administration to subjects whose glutathione concentration in immune cells has decreased, <a13> ~ <a24>A composition as described in any one of the following. <a26>The subjects in whom the glutathione concentration in the immune cells described above decreased were humans aged 40 or older. <a25>The composition described above. <a27>The above immune cells are immune cells that possess phagocytic ability. <a1> ~ <a26>A composition as described in any one of the following. <b1>A method for increasing the concentration of glutathione in immune cells, comprising having a target ingest or administer lactic acid bacteria that are phagocytosed by immune cells. <b2>The above immune cells are peripheral blood mononuclear cells. <b1>Methods used. <b3>The above immune cells are at least one selected from the group consisting of plasmacytoid dendritic cells and myeloid dendritic cells. <b1>or <b2>Methods used. <b4>The above lactic acid bacteria is at least one species selected from the group consisting of Lactococcus, Bifidobacterium, Lactobacillus, Rimosilactobacillus, Lacticaseibacillus, Pediococcus, and Lactiplantybacillus. <b1> ~ <b3>One of the following methods. <b5>The above lactic acid bacteria include Lactococcus lactis, Lactococcus lactis subsp. lactis, Bifidobacterium longum, Bifidobacterium longum subsp. longum, Lactobacillus acidophilus, Lactobacillus helveticus, Limosilactobacillus reuteri, Limosilactobacillus reuteri subsp. reuteri, and Lacticaseibacillus paracasei. Lacticaseibacillus paracasei subsp. paracasei, Lacticaseibacillus casei, Lactobacillus crispatus, Lactobacillus johnsonii, Pediococcus acidilactici, Pediococcus pentosaceus, Lacticaseibacillus rhamnosus, Lactiplantibacillus plantarum It is at least one species selected from the group consisting of Lactiplantibacillus plantarum subsp. plantarum and Lactobacillus plantarum. <b1> ~ <b4>One of the following methods. <b6>The above lactic acid bacteria are Lactococcus lactis subsp. lactis JCM 5805, Bifidobacterium longum subsp. longum JCM 11340, Lactobacillus acidophilus JCM 1021, Lactobacillus helveticus JCM 1003, Limosilactobacillus reuteri subsp. reuteri JCM 1112, and Lacticaseibacillus paracasei subsp. paracasei JCM 1053, Lacticaseibacillus casei JCM 1134, Lactobacillus crispatus JCM 1185, Lactobacillus johnsonii JCM 2012, Pediococcus acidilactici JCM 2014, Pediococcus acidilactici JCM 8797, Pediococcus pentosaceus JCM 5890, Lactobacillus acidophilus JCM 1132, Lacticaseibacillus rhamnosus rhamnosus) JCM 1136, Lactiplantibacillus plantarum subsp.It is at least one species selected from the group consisting of Lactobacillus plantarum JCM 1149 and Lactobacillus plantarum L-137. <b1> ~ <b5>One of the following methods. <b7>The above lactic acid bacterium is Lactococcus lactis subsp. lactis JCM 5805. <b1> ~ <b6>One of the following methods. <b8>The subjects mentioned above are those in which the glutathione concentration in immune cells has decreased. <b1> ~ <b7>One of the following methods. <b9>The subjects in whom the glutathione concentration in the immune cells described above decreased were humans aged 40 or older. <b8>Methods used. <b10>This includes increasing the expression level of the NRF2 protein and / or the mRNA encoding it within the immune cells described above. <b1> ~ <b9>One of the following methods. <b11>The present invention includes at least one selected from the group consisting of protecting immune cells and suppressing the decrease of immune cells. <b1> ~ <b10>One of the following methods. <b12>The above subjects include at least one selected from the group consisting of antioxidant activity and suppression of intracellular oxidative stress, <b1> ~ <b11>One of the following methods. <b13>A method selected from the group consisting of a method for protecting immune cells, a method for suppressing the decrease of immune cells, an antioxidant method, and a method for suppressing intracellular oxidative stress, comprising administering or having a target ingest lactic acid bacteria that are phagocytosed by immune cells. <b14>A method selected from the group consisting of a method for protecting immune cells and a method for suppressing the decrease of immune cells, comprising administering or having a target ingest lactic acid bacteria that are phagocytosed by immune cells. <b15>At least one method selected from the group consisting of methods for antioxidant activity and methods for suppressing intracellular oxidative stress, which include administering or allowing a target to ingest lactic acid bacteria that are phagocytosed by immune cells. <b16>This includes increasing the expression level of the NRF2 protein and / or the mRNA encoding it within the immune cells described above. <b13> ~ <b15>One of the following methods. <b17>This includes increasing the glutathione concentration in the immune cells of the above target, <b13> ~ <b16>One of the following methods. <b18>The above immune cells are selected from the group consisting of plasmacytoid dendritic cells and myeloid dendritic cells, and peripheral blood mononuclear cells. <b13> ~ <b17>One of the following methods. <b19>The above immune cells are peripheral blood mononuclear cells. <b13> ~ <b18>One of the following methods. <b20>The above lactic acid bacteria is at least one species selected from the group consisting of Lactococcus, Bifidobacterium, Lactobacillus, Rimosilactobacillus, Lacticaseibacillus, Pediococcus, and Lactiplantybacillus. <b13> ~ <b19>One of the following methods. <b21>The above lactic acid bacteria include Lactococcus lactis, Lactococcus lactis subsp. lactis, Bifidobacterium longum, Bifidobacterium longum subsp. longum, Lactobacillus acidophilus, Lactobacillus helveticus, Limosilactobacillus reuteri, Limosilactobacillus reuteri subsp. reuteri, and Lacticaseibacillus paracasei. Lacticaseibacillus paracasei subsp. paracasei, Lacticaseibacillus casei, Lactobacillus crispatus, Lactobacillus johnsonii, Pediococcus acidilactici, Pediococcus pentosaceus, Lacticaseibacillus rhamnosus, Lactiplantibacillus plantarum It is at least one species selected from the group consisting of Lactiplantibacillus plantarum subsp. plantarum and Lactobacillus plantarum. <b13> ~ <b20>One of the following methods. <b22>The above lactic acid bacteria are Lactococcus lactis subsp. lactis JCM 5805, Bifidobacterium longum subsp. longum JCM 11340, Lactobacillus acidophilus JCM 1021, Lactobacillus helveticus JCM 1003, Limosilactobacillus reuteri subsp. reuteri JCM 1112, and Lacticaseibacillus paracasei subsp. paracasei JCM 1053, Lacticaseibacillus casei JCM 1134, Lactobacillus crispatus JCM 1185, Lactobacillus johnsonii JCM 2012, Pediococcus acidilactici JCM 2014, Pediococcus acidilactici JCM 8797, Pediococcus pentosaceus JCM 5890, Lactobacillus acidophilus JCM 1132, Lacticaseibacillus rhamnosus rhamnosus) JCM 1136, Lactiplantibacillus plantarum subsp.It is at least one species selected from the group consisting of Lactobacillus plantarum JCM 1149 and Lactobacillus plantarum L-137. <b13> ~ <b21>One of the following methods. <b23>The above lactic acid bacterium is Lactococcus lactis subsp. lactis JCM 5805. <b13> ~ <b22>One of the following methods. <b24>The subjects mentioned above are those in which the glutathione concentration in immune cells has decreased. <b13> ~ <b23>One of the following methods. <b25>The subjects in whom the glutathione concentration in the immune cells described above decreased were humans aged 40 or older. <b24>Methods used. <b26>The subject mentioned above is a human. <b1> ~ <b25>One of the following methods. <b27>The above lactic acid bacteria are administered or given to those who need them. <b1> ~ <b26>One of the following methods. <b28>The above immune cells are immune cells that possess phagocytic ability. <b1> ~ <b27>One of the following methods. <c1>A method for increasing the concentration of glutathione in immune cells, comprising administering to a subject a composition containing lactic acid bacteria that are phagocytosed by immune cells. <c2>The above immune cells are at least one selected from the group consisting of plasmacytoid dendritic cells and myeloid dendritic cells. <c1>Methods used. <c3>The above immune cells are peripheral blood mononuclear cells. <c1>or <c2>Methods used. <c4>The above lactic acid bacteria is at least one species selected from the group consisting of Lactococcus, Bifidobacterium, Lactobacillus, Rimosilactobacillus, Lacticaseibacillus, Pediococcus, and Lactiplantybacillus. <c1> ~ <c3>One of the following methods. <c5>The above lactic acid bacteria include Lactococcus lactis, Lactococcus lactis subsp. lactis, Bifidobacterium longum, Bifidobacterium longum subsp. longum, Lactobacillus acidophilus, Lactobacillus helveticus, Limosilactobacillus reuteri, Limosilactobacillus reuteri subsp. reuteri, and Lacticaseibacillus paracasei. Lacticaseibacillus paracasei subsp. paracasei, Lacticaseibacillus casei, Lactobacillus crispatus, Lactobacillus johnsonii, Pediococcus acidilactici, Pediococcus pentosaceus, Lacticaseibacillus rhamnosus, Lactiplantibacillus plantarum It is at least one species selected from the group consisting of Lactiplantibacillus plantarum subsp. plantarum and Lactobacillus plantarum. <c1> ~ <c4>One of the following methods. <c6>The above lactic acid bacteria are Lactococcus lactis subsp. lactis JCM 5805, Bifidobacterium longum subsp. longum JCM 11340, Lactobacillus acidophilus JCM 1021, Lactobacillus helveticus JCM 1003, Limosilactobacillus reuteri subsp. reuteri JCM 1112, and Lacticaseibacillus paracasei subsp. paracasei JCM 1053, Lacticaseibacillus casei JCM 1134, Lactobacillus crispatus JCM 1185, Lactobacillus johnsonii JCM 2012, Pediococcus acidilactici JCM 2014, Pediococcus acidilactici JCM 8797, Pediococcus pentosaceus JCM 5890, Lactobacillus acidophilus JCM 1132, Lacticaseibacillus rhamnosus rhamnosus) JCM 1136, Lactiplantibacillus plantarum subsp.It is at least one species selected from the group consisting of Lactobacillus plantarum JCM 1149 and Lactobacillus plantarum L-137. <c1> ~ <c5>One of the following methods. <c7>The above lactic acid bacterium is Lactococcus lactis subsp. lactis JCM 5805. <c1> ~ <c6>One of the following methods. <c8>The subjects mentioned above are those in which the glutathione concentration in immune cells has decreased. <c1> ~ <c7>One of the following methods. <c9>The subjects in whom the glutathione concentration in the immune cells described above decreased were humans aged 40 or older. <c8>Methods used. <c10>This includes increasing the expression level of the NRF2 protein and / or the mRNA encoding it within the immune cells described above. <c1> ~ <c9>One of the following methods. <c11>The present invention includes at least one selected from the group consisting of protecting immune cells and suppressing the decrease of immune cells. <c1> ~ <c10>One of the following methods. <c12>The above subjects include at least one selected from the group consisting of antioxidant activity and suppression of intracellular oxidative stress, <c1> ~ <c11>One of the following methods. <c13>A method selected from the group consisting of a method for protecting immune cells, a method for suppressing the decrease of immune cells, an antioxidant method, and a method for suppressing intracellular oxidative stress, comprising administering to a subject a composition containing lactic acid bacteria that are phagocytosed by immune cells. <c14>A method selected from the group consisting of a method for protecting immune cells and a method for suppressing the decrease of immune cells, comprising administering to a subject a composition containing lactic acid bacteria that are phagocytosed by immune cells. <c15>At least one method selected from the group consisting of methods for antioxidant activity and methods for suppressing intracellular oxidative stress, comprising administering to a subject a composition containing lactic acid bacteria that are phagocytosed by immune cells. <c16>This includes increasing the expression level of the NRF2 protein and / or the mRNA encoding it within the immune cells described above. <c13> ~ <c15>One of the following methods. <c17>This includes increasing the glutathione concentration in the immune cells of the above target, <c13> ~ <c16>One of the following methods. <c18>The above immune cells are peripheral blood mononuclear cells. <c13> ~ <c17>One of the following methods. <c19>The above immune cells are at least one selected from the group consisting of plasmacytoid dendritic cells and myeloid dendritic cells. <c13> ~ <c18>One of the following methods. <c20>The above lactic acid bacteria is at least one species selected from the group consisting of Lactococcus, Bifidobacterium, Lactobacillus, Rimosilactobacillus, Lacticaseibacillus, Pediococcus, and Lactiplantybacillus. <c13> ~ <c19>One of the following methods. <c21>The above lactic acid bacteria include Lactococcus lactis, Lactococcus lactis subsp. lactis, Bifidobacterium longum, Bifidobacterium longum subsp. longum, Lactobacillus acidophilus, Lactobacillus helveticus, Limosilactobacillus reuteri, Limosilactobacillus reuteri subsp. reuteri, and Lacticaseibacillus paracasei. Lacticaseibacillus paracasei subsp. paracasei, Lacticaseibacillus casei, Lactobacillus crispatus, Lactobacillus johnsonii, Pediococcus acidilactici, Pediococcus pentosaceus, Lacticaseibacillus rhamnosus, Lactiplantibacillus plantarum It is at least one species selected from the group consisting of Lactiplantibacillus plantarum subsp. plantarum and Lactobacillus plantarum. <c13> ~ <c20>One of the following methods. <c22>The above lactic acid bacteria are Lactococcus lactis subsp. lactis JCM 5805, Bifidobacterium longum subsp. longum JCM 11340, Lactobacillus acidophilus JCM 1021, Lactobacillus helveticus JCM 1003, Limosilactobacillus reuteri subsp. reuteri JCM 1112, and Lacticaseibacillus paracasei subsp. paracasei JCM 1053, Lacticaseibacillus casei JCM 1134, Lactobacillus crispatus JCM 1185, Lactobacillus johnsonii JCM 2012, Pediococcus acidilactici JCM 2014, Pediococcus acidilactici JCM 8797, Pediococcus pentosaceus JCM 5890, Lactobacillus acidophilus JCM 1132, Lacticaseibacillus rhamnosus rhamnosus) JCM 1136, Lactiplantibacillus plantarum subsp.It is at least one species selected from the group consisting of Lactobacillus plantarum JCM 1149 and Lactobacillus plantarum L-137. <c13> ~ <c21>One of the following methods. <c23>The above lactic acid bacterium is Lactococcus lactis subsp. lactis JCM 5805. <c13> ~ <c22>One of the following methods. <c24>The subjects mentioned above are those in which the glutathione concentration in immune cells has decreased. <c13> ~ <c23>One of the following methods. <c25>The subjects in whom the glutathione concentration in the immune cells described above decreased were humans aged 40 or older. <c24>Methods used. <c26>The subject mentioned above is a human. <c13> ~ <c25>One of the following methods. <c27>The above composition is administered or given to a subject that requires it. <c1> ~ <c26>One of the following methods. <c28>The above immune cells are immune cells that possess phagocytic ability. <c1> ~ <c27>One of the following methods. <d1>Lactobacillus phagocytosed by immune cells for use in increasing glutathione concentration within immune cells. <d2>The above immune cells are peripheral blood mononuclear cells. <d1>Lactic acid bacteria for use as described above. <d3>The above immune cells are at least one selected from the group consisting of plasmacytoid dendritic cells and myeloid dendritic cells. <d1>or <d2>Lactic acid bacteria for use as described above. <d4>The above lactic acid bacteria is at least one species selected from the group consisting of Lactococcus, Bifidobacterium, Lactobacillus, Rimosilactobacillus, Lacticaseibacillus, Pediococcus, and Lactiplantybacillus. <d1> ~ <d3>Lactic acid bacteria for use, as described in any one of the following. <d5>The above lactic acid bacteria include Lactococcus lactis, Lactococcus lactis subsp. lactis, Bifidobacterium longum, Bifidobacterium longum subsp. longum, Lactobacillus acidophilus, Lactobacillus helveticus, Limosilactobacillus reuteri, Limosilactobacillus reuteri subsp. reuteri, and Lacticaseibacillus paracasei. Lacticaseibacillus paracasei subsp. paracasei, Lacticaseibacillus casei, Lactobacillus crispatus, Lactobacillus johnsonii, Pediococcus acidilactici, Pediococcus pentosaceus, Lacticaseibacillus rhamnosus, Lactiplantibacillus plantarum It is at least one species selected from the group consisting of Lactiplantibacillus plantarum subsp. plantarum and Lactobacillus plantarum. <d1> ~ <d4>Lactic acid bacteria for use, as described in any one of the following. <d6>The above lactic acid bacteria are Lactococcus lactis subsp. lactis JCM 5805, Bifidobacterium longum subsp. longum JCM 11340, Lactobacillus acidophilus JCM 1021, Lactobacillus helveticus JCM 1003, Limosilactobacillus reuteri subsp. reuteri JCM 1112, and Lacticaseibacillus paracasei subsp. paracasei JCM 1053, Lacticaseibacillus casei JCM 1134, Lactobacillus crispatus JCM 1185, Lactobacillus johnsonii JCM 2012, Pediococcus acidilactici JCM 2014, Pediococcus acidilactici JCM 8797, Pediococcus pentosaceus JCM 5890, Lactobacillus acidophilus JCM 1132, Lacticaseibacillus rhamnosus rhamnosus) JCM 1136, Lactiplantibacillus plantarum subsp.It is at least one species selected from the group consisting of Lactobacillus plantarum JCM 1149 and Lactobacillus plantarum L-137. <d1> ~ <d5>Lactic acid bacteria for use, as described in any one of the following. <d7>The above lactic acid bacterium is Lactococcus lactis subsp. lactis JCM 5805. <d1> ~ <d6>Lactic acid bacteria for use, as described in any one of the following. <d8>It is administered to subjects with decreased glutathione levels in immune cells. <d1> ~ <d7>Lactic acid bacteria for use, as described in any one of the following. <d9>The subjects in whom the glutathione concentration in the immune cells described above decreased were humans aged 40 or older. <d8>Lactic acid bacteria for use as described above. <d10>To increase the expression level of the NRF2 protein and / or the mRNA encoding it within the above-mentioned immune cells, <d1> ~ <d9>Lactic acid bacteria for use, as described in any one of the following. <d11>The above lactic acid bacteria are used for at least one selected from the group consisting of protection of immune cells and suppression of the decrease of immune cells. <d1> ~ <d10>Lactic acid bacteria for use, as described in any one of the following. <d12>The above lactic acid bacteria are used for at least one selected from the group consisting of antioxidant and intracellular oxidative stress suppression. <d1> ~ <d11>Lactic acid bacteria for use, as described in any one of the following. <d13>Lactobacillus that is phagocytosed by immune cells, for use in at least one of the following purposes selected from the group: protecting immune cells, suppressing the decrease of immune cells, providing antioxidant effects, and suppressing intracellular oxidative stress. <d14>For use in at least one selected from the group consisting of protecting immune cells and suppressing the decrease of immune cells, <d13>Lactic acid bacteria for use as described above. <d15>For use in at least one selected from the group consisting of antioxidant activity and suppression of intracellular oxidative stress, <d13>Lactic acid bacteria for use as described above. <d16>To increase the expression level of the NRF2 protein and / or the mRNA encoding it within the above-mentioned immune cells, <d13> ~ <d15>Lactic acid bacteria for use, as described in any one of the following. <d17>The above-mentioned lactic acid bacteria are used to increase glutathione concentration in immune cells. <d13> ~ <d16>Lactic acid bacteria for use, as described in any one of the following. <d18>The above immune cells are peripheral blood mononuclear cells. <d13> ~ <d17>Lactic acid bacteria for use, as described in any one of the following. <d19>The above immune cells are at least one selected from the group consisting of plasmacytoid dendritic cells and myeloid dendritic cells. <d13> ~ <d18>Lactic acid bacteria for use, as described in any one of the following. <d20>The above lactic acid bacteria is at least one species selected from the group consisting of Lactococcus, Bifidobacterium, Lactobacillus, Rimosilactobacillus, Lacticaseibacillus, Pediococcus, and Lactiplantybacillus. <d13> ~ <d19>Lactic acid bacteria for use, as described in any one of the following. <d21>The above lactic acid bacteria include Lactococcus lactis, Lactococcus lactis subsp. lactis, Bifidobacterium longum, Bifidobacterium longum subsp. longum, Lactobacillus acidophilus, Lactobacillus helveticus, Limosilactobacillus reuteri, Limosilactobacillus reuteri subsp. reuteri, and Lacticaseibacillus paracasei. Lacticaseibacillus paracasei subsp. paracasei, Lacticaseibacillus casei, Lactobacillus crispatus, Lactobacillus johnsonii, Pediococcus acidilactici, Pediococcus pentosaceus, Lacticaseibacillus rhamnosus, Lactiplantibacillus plantarum It is at least one species selected from the group consisting of Lactiplantibacillus plantarum subsp. plantarum and Lactobacillus plantarum. <d13> ~ <d20>Lactic acid bacteria for use, as described in any one of the following. <d22>The above lactic acid bacteria are Lactococcus lactis subsp. lactis JCM 5805, Bifidobacterium longum subsp. longum JCM 11340, Lactobacillus acidophilus JCM 1021, Lactobacillus helveticus JCM 1003, Limosilactobacillus reuteri subsp. reuteri JCM 1112, and Lacticaseibacillus paracasei subsp. paracasei JCM 1053, Lacticaseibacillus casei JCM 1134, Lactobacillus crispatus JCM 1185, Lactobacillus johnsonii JCM 2012, Pediococcus acidilactici JCM 2014, Pediococcus acidilactici JCM 8797, Pediococcus pentosaceus JCM 5890, Lactobacillus acidophilus JCM 1132, Lacticaseibacillus rhamnosus rhamnosus) JCM 1136, Lactiplantibacillus plantarum subsp.It is at least one species selected from the group consisting of Lactobacillus plantarum JCM 1149 and Lactobacillus plantarum L-137. <d13> ~ <d21>Lactic acid bacteria for use, as described in any one of the following. <d23>The above lactic acid bacterium is Lactococcus lactis subsp. lactis JCM 5805. <d13> ~ <d22>Lactic acid bacteria for use, as described in any one of the following. <d24>It is administered to subjects with decreased glutathione levels in immune cells. <d13> ~ <d23>Lactic acid bacteria for use, as described in any one of the following. <d25>The subjects in whom the glutathione concentration in the immune cells described above decreased were humans aged 40 or older. <d24>Lactic acid bacteria for use as described above. <d26>Administered to humans, <d1> ~ <d25>Lactic acid bacteria for use, as described in any one of the following. <d27>The above immune cells are immune cells that possess phagocytic ability. <d1> ~ <d26>Lactic acid bacteria for use, as described in any one of the following. <e1>A composition containing lactic acid bacteria that are phagocytosed by immune cells, for use in increasing glutathione concentration within immune cells. <e2>The above immune cells are peripheral blood mononuclear cells. <e1>The composition for use described above. <e3>The above immune cells are at least one selected from the group consisting of plasmacytoid dendritic cells and myeloid dendritic cells. <e1>or <e2>The composition for use described above. <e4>The above lactic acid bacteria is at least one species selected from the group consisting of Lactococcus, Bifidobacterium, Lactobacillus, Rimosilactobacillus, Lacticaseibacillus, Pediococcus, and Lactiplantybacillus. <e1> ~ <e3>A composition for use as described in any one of the following. <e5>The above lactic acid bacteria include Lactococcus lactis, Lactococcus lactis subsp. lactis, Bifidobacterium longum, Bifidobacterium longum subsp. longum, Lactobacillus acidophilus, Lactobacillus helveticus, Limosilactobacillus reuteri, Limosilactobacillus reuteri subsp. reuteri, and Lacticaseibacillus paracasei. Lacticaseibacillus paracasei subsp. paracasei, Lacticaseibacillus casei, Lactobacillus crispatus, Lactobacillus johnsonii, Pediococcus acidilactici, Pediococcus pentosaceus, Lacticaseibacillus rhamnosus, Lactiplantibacillus plantarum It is at least one species selected from the group consisting of Lactiplantibacillus plantarum subsp. plantarum and Lactobacillus plantarum. <e1> ~ <e4>A composition for use as described in any one of the following. <e6>The above lactic acid bacteria are Lactococcus lactis subsp. lactis JCM 5805, Bifidobacterium longum subsp. longum JCM 11340, Lactobacillus acidophilus JCM 1021, Lactobacillus helveticus JCM 1003, Limosilactobacillus reuteri subsp. reuteri JCM 1112, and Lacticaseibacillus paracasei subsp. paracasei JCM 1053, Lacticaseibacillus casei JCM 1134, Lactobacillus crispatus JCM 1185, Lactobacillus johnsonii JCM 2012, Pediococcus acidilactici JCM 2014, Pediococcus acidilactici JCM 8797, Pediococcus pentosaceus JCM 5890, Lactobacillus acidophilus JCM 1132, Lacticaseibacillus rhamnosus rhamnosus) JCM 1136, Lactiplantibacillus plantarum subsp.It is at least one species selected from the group consisting of Lactobacillus plantarum JCM 1149 and Lactobacillus plantarum L-137. <e1> ~ <e5>A composition for use as described in any one of the following. <e7>The above lactic acid bacterium is Lactococcus lactis subsp. lactis JCM 5805. <e1> ~ <e6>A composition for use as described in any one of the following. <e8>It is administered to subjects with decreased glutathione levels in immune cells. <e1> ~ <e7>A composition for use as described in any one of the following. <e9>The subjects in whom the glutathione concentration in the immune cells described above decreased were humans aged 40 or older. <e8>The composition for use described above. <e10>To increase the expression level of the NRF2 protein and / or the mRNA encoding it within the above-mentioned immune cells, <e1> ~ <e9>A composition for use as described in any one of the following. <e11>The above composition is used for at least one selected from the group consisting of protection of the above immune cells and suppression of the decrease of the above immune cells. <e1> ~ <e10>A composition for use as described in any one of the following. <e12>The above composition is used for at least one selected from the group consisting of antioxidant and intracellular oxidative stress suppression. <e1> ~ <e11>A composition for use as described in any one of the following. <e13>A composition containing lactic acid bacteria that are phagocytosed by immune cells, for use in at least one selected from the group consisting of protecting immune cells, suppressing the decrease of immune cells, providing antioxidant effects, and suppressing intracellular oxidative stress. <e14>For use in at least one selected from the group consisting of protecting immune cells and suppressing the decrease of immune cells, <e13>The composition for use described above. <e15>For use in at least one selected from the group consisting of antioxidant activity and suppression of intracellular oxidative stress, <e13>The composition for use described above. <e16>To increase the expression level of the NRF2 protein and / or the mRNA encoding it within the above-mentioned immune cells, <e13> ~ <e15>A composition for use as described in any one of the following. <e17>The above composition is used to increase the glutathione concentration in immune cells. <e13> ~ <e16>A composition for use as described in any one of the following. <e18>The above immune cells are at least one selected from the group consisting of plasmacytoid dendritic cells, myeloid dendritic cells, and peripheral blood mononuclear cells. <e13> ~ <e17>A composition for use as described in any one of the following. <e19>The above immune cells are peripheral blood mononuclear cells. <e13> ~ <e18>A composition for use as described in any one of the following. <e20>The above lactic acid bacteria is at least one species selected from the group consisting of Lactococcus, Bifidobacterium, Lactobacillus, Rimosilactobacillus, Lacticaseibacillus, Pediococcus, and Lactiplantybacillus. <e13> ~ <e19>A composition for use as described in any one of the following. <e21>The above lactic acid bacteria include Lactococcus lactis, Lactococcus lactis subsp. lactis, Bifidobacterium longum, Bifidobacterium longum subsp. longum, Lactobacillus acidophilus, Lactobacillus helveticus, Limosilactobacillus reuteri, Limosilactobacillus reuteri subsp. reuteri, and Lacticaseibacillus paracasei. Lacticaseibacillus paracasei subsp. paracasei, Lacticaseibacillus casei, Lactobacillus crispatus, Lactobacillus johnsonii, Pediococcus acidilactici, Pediococcus pentosaceus, Lacticaseibacillus rhamnosus, Lactiplantibacillus plantarum It is at least one species selected from the group consisting of Lactiplantibacillus plantarum subsp. plantarum and Lactobacillus plantarum. <e13> ~ <e20>A composition for use as described in any one of the following. <e22>The above lactic acid bacteria are Lactococcus lactis subsp. lactis JCM 5805, Bifidobacterium longum subsp. longum JCM 11340, Lactobacillus acidophilus JCM 1021, Lactobacillus helveticus JCM 1003, Limosilactobacillus reuteri subsp. reuteri JCM 1112, and Lacticaseibacillus paracasei subsp. paracasei JCM 1053, Lacticaseibacillus casei JCM 1134, Lactobacillus crispatus JCM 1185, Lactobacillus johnsonii JCM 2012, Pediococcus acidilactici JCM 2014, Pediococcus acidilactici JCM 8797, Pediococcus pentosaceus JCM 5890, Lactobacillus acidophilus JCM 1132, Lacticaseibacillus rhamnosus rhamnosus) JCM 1136, Lactiplantibacillus plantarum subsp.It is at least one species selected from the group consisting of Lactobacillus plantarum JCM 1149 and Lactobacillus plantarum L-137. <e13> ~ <e21>A composition for use as described in any one of the following. <e23>The above lactic acid bacterium is Lactococcus lactis subsp. lactis JCM 5805. <e13> ~ <e22>A composition for use as described in any one of the following. <e24>It is administered to subjects with decreased glutathione levels in immune cells. <e13> ~ <e23>A composition for use as described in any one of the following. <e25>The subjects in whom the glutathione concentration in the immune cells described above decreased were humans aged 40 or older. <e24>The composition for use described above. <e26>Administered to humans, <e1> ~ <e25>A composition for use as described in any one of the following. <e27>The above immune cells are immune cells that possess phagocytic ability. <e1> ~ <e26>A composition for use as described in any one of the following. <f1>The use of lactic acid bacteria phagocytosed by the aforementioned immune cells in increasing glutathione concentration within immune cells. <f2>The above immune cells are peripheral blood mononuclear cells. <f1>Use as described above. <f3>The above immune cells are at least one selected from the group consisting of plasmacytoid dendritic cells and myeloid dendritic cells. <f1>or <f2>Use as described above. <f4>The above lactic acid bacteria is at least one species selected from the group consisting of Lactococcus, Bifidobacterium, Lactobacillus, Rimosilactobacillus, Lacticaseibacillus, Pediococcus, and Lactiplantybacillus. <f1> ~ <f3>Use as described in any one of the following. <f5>The above lactic acid bacteria include Lactococcus lactis, Lactococcus lactis subsp. lactis, Bifidobacterium longum, Bifidobacterium longum subsp. longum, Lactobacillus acidophilus, Lactobacillus helveticus, Limosilactobacillus reuteri, Limosilactobacillus reuteri subsp. reuteri, and Lacticaseibacillus paracasei. Lacticaseibacillus paracasei subsp. paracasei, Lacticaseibacillus casei, Lactobacillus crispatus, Lactobacillus johnsonii, Pediococcus acidilactici, Pediococcus pentosaceus, Lacticaseibacillus rhamnosus, Lactiplantibacillus plantarum It is at least one species selected from the group consisting of Lactiplantibacillus plantarum subsp. plantarum and Lactobacillus plantarum. <f1> ~ <f4>Use as described in any one of the following. <f6>The above lactic acid bacteria are Lactococcus lactis subsp. lactis JCM 5805, Bifidobacterium longum subsp. longum JCM 11340, Lactobacillus acidophilus JCM 1021, Lactobacillus helveticus JCM 1003, Limosilactobacillus reuteri subsp. reuteri JCM 1112, and Lacticaseibacillus paracasei subsp. paracasei JCM 1053, Lacticaseibacillus casei JCM 1134, Lactobacillus crispatus JCM 1185, Lactobacillus johnsonii JCM 2012, Pediococcus acidilactici JCM 2014, Pediococcus acidilactici JCM 8797, Pediococcus pentosaceus JCM 5890, Lactobacillus acidophilus JCM 1132, Lacticaseibacillus rhamnosus rhamnosus) JCM 1136, Lactiplantibacillus plantarum subsp.It is at least one species selected from the group consisting of Lactobacillus plantarum JCM 1149 and Lactobacillus plantarum L-137. <f1> ~ <f5>Use as described in any one of the following. <f7>The above lactic acid bacterium is Lactococcus lactis subsp. lactis JCM 5805. <f1> ~ <f6>Use as described in any one of the following. <f8>The above lactic acid bacteria are ingested by individuals whose glutathione levels in immune cells have decreased. <f1> ~ <f7>Use as described in any one of the following. <f9>The subjects in whom the glutathione concentration in the immune cells described above decreased were humans aged 40 or older. <f8>Use as described above. <f10>To increase the expression level of the NRF2 protein and / or the mRNA encoding it within the above-mentioned immune cells, <f1> ~ <f9>Use as described in any one of the following. <f11>For at least one selected from the group consisting of protection of immune cells and suppression of immune cell decline, <f1> ~ <f10>Use as described in any one of the following. <f12>For at least one selected from the group consisting of antioxidant and intracellular oxidative stress suppression, <f1> ~ <f11>Use as described in any one of the following. <f13>The use of lactic acid bacteria that are phagocytosed by immune cells, in which at least one of the following is selected from the group consisting of protecting immune cells, suppressing the decrease of immune cells, providing antioxidant effects, and suppressing intracellular oxidative stress. <f14>At least one selected from the group consisting of protecting immune cells and suppressing the decrease of immune cells, <f13>Use as described above. <f15>At least one selected from the group consisting of antioxidant activity and suppression of intracellular oxidative stress, <f13>Use as described above. <f16>To increase the expression level of the NRF2 protein and / or the mRNA encoding it within the above-mentioned immune cells, <f13> ~ <f15>Use as described in any one of the following. <f17>To increase glutathione concentration in immune cells, <f13> ~ <f16>Use as described in any one of the following. <f18>The above immune cells are peripheral blood mononuclear cells. <f13> ~ <f17>Use as described in any one of the following. <f19>The above immune cells are at least one selected from the group consisting of plasmacytoid dendritic cells and myeloid dendritic cells. <f13> ~ <f18>Use as described in any one of the following. <f20>The above lactic acid bacteria is at least one species selected from the group consisting of Lactococcus, Bifidobacterium, Lactobacillus, Rimosilactobacillus, Lacticaseibacillus, Pediococcus, and Lactiplantybacillus. <f13> ~ <f19>Use as described in any one of the following. <f21>The above lactic acid bacteria include Lactococcus lactis, Lactococcus lactis subsp. lactis, Bifidobacterium longum, Bifidobacterium longum subsp. longum, Lactobacillus acidophilus, Lactobacillus helveticus, Limosilactobacillus reuteri, Limosilactobacillus reuteri subsp. reuteri, and Lacticaseibacillus paracasei. Lacticaseibacillus paracasei subsp. paracasei, Lacticaseibacillus casei, Lactobacillus crispatus, Lactobacillus johnsonii, Pediococcus acidilactici, Pediococcus pentosaceus, Lacticaseibacillus rhamnosus, Lactiplantibacillus plantarum It is at least one species selected from the group consisting of Lactiplantibacillus plantarum subsp. plantarum and Lactobacillus plantarum. <f13> ~ <f20>Use as described in any one of the following. <f22>The above lactic acid bacteria are Lactococcus lactis subsp. lactis JCM 5805, Bifidobacterium longum subsp. longum JCM 11340, Lactobacillus acidophilus JCM 1021, Lactobacillus helveticus JCM 1003, Limosilactobacillus reuteri subsp. reuteri JCM 1112, and Lacticaseibacillus paracasei subsp. paracasei JCM 1053, Lacticaseibacillus casei JCM 1134, Lactobacillus crispatus JCM 1185, Lactobacillus johnsonii JCM 2012, Pediococcus acidilactici JCM 2014, Pediococcus acidilactici JCM 8797, Pediococcus pentosaceus JCM 5890, Lactobacillus acidophilus JCM 1132, Lacticaseibacillus rhamnosus rhamnosus) JCM 1136, Lactiplantibacillus plantarum subsp.It is at least one species selected from the group consisting of Lactobacillus plantarum JCM 1149 and Lactobacillus plantarum L-137. <f13> ~ <f21>Use as described in any one of the following. <f23>The above lactic acid bacterium is Lactococcus lactis subsp. lactis JCM 5805. <f13> ~ <f22>Use as described in any one of the following. <f24>The above lactic acid bacteria are ingested by individuals whose glutathione levels in immune cells have decreased. <f13> ~ <f23>Use as described in any one of the following. <f25>The subjects in whom the glutathione concentration in the immune cells described above decreased were humans aged 40 or older. <f24>Use as described above. <f26>The above lactic acid bacteria are ingested by humans. <f1> ~ <f25>Use as described in any one of the following. <f27>It is a non-therapeutic use. <f1> ~ <f26>Use as described in any one of the following. <f28>The above immune cells are immune cells that possess phagocytic ability. <f1> ~ <f27>Use as described in any one of the following. <g1>The use of a composition containing lactic acid bacteria that are phagocytosed by the immune cells in order to increase the glutathione concentration in immune cells. <g2>The above immune cells are peripheral blood mononuclear cells. <g1>Use as described above. <g3>The above immune cells are at least one selected from the group consisting of plasmacytoid dendritic cells and myeloid dendritic cells. <g1>or <g2>Use as described above. <g4>The above lactic acid bacteria is at least one species selected from the group consisting of Lactococcus, Bifidobacterium, Lactobacillus, Rimosilactobacillus, Lacticaseibacillus, Pediococcus, and Lactiplantybacillus. <g1> ~ <g3>Use as described in any one of the following. <g5>The above lactic acid bacteria include Lactococcus lactis, Lactococcus lactis subsp. lactis, Bifidobacterium longum, Bifidobacterium longum subsp. longum, Lactobacillus acidophilus, Lactobacillus helveticus, Limosilactobacillus reuteri, Limosilactobacillus reuteri subsp. reuteri, and Lacticaseibacillus paracasei. Lacticaseibacillus paracasei subsp. paracasei, Lacticaseibacillus casei, Lactobacillus crispatus, Lactobacillus johnsonii, Pediococcus acidilactici, Pediococcus pentosaceus, Lacticaseibacillus rhamnosus, Lactiplantibacillus plantarum It is at least one species selected from the group consisting of Lactiplantibacillus plantarum subsp. plantarum and Lactobacillus plantarum. <g1> ~ <g4>Use as described in any one of the following. <g6>The above lactic acid bacteria are Lactococcus lactis subsp. lactis JCM 5805, Bifidobacterium longum subsp. longum JCM 11340, Lactobacillus acidophilus JCM 1021, Lactobacillus helveticus JCM 1003, Limosilactobacillus reuteri subsp. reuteri JCM 1112, and Lacticaseibacillus paracasei subsp. paracasei JCM 1053, Lacticaseibacillus casei JCM 1134, Lactobacillus crispatus JCM 1185, Lactobacillus johnsonii JCM 2012, Pediococcus acidilactici JCM 2014, Pediococcus acidilactici JCM 8797, Pediococcus pentosaceus JCM 5890, Lactobacillus acidophilus JCM 1132, Lacticaseibacillus rhamnosus rhamnosus) JCM 1136, Lactiplantibacillus plantarum subsp.It is at least one species selected from the group consisting of Lactobacillus plantarum JCM 1149 and Lactobacillus plantarum L-137. <g1> ~ <g5>Use as described in any one of the following. <g7>The above lactic acid bacterium is Lactococcus lactis subsp. lactis JCM 5805. <g1> ~ <g6>Use as described in any one of the following. <g8>The above composition is ingested by a subject whose glutathione concentration in immune cells has decreased. <g1> ~ <g7>Use as described in any one of the following. <g9>The subjects in whom the glutathione concentration in the immune cells described above decreased were humans aged 40 or older. <g8>Use as described above. <g10>To increase the expression level of the NRF2 protein and / or the mRNA encoding it within the above-mentioned immune cells, <g1> ~ <g9>Use as described in any one of the following. <g11>For at least one selected from the group consisting of protection of immune cells and suppression of immune cell decline, <g1> ~ <g10>Use as described in any one of the following. <g12>For at least one selected from the group consisting of antioxidant and intracellular oxidative stress suppression, <g1> ~ <g11>Use as described in any one of the following. <g13>The use of a composition containing lactic acid bacteria that are phagocytosed by immune cells, wherein the function is at least one selected from the group consisting of protecting immune cells, suppressing the decrease of immune cells, providing antioxidant effects, and suppressing intracellular oxidative stress. <g14>At least one selected from the group consisting of protecting immune cells and suppressing the decrease of immune cells, <g13>Use as described above. <g15>At least one selected from the group consisting of antioxidant activity and suppression of intracellular oxidative stress, <g13>Use as described above. <g16>To increase the expression level of the NRF2 protein and / or the mRNA encoding it within the above-mentioned immune cells, <g13> ~ <g15>Use as described in any one of the following. <g17>To increase glutathione concentration in immune cells, <g13> ~ <g16>Use as described in any one of the following. <g18>The above immune cells are peripheral blood mononuclear cells. <g13> ~ <g17>Use as described in any one of the following. <g19>The above immune cells are at least one selected from the group consisting of plasmacytoid dendritic cells and myeloid dendritic cells. <g13> ~ <g18>Use as described in any one of the following. <g20>The above lactic acid bacteria is at least one species selected from the group consisting of Lactococcus, Bifidobacterium, Lactobacillus, Rimosilactobacillus, Lacticaseibacillus, Pediococcus, and Lactiplantybacillus. <g13> ~ <g19>Use as described in any one of the following. <g21>The above lactic acid bacteria include Lactococcus lactis, Lactococcus lactis subsp. lactis, Bifidobacterium longum, Bifidobacterium longum subsp. longum, Lactobacillus acidophilus, Lactobacillus helveticus, Limosilactobacillus reuteri, Limosilactobacillus reuteri subsp. reuteri, and Lacticaseibacillus paracasei. Lacticaseibacillus paracasei subsp. paracasei, Lacticaseibacillus casei, Lactobacillus crispatus, Lactobacillus johnsonii, Pediococcus acidilactici, Pediococcus pentosaceus, Lacticaseibacillus rhamnosus, Lactiplantibacillus plantarum It is at least one species selected from the group consisting of Lactiplantibacillus plantarum subsp. plantarum and Lactobacillus plantarum. <g13> ~ <g20>Use as described in any one of the following. <g22>The above lactic acid bacteria are Lactococcus lactis subsp. lactis JCM 5805, Bifidobacterium longum subsp. longum JCM 11340, Lactobacillus acidophilus JCM 1021, Lactobacillus helveticus JCM 1003, Limosilactobacillus reuteri subsp. reuteri JCM 1112, and Lacticaseibacillus paracasei subsp. paracasei JCM 1053, Lacticaseibacillus casei JCM 1134, Lactobacillus crispatus JCM 1185, Lactobacillus johnsonii JCM 2012, Pediococcus acidilactici JCM 2014, Pediococcus acidilactici JCM 8797, Pediococcus pentosaceus JCM 5890, Lactobacillus acidophilus JCM 1132, Lacticaseibacillus rhamnosus rhamnosus) JCM 1136, Lactiplantibacillus plantarum subsp.It is at least one species selected from the group consisting of Lactobacillus plantarum JCM 1149 and Lactobacillus plantarum L-137. <g13> ~ <g21>Use as described in any one of the following. <g23>The above lactic acid bacterium is Lactococcus lactis subsp. lactis JCM 5805. <g13> ~ <g22>Use as described in any one of the following. <g24>The above composition is ingested by a subject whose glutathione concentration in immune cells has decreased. <g13> ~ <g23>Use as described in any one of the following. <g25>The subjects in whom the glutathione concentration in the immune cells described above decreased were humans aged 40 or older. <g24>Use as described above. <g26>The above lactic acid bacteria are ingested by humans. <g1> ~ <g25>Use as described in any one of the following. <g27>It is a non-therapeutic use. <g1> ~ <g26>Use as described in any one of the following. <g28>The above immune cells are immune cells that possess phagocytic ability. <g1> ~ <g27>Use as described in any one of the following. <h1>The use of lactic acid bacteria that are phagocytosed by the immune cells in the production of a composition for increasing glutathione concentration in immune cells. < / h1> <h2>The above immune cells are peripheral blood mononuclear cells.< / h2> <h1>Use as described above. < / h1> <h3> The above immune cells are at least one selected from the group consisting of plasmacytoid dendritic cells and myeloid dendritic cells.< / h3> <h1> or< / h1> <h2>Use as described above. < / h2> <h4> The above lactic acid bacteria is at least one species selected from the group consisting of Lactococcus, Bifidobacterium, Lactobacillus, Rimosilactobacillus, Lacticaseibacillus, Pediococcus, and Lactiplantybacillus.< / h4> <h1>~< / h1> <h3>Use as described in any one of the following. < / h3> <h5>The above lactic acid bacteria include Lactococcus lactis, Lactococcus lactis subsp. lactis, Bifidobacterium longum, Bifidobacterium longum subsp. longum, Lactobacillus acidophilus, Lactobacillus helveticus, Limosilactobacillus reuteri, Limosilactobacillus reuteri subsp. reuteri, and Lacticaseibacillus paracasei. Lacticaseibacillus paracasei subsp. paracasei, Lacticaseibacillus casei, Lactobacillus crispatus, Lactobacillus johnsonii, Pediococcus acidilactici, Pediococcus pentosaceus, Lacticaseibacillus rhamnosus, Lactiplantibacillus plantarum It is at least one species selected from the group consisting of Lactiplantibacillus plantarum subsp. plantarum and Lactobacillus plantarum.< / h5> <h1>~< / h1> <h4>Use as described in any one of the following. < / h4> <h6>The above lactic acid bacteria are Lactococcus lactis subsp. lactis JCM 5805, Bifidobacterium longum subsp. longum JCM 11340, Lactobacillus acidophilus JCM 1021, Lactobacillus helveticus JCM 1003, Limosilactobacillus reuteri subsp. reuteri JCM 1112, and Lacticaseibacillus paracasei subsp. paracasei JCM 1053, Lacticaseibacillus casei JCM 1134, Lactobacillus crispatus JCM 1185, Lactobacillus johnsonii JCM 2012, Pediococcus acidilactici JCM 2014, Pediococcus acidilactici JCM 8797, Pediococcus pentosaceus JCM 5890, Lactobacillus acidophilus JCM 1132, Lacticaseibacillus rhamnosus rhamnosus) JCM 1136, Lactiplantibacillus plantarum subsp.It is at least one species selected from the group consisting of Lactobacillus plantarum JCM 1149 and Lactobacillus plantarum L-137.< / h6> <h1>~< / h1> <h5>Use as described in any one of the following terms. <h7>The above lactic acid bacterium is Lactococcus lactis subsp. lactis JCM 5805. <h1>~< / h1> <h6>Use as described in any one of the following terms. <h8>The above composition is intended to be administered to or ingested by subjects whose glutathione concentration in immune cells has decreased. <h1>~ <h7>Use as described in any one of the following terms. <h9>The subjects in whom the glutathione concentration in the immune cells described above decreased were humans aged 40 or older. <h8>Use as described above. <h10>The above composition is for increasing the expression level of the NRF2 protein and / or the mRNA encoding it within the immune cells. <h1>~ <h9>Use as described in any one of the following. <h11>The above composition is used for at least one selected from the group consisting of protection of the above immune cells and suppression of the decrease of the above immune cells. <h1>~ <h10>Use as described in any one of the following terms. <h12>The above composition is used for at least one selected from the group consisting of antioxidant and intracellular oxidative stress suppression. <h1>~ <h11>Use as described in any one of the following terms. <h13>The use of lactic acid bacteria that are phagocytosed by immune cells in the production of at least one composition selected from the group consisting of compositions for protecting immune cells, compositions for suppressing the decrease of immune cells, antioxidant compositions, and compositions for suppressing intracellular oxidative stress. <h14>The use of lactic acid bacteria that are phagocytosed by immune cells in the production of at least one composition selected from compositions for protecting immune cells and compositions for suppressing the reduction of immune cells. <h15>The use of lactic acid bacteria that are phagocytosed by immune cells in the production of at least one composition selected from the group consisting of antioxidant compositions and compositions for suppressing intracellular oxidative stress. <h16>The above composition is for increasing the expression level of the NRF2 protein and / or the mRNA encoding it within the immune cells. <h13> ~ <h15>Use as described in any one of the following. <h17>The above composition is used to increase the glutathione concentration in the above immune cells. <h13> ~ <h16>Use as described in any one of the following terms. <h18>The above immune cells are peripheral blood mononuclear cells. <h13> ~ <h17>Use as described in any one of the following. <h19>The above immune cells are at least one selected from the group consisting of plasmacytoid dendritic cells and myeloid dendritic cells. <h13> ~ <h18>Use as described in any one of the following terms. <h20>The above lactic acid bacteria is at least one species selected from the group consisting of Lactococcus, Bifidobacterium, Lactobacillus, Rimosilactobacillus, Lacticaseibacillus, Pediococcus, and Lactiplantybacillus. <h13> ~ <h19>Use as described in any one of the following. <h21>The above lactic acid bacteria include Lactococcus lactis, Lactococcus lactis subsp. lactis, Bifidobacterium longum, Bifidobacterium longum subsp. longum, Lactobacillus acidophilus, Lactobacillus helveticus, Limosilactobacillus reuteri, Limosilactobacillus reuteri subsp. reuteri, and Lacticaseibacillus paracasei. Lacticaseibacillus paracasei subsp. paracasei, Lacticaseibacillus casei, Lactobacillus crispatus, Lactobacillus johnsonii, Pediococcus acidilactici, Pediococcus pentosaceus, Lacticaseibacillus rhamnosus, Lactiplantibacillus plantarum It is at least one species selected from the group consisting of Lactiplantibacillus plantarum subsp. plantarum and Lactobacillus plantarum. <h13> ~ <h20>Use as described in any one of the following. <h22>The above lactic acid bacteria are Lactococcus lactis subsp. lactis JCM 5805, Bifidobacterium longum subsp. longum JCM 11340, Lactobacillus acidophilus JCM 1021, Lactobacillus helveticus JCM 1003, Limosilactobacillus reuteri subsp. reuteri JCM 1112, and Lacticaseibacillus paracasei subsp. paracasei JCM 1053, Lacticaseibacillus casei JCM 1134, Lactobacillus crispatus JCM 1185, Lactobacillus johnsonii JCM 2012, Pediococcus acidilactici JCM 2014, Pediococcus acidilactici JCM 8797, Pediococcus pentosaceus JCM 5890, Lactobacillus acidophilus JCM 1132, Lacticaseibacillus rhamnosus rhamnosus) JCM 1136, Lactiplantibacillus plantarum subsp.It is at least one species selected from the group consisting of Lactobacillus plantarum JCM 1149 and Lactobacillus plantarum L-137. <h13> ~ <h21>Use as described in any one of the following terms. <h23>The above lactic acid bacterium is Lactococcus lactis subsp. lactis JCM 5805. <h13> ~ <h22>Use as described in any one of the following. <h24>The above composition is intended to be administered to or ingested by subjects whose glutathione concentration in immune cells has decreased. <h13> ~ <h23>Use as described in any one of the following. <h25>The subjects in whom the glutathione concentration in the immune cells described above decreased were humans aged 40 or older. <h24>Use as described above. <h26>The above immune cells are immune cells that possess phagocytic ability. <h1>~ <h25>Use as described in any one of the following. [Effects of the Invention]

[0011] This disclosure provides compositions for increasing glutathione concentration in immune cells. Furthermore, this disclosure also provides compositions for protecting immune cells, suppressing immune cell decline, antioxidant compositions and / or suppressing intracellular oxidative stress, and compositions for increasing the expression levels of NRF2 protein and / or the mRNA encoding it. [Brief explanation of the drawing]

[0012] [Figure 1] This figure shows the results of evaluating intracellular GSH concentration using CAL-1 cells in Example 1. [Figure 2] This figure shows the results of evaluating intracellular GSH concentration using BMDC cells in Example 1. [Figure 3] This figure shows the results of evaluating the effect of changes in intracellular GSH concentration on cell number using CAL-1 cells in Example 1. [Figure 4] This figure shows the results of evaluating the intracellular GSH concentration in CAL-1 cells according to whether or not they were exposed to lactic acid bacteria in Example 2. [Figure 5] This figure shows the results of evaluating intracellular GSH concentration in BMDC cells in Example 2, depending on whether or not they were exposed to lactic acid bacteria. [Figure 6] This figure shows the change in GSH concentration in immune cells caused by exposure to LC-Plasma, with and without phagocytosis suppression using Cyt-D, in Example 3. [Figure 7] This figure shows the results of evaluating the intracellular GSH concentration when CAL-1 cells were exposed to various lactic acid bacteria in Example 4. [Figure 8] This figure shows the results of evaluating the intracellular GSH concentration when CAL-1 cells were exposed to various lactic acid bacteria in Example 4. [Figure 9] This figure shows the results of evaluating the amount of various lactic acid bacteria phagocytosed by CAL-1 cells in Example 4. [Figure 10] This figure shows the results of evaluating the amount of various lactic acid bacteria phagocytosed by CAL-1 cells in Example 4. [Figure 11] This figure shows the correlation between intracellular GSH concentration and phagocytosis amount in CAL-1 cells exposed to various lactic acid bacteria, as prepared based on Figures 7 and 9 in Example 4. [Figure 12] This figure shows the correlation between intracellular GSH concentration and phagocytosis amount in CAL-1 cells exposed to various lactic acid bacteria, as prepared based on Figures 8 and 10 in Example 4. [Figure 13] This figure shows the results of evaluating Nfe2l2 gene expression using CAL-1 cells in Example 5 (N=3). In the figure, "LC-Plasma" and "CT" indicate the LC-Plasma-added group and the LC-Plasma-free group (control group), respectively. [Figure 14] This figure shows the results of evaluating Nfe2l2 gene expression using BMDC in Example 5 (N=3). In the figure, "LC-Plasma" and "CT" indicate the LC-Plasma-added group and the LC-Plasma-free group (control group), respectively. [Modes for carrying out the invention]

[0013] The following describes the forms for implementing this disclosure, but this disclosure should not be construed as being limited to the following embodiments.

[0014] In this disclosure, the phrase "at least one selected from the group consisting of" includes one element of that group or all possible combinations of two or more elements, for example, one of the elements of that group, or any combination of two, three, four, five, six, seven, eight, nine or more elements of that group.

[0015] <Lactic acid bacteria>

[0016] The lactic acid bacteria relating to this disclosure are bacteria that produce lactic acid as a metabolite. Examples of lactic acid bacteria include, but are not limited to, the genera Oenococcus, Bifidobacterium, Weissella, Tetragenococcus, Lactococcus, Leuconostoc, Pediococcus, Streptococcus, Enterococcus, Lactobacillus, acetic acid bacteria, and Hendrickxia (formerly classified as a Bacillus bacterium).

[0017] In this specification, the term "Lactobacillus" includes bacteria that were classified under the genus Lactobacillus before the reclassification of the genus. For example, with the reclassification of the Lactobacillus genus, new genera have been added: Acetilactobacillus, Agrilactobacillus, Amylolactobacillus, Apilactobacillus, Bombilactobacillus, Companilactobacillus, Dellaglioa, Fructilactobacillus, Furfurilactobacillus, Holzapfelia, Lacticaseibacillus, Lactiplantibacillus, and Lapidilactobacillus. This includes bacteria classified under genera such as Lapidilactobacillus, Latilactobacillus, Lentilactobacillus, Levilactobacillus, Ligilactobacillus, Limosilactobacillus, Liquorilactobacillus, Loigolactobacillus, Paralactobacillus, Paucilactobacillus, Schleiferilactobacillus, and Secundilactobacillus.

[0018] Among the above, bacteria of the following genera are preferred: Oenococcus, Bifidobacterium, Lentilactobacillus, Weissella, Tetragenococcus, Lactococcus, Leuconostoc, Pediococcus, Enterococcus, Lactobacillus, Lactiplantibacillus, Lacticaseibacillus, and Limosilactobacillus.

[0019] While not limited to specific species, the genus Oenococcus includes, for example, Oenococcus oeni. A specific example of Oenococcus is Oenococcus oeni JCM 6125.

[0020] Examples of Bifidobacterium species include, but are not limited to, Bifidobacterium animalis subsp. lactis, Bifidobacterium pseudolongum, Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium longum subsp. infantis, and Bifidobacterium longum subsp. longum. Specific examples of Bifidobacterium species include Bifidobacterium animalis subspecies lactis JCM 10602, Bifidobacterium animalis subspecies lactis BB-12, Bifidobacterium longum subspecies infantis JCM 1222, Bifidobacterium longum subspecies infantis M-63, Bifidobacterium longum subspecies longum BB536, Bifidobacterium longum subspecies longum N61, Bifidobacterium bifidum OLB 6378, Bifidobacterium breve M-16V, Bifidobacterium breve MCC 1274, and Bifidobacterium pseudolongum JCM Examples include 1205 and Bifidobacterium longum subspecies longum JCM 11340.

[0021] Weissella species are not limited to those listed, but examples include Weissella paramesenteroides and Weissella viridescens. Specific examples of Weissella species include Weissella paramesenteroides JCM 9890 and Weissella viridescens JCM 1174.

[0022] While not particularly limited, examples of Tetragenococcus species include Tetragenococcus halophilus. Specific examples of Tetragenococcus species include Tetragenococcus halophilus NRIC 0098 and Tetragenococcus halophilus No. 1.

[0023] Examples of Lactococcus species include, but are not limited to, Lactococcus lactis, Lactococcus lactis subsp. lactis, Lactococcus garvieae, Lactococcus lactis subsp. cremoris, Lactococcus lactis subsp. hordniae, and Lactococcus plantarum.

[0024] Specific examples of Lactococcus species include Lactococcus lactis subspecies lactis JCM 5805, Lactococcus lactis subspecies lactis NBRC 12007, Lactococcus lactis subspecies lactis NRIC 1150, Lactococcus lactis subspecies lactis JCM 20101, Lactococcus lactis subspecies lactis JCM 7638, Lactococcus lactis subspecies lactis ATCC 7963, Lactococcus lactis subspecies lactis ATCC 7962, Lactococcus lactis subspecies lactis ATCC 29146, and Lactococcus lactis subspecies lactis ATCC 27861, Lactococcus lactis subspecies lactis ATCC 19435, Lactococcus lactis subspecies lactis ATCC 15346, Lactococcus lactis subspecies lactis ATCC 13675, Lactococcus lactis subspecies lactis ATCC 12929, Lactococcus lactis subspecies lactis ATCC 11955, Lactococcus lactis subspecies lactis ATCC 11454, Lactococcus lactis subspecies lactis ATCC 11007, Lactococcus garvieae NBRC 100934, Lactococcus lactis subspecies cremoris JCM Examples include Lactococcus lactis subspecies cremoris NBRC 100676, Lactococcus lactis subspecies heldniae JCM 1180, Lactococcus lactis subspecies heldniae JCM 11040, and Lactococcus plantarum JCM 11056.

[0025] Examples of Leuconostoc species include Leuconostoc carnosum and Leuconostoc lactis. Specific examples of Leuconostoc species include Leuconostoc carnosum JCM 9695 and Leuconostoc lactis NBRC 12455.

[0026] Examples of species belonging to the genus Pediococcus include, but are not limited to, Pediococcus acidilactici, Pediococcus pentosaceus, Pediococcus cellicola, Pediococcus claussenii, Pediococcus damnosus, Pediococcus ethanolidurans, Pediococcus inopinatus, Pediococcus parvulus, and Pediococcus stilesii. Specific examples of Pediococcus species include Pediococcus acidilactici JCM 2014, Pediococcus acidilactici JCM 8797, Pediococcus acidilactici K15, Pediococcus pentosaceus JCM 5890, and Pediococcus damnosus JCM 5886.

[0027] While not limited to all species, *Streptococcus* species include *Streptococcus thermophilus*. A specific example of *Streptococcus* species is *Streptococcus thermophilus* SBC 8781.

[0028] Enterococcus species are not limited to these, but examples include Enterococcus alcedinis and Enterococcus faecalis. Specific examples of Enterococcus species include Enterococcus faecalis EC-12, Enterococcus faecalis JCM 5803T, Enterococcus faecalis JCM 20307, ​​Enterococcus faecium JCM 5804T, and Enterococcus faecium JCM 8903.

[0029] While not particularly limited to Lactobacillus species, examples include Lactobacillus paracasei, Lactobacillus paracasei subsp. paracasei, Lacticaseibacillus paracasei subsp. paracasei, Lactobacillus delbrueckii, Lactobacillus casei, Lacticaseibacillus casei, Lactobacillus fructivorans, and Lactobacillus hilgardii. Lactobacillus hilgardii), Lactobacillus rhamnosus, Lacticaseibacillus rhamnosus, Lactobacillus gasseri, Lactobacillus acidophilus, Lactobacillus bulgaricus, Lactobacillus parakefiri, Lentilactobacillus parakefiri, Lactobacillus plantarum, Lactiplantibacillus plantarum, Lactobacillus plantarum subsp. Lactiplantibacillus plantarum subsp.Examples include Lactobacillus plantarum, Lactobacillus pentosus, Lactiplantibacillus pentosus, Lactobacillus helveticus, Limosilactobacillus reuteri subsp. reuteri, Lactobacillus crispatus, and Lactobacillus johnsonii.

[0030] Specific examples of Lactobacillus species include Lactobacillus (Lacticaseibacillus in the new classification) paracasei KW3110, Lactobacillus paracasei MCC 1849, Lactobacillus paracasei K71, Lactobacillus paracasei K-2, Lactobacillus rhamnosus GG, Lactobacillus rhamnosus CRL 1505, Lactobacillus (Lacticaseibacillus in the new classification) rhamnosus JCM 1136, Lactobacillus gasseri SBT 2055, Lactobacillus gasseri OLL 2716, Lactobacillus gasseri PA-3, Lactobacillus acidophilus L-92, and Lactobacillus casei subspecies casei. 327, Lactobacillus (new classification: Lacticaseibacillus) casei Shirota, Lactobacillus (new classification: Lacticaseibacillus) casei JCM 1134, Lactobacillus (new classification: Lacticaseibacillus) paracasei subspecies paracasei JCM 1053, Lactobacillus bulgaricus OLL1073R-1, Lactobacillus bulgaricus 2038, Lactobacillus (new classification: Lentilactobacillus) parakefiri JCM 8573, Lactobacillus (new classification: Lactipruntilabacillus) plantarum L-137, Lactobacillus (new classification: Lactipruntilabacillus) plantarum subspecies plantarum JCM 1149, Lactobacillus (new classification: Lactipruntilabacillus) pentosa ONRICb Examples include Lactobacillus acidophilus JCM 1021, Lactobacillus acidophilus JCM 1132, Lactobacillus helveticus JCM 1003, Rimosilactobacillus reuteri subspecies reuteri JCM 1112, Lactobacillus crispatus JCM 1185, and Lactobacillus johnsonii JCM 2012.

[0031] While not limited to all species, the genus Hendrickxia includes species such as Hendrickxia coagulans (also known as Bacillus coagulans). Specific examples of Hendrickxia species include Hendrickxia (Bacillus) coagulans SANK 70258 and Hendrickxia (Bacillus) coagulans BC99.

[0032] The acetic acid bacteria are not particularly limited, but examples include bacteria of the genus Gluconacetobacter, Acetobacter, and Gluconobacter, with Gluconacetobacter being preferred, Gluconacetobacter hanzenii being more preferred, and Gluconacetobacter hanzenii GK-1 being even more preferred.

[0033] In addition to the above, the lactic acid bacteria may also be of the genera Akkermansia, Bacteroides, Blautia, Clostridium, Collinsella, Faecalibacterium, Faecalicatena, Lacrimispora, Paeniclostridium, Parabacteroides, or Roseburia.

[0034] Specific examples of fungi belonging to the genus Akkermansia include, for instance, Akkermansia muciniphila JCM 30893.

[0035] Specific examples of Bacteroides species include, for example, Bacteroides caccae JCM 9498T, Bacteroides fragilis JCM 11019T, Bacteroides fragilis JCM 11017, Bacteroides fragilis JCM 17586, Bacteroides fragilis JCM 17587, Bacteroides ovatus JCM 5824T, Bacteroides setaiotaomicron ATCC 29148T, Bacteroides setaiotaomicron ATCC 29741, Bacteroides setaiotaomicron ATCC 12290, Bacteroides uniformis JCM 5828T, Bacteroides uniformis JCM 13286, and Bacteroides uniformis JCM Examples include 13287 and Bacteroides uniformis JCM 13288.

[0036] Specific examples of Blautia species include, for example, Blautia acetategigens JCM 34803T, Blautia ammonialitica JCM 34802T, Blautia algi JCM 31394T, Blautia caecimulis JCM 34498T, Blautia coccoides JCM 1395T, Blautia fexis JCM 17205T, Blautia gluceracea JCM 17039T, Blautia hansenii JCM 14655, Blautia hansenii JCM 35484, Blautia hominis JCM 32276T, Blautia hydrogenotropica JCM 31266, Blautia liqualis JCM 34225T, and Blautia lutii JCM Examples include 17040T, Brautia obeum JCM 31340, Brautia producta JCM 1471T, Brautia pseudococcoides JCM 35243T, Brautia cinckii JCM 14657T, Brautia vexlerae JCM 31267, and Brautia vexlerae JCM 35486.

[0037] Specific examples of bacteria belonging to the genus Clostridium include, for example, Clostridium butyricum JCM NT, Clostridium nexile JCM 31500T, and Clostridium symbiosum JCM 1297T, etc.

[0038] Specific examples of bacteria belonging to the genus Collinsella include, for example, Collinsella aerofaciens JCM 10188T, Collinsella intestinalis JCM 10643T, Collinsella stercoris JCM 10641T, and Collinsella tanakaei JCM 16071T, etc.

[0039] Specific examples of bacteria belonging to the genus Faecalibacterium include, for example, Faecalibacterium hathewayi JCM 39210, Faecalibacterium longum JCM 39208, Faecalibacterium prausnitzii JCM 31915, Faecalibacterium prausnitzii JCM 39207, and Faecalibacterium prausnitzii JCM 39209, etc.

[0040] Specific examples of bacteria belonging to the genus Faecalicatena include, for example, Faecalicatena oroticum JCM 1429T, etc.

[0041] Specific examples of bacteria belonging to the genus Lacrimispora include, for example, Lacrimispora selenoides JCM 15734T, Lacrimispora sphenoides JCM 1415T, and Lacrimispora xylanolitica JCM 15735T, etc.

[0042] Specific examples of bacteria belonging to the genus Paeniclostridium include, for example, Paeniclostridium sordellii JCM 3814T, etc.

[0043] Specific examples of bacteria belonging to the genus Parabacteroides include, for example, Parabacteroides meldae JCM 9497T.

[0044] Specific examples of fungi belonging to the genus Roseburia include, for example, Roseburia hominis JCM 17582, Roseburia intestinalis JCM 17583, and Roseburia inulinovorans JCM 17584.

[0045] The bacterial strains listed above can be obtained from public depositary institutions, etc. For example, the JCM strain can be obtained from the Microbial Materials Development Laboratory, BioResource Center, RIKEN (3-1-1 Takanodai, Tsukuba, Ibaraki Prefecture), the NBRC strain from the Biological Genetics Division, National Institute of Technology and Evaluation (2-5-8 Kazusa-Kamatari, Kisarazu, Chiba Prefecture), the NRIC strain from the Strain Preservation Room, Tokyo University of Agriculture (1-1-1 Sakuragaoka, Setagaya-ku, Tokyo), and the ATCC strain from the American Type Culture Collection (USA).

[0046] The lactic acid bacteria relating to this disclosure may be, for example, lactic acid bacteria other than those of the genus Lactobacillus, and may also be lactic acid bacteria other than Lactobacillus pentosus, Lactobacillus casei, and Lactobacillus paracasei.

[0047] In a preferred embodiment, the lactic acid bacteria relating to this disclosure may be bacteria belonging to any one of the genera Lactococcus, Lactobacillus, Bifidobacterium, Pediococcus, Hendricksia, or Leuconostoc, from the viewpoint of increasing the amount phagocytosed by immune cells, increasing the glutathione concentration in immune cells, protecting immune cells, and / or suppressing the decrease of immune cells. Among these, the lactic acid bacteria relating to this disclosure are more preferably Lactococcus bacteria from the viewpoint of increasing the amount phagocytosed by immune cells, increasing the glutathione concentration in immune cells, protecting immune cells, and / or suppressing the decrease of immune cells.

[0048] In a more preferred embodiment of this disclosure, the lactic acid bacteria include Lactococcus lactis subsp. lactis JCM 5805 or its mutants, Bifidobacterium longum subsp. longum JCM 11340, Lactobacillus acidophilus JCM 1021, Lactobacillus helveticus JCM 1003, and Limosilactobacillus reuteri subsp. reuteri JCM. 1112, Lacticaseibacillus paracasei subsp. paracasei JCM 1053, Lacticaseibacillus casei JCM 1134, Lactobacillus crispatus JCM 1185, Lactobacillus johnsonii JCM 2012, Pediococcus acidilactici JCM 2014, Pediococcus acidilactici JCM 8797, Pediococcus pentosaceus JCM 5890, Lactobacillus acidophilus JCM 1132, Lacticaseibacillus rhamnosus JCM 1136, Lactiplantibacillus plantarum subsp.The lactic acid bacterium may be at least one selected from the group consisting of Lactobacillus plantarum JCM 1149 and Lactobacillus plantarum L-137. When the lactic acid bacterium is at least one selected from this group, it can suitably increase glutathione concentration in immune cells.

[0049] In one particularly preferred embodiment of this disclosure, the lactic acid bacteria may be Lactococcus lactis subspecies lactis JCM 5805 or a mutant thereof, with respect to the amount of phagocytosis by immune cells, the increase in glutathione concentration within immune cells, the protection of immune cells and / or the suppression of immune cell decline, and in one most preferred embodiment, it may be Lactococcus lactis subspecies lactis JCM 5805. As described above, Lactococcus lactis subspecies lactis JCM 5805 can be obtained from the Laboratory of Microbial Materials Development, BioResource Center, RIKEN, but in this invention, the same strain of Lactococcus lactis subspecies lactis JCM 5805 stored in a storage facility other than the Laboratory of Microbial Materials Development, RIKEN can be used. Specifically, the same strain of Lactococcus lactis subspecies lactis JCM 5805 can be obtained from the National Institute of Technology and Evaluation (NIITE) Biological Genetics Division (2-5-8 Kazusa-Kamatari, Kisarazu City, Chiba Prefecture), Tokyo University of Agriculture Strain Preservation Room (1-1-1 Sakuragaoka, Setagaya-ku, Tokyo), and the American type culture collection (USA), among others. Lactococcus lactis subspecies lactis JCM 5805 is deposited in the American type culture collection as Lactococcus lactis subspecies lactis ATCC 9936 and Lactococcus lactis subspecies lactis ATCC 19435.

[0050] The mutant strain of Lactococcus lactis subspecies lactis JCM 5805 only needs to have properties that can achieve the objectives of this technology (for example, properties that allow it to be phagocytosed by immune cells, properties that increase glutathione concentration in immune cells, properties that protect immune cells and / or suppress the decrease of immune cells, etc.). Furthermore, it is preferable that the mutant strain has the same mycological properties as Lactococcus lactis subspecies lactis JCM 5805 and possesses phagocytic ability by immune cells, ability to increase glutathione concentration in immune cells, and ability to protect immune cells and / or suppress the decrease of immune cells that is equal to or greater than that of Lactococcus lactis subspecies lactis JCM 5805. Whether a particular mutant strain possesses "phagocytic ability by immune cells, ability to increase glutathione concentration in immune cells, ability to protect immune cells and / or suppress the decrease of immune cells" equivalent to or greater than that of Lactococcus lactis subspecies lactis JCM 5805 can be confirmed, for example, by the evaluation method described later or by the method of the examples described later.

[0051] Such mutant strains may be constructed by non-artificially introducing mutations into the above-mentioned Lactococcus lactis subspecies lactis JCM 5805. Alternatively, such mutant strains may be constructed by artificially introducing mutations into the above-mentioned Lactococcus lactis subspecies lactis JCM 5805, for example by introducing mutations into the above-mentioned bacterium by treatment with a mutagens such as ultraviolet light (UV) or DNA alkylating agents, or by introducing mutations into the above-mentioned strain by known genetic engineering methods such as genetic recombination or gene editing represented by CRISPR-Cas9.

[0052] The lactic acid bacteria relating to this disclosure may be live or dead, and in one embodiment may be dead. If the lactic acid bacteria relating to this disclosure are dead, they can be produced by, for example, killing live bacteria by heat treatment, pressurization treatment, high-pressure steam treatment, electromagnetic wave treatment, electron beam treatment, radiation treatment, ultraviolet treatment, alcohol treatment, or electrolyzed water treatment, and then drying them as necessary by freeze-drying, spray drying, drum drying, hot air drying, or vacuum drying.

[0053] <Immune cells> The immune cells relating to this disclosure are cells involved in the immune system. The immune cells relating to this disclosure may be, for example, cells involved in the innate immune system and / or the adaptive immune system, the adaptive immune system may be, for example, cellular immunity and / or humoral immunity. In one embodiment, the immune cells may be cells involved in the innate immune system. In a preferred embodiment, the immune cells may be immune cells having phagocytic ability. In a preferred embodiment, the immune cells may include, or may be dendritic cells. In another preferred embodiment, the immune cells may include, or may be such cells, cells involved in cytokine production and / or antigen presentation, the cytokine may be, for example, interferon-alpha (IFN-α). In these, the involvement may be, for example, enhanced. The immune cells may be at least one selected from the group consisting of, for example, plasmacytoid dendritic cells (pDCs), myeloid dendritic cells (mDCs), neutrophils and macrophages. In a more preferred embodiment, the immune cells may be at least one selected from the group consisting of plasmacytoid dendritic cells (pDCs) and myeloid dendritic cells (mDCs) from the viewpoint of the amount of lactic acid bacteria phagocytosed, the effect of lactic acid bacteria on increasing intracellular glutathione concentration, the cytoprotective effect of lactic acid bacteria, and / or the effect of lactic acid bacteria on suppressing cell loss. In a particularly preferred embodiment, the immune cells may be plasmacytoid dendritic cells (pDCs) from the viewpoint of the amount of lactic acid bacteria phagocytosed, the effect of lactic acid bacteria on increasing intracellular glutathione concentration, the cytoprotective effect of lactic acid bacteria, and / or the effect of lactic acid bacteria on suppressing cell loss.

[0054] Plasmacytoid dendritic cells (pDCs), also known as plasmacytoid dendritic cells, are a type of dendritic cell that constitutes the innate immune system. pDCs are the main producers of the cytokine type I interferon in the body and play an extremely important role in the body's defense. Type I interferon exhibits inhibitory activity against viruses and other pathogens. Through the production of type I interferon, pDCs are involved in the activation of immune cells such as NK cells, killer T cells, helper T cells, and B cells.

[0055] The effects of lactic acid bacteria on immune cells (e.g., increase in glutathione concentration in immune cells, protection of immune cells, and / or suppression of immune cell decline) may be evaluated, for example, using primary cultured cells, cell lines, or model cells of the immune cells, and these cells may be, for example, derived from humans or non-human animals, and in one embodiment, may be derived from humans. For example, if immune cells are pDCs, the effects of lactic acid bacteria on pDCs (e.g., increasing glutathione concentration in pDCs, protecting pDCs, and / or suppressing pDC decline) may be evaluated using, for example, primary cultured cells, cell lines, or model cells of pDCs, and these cells may be, for example, derived from humans or non-human animals, and in one embodiment may be derived from humans.

[0056] In a particular embodiment, the effect of lactic acid bacteria on pDCs may be evaluated using CAL-1 cells. CAL-1 cells are a cancer cell line of human plasmacytoid dendritic cells (pDCs) established from tumor cells in the peripheral blood of patients, and are deposited with the National Institute of Technology and Evaluation (NITE) Biotechnology Center Patent Microorganism Depository Center (NPMD, Japan) under depositary number FERM BP-10914. CAL-1 cells are expected to be applied to the search for substances involved in the immune response in humans or drugs that control the antigen-presenting function of dendritic cells (Japanese Patent Publication No. 2007-044008).

[0057] Myeloid dendritic cells (mDCs) are a type of dendritic cell that constitutes the innate immune system. mDCs are dendritic cells that arise from the differentiation of myeloid progenitor cells. In addition to antigen presentation, mDCs also secrete cytokines as their primary function.

[0058] The effects of lactic acid bacteria on mDCs (e.g., increase in glutathione concentration in mDCs, protection of mDCs, and / or suppression of mDC decline) may be evaluated using, for example, primary cultured mDC cells, cell lines, or model cells, and these cells may be, for example, derived from humans or non-human animals.

[0059] In a particular embodiment, the effect of lactic acid bacteria on mDCs may be evaluated using bone marrow-derived dendritic cells (BMDCs). BMDCs are dendritic cells containing pDCs and mDCs obtained by culturing bone marrow cells, and are particularly rich in mDCs. BMDCs are commonly used when evaluating the effects of a substance on pDCs and mDCs. Therefore, the effects of lactic acid bacteria on pDCs and mDCs can be evaluated based on their effects on BMDCs. For example, lactic acid bacteria that cause an increase in glutathione concentration in BMDCs can be evaluated as lactic acid bacteria that cause an increase in glutathione concentration in pDCs and mDCs. Also, for example, lactic acid bacteria that show a protective effect on BMDCs can be evaluated as lactic acid bacteria that show a protective effect on pDCs and mDCs. Furthermore, for example, lactic acid bacteria that suppress the decrease of BMDCs can be evaluated as lactic acid bacteria that suppress the decrease of pDCs and mDCs.

[0060] The immune cells according to one aspect may be peripheral blood mononuclear cells (PBMCs) from the perspective of the phagocytic capacity of lactic acid bacteria, the effect of increasing the intracellular glutathione concentration by lactic acid bacteria, the cell protection effect by lactic acid bacteria, and / or the effect of suppressing cell reduction by lactic acid bacteria. PBMCs are a general term for monocytes contained in peripheral blood. PBMCs contain dendritic cells and the like at a low ratio, while the majority of cells are cells directly responsible for the defense mechanism in the immune system, such as NK cells, killer T cells, helper T cells, and B cells. Therefore, it can be said that the influence of lactic acid bacteria on PBMCs and / or the immune cells contained therein strongly reflects the influence of lactic acid bacteria on a wide range of immune cells, not limited to dendritic cells. The influence of lactic acid bacteria on PBMCs and / or the immune cells contained therein can be evaluated using PBMCs isolated according to a conventional method from peripheral blood collected from, for example, humans or non-human animals. In one aspect, it may also be evaluated using isolated human-derived PBMCs.

[0061] <Phagocytosis> Phagocytosis is a phenomenon that occurs when a cell takes in relatively large objects such as solid particles, other cells, and bacteria. In phagocytosis, the cell extends its cell membrane to wrap around the object and takes it into the cell. After that, the vesicle (phagosome) containing the ingested object fuses with the lysosome to decompose the contents.

[0062] The lactic acid bacteria relating to this disclosure are lactic acid bacteria that are phagocytosed by immune cells. Whether lactic acid bacteria are phagocytosed by immune cells can be evaluated according to the evaluation method using lactic acid bacteria labeled with a fluorescent or fluorescent dye described later, for example, based on the detection of fluorescence from within immune cells or the increase in fluorescence intensity within immune cells over time. Alternatively, whether lactic acid bacteria are phagocytosed by immune cells can be evaluated, for example, by the decrease in uptake of lactic acid bacteria by immune cells when phagocytosis by immune cells is inhibited. More specifically, for example, if the efficiency of uptake by immune cells whose phagocytosis is inhibited by an actin polymerization inhibitor (e.g., cytochalasin D, latruncrin B) is significantly lower than the efficiency of uptake by immune cells whose polymerization is not inhibited, then the lactic acid bacteria can be evaluated as phagocytosed by immune cells. The efficiency of uptake of lactic acid bacteria by immune cells may be indicated, for example, by the amount of uptake at a predetermined time after the addition of lactic acid bacteria to immune cells.

[0063] The lactic acid bacteria relating to this disclosure may be lactic acid bacteria whose amount phagocytosed by immune cells is 0.01 times or more, 0.1 times or more, 0.3 times or more, 0.5 times or more, 0.7 times or more, 0.9 times or more, 1.0 times or more, 1.1 times or more, 1.2 times or more, 1.5 times or more, or 2.0 times or more than the amount phagocytosed by immune cells of Lactococcus lactis subsp. lactis JCM 5805. Furthermore, the lactic acid bacteria relating to this disclosure may be lactic acid bacteria in which the amount phagocytosed by immune cells is more than 1.0 times, 1.2 times or more, 1.5 times or more, 2.0 times or more, 3.0 times or more, 4.0 times or more, 5.0 times or more, 7.0 times or more, 10 times or more, 15 times or more, 20 times or more, 25 times or more, 30 times or more, 35 times or more, 40 times or more, 45 times or more, 50 times or more, 60 times or more, 100 times or more, 200 times or more, 300 times or more, or 500 times or more than the amount phagocytosed by immune cells of Lactococcus lactis subsp. lactis ATCC 15577.

[0064] In these cases, the amount of phagocytosis by immune cells is not particularly limited as long as it is an index value indicating the amount of phagocytosis by immune cells, and the evaluation of the amount of phagocytosis by immune cells can be done using methods that are commonly used by those skilled in the art to measure the amount of phagocytosis. For example, the amount of phagocytosis by immune cells may be the fluorescence intensity of immune cells measured after contact with lactic acid bacteria labeled with a fluorescent dye or fluorescent dye. As a more detailed example, the amount of phagocytosis by immune cells can be evaluated using the fluorescence detected from immune cells as an indicator when lactic acid bacteria labeled with a fluorescent dye that becomes strongly fluorescent in the acidic environment of endosomes (e.g., pHrodo Red SE, Invitrogen, P36600) are in contact with immune cells for a sufficient time (e.g., 24 hours). As an indicator of fluorescence, one that is commonly used by those skilled in the art may be used. For example, one may use the area or percentage in a fluorescence image where the fluorescence intensity is greater than a predetermined value, the value obtained by multiplying the area value where the fluorescence intensity is greater than a predetermined value by the average fluorescence intensity, the average, median, or histogram of fluorescence intensity in a fluorescence image, a histogram of fluorescence intensity obtained by flow cytometry analysis, the percentage of cells included in the gate when gating is performed on fluorescence intensity, or the fluorescence intensity of bulk cells contained in a cell suspension or microwells for analysis using a microwell plate reader. Furthermore, the amount of phagocytosis by immune cells may be evaluated using the expression level of a biomarker whose expression level fluctuates in accordance with the amount of phagocytosis by immune cells as an indicator. The values ​​described above can be treated as "amount of phagocytosis by immune cells" in this disclosure.

[0065] The amount of phagocytosis by immune cells may be the amount evaluated by the method described below as "Evaluation method using lactic acid bacteria labeled with a fluorescent dye," as a detailed example. The amount of phagocytosis by immune cells may also be the amount evaluated by the method described in the examples, as a more detailed example.

[0066] [Evaluation method using lactic acid bacteria labeled with a fluorescent dye] (Phasophagous experiment) Using a serum-free medium (for example, RPMI-1640 medium (Sigma, R8758) supplemented with a final concentration of 1.0 vol% penicillin / streptomycin (Gibco, 15140-12)), a cell suspension containing immune cells (e.g., 5.0 × 10⁶) was prepared. 5 Prepare a cell suspension (e.g., 2.0 × 10⁶ cells / mL), seed the cell suspension into a culture dish, and culture for 16 hours. Then, collect the immune cells by pipetting. Resuspend the collected immune cells in the same medium (e.g., 2.0 × 10⁶ cells / mL). 5 The cells (cells / mL) are added and seeded at 200 μL / well in each well of a 96-well microplate. Lactobacillus stained with pHrodo Red SE (Invitrogen, P36600) by the method described below is added (e.g., final concentration of 10 μg / mL), and the fluorescence of pHrodo Red SE in each well is measured over time using the Incucyte® SX5 Live-Cell Analysis System (Sartorius).

[0067] (Staining of lactic acid bacteria with pHrodo Red SE) Dissolve pHrodo Red SE (Invitrogen, P36600) in DMSO to prepare a 10.2 mM solution. Weigh the bacterial powder into a 2 mL tube and add a 0.1 M sodium bicarbonate aqueous solution adjusted to pH 9.0 to prepare a 20 mg / mL lactic acid bacteria suspension. Transfer 95 μL of the lactic acid bacteria solution to a new 2 mL tube and add 5 μL of the 10.2 mM pHrodo Red SE prepared as described above. After dispersing the lactic acid bacteria by vortexing, cover with aluminum foil to protect from light and incubate at room temperature for 60 minutes. Then, add 1.5 mL of methanol (Wako Pure Chemical Industries, 131-01826), vortex, and centrifuge at 20,000 × g for 2 minutes at room temperature. Discard 1.55 mL of the supernatant, add 1.5 mL of PBS, and vortex to completely suspend the precipitate. After centrifugation again at room temperature under conditions of 20,000 × g for 2 minutes, discard 1.5 mL of the supernatant. Add 140 μL of PBS and suspend to prepare a 10 mg / mL bacterial suspension of stained lactic acid bacteria. Store in a light-shielded aluminum foil at 4°C until use. Dilute the stained lactic acid bacteria 10-fold with PBS immediately before use to prepare a 1 mg / mL bacterial suspension. Note that the stained lactic acid bacteria suspension should be used within 24 hours of preparation.

[0068] (Evaluation of phagocytic intake) The entire field of view (0.572 mm) to be evaluated was obtained from each well of the plate. 2 The amount of lactic acid bacteria phagocytosed by immune cells is quantified using the total area (fluorescence detection area) where fluorescence of pHrodo Red SE is detected as an indicator. Using the Incucyte® SX5 Live-Cell Analysis System (Sartorius), one image (0.572 mm) is used depending on the number of images to be evaluated. 2 ) fluorescence detection area per unit (e.g., μm) 2 Analyzing ( / image) allows for the evaluation of the phagocytic capacity. At this time, even if the stained lactic acid bacteria are not phagocytosed, they fluoresce slightly. Therefore, to eliminate the influence of fluorescence not due to phagocytosis, the Threshold value of the Orange Channel is set to 5.0. Also, depending on the type of lactic acid bacteria, the cells may form aggregates and fluoresce beyond the Threshold value even if not phagocytosed. Therefore, by setting the Area of the Filters of the Orange Channel to 20, the influence of overly large aggregates is eliminated.

[0069] Also, the phagocytic capacity of lactic acid bacteria by immune cells can be evaluated as follows, for example, in an evaluation method using lactic acid bacteria labeled with the above-described fluorescent or fluorescent dye. First, immune cells with the same number of cells (or the same cell concentration) are contacted with the lactic acid bacteria according to the present disclosure and control lactic acid bacteria under the same conditions for a certain period of time. Then, the lactic acid bacteria are removed from the medium, and the phagocytic capacity is evaluated using the fluorescence area per unit area of the observation field of a fluorescence microscope in the immune cells (e.g., μm 2 / image) as an index. In this case, the phagocytic capacity may be the average value of a plurality (2 or more, 3 or more, 5 or more, 7 or more, or 10 or more) of fields of view or a plurality (2 or more, 3 or more, 5 or more, 7 or more, or 10 or more) of samples. When evaluating the phagocytic capacity of the lactic acid bacteria according to the present disclosure by immune cells using the evaluation method using lactic acid bacteria labeled with the above-described fluorescent or fluorescent dye, the phagocytic capacity by immune cells is 10 μm 2 / image or more, 20 μm 2 / image or more, 30 μm 2 / image or more, 50 μm 2 / image or more, 100 μm 2 / image or more, 200 μm 2 / image or more, 400 μm 2 / image or more, 500 μm 2 / image or more, 600 μm 2 / image or more, 700 μm 2 / image or more, 800 μm 2 / image or more, or 900 μm 2 It can be greater than or equal to / image. Here, "image" is 0.572mm. 2 It means the field of view.

[0070] Furthermore, in the case of the lactic acid bacteria relating to this disclosure, for example, when the amount of phagocytosis by immune cells is evaluated using the evaluation method using lactic acid bacteria labeled with the above-mentioned fluorescent or fluorescent dye, the difference when the amount of phagocytosis by immune cells of the lactic acid bacteria minus the amount of phagocytosis by immune cells of the control lactic acid bacteria (e.g., Lactococcus lactis subspecies lactis ATCC 15577) is 1 μm. 2 / image or more, 20μm 2 / image or more, 50μm 2 / image or more, 70μm 2 / image or more, 100μm 2 / image or more, 140μm 2 / image or more, 200μm 2 / image or more, 300μm 2 / image or more, 400μm 2 / image or more, 500μm 2 / image or more, 600μm 2 / image or more, 700μm 2 / image or larger or 900μm 2 Lactic acid bacteria that are larger than / image are also acceptable. Here, "image" refers to 0.572 mm. 2 It means the field of view.

[0071] Thus, immune cells that engulf lactic acid bacteria may be immune cells that possess phagocytic ability. Whether an immune cell possesses phagocytic ability can be determined, for example, by performing a phagocytic evaluation using the immune cell and lactic acid bacteria known to be phagocytosed by immune cells, and judging that the lactic acid bacteria are phagocytosed.

[0072] <Increase in glutathione concentration> In this disclosure, for example, if a substance or method increases the glutathione concentration in immune cells by 0.01 mM or more, 0.02 mM or more, 0.04 mM or more, 0.06 mM or more, 0.09 mM or more, 0.12 mM or more, or 0.15 mM or more, it may be determined that the substance or method has increased the glutathione concentration in immune cells.

[0073] In this disclosure, for example, if the increase in glutathione concentration in immune cells caused by a certain substance or method is suppressed by inhibiting phagocytosis by the immune cells, for example by 0.10 mM or more, 0.20 mM or more, 0.30 mM or more, 0.40 mM or more, or 0.50 mM or more, the substance or method may be judged to increase glutathione concentration in immune cells, and in particular the substance or method may be judged to increase glutathione concentration in immune cells via phagocytosis by immune cells. Furthermore, in this disclosure, for example, if the increase in glutathione concentration in immune cells caused by a certain substance or method is suppressed by inhibiting phagocytosis by the immune cells, for example by 20% or more, 40% or more, 60% or more, 80% or more, or 100%, the substance or method may be judged to increase glutathione concentration in immune cells, and in particular the substance or method may be judged to increase glutathione concentration in immune cells via phagocytosis by immune cells. In these cases, inhibiting phagocytosis by immune cells may be done, for example, by treating the immune cells with actin polymerization inhibitors (e.g., cytochalasin D, latruncrin B).

[0074] An increase in intracellular glutathione concentration can occur, for example, through the induction of glutathione production, the promotion of reduction of oxidized glutathione, the inhibition of glutathione oxidation, and / or the inhibition of glutathione degradation. Thus, a substance or method for increasing glutathione concentration in immune cells may be, for example, a substance or method that induces glutathione production, promotes reduction of oxidized glutathione, inhibits glutathione oxidation, and / or inhibits glutathione degradation in immune cells.

[0075] The glutathione concentration in immune cells can be measured according to conventional methods, and the measurement method is not particularly limited. For example, the glutathione concentration in immune cells can be indirectly measured by labeling glutathione in the lysate of immune cells with a thiol-labeling dye (e.g., bromoviman), and then quantifying the labeled glutathione by chromatography using the absorbance of the dye, the fluorescence intensity of the dye, and / or the intensity of mass spectrometry as signals. In this case, the chromatography can be, for example, liquid-phase chromatography, or reverse-phase chromatography.

[0076] An increase in intracellular glutathione concentration can, without any particular limitations, lead to an increase in extracellular glutathione concentration. That is, an increase in extracellular glutathione concentration can result from the outflow of glutathione from the intracellular space. An increase in extracellular glutathione concentration can, without any particular limitations, be, for example, an increase in blood glutathione concentration. Extracellular glutathione concentration in immune cells can be measured according to conventional methods, and the measurement method is not particularly limited. For example, glutathione in plasma or immune cell culture medium can be labeled with a thiol-labeling dye (e.g., bromoviman), and then the labeled glutathione can be quantified by chromatography using the absorbance of the dye, the fluorescence intensity of the dye, and / or the intensity of mass spectrometry as signals, thereby indirectly measuring the glutathione concentration in immune cells. In this case, the chromatography can be, for example, liquid-phase chromatography, or it may be reverse-phase chromatography.

[0077] <Antioxidant effect; suppression of oxidative stress in cells> Glutathione is known to exhibit antioxidant activity and to suppress oxidative stress within cells. Therefore, substances and methods that increase glutathione in immune cells are also antioxidant substances and methods, for example, substances and methods that suppress antioxidant activity in immune cells. Furthermore, substances and methods that increase glutathione in immune cells are also substances and methods that suppress oxidative stress within cells, for example, substances and methods that suppress oxidative stress within immune cells. Antioxidant activity and the suppression of oxidative stress within cells can be measured according to conventional methods, and the measurement method is not particularly limited. For example, oxidative stress within immune cells can be indirectly measured by using a probe that emits fluorescence when oxidized (e.g., CellROX®) and detecting it with a fluorescence microscope or flow cytometry. For example, oxidative stress within immune cells can also be indirectly measured by measuring the amount of oxidized proteins, DNA, or lipids within cells. The amount of oxidized proteins can be evaluated, for example, by Western blotting using 2,4-dinitrophenylhydrazine (DNPH) and an anti-DNPH antibody. The amount of oxidized DNA can be indicated by, for example, the quantification of 8-oxoguanine produced by the oxidation of guanine using ELISA, or by quantifying nucleosides containing 8-oxoguanine after enzymatically differentiating DNA recovered from immune cells into nucleosides using high-performance liquid chromatography. The amount of oxidized lipids can be indicated by, for example, the indirect quantification of the amount of malondialdehyde contained in lipids recovered from immune cells by contacting it with thiobarbituric acid and quantifying the resulting substance using a colorimetric method. Furthermore, as mentioned above, glutathione exhibits antioxidant and oxidative stress inhibitory effects within cells, so the level of intracellular glutathione concentration may be used as an indicator to evaluate its antioxidant and intracellular oxidative stress inhibitory effects.

[0078] <Protection of immune cells and suppression of immune cell decline> In this disclosure, protection of immune cells means that, under physiological conditions, immune cells are more likely to increase in number compared to when they are not protected. In this disclosure, for example, if the number of immune cells is significantly higher when a substance or method is used compared to when it is not used, that substance or method may be evaluated as protecting immune cells or suppressing the decrease in immune cells. In this disclosure, for example, if the number of immune cells is 3% or more, 6% or more, 10% or more, 15% or more, 20% or more, or 30% or more when a substance or method is used compared to when it is not used, that substance or method may be evaluated as protecting immune cells or suppressing the decrease in immune cells. In this disclosure, for example, if the cell viability of immune cells is significantly higher when a perturbation that induces cell death (e.g., induction of apoptosis or inhibition of glutathione synthesis) is applied using a substance or method compared to when the same perturbation is applied using a substance or method, that substance or method may be evaluated as protecting immune cells or suppressing the decrease in immune cells. Furthermore, in this disclosure, for example, if the cell viability of immune cells is 3% or more, 6% or more, 10% or more, 15% or more, 20% or more, or 30% or more higher when the same perturbation is applied using a substance or method compared to when a perturbation that induces cell death (e.g., induction of apoptosis or inhibition of glutathione synthesis) is applied without using a substance or method, then the substance or method may be evaluated as protecting immune cells or suppressing the decrease of immune cells. In these cases, the method for evaluating cell number and cell viability is not particularly limited and can be evaluated, for example, by cell counting using a microscope, imaging or fluorescence intensity measurement after labeling living and / or dead cells, or by quantitative analysis of metabolites by adding substrates for living cell-specific enzymatic reactions (e.g., MTT ((3-(4,5-di-methylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, yellow tetrazole)) and its analogues, and WST (Water soluble Tetrazolium salts)).

[0079] Oxidative stress within cells causes cell death through mechanisms such as apoptosis. Therefore, it is believed that suppressing oxidative stress in cells protects those cells and / or inhibits their decline. Glutathione is also known to exhibit an inhibitory effect on oxidative stress within cells. Thus, substances or methods that increase glutathione levels in immune cells are also substances or methods that protect immune cells. Furthermore, substances or methods that increase glutathione levels in immune cells are also substances or methods that suppress the decline of immune cells.

[0080] Furthermore, it is known that glutathione concentrations in immune cells are lower in elderly individuals, and that this decrease in glutathione concentrations may be related to the decline in immune function in the elderly (Non-Patent Literature 2). A decrease in glutathione concentrations in immune cells may also lead to a decrease in the cell viability of immune cells. Therefore, substances or methods that increase glutathione in immune cells are also substances or methods that improve the cell viability of immune cells. Such substances or methods, for example, suppress the decrease in the cell viability of immune cells in a subject (e.g., a human). The decrease in the cell viability of immune cells can be measured according to conventional methods, and the measurement method is not particularly limited. For example, cell viability can be evaluated by cell counting using a microscope, imaging or fluorescence intensity measurement after labeling live and / or dead cells, or quantification of metabolites by adding substrates for live cell-specific enzymatic reactions (e.g., MTT ((3-(4,5-di-methylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, yellow tetrazole)) and its analogues, and WST (Water soluble Tetrazolium salts)).

[0081] Similarly, it is known that glutathione concentrations in immune cells are lower in elderly individuals, and that this decrease in glutathione concentrations may be related to the decline in immune function in the elderly (Non-Patent Literature 2). Therefore, it is considered that increasing glutathione concentration in individuals whose glutathione concentrations in immune cells have decreased due to aging or other factors is more effective in protecting immune cells and suppressing their decline. For example, if cells with low glutathione concentrations in immune cells (e.g., cells from elderly individuals) and cells with high glutathione concentrations in immune cells (e.g., cells from young individuals) are compared, and without the application of a certain substance or method, the cells with low glutathione concentrations in immune cells show a lower survival rate, while with the application of a certain substance or method, both show an increase in glutathione concentration and / or cell survival rate, and the increase is greater in the cells with low glutathione concentrations in immune cells, then the substance or method can be said to be more effective in protecting immune cells and / or suppressing their decline in individuals whose glutathione concentrations in immune cells have decreased.

[0082] <Composition> The first embodiment of this disclosure relates to a composition containing lactic acid bacteria. The lactic acid bacteria in this embodiment are lactic acid bacteria that are phagocytosed by immune cells. The composition of this embodiment may contain lactic acid bacteria as an active ingredient. The composition of this embodiment may contain an effective amount of lactic acid bacteria. In this disclosure, "<use> composition" can also be said to be "<use> agent".

[0083] The composition of this embodiment may be a composition for increasing glutathione concentration in immune cells. In this case, the composition for increasing glutathione concentration in immune cells may be a composition for inducing glutathione production in immune cells, a composition for promoting the reduction of oxidized glutathione, a composition for inhibiting the oxidation of glutathione, and / or a composition for inhibiting glutathione degradation. In this case, the composition of this embodiment may be used for at least one selected from the group consisting of protection of immune cells, inhibition of immune cell decline, antioxidant and inhibition of intracellular oxidative stress, and may be used for at least one selected from the group consisting of protection of immune cells and inhibition of immune cell decline, and may be used for at least one selected from the group consisting of antioxidant and inhibition of intracellular oxidative stress. The inventors have found that the effect of increasing glutathione concentration in immune cells is determined by the phagocytosis of lactic acid bacteria by immune cells.

[0084] The composition of this embodiment may be at least one composition selected from the group consisting of compositions for protecting immune cells, compositions for suppressing the decrease of immune cells, antioxidant compositions, and compositions for suppressing intracellular oxidative stress, and may be a composition for protecting immune cells and / or a composition for suppressing the decrease of immune cells, or an antioxidant composition and / or a composition for suppressing intracellular oxidative stress. In a preferred embodiment, the composition of this embodiment may be a composition for protecting immune cells and / or a composition for suppressing the decrease of immune cells. The inventors have found that when lactic acid bacteria are phagocytosed by immune cells, the immune cells are protected and the decrease of the immune cells is suppressed. In these cases, the composition of this embodiment may be used to increase the glutathione concentration in immune cells, for example, to induce glutathione production in immune cells, to promote the reduction of oxidized glutathione, to suppress the oxidation of glutathione and / or to suppress the degradation of glutathione.

[0085] The composition of this embodiment may increase the expression level of NRF2 protein in immune cells, and may be a composition for increasing the expression level of NRF2 protein in immune cells. The composition of this embodiment may increase the expression level of mRNA (messenger RNA) encoding NRF2 protein in immune cells, and may be a composition for increasing the expression level of mRNA encoding NRF2 protein in immune cells. NRF2 (NFE2-Related Factor 2, NFE2L2, Nuclear Factor Erythroid-Derived 2-Like 2) is a transcription factor that, by binding to antioxidant response elements (AREs) in the promoter region of target genes, enhances the expression of proteins responsible for defense mechanisms against oxidative stress, including antioxidant enzymes. Therefore, a composition that increases the expression level of NRF2 protein or mRNA encoding it in immune cells has the effect of activating the antioxidant mechanism of the immune cells and suppressing oxidative stress in the immune cells. In humans, the NRF2 protein has Ref.Seq. numbers designated by the National Center for Biotechnology Information (NCBI) of the National Institutes of Health (NIH): NP_006155.2 (isoform 1), NP_001138884.1 (isoform 2), NP_001300829.1 (isoform 2), NP_001300830.1 (isoform 2), NP_001138885.1 (isoform 3), NP_001300831.1 (isoform 4), NP_001300832.1 (isoform 5), and NP_00 The mRNA encoding is 1300833.1 (isoform 6), and its Ref.Seq. numbers are NM_006164.5 (isoform 1), NM_001145412.3 (isoform 2), NM_001313900.1 (isoform 2), NM_001313901.1 (isoform 2), NM_001145413.3 (isoform 3), NM_001313902.2 (isoform 4), NM_001313903.2 (isoform 5), and NM_001313904.1 (isoform 6).

[0086] The composition of this embodiment may increase the expression level of NRF2 protein or the mRNA encoding it in immune cells by, for example, 5% or more, 10% or more, 15% or more, 20% or more, 25% or more, 30% or more, 35% or more, 40% or more, 45% or more, or 50% or more compared to when the composition of this embodiment is not ingested or administered. The expression level of NRF2 protein in immune cells may be an amount evaluated according to a method commonly used by those skilled in the art, for example, an amount evaluated by ELISA after lysating immune cells. The expression level of mRNA encoding NRF2 protein in immune cells may be an amount evaluated according to a method commonly used by those skilled in the art, for example, an amount evaluated by RT-qPCR (Reverse Transcription Quantitative Polymerase Chain Reaction) of nucleic acid extracted from immune cells or in the lysate of immune cells, and as a detailed example, an amount evaluated according to the protocol performed in Example 5 of this disclosure.

[0087] In the composition of this embodiment, the lactic acid bacteria content is not particularly limited and only needs to be an amount that satisfies the effective amount for the composition's intended use (e.g., increasing glutathione concentration in immune cells). Therefore, it may vary depending on the form of the composition of this embodiment. For example, with respect to the total dry weight of the composition of this embodiment, the dry weight of lactic acid bacteria may be 0.0001% by mass or more, 0.001% by mass or more, 0.005% by mass or more, 0.01% by mass or more, 0.02% by mass or more, 0.05% by mass or more, 0.10% by mass or more, 0.30% by mass or more, 1.0% by mass or more, 1.5% by mass or more, 2.0% by mass or more, 2.5% by mass or more, 3.0% by mass or more, or 5.0% by mass or more. It may be 7.0% by mass or more, 10.0% by mass or more, 80.0% by mass or more, 90.0% by mass or more, 95.0% by mass or more, 99.0% by mass or more, or 100% by mass, and may also be 100% by mass or less, 95% by mass or less, 90% by mass or less, 80% by mass or less, 70% by mass or less, 60% by mass or less, 50% by mass or less, 30% by mass or less, 25% by mass or less, 20% by mass or less, or 15% by mass or less. These lower and upper limits can be combined arbitrarily. For example, with respect to the total dry weight of the composition of this embodiment, the dry weight of lactic acid bacteria may be 0.0001% to 100%, 0.0001% to 95%, 0.0001% to 90%, 0.0001% to 80%, 0.0001% to 70%, 0.0001% to 60%, 0.0001% to 50%, 0.0001% to 30%, 0.0001% to 25%, 0.0001% to 20%, or 0.0001% to 15%. , 0.0001 mass% to 10 mass%, 0.001 mass% to 100 mass%, 0.001 mass% to 95 mass%, 0.001 mass% to 90 mass%, 0.001 mass% to 80 mass%, 0.001 mass% to 70 mass%, 0.001 mass% to 60 mass%, 0.001 mass% or more 50 mass% or less, 0.001 mass% or more and 30 mass% or less, 0.001 mass% or more and 25 mass% or less, 0.001 mass% or more and 20 mass% or less, 0.001 mass% or more and 15 mass% or less, 0.001 mass% or more and 10 mass% or less, 0.005 mass% or more and 100 mass% or less, 0.005 mass% or more and 95 mass% or less, 0.0.005% to 90% of mass, 0.005% to 80% of mass, 0.005% to 70% of mass, 0.005% to 60% of mass, 0.005% to 50% of mass, 0.005% to 30% of mass, 0.005% to 25% of mass, 0.005% to 20% of mass, 0.005% to 15% of mass, 0.005% to 10% of mass, 0.01% to 100% of mass, 0.01% to 95% of mass, 0.01% to 90% of mass, 0.01% to 80% of mass, 0.0 1% to 70% by mass, 0.01% to 60% by mass, 0.01% to 50% by mass, 0.01% to 30% by mass, 0.01% to 25% by mass, 0.01% to 20% by mass, 0.01% to 15% by mass, 0.01% to 10% by mass, 0.02% to 100% by mass, 0.02% to 95% by mass, 0.02% to 90% by mass, 0.02% to 80% by mass, 0.02% to 70% by mass, 0.02% to 60% by mass, 0.02% to 50% by mass. Below, 0.02% by mass and below 30% by mass, 0.02% by mass and below 25% by mass, 0.02% by mass and below 20% by mass, 0.02% by mass and below 15% by mass, 0.02% by mass and below 10% by mass, 0.05% by mass and below 100% by mass, 0.05% by mass and below 95% by mass, 0.05% by mass and below 90% by mass, 0.05% by mass and below 80% by mass, 0.05% by mass and below 70% by mass, 0.05% by mass and below 60% by mass, 0.05% by mass and below 50% by mass, 0.05% by mass and below 30% by mass, 0.05% by mass and below 25% by mass, 0.05% by mass and below Above 20% by mass, 0.05% by mass but below 15% by mass, 0.05% by mass but below 10% by mass, 0.10% by mass but below 100% by mass, 0.10% by mass but below 95% by mass, 0.10% by mass but below 90% by mass, 0.10% by mass but below 80% by mass, 0.10% by mass but below 70% by mass, 0.10% by mass but below 60% by mass, 0.10% by mass but below 50% by mass, 0.10% by mass but below 30% by mass, 0.10% by mass but below 25% by mass, 0.10% by mass but below 20% by mass, 0.10% by mass but below 15% by mass, 0.10% by mass but below 10% by mass, 0.30% to 100% mass, 0.30% to 95% mass, 0.30% to 90% mass, 0.30% to 80% mass, 0.30% to 70% mass, 0.30% to 60% mass, 0.30% to 50% mass, 0.30% to 30% mass, 0.30% to 25% mass, 0.30% to 20% mass, 0.30% to 15% mass, 0.30% to 10% mass, 1.0% to 100% mass, 1.0% to 95% mass, 1.0% to 90% mass Below 1%, 1.0% to 80% of mass, 1.0% to 70% of mass, 1.0% to 60% of mass, 1.0% to 50% of mass, 1.0% to 30% of mass, 1.0% to 25% of mass, 1.0% to 20% of mass, 1.0% to 15% of mass, 1.0% to 10% of mass, 1.5% to 100% of mass, 1.5% to 95% of mass, 1.5% to 90% of mass, 1.5% to 80% of mass, 1.5% to 70% of mass, 1.5% to 60% of mass, 1.5% of mass... Quantity ≥ 50% but less than 50% of mass, 1.5% or more but less than 30% of mass, 1.5% or more but less than 25% of mass, 1.5% or more but less than 20% of mass, 1.5% or more but less than 15% of mass, 1.5% or more but less than 10% of mass, 2.0% or more but less than 100% of mass, 2.0% or more but less than 95% of mass, 2.0% or more but less than 90% of mass, 2.0% or more but less than 80% of mass, 2.0% or more but less than 70% of mass, 2.0% or more but less than 60% of mass, 2.0% or more but less than 50% of mass, 2.0% or more but less than 30% of mass, 2.0% or more but less than 25% of mass, 2.0% or more but less than 20% of mass Less than 10% of mass, 2.0% to 15% of mass, 2.0% to 10% of mass, 2.5% to 100% of mass, 2.5% to 95% of mass, 2.5% to 90% of mass, 2.5% to 80% of mass, 2.5% to 70% of mass, 2.5% to 60% of mass, 2.5% to 50% of mass, 2.5% to 30% of mass, 2.5% to 25% of mass, 2.5% to 20% of mass, 2.5% to 15% of mass, 2.5% to 10% of mass, 3.0% to 100% of mass, 3.0% to 95% mass, 3.0% to 90% mass, 3.0% to 80% mass, 3.0% to 70% mass, 3.0% to 60% mass, 3.0% to 50% mass, 3.0% to 30% mass, 3.0% to 25% mass, 3.0% to 20% mass, 3.0% to 15% mass, 3.0% to 10% mass, 5.0% to 100% mass, 5.0% to 95% mass, 5.0% and above mass. Below 90% mass, 5.0% to 80% mass, 5.0% to 70% mass, 5.0% to 60% mass, 5.0% to 50% mass, 5.0% to 30% mass, 5.0% to 25% mass, 5.0% to 20% mass, 5.0% to 15% mass, 5.0% to 10% mass, 7.0% to 100% mass, 7.0% to 95% mass, 7.0% to 90% mass, 7.0% to 80% mass and below Below, 7.0% quality or higher and below 70% quality, 7.0% quality or higher and below 60% quality, 7.0% quality or higher and below 50% quality, 7.0% quality or higher and below 30% quality, 7.0% quality or higher and below 25% quality, 7.0% quality or higher and below 20% quality, 7.0% quality or higher and below 15% quality, 7.0% quality or higher and below 10% quality, 10.0% quality or higher and below 10% quality, 10.0% quality or higher and below 100% quality, 10.0% quality or higher and below 95% quality, 10.0% quality or higher and below 90% quality, 10.0% quality or higher and below 80% quality, 10.0% quality or higher and below 70% quality. 、10.0% or more quality, 60% or less quality, 10.0% or more quality, 50% or less quality, 10.0% or more quality, 30% or less quality, 10.0% or more quality, 25% or less quality, 10.0% or more quality, 20% or less quality, 10.0% or more quality, 15% or less quality, 80.0% or more quality, 100% or more quality, 80.0% or more quality, 95% or less quality, 80.0% or more quality, 90% or more quality, 100% or more quality, 90% or more quality, 95% or more quality. (Also, 95.0% or more quality, 100% or less quality.)

[0088] When the composition of this application form is in liquid form, the number of lactic acid bacteria, 1.0×10 3 Cells / mL or higher, 1.0 × 10 4 Cells / mL or higher, 1.0 × 10 5 Cells / mL or more, 1.0×10 6 Cells / mL or more, 1.0×10 7 Cells / mL or more or 4.0 × 10 7 The concentration may be greater than or equal to 1.0 × 10⁻¹⁰ cells / mL. 11 Cells / mL or less, 1.0×10 10 Cells / mL or less, 3.0×10 9 Cells / mL or less or 1.0 × 10 9 The number of cells / mL or less may also be less. These lower and upper limits can be combined in any way and are not particularly limited. For example, the number of lactic acid bacteria contained in the composition according to this embodiment is 1.0 × 10⁶ 3 cells / mL or more 1.0×10 11 Cells / mL or less, 1.0×10 3 cells / mL or more 1.0×10 10 Cells / mL or less, 1.0×10 3 cells / mL or more 3.0×10 9 Cells / mL or less, 1.0×10 3 cells / mL or more 1.0×10 9 Cells / mL or less, 1.0×10 4 cells / mL or more 1.0×10 11 Cells / mL or less, 1.0×10 4 cells / mL or more 1.0×10 10 Cells / mL or less, 1.0×10 4 cells / mL or more 3.0×10 9 Cells / mL or less, 1.0×10 4 cells / mL or more 1.0×10 9 Cells / mL or less, 1.0×10 5 cells / mL or more 1.0×10 11 Cells / mL or less, 1.0×10 5 cells / mL or more 1.0×10 10 Cells / mL or less, 1.0×10 5 cells / mL or more 3.0×10 9 Cells / mL or less, 1.0×10 5 cells / mL or more 1.0×10 9 Cells / mL or less, 1.0×10 6 cells / mL or more 1.0×10 11 Cells / mL or less, 1.0×10 6 cells / mL or more 1.0×10 10 cells / mL or less, 1.0×10 6 cells / mL or more and 3.0×10 9 cells / mL or less, 1.0×10 6 cells / mL or more and 1.0×10 9 cells / mL or less, 1.0×10 7 cells / mL or more and 1.0×10 11 cells / mL or less, 1.0×10 7 cells / mL or more and 1.0×10 10 cells / mL or less, 1.0×10 7 cells / mL or more and 3.0×10 9 cells / mL or less, 1.0×10 7 cells / mL or more and 1.0×10 9 cells / mL or less, 4.0×10 7 cells / mL or more and 1.0×10 11 cells / mL or less, 4.0×10 7 cells / mL or more and 1.0×10 10 cells / mL or less, 4.0×10 7 cells / mL or more and 3.0×10 9 cells / mL or less or 4.0×10 7 cells / mL or more and 1.0×10 9 cells / mL or less may be present. In this case, the daily dosage or intake of the liquid composition may be 10 mL to 1,000 mL, 10 mL to 800 mL, 10 mL to 500 mL, 10 mL to 250 mL, 30 mL to 1,000 mL, 30 mL to 800 mL, 30 mL to 500 mL, 30 mL to 250 mL, 50 mL to 1,000 mL, 50 mL to 800 mL, 50 to 50 mL, 50 mL to 250 mL, 10 mL to 1,000 mL, 100 mL to 800 mL, 100 to 500 mL or [[ID=<

[0089] [[ID=<<000106>>In the composition of this embodiment, the number of lactic acid bacteria per unit package is 1.0×10 4 or more, 5.0×10 4 or more, 1.0×10 5 or more, 3.0×10 5 or more, 1.0×10 6 or more, 3.0×10 6 or more, 1.0×10 7 ​pcs or more, 3.0×10 7 pcs or more, 1.0×10 8 pcs or more, 3.0×10 8 pcs or more, 5.0×10 8 pcs or more, 1.0×10 9 pcs or more, 5.0×10 9 pcs or more, 1.0×10 10 pcs or more, 5.0×10 10 One or more or 1.0 × 10 11 There may be more than 1.0 × 10 14 pcs or less, 1.0×10 13 1 or fewer, or 1.0 × 10 12 The number may be less than or equal to 10. Furthermore, these upper and lower limits can be combined arbitrarily, and in the composition of this embodiment, the number of lactic acid bacteria per unit package is, for example, 1.0 × 10. 4 pcs or more 1.0×10 14 pcs or less, 1.0×10 4 pcs or more 1.0×10 13 pcs or less, 1.0×10 4 pcs or more 1.0×10 12 Less than or equal to 5.0×10 4 pcs or more 1.0×10 14 Less than or equal to 5.0×10 4 pcs or more 1.0×10 13 Less than or equal to 5.0×10 4 pcs or more 1.0×10 12 pcs or less, 1.0×10 5 pcs or more 1.0×10 14 pcs or less, 1.0×10 5 pcs or more 1.0×10 13 pcs or less, 1.0×10 5 pcs or more 1.0×10 12 pcs or less, 3.0×10 5 pcs or more 1.0×10 14 pcs or less, 3.0×10 5 pcs or more 1.0×10 13 pcs or less, 3.0×10 5 pcs or more 1.0×10 12 pcs or less, 1.0×10 6 pcs or more 1.0×10 14 pcs or less, 1.0×10 6 pcs or more 1.0×10 13 pcs or less, 1.0×10 6 More than 1.0 × 10 12 Less than 3.0 × 10 6 More than 1.0 × 10 14 Less than 3.0 × 10 6 More than 1.0 × 10 13 Less than 3.0 × 10 6 More than 1.0 × 10 12 Less than 1.0 × 10 7 More than 1.0 × 10 14 Less than 1.0 × 10 7 More than 1.0 × 10 13 Less than 1.0 × 10 7 More than 1.0 × 10 12 Less than 3.0 × 10 7 More than 1.0 × 10 14 Less than 3.0 × 10 7 More than 1.0 × 10 13 Less than 3.0 × 10 7 More than 1.0 × 10 12 Less than 1.0 × 10 8 More than 1.0 × 10 14 Less than 1.0 × 10 8 More than 1.0 × 10 13 Less than 1.0 × 10 8 More than 1.0 × 10 12 Less than 3.0 × 10 8 More than 1.0 × 10 14 Less than 3.0 × 10 8 More than 1.0 × 10 13 Less than 3.0 × 10 8 More than 1.0 × 10 12 Less than 5.0 × 10 8 More than 1.0 × 10 14 Less than 5.0 × 10 8 More than 1.0 × 10 13 Less than 5.0 × 10 8 More than 1.0 × 10 12 Less than 1.0 × 10 9 More than 1.0 × 10 14 Less than 1.0 × 10 9 More than 1.0 × 10 13 Less than 1.0 × 10 9 More than 1.0 × 10 12 Less than 5.0 × 10 9 pcs or more 1.0×10 14 Less than or equal to 5.0×10 9 pcs or more 1.0×10 13 Less than or equal to 5.0×10 9 pcs or more 1.0×10 12 pcs or less, 1.0×10 10 pcs or more 1.0×10 14 pcs or less, 1.0×10 10 pcs or more 1.0×10 13 pcs or less, 1.0×10 10 pcs or more 1.0×10 12 Less than or equal to 5.0×10 10 pcs or more 1.0×10 14 Less than or equal to 5.0×10 10 pcs or more 1.0×10 13 Less than or equal to 5.0×10 10 pcs or more 1.0×10 12 pcs or less, 1.0×10 11 pcs or more 1.0×10 14 pcs or less, 1.0×10 11 pcs or more 1.0×10 13 1 or less or 1.0 × 10 11 pcs or more 1.0×10 12 It may be one or fewer.

[0090] The administration or ingestion form of the composition according to this embodiment is not particularly limited, but from the viewpoint of reducing the burden on the recipient, oral administration or ingestion is preferred, and oral ingestion is more preferred. In this disclosure, oral ingestion means that the recipient actively takes in the composition orally. When used for oral administration or ingestion, the lactic acid bacteria and / or the composition containing them may have high resistance to gastric juice and intestinal juice, etc., and is not particularly limited, but for example, it is preferable that they have strong acid resistance.

[0091] The composition according to this embodiment may be intended for administration or ingestion by humans and / or non-human mammals, and in one embodiment may be intended for administration or ingestion by humans. In other words, the target to which the composition according to this embodiment is administered or ingested may be humans and / or non-human mammals, and may be humans.

[0092] The composition of this embodiment may be administered to or ingested by a subject that needs it, for example, by administering to or ingesting a subject that needs the composition's intended use (e.g., increasing glutathione concentration in immune cells). The subject that needs the composition's intended use (e.g., increasing glutathione concentration in immune cells) may be a healthy person or an unhealthy person. Furthermore, the subject that needs the composition's intended use (e.g., increasing glutathione concentration in immune cells) is not particularly limited, but examples include subjects with decreased glutathione concentration in immune cells, subjects aged 40 or older, 60 or older, or 65 or older, subjects infected with a virus, subjects who wish to prevent viral infection, subjects with a cold, subjects who wish to prevent a cold, subjects with reduced immune cells, subjects with reduced pDCs, subjects with reduced mDCs, subjects with reduced PBMCs, subjects who regularly experience fatigue or stress, subjects who habitually consume alcohol, and subjects whose immunity has been weakened by exercise.

[0093] In this disclosure, subjects with reduced glutathione concentration in immune cells may be subjects whose glutathione concentration in immune cells is lower compared to healthy individuals of the same race aged 20 to under 40 years. For example, subjects with reduced glutathione concentration in immune cells may be those whose glutathione concentration in immune cells is 90% or less, 80% or less, 70% or less, 60% or less, 50% or less, or 40% or less compared to healthy individuals of the same race aged 20 to under 40 years. Furthermore, subjects with reduced glutathione concentration in immune cells may be those whose average glutathione concentration in immune cells (e.g., lymphocytes) is 21.0 nmol / mg protein or less, 18.0 nmol / mg protein or less, 15.0 nmol / mg protein or less, 13.0 nmol / mg protein or less, or 10.0 nmol / mg protein or less, based on the amount of protein obtained when the immune cells are lysated. In these cases, the glutathione concentration in immune cells may be measured using a value obtained by standardizing the amount of glutathione quantified by high-performance liquid chromatography after, for example, lysating immune cells (e.g., lymphocytes) and labeling the glutathione contained in the lysate with monobromobiman, based on the mass of protein contained in the lysate.

[0094] Furthermore, it is known that glutathione levels in immune cells decrease with age in humans. For example, it has been reported that glutathione levels in immune cells decrease to about 80% in individuals aged 40-60 compared to those aged 20-40, and further decrease to about 60% in individuals aged 60-80 (e.g., Esther MM van Lieshout and Wilbert HM Peters, "Age and gender dependent levels of glutathione and glutathione S-transferases in humanlymphocytes", Carcinogenesis vol.19 no.10 pp.1873-1875, 1998). Therefore, in one embodiment, subjects with decreased glutathione levels in immune cells may be individuals aged 40 or older, 60 or older, 65 or older, or 68 or older.

[0095] The daily dose or intake of the composition according to this embodiment can be determined depending on the recipient's sex, age and weight, symptoms, administration time or intake time, dosage form, route of administration or intake, and the materials or drugs to be combined with it. The daily dose or intake of the composition according to this embodiment (for example, the daily dose or intake for an adult) is not particularly limited, but for example, based on the number of lactic acid bacteria, 1.0 × 10 4 pcs or more, 5.0×10 4 pcs or more, 1.0×10 5 pcs or more, 3.0×10 5 pcs or more, 1.0×10 6 pcs or more, 3.0×10 6 pcs or more, 1.0×10 7 pcs or more, 3.0×10 7 pcs or more, 1.0×10 8 pcs or more, 3.0×10 8 pcs or more, 5.0×10 8 pcs or more, 1.0×10 9 pcs or more, 5.0×10 9 One or more or 1.0 × 10 10 There may be more than 1.0 × 10 14 pcs or less, 1.0×10 13 1 or less or 1.0 × 10 12 The number may be less than or equal to 10. Furthermore, these upper and lower limits can be combined arbitrarily and are not particularly limited. For example, the daily dose or intake of the composition according to this embodiment (for example, the daily dose or intake for an adult) is 1.0 × 10 based on the number of lactic acid bacteria. 4 pcs or more 1.0×10 14 pcs or less, 1.0×10 4 pcs or more 1.0×10 13 pcs or less, 1.0×10 4 pcs or more 1.0×10 12 Less than or equal to 5.0×10 4 pcs or more 1.0×10 14 Less than or equal to 5.0×10 4 pcs or more 1.0×10 13 Less than or equal to 5.0×10 4 pcs or more 1.0×10 12 pcs or less, 1.0×10 5 pcs or more 1.0×10 14 pcs or less, 1.0×10 5 pcs or more 1.0×10 13 pcs or less, 1.0×10 5 pcs or more 1.0×10 12 pcs or less, 3.0×10 5 pcs or more 1.0×10 14 pcs or less, 3.0×10 5 pcs or more 1.0×10 13 pcs or less, 3.0×10 5 pcs or more 1.0×10 12 pcs or less, 1.0×10 6 pcs or more 1.0×10 14 pcs or less, 1.0×10 6 pcs or more 1.0×10 13 pcs or less, 1.0×10 6 pcs or more 1.0×10 12 pcs or less, 3.0×10 6 pcs or more 1.0×10 14 pcs or less, 3.0×10 6 pcs or more 1.0×10 13 pcs or less, 3.0×10 6 pcs or more 1.0×10 12 pcs or less, 1.0×10 7 pcs or more 1.0×10 14 pcs or less, 1.0×10 7 pcs or more 1.0×10 13 pcs or less, 1.0×10 7 pcs or more 1.0×10 12 pcs or less, 3.0×10 7 pcs or more 1.0×10 14 pcs or less, 3.0×10 7 pcs or more 1.0×10 13 pcs or less, 3.0×10 7 pcs or more 1.0×10 12 pcs or less, 1.0×10 8 pcs or more 1.0×10 14 pcs or less, 1.0×10 8 pcs or more 1.0×10 13 pcs or less, 1.0×10 8 pcs or more 1.0×10 12 pcs or less, 3.0×10 8 pcs or more 1.0×10 14 pcs or less, 3.0×10 8 pcs or more 1.0×10 13 pcs or less, 3.0×10 8 pcs or more 1.0×10 12 Less than or equal to 5.0×10 8 pcs or more 1.0×10 14 Less than or equal to 5.0×10 8 pcs or more 1.0×10 13 Less than or equal to 5.0×10 8 pcs or more 1.0×10 12 pcs or less, 1.0×10 9 pcs or more 1.0×10 14 pcs or less, 1.0×10 9 pcs or more 1.0×10 13 pcs or less, 1.0×10 9 pcs or more 1.0×10 12 Less than or equal to 5.0×10 9 pcs or more 1.0×10 14 Less than or equal to 5.0×10 9 pcs or more 1.0×10 13 Less than or equal to 5.0×10 9 pcs or more 1.0×10 12 pcs or less, 1.0×10 10 pcs or more 1.0×10 14 pcs or less, 1.0×10 10 pcs or more 1.0×10 13 1 or less or 1.0 × 10 10 pcs or more 1.0×10 12 The number of lactic acid bacteria may be less than or equal to 10. The number of lactic acid bacteria can be measured using a known microscope, flow cytometer, or non-culture microbial rapid testing device (e.g., ELESTA PixeeMo (AFI Technology Co., Ltd.)), but from the standpoint of high versatility, it may also be measured by microscope.

[0096] The daily dose or intake of the composition according to this embodiment is not particularly limited, but can be specified, for example, by the dry cell mass of lactic acid bacteria. The daily dose or intake of the composition according to this embodiment (for example, the daily dose or intake for an adult) is, for example, 2.5 × 10⁻⁶ -2 mg or more, 2.5×10 -1 It may be mg or more, 2.5 mg or more, or 2.5 × 10 mg or more, 2.5 × 10 4 mg or less, 2.5×10 3 mg or less, 2.5×10 2 mg or less or 1.0 × 10 2 The amount may be less than or equal to mg, and these upper and lower limits can be combined arbitrarily. The daily dose or intake of the composition according to this embodiment (for example, the daily dose or intake for an adult) is, for example, 2.5 × 10 -2 mg or more 2.5×10 4 mg or less, 2.5×10 -2 mg or more 2.5×10 3 mg or less, 2.5×10 -2 mg or more 2.5×10 2 mg or less, 2.5×10 -2 mg or more 1.0×10 2 mg or less, 2.5×10 -1 mg or more 2.5×10 4 mg or less, 2.5×10 -1 mg or more 2.5×10 3 mg or less, 2.5×10 -1 mg or more 2.5×10 2 mg or less, 2.5×10 -1 mg or more 1.0×10 2 mg or less, 2.5 mg or more 2.5×10 4 mg or less, 2.5 mg or more 2.5×10 3 mg or less, 2.5 mg or more 2.5×10 2 mg or less, 2.5 mg or more 1.0×10 2 mg or less, 2.5 x 10 mg or more 2.5 x 10 4 mg or less, 2.5 x 10 mg or more 2.5 x 10 3 mg or less, 2.5 x 10 mg or more 2.5 x 10 2 mg or less or 2.5 × 10 mg or more, 1.0 × 10 2 It may be less than or equal to mg.

[0097] The composition of this embodiment is preferably administered or ingested for the duration of the period during which the intended use of the composition (e.g., an increase in glutathione concentration in immune cells) is expected. From the viewpoint of better demonstrating the effects related to the intended use of the composition (e.g., an increase in glutathione concentration in immune cells), the administration or ingestion period of the above daily dose can be, for example, 1 day or more, 1 week or more, 2 weeks or more, 3 weeks or more, preferably 1 month or more (4 weeks or more). The administration interval or ingestion interval of the active ingredient of the present invention can be once every 3 days, once every 2 days, or once a day, with the above daily dose being preferably once a day.

[0098] The composition of this embodiment may be a food composition, a pharmaceutical composition, a quasi-drug, bacterial powder (such as a powder obtained by drying bacterial cells or a powder containing the same), an additive, or animal feed, and preferably a food composition or bacterial powder.

[0099] If the composition according to this embodiment is a food composition, the food composition may contain lactic acid bacteria in an effective amount. In other words, the food composition may contain lactic acid bacteria as an active ingredient. Here, "containing in an effective amount" means that when the amount normally consumed in each food composition is ingested, the active ingredient of the present invention is ingested to the extent that the effect related to the intended use of the composition (e.g., increasing glutathione concentration in immune cells) is exerted. Furthermore, the term "food composition" is used to include health foods, functional foods, nutritional supplements, health functional foods (e.g., foods for specified health uses, nutritional functional foods, foods with functional claims), foods for special dietary uses (e.g., foods for infants, foods for pregnant and lactating women, foods for the sick), and supplements. It goes without saying that when the active ingredient of the present invention is ingested by mammals other than humans, the food referred to in the present invention is used as feed.

[0100] The composition of this embodiment has effects related to its intended use (for example, increasing glutathione concentration in immune cells), and therefore can be provided by being included in foods consumed daily. In this case, the composition of this embodiment can be provided in a unit package form in which the amount to be consumed per serving is predetermined. Examples of unit package forms per serving include packs, packaging, cans, or bottles that specify a fixed amount. In order to better exert the various effects of the composition according to this embodiment, the amount to be consumed per serving may be determined according to the daily intake of lactic acid bacteria as described above. The food of this embodiment may be provided with information regarding the amount to be consumed displayed on the packaging, or together with a document containing such information.

[0101] The predetermined intake amount per serving in the unit packaging form may be the effective daily intake amount, or it may be the effective daily intake amount divided into two or more (preferably two to six) doses. Therefore, the unit packaging form of the composition of this embodiment can contain the active ingredient of the present invention in the amount of the daily intake amount described later, or it can contain the active ingredient of the present invention in an amount of one-half to one-sixth of the amount of the daily intake amount described later. For the convenience of intake, it is preferable to provide the composition of this embodiment in a unit packaging form per serving (i.e., a unit packaging form per day) in which the intake amount per serving is the effective daily intake amount.

[0102] The form of the "food composition" in this embodiment is not particularly limited and may be, for example, a beverage, a semi-liquid or gel-like form, a solid or powder-like form. Examples of "supplements" include tablets produced by mixing the active ingredient of this embodiment with excipients, binders, etc., and then compressing them; granules produced by granulating the active ingredient of the present invention with excipients, binders, etc.; orally disintegrating tablets; and capsules containing the active ingredient of the present invention enclosed in capsules, etc. When providing as a supplement, in addition to the above-mentioned per-serving or per-day unit packaging, it is also preferable to provide it in per-week, per-two-week, per-month, or per-two-month unit packaging. In the latter unit packaging, it is preferable to display, for example, the amount to be consumed per serving or per day, so that the consumer can effectively ingest the active ingredient of the present invention according to that indication.

[0103] If the food composition provided as a composition according to this embodiment is a health food, functional food, nutritional composition, nutritional supplement, supplement, health food, food for specified health uses, nutrient function food, or food with functional claims, then such a food composition may be labeled with claims such as: suppressing oxidative stress, preventing oxidative stress, maintaining antioxidant capacity, preventing a decrease in antioxidant capacity, suppressing a decrease in antioxidant capacity, suppressing a decrease in immune cells, maintaining immune cells, maintaining the number of immune cells, for those concerned about a decrease in immune cells, suppressing a decrease in pDCs, maintaining pDCs, maintaining the number of pDCs, for those concerned about a decrease in pDCs, suppressing a decrease in mDCs, maintaining mDCs, maintaining the number of mDCs, for those concerned about a decrease in mDCs, suppressing a decrease in PBMCs, maintaining PBMCs, maintaining the number of PBMCs, for those concerned about a decrease in PBMCs, increasing NRF2 in immune cells, increasing NRF2 in pDCs, etc.

[0104] The food composition provided as the composition of this embodiment is not particularly limited as long as it contains the active ingredient of the present invention, but examples include: soft drinks, carbonated drinks, fruit juice drinks, vegetable juice drinks, fruit and vegetable juice drinks, milk and other dairy products, soy milk, dairy beverages, drinkable yogurt, drinkable or stick-type jellies, coffee, cocoa, tea beverages, nutritional drinks, energy drinks, sports drinks, mineral water (including both sparkling and non-sparkling), near water, non-alcoholic beverages such as non-alcoholic beer-flavored beverages; carbohydrate-containing foods and beverages such as rice dishes, noodles, bread or pasta; cheeses, hard or soft yogurts, and fresh creams made from dairy products and other oil and fat raw materials. Dairy products such as ice cream; Western-style confectionery such as cookies, cakes, and chocolates; Japanese-style confectionery such as manju or yokan; tablet candies such as ramune (refreshing candies); candies, gums, gummies, frozen desserts and ice cream such as jelly or pudding; various confectionery such as snack foods; alcoholic beverages such as whiskey, bourbon, spirits, liqueurs, wine, fruit wine, sake, Chinese liquor, shochu, beer, non-alcoholic beer with an alcohol content of 1% or less, sparkling wine, other miscellaneous alcoholic beverages, and chuhai; processed foods such as processed egg products, processed seafood or meat products (including offal such as liver) (including delicacies), soups such as miso soup, seasonings such as miso, soy sauce, furikake, and other seasonings, or liquid foods such as high-calorie liquid foods.

[0105] Tea beverages include fermented teas, semi-fermented teas, and unfermented teas, such as black tea, green tea, barley tea, brown rice tea, sencha, gyokuro tea, hojicha, oolong tea, turmeric tea, pu-erh tea, rooibos tea, rose tea, chrysanthemum tea, ginkgo leaf tea, and herbal teas (for example, mint tea, jasmine tea).

[0106] Fruits used in fruit juice beverages and beverages containing both fruit and vegetable juices include, for example, apples, oranges, grapes, bananas, pears, peaches, mangoes, acai, blueberries, and plums. Vegetables used in vegetable juice beverages and beverages containing both fruit and vegetable juices include, for example, tomatoes, carrots, celery, pumpkins, cucumbers, and watermelons.

[0107] When providing the composition of this embodiment as animal feed, it can be carried out in accordance with the above description of food products.

[0108] When the composition of this embodiment is provided as a pharmaceutical composition or quasi-drug, it can be formulated as an oral or parenteral preparation. Examples of oral preparations include granules, powders, tablets (including sugar-coated tablets), pills, capsules, syrups, liquids, jellies, emulsions, and suspensions. Examples of parenteral preparations include injectable preparations suitable for local administration (including intradermal, subcutaneous, intramuscular, and intravenous injections), inhalants (e.g., inhaled aerosols, inhaled powders, inhaled solutions), nasal drops (e.g., nasal powders, nasal solutions), ointments, creams, gels, suppositories, patches, and compresses. These preparations can be formulated using pharmaceutically acceptable carriers by methods commonly practiced in the art. Examples of pharmaceutically acceptable carriers include excipients, binders, diluents, additives, fragrances, buffers, thickeners, colorants, stabilizers, emulsifiers, dispersants, suspending agents, and preservatives.

[0109] When the composition of this embodiment is used as a pharmaceutical composition or quasi-drug, the target diseases include, for example, cancers such as renal cancer, multiple myeloma, chronic myeloid leukemia, hairy cell leukemia, glioblastoma, medulloblastoma, astrocytoma, malignant melanoma, mycosis fungoides, and adult T-cell leukemia, which are already known to be indications for Type I IFN; viral infections such as subacute sclerosing panencephalitis, HTLV-1 myelopathy, hepatitis B, and hepatitis C; bacterial infections such as Chlamydia (sexually transmitted disease), Mycobacterium (tuberculosis), Listeria (sepsis, etc.), Staphylococcus (food poisoning), and Helicobacter (gastritis); and autoimmune diseases such as multiple sclerosis. The composition of this embodiment can be used for the prevention or treatment of the above diseases. Furthermore, since the activity of Type I IFN in the composition of this embodiment is known to be the inhibitory function of differentiation from osteoblasts to osteoclasts, it can also be used for the prevention or treatment of osteoporosis, etc. Furthermore, the composition of this embodiment can also be used to prevent or treat diseases that may be treated with glutathione administration, such as drug poisoning, acetonemic vomiting (autointoxication, cyclic vomiting syndrome), metal poisoning, hyperemesis gravidarum, and gestational hypertension.

[0110] The composition of this embodiment may be a lactic acid bacteria cell powder (a powder obtained by drying bacterial cells or a powder containing the same). Such a lactic acid bacteria cell powder can be obtained, for example, by culturing, sterilizing, and drying lactic acid bacteria according to a conventional manufacturing method.

[0111] The bacterial cell powder of this embodiment may contain, in addition to lactic acid bacteria and components derived from the culture medium used during lactic acid bacteria culture, components that are acceptable as food, pharmaceuticals or animal feed, and may further contain at least one selected from the group consisting of sugars, proteins, lipids, amino acids, vitamins, minerals, flavonoids, quinones, polyphenols, nucleic acids, fatty acids, acidulants, sweeteners, colorants, flavorings, seasonings, salt, emulsifiers, stabilizers, cooling agents, binders, disintegrants, lubricants, colorants, preservatives, sustained-release regulators, surfactants, and solubilizers.

[0112] The bacterial cell powder of this embodiment can be used as a raw material for the food composition, pharmaceutical composition, or animal feed of this embodiment.

[0113] When providing the composition of this embodiment as an additive, it can be implemented in accordance with the above-described descriptions of food compositions, animal feed, quasi-drugs, pharmaceutical compositions, or bacterial powders.

[0114] Another embodiment of the present disclosure is a method comprising administering or allowing a subject to ingest a composition containing lactic acid bacteria, the detailed aspects of which are described above with respect to the composition of the first embodiment.

[0115] <Method> A second embodiment of this disclosure is a method comprising administering or allowing a subject to ingest lactic acid bacteria that are phagocytosed by immune cells. The lactic acid bacteria may be contained, for example, in the composition of the first embodiment described above.

[0116] The method of this embodiment may include increasing the glutathione concentration in the immune cells of the administered or ingested subject. In this case, the method of this embodiment may include, for example, inducing glutathione production in the immune cells of the subject, promoting the reduction of oxidized glutathione in the immune cells of the subject, suppressing the oxidation of glutathione in the immune cells of the subject, and / or suppressing the degradation of glutathione in the immune cells of the subject.

[0117] The method of this embodiment may further include at least one selected from the group consisting of protecting immune cells, suppressing the decrease of immune cells, providing antioxidant effects, and suppressing intracellular oxidative stress.

[0118] In one embodiment, the method of this embodiment may be a method for increasing the concentration of glutathione in immune cells. The method of this embodiment may, for example, be a method for inducing the production of glutathione in immune cells, a method for promoting the reduction of oxidized glutathione in immune cells, a method for suppressing the oxidation of glutathione in immune cells, and / or a method for suppressing the degradation of glutathione in immune cells. The method of this embodiment may be used for at least one selected from the group consisting of protection of immune cells, suppression of immune cell decline, antioxidant and suppression of intracellular oxidative stress.

[0119] In one embodiment, the method of this embodiment may be at least one method selected from the group consisting of a method for protecting immune cells, a method for suppressing the decrease of immune cells, an antioxidant method, and a method for suppressing intracellular oxidative stress; or it may be at least one method selected from the group consisting of a method for protecting immune cells and a method for suppressing the decrease of immune cells; or, in the case of the subject, it may be at least one method selected from the group consisting of an antioxidant method and a method for suppressing intracellular oxidative stress.

[0120] The daily dose or intake of lactic acid bacteria can be determined depending on the recipient's sex, age and weight, symptoms, administration or intake time, dosage form, route of administration or intake, and the materials or drugs being combined. The daily dose or intake of lactic acid bacteria (for example, the daily dose or intake for adults) is not particularly limited, but for example, 1.0 × 10⁻⁶ 4 pcs or more, 5.0×10 4 pcs or more, 1.0×10 5 pcs or more, 3.0×10 5 pcs or more, 1.0×10 6 pcs or more, 3.0×10 6 pcs or more, 1.0×10 7 pcs or more, 3.0×10 7 pcs or more, 1.0×10 8 pcs or more, 3.0×10 8 pcs or more, 5.0×10 8 pcs or more, 1.0×10 9 pcs or more, 5.0×10 9 One or more or 1.0 × 10 10 There may be more than 1.0 × 10 14 pcs or less, 1.0×10 13 1 or less or 1.0 × 10 12 The number may be less than or equal to 10. Furthermore, these upper and lower limits can be combined in any way and are not particularly limited. For example, the daily dose or intake of lactic acid bacteria (e.g., the daily dose or intake for adults) may be 1.0 × 10. 4 pcs or more 1.0×10 14 pcs or less, 1.0×10 4 pcs or more 1.0×10 13 pcs or less, 1.0×10 4 pcs or more 1.0×10 12 Less than or equal to 5.0×10 4 pcs or more 1.0×10 14 Less than or equal to 5.0×10 4 pcs or more 1.0×10 13 Less than or equal to 5.0×10 4 pcs or more 1.0×10 12 pcs or less, 1.0×10 5 pcs or more 1.0×10 14 pcs or less, 1.0×10 5 pcs or more 1.0×10 13 pcs or less, 1.0×10 5 pcs or more 1.0×10 12 pcs or less, 3.0×10 5 pcs or more 1.0×10 14 pcs or less, 3.0×10 5 pcs or more 1.0×10 13 pcs or less, 3.0×10 5 pcs or more 1.0×10 12 pcs or less, 1.0×10 6 pcs or more 1.0×10 14 pcs or less, 1.0×10 6 pcs or more 1.0×10 13 pcs or less, 1.0×10 6 pcs or more 1.0×10 12 pcs or less, 3.0×10 6 pcs or more 1.0×10 14 pcs or less, 3.0×10 6 More than 1.0 × 10 13 Less than 3.0 × 10 6 More than 1.0 × 10 12 Less than 1.0 × 10 7 More than 1.0 × 10 14 Less than 1.0 × 10 7 More than 1.0 × 10 13 Less than 1.0 × 10 7 More than 1.0 × 10 12 Less than 3.0 × 10 7 More than 1.0 × 10 14 Less than 3.0 × 10 7 More than 1.0 × 10 13 Less than 3.0 × 10 7 More than 1.0 × 10 12 Less than 1.0 × 10 8 More than 1.0 × 10 14 Less than 1.0 × 10 8 More than 1.0 × 10 13 Less than 1.0 × 10 8 More than 1.0 × 10 12 Less than 3.0 × 10 8 More than 1.0 × 10 14 Less than 3.0 × 10 8 More than 1.0 × 10 13 Less than 3.0 × 10 8 More than 1.0 × 10 12 Less than 5.0 × 10 8 More than 1.0 × 10 14 Less than 5.0 × 10 8 More than 1.0 × 10 13 Less than 5.0 × 10 8 More than 1.0 × 10 12 Less than 1.0 × 10 9 More than 1.0 × 10 14 Less than 1.0 × 10 9 More than 1.0 × 10 13 Less than 1.0 × 10 9 More than 1.0 × 10 12 Less than 5.0 × 10 9 More than 1.0 × 10 14 Less than 5.0 × 10 9 More than 1.0 × 10 13 Less than 5.0 × 10 9 pcs or more 1.0×10 12 pcs or less, 1.0×10 10 pcs or more 1.0×10 14 pcs or less, 1.0×10 10 pcs or more 1.0×10 13 1 or less or 1.0 × 10 10 pcs or more 1.0×10 12 The number of lactic acid bacteria may be less than or equal to 10. The number of lactic acid bacteria can be measured using a known microscope, flow cytometer, or non-culture microbial rapid testing device (e.g., ELESTA PixeeMo (AFI Technology Co., Ltd.)), but from the standpoint of high versatility, it may also be measured by microscope.

[0121] The daily dose or intake of lactic acid bacteria is not particularly limited, but can be determined, for example, by the dry cell mass of the lactic acid bacteria. The daily dose or intake of lactic acid bacteria (for example, the daily dose or intake for adults) is, for example, 2.5 × 10⁻⁶. -2 mg or more, 2.5×10 -1 It may be mg or more, 2.5 mg or more, or 2.5 × 10 mg or more, 2.5 × 10 4 mg or less, 2.5×10 3 mg or less, 2.5×10 2 mg or less or 1.0 × 10 2 The amount may be less than or equal to mg, and these upper and lower limits can be combined arbitrarily. The daily dose or intake of lactic acid bacteria (for example, the daily dose or intake for adults) is, for example, 2.5 × 10 -2 mg or more 2.5×10 4 mg or less, 2.5×10 -2 mg or more 2.5×10 3 mg or less, 2.5×10 -2 mg or more 2.5×10 2 mg or less, 2.5×10 -2 mg or more 1.0×10 2 mg or less, 2.5×10 -1 mg or more 2.5×10 4 mg or less, 2.5×10 -1 mg or more 2.5×10 3 mg or less, 2.5×10 -1 mg or more 2.5×10 2 mg or less, 2.5×10 -1 mg or more 1.0×10 2 mg or less, 2.5 mg or more 2.5×10 4 mg or less, 2.5 mg or more 2.5×10 3 mg or less, 2.5 mg or more 2.5×10 2 mg or less, 2.5 mg or more 1.0×10 2 mg or less, 2.5 x 10 mg or more 2.5 x 10 4 mg or less, 2.5 x 10 mg or more 2.5 x 10 3 mg or less, 2.5 x 10 mg or more 2.5 x 10 2 mg or less or 2.5 × 10 mg or more, 1.0 × 10 2 It may be less than or equal to mg.

[0122] The form of administration or intake of lactic acid bacteria is not particularly limited, but from the viewpoint of reducing the burden on the recipient, oral administration or ingestion is preferred, and oral ingestion is more preferred. When used for oral administration or ingestion, the lactic acid bacteria and / or compositions containing them may have high resistance to gastric juice and intestinal juice, etc., and are not particularly limited, but for example, it is preferable that they have strong acid resistance.

[0123] The subjects to whom lactic acid bacteria are administered or ingested may be humans and / or non-human mammals, and may be humans.

[0124] Lactic acid bacteria may be administered to or ingested by subjects who require them. Such subjects may be, for example, those who require the objective of the method (e.g., an increase in glutathione concentration in immune cells). Subjects who require the objective of the method (e.g., an increase in glutathione concentration in immune cells) are not particularly limited, but include, for example, subjects with decreased glutathione concentration in immune cells, subjects aged 65 or older, subjects infected with a virus, subjects who wish to prevent viral infection, subjects with a cold, subjects who wish to prevent a cold, subjects with reduced immune cells, subjects with reduced pDCs, subjects with reduced mDCs, subjects with reduced PBMCs, subjects who regularly experience fatigue or stress, subjects who habitually consume alcohol, and subjects whose immunity has been weakened by exercise.

[0125] It is preferable to continue administering or ingesting lactic acid bacteria for the duration of the period during which the objective of the method (e.g., an increase in glutathione concentration in immune cells) is expected. From the viewpoint of better demonstrating the effect related to the objective of the method (e.g., an increase in glutathione concentration in immune cells), the administration or ingestion period of the above daily amount can be, for example, 1 day or more, 1 week or more, 2 weeks or more, 3 weeks or more, preferably 1 month or more (4 weeks or more). The administration interval or ingestion interval of the active ingredient of the present invention can be once every 3 days, once every 2 days, or once a day, with the above daily amount being preferably once a day.

[0126] <Use of lactic acid bacteria or compositions containing them> Other embodiments of this disclosure relate to the use of lactic acid bacteria phagocytosed by immune cells in increasing glutathione concentrations within immune cells. Such uses may include, for example, inducing glutathione production within immune cells, promoting the reduction of oxidized glutathione within immune cells, inhibiting the oxidation of glutathione within immune cells, and / or inhibiting the degradation of glutathione within immune cells. Detailed embodiments of the lactic acid bacteria and their use according to this embodiment may be, for example, those described in the method of the second embodiment described above.

[0127] Further embodiments of this disclosure relate to the use of lactic acid bacteria-containing compositions in increasing glutathione concentrations in immune cells. Such uses may include, for example, inducing glutathione production in immune cells, promoting the reduction of oxidized glutathione in immune cells, inhibiting the oxidation of glutathione in immune cells, and / or inhibiting the degradation of glutathione in immune cells. Detailed embodiments of compositions and their uses according to these embodiments may be, for example, those described for the compositions of the first embodiment described above.

[0128] The use of these two embodiments may be for at least one selected from the group consisting of protection of immune cells, inhibition of immune cell decline, antioxidant and suppression of intracellular oxidative stress, or it may be for at least one selected from the group consisting of protection of immune cells and inhibition of immune cell decline, or it may be for at least one selected from the group consisting of antioxidant and suppression of intracellular oxidative stress.

[0129] Further embodiments of this disclosure relate to the use of lactic acid bacteria phagocytosed by immune cells in at least one selected from the group consisting of protecting immune cells, inhibiting the decrease of immune cells, providing antioxidant effects, and suppressing intracellular oxidative stress; the use of lactic acid bacteria phagocytosed by immune cells with phagocytic ability in at least one selected from the group consisting of protecting immune cells and inhibiting the decrease of immune cells; and the use of lactic acid bacteria phagocytosed by immune cells with phagocytic ability in at least one selected from the group consisting of providing antioxidant effects and suppressing intracellular oxidative stress. Detailed embodiments of the lactic acid bacteria and their use according to this embodiment may be, for example, embodiments described in the method of the second embodiment described above.

[0130] Further embodiments of this disclosure relate to the use of a composition containing lactic acid bacteria that are phagocytosed by immune cells in at least one selected from the group consisting of protecting immune cells, inhibiting the decrease of immune cells, providing antioxidant effects, and suppressing intracellular oxidative stress; the use of a composition containing lactic acid bacteria that are phagocytosed by immune cells with phagocytic ability in at least one selected from the group consisting of protecting immune cells and inhibiting the decrease of immune cells; and the use of a composition containing lactic acid bacteria that are phagocytosed by immune cells with phagocytic ability in at least one selected from the group consisting of providing antioxidant effects and suppressing intracellular oxidative stress. Detailed aspects of the compositions and their uses according to these embodiments may be, for example, those described with respect to the compositions of the first embodiment described above.

[0131] The use of these two embodiments may be for the purpose of increasing glutathione concentration in immune cells. Such use may be, for example, to induce glutathione production in immune cells, to promote the reduction of oxidized glutathione in immune cells, to suppress the oxidation of glutathione in immune cells, and / or to suppress the degradation of glutathione in immune cells.

[0132] The use in these embodiments may be non-therapeutic and / or therapeutic, and is preferably non-therapeutic.

[0133] In this disclosure, “therapeutic” use means use in the treatment of the human or animal body. Therapeutic use in this disclosure may be, for example, use for the purpose of or in conjunction with a medical procedure. Therapeutic use in this disclosure may involve, for example, a healthcare professional administering or causing a human or animal to ingest the substance, or instructing a human or animal to administer or ingest the substance. Therapeutic use in this disclosure may be, for example, use for therapeutic or preventive purposes, use for therapeutic purposes, or preventive use involving the ingestion of a food composition, or use for therapeutic purposes. Therapeutic use in this disclosure may be, for example, use in a non-healthy person.

[0134] In this disclosure, “non-therapeutic” use means use of the substance that does not constitute therapeutic use. Non-therapeutic use in this disclosure may, for example, be use that is not intended for and / or does not involve medical practice. Non-therapeutic use in this disclosure does not, for example, involve a healthcare professional administering or causing a person or animal to ingest the substance, and / or instructing a person or animal to administer or ingest the substance. Non-therapeutic use in this disclosure may, for example, be use for preventive or health-promoting purposes, and may be use for preventive or health-promoting purposes that involves the administration or ingestion of a pharmaceutical composition or quasi-drug. Non-therapeutic use in this disclosure may, for example, be use on healthy individuals.

[0135] <Lactic acid bacteria or compositions containing them for use> Other embodiments of this disclosure relate to lactic acid bacteria that are phagocytosed by immune cells for use in increasing glutathione concentrations in immune cells. Such lactic acid bacteria may be for use in, for example, in inducing glutathione production in immune cells, promoting the reduction of oxidized glutathione in immune cells, inhibiting the oxidation of glutathione in immune cells, and / or inhibiting the degradation of glutathione in immune cells. Detailed embodiments of the lactic acid bacteria and their use according to this embodiment may be, for example, those described in the method of the second embodiment described above. Use in this embodiment is, for example, therapeutic use.

[0136] Further embodiments of this disclosure relate to compositions containing lactic acid bacteria that are phagocytosed by immune cells for use in increasing glutathione concentrations in immune cells. Such compositions may be for use, for example, in inducing glutathione production in immune cells, promoting the reduction of oxidized glutathione in immune cells, inhibiting the oxidation of glutathione in immune cells, and / or inhibiting the degradation of glutathione in immune cells. Detailed embodiments of the compositions and their uses according to these embodiments may be, for example, those described for the compositions of the first embodiment described above. Uses in these embodiments are, for example, therapeutic uses.

[0137] The lactic acid bacteria of these two embodiments or compositions containing the same may be used for at least one selected from the group consisting of protection of immune cells, inhibition of the decrease of immune cells, antioxidant and inhibition of intracellular oxidative stress, or they may be used for at least one selected from the group consisting of protection of immune cells and inhibition of the decrease of immune cells, or they may be used for at least one selected from the group consisting of antioxidant and inhibition of intracellular oxidative stress.

[0138] Other embodiments of this disclosure relate to lactic acid bacteria that are phagocytosed by immune cells for use in at least one selected from the group consisting of protecting immune cells, inhibiting the reduction of immune cells, antioxidant, and suppressing intracellular oxidative stress; for use in at least one selected from the group consisting of protecting immune cells and inhibiting the reduction of immune cells; or for use in at least one selected from the group consisting of antioxidant and suppressing intracellular oxidative stress. Detailed embodiments of the lactic acid bacteria and their use according to these embodiments may be, for example, those described in the method of the second embodiment described above. Use in these embodiments is, for example, therapeutic use.

[0139] Further embodiments of this disclosure relate to compositions containing lactic acid bacteria that are phagocytosed by immune cells for use in at least one selected from the group consisting of protecting immune cells, inhibiting the reduction of immune cells, antioxidant, and suppressing intracellular oxidative stress; for use in at least one selected from the group consisting of protecting immune cells and inhibiting the reduction of immune cells; or for use in at least one selected from the group consisting of antioxidant and suppressing intracellular oxidative stress. Detailed aspects of the compositions and their uses according to these embodiments may be, for example, those described for the compositions of the first embodiment described above. Use in these embodiments is, for example, therapeutic use.

[0140] The lactic acid bacteria or compositions containing the same in these two embodiments may be used to increase the glutathione concentration in immune cells. Such lactic acid bacteria or compositions containing the same may be used, for example, to induce glutathione production in immune cells, to promote the reduction of oxidized glutathione in immune cells, to suppress the oxidation of glutathione in immune cells, and / or to suppress the degradation of glutathione in immune cells.

[0141] <Use of lactic acid bacteria in the manufacture of compositions> Further embodiments of this disclosure also relate to the use of lactic acid bacteria in the preparation of the composition of the first embodiment. Detailed aspects of the composition according to this embodiment, its preparation and use may be, for example, those described above for the composition of the first embodiment. [Examples]

[0142] The present disclosure will be described in more detail below with reference to examples, but the present disclosure is not limited to the following examples.

[0143] In this embodiment, the results with error ranges are expressed as mean ± standard deviation unless otherwise specified.

[0144] <cell> In the following examples, the CAL-1 cells used were CAL-1 cells (deposit number FERM BP-10914) obtained from Nagasaki University, a national university corporation, and used as the sample (hereinafter referred to as "the sample"). All rights to the sample belong to Nagasaki University, a national university corporation, and permission to use the sample was obtained from Nagasaki University. As the basal medium for culturing CAL-1 cells and for tests using CAL-1 cells, RPMI-1640 medium (Sigma, R8758) was used, supplemented with 1.0 vol% penicillin / streptomycin (Gibco, 15140-12) and 1.0 vol% MEM Non-Essential Amino Acids Solution (Gibco, 11140050) (hereinafter also referred to as "serum-free medium"). Cell culture was carried out under conditions of 37°C and 5% CO2.

[0145] <Lactic acid bacteria> In the following examples, lactic acid bacteria were cultured according to the culture method described in Table 2 in accordance with the correspondence between A and B shown in Table 1, and then used as bacterial raw material powder (dried bacterial cells or powder containing them, etc.) prepared as follows: Bacteria cultured in MRS medium (MRSBROTH, CODE:CM0359, Oxoid Co., Ltd.) were subjected to centrifugation (5000 rpm) of the culture solution, and the supernatant was removed to obtain a bacterial suspension. Subsequently, the obtained bacterial suspension and phosphate-buffered saline (Takara Bio Co., Ltd.) were mixed in a volume ratio of 1:19 and washed twice by centrifugation (5000 rpm). The lactic acid bacteria in the bacterial suspension were killed by heat treatment after washing. The heat treatment involved raising the temperature from room temperature to 80°C over 30 minutes, holding at 80°C for 30 minutes, and then cooling down to room temperature over 30 minutes. After cooling, freeze-drying was performed to obtain bacterial raw material powder.

[0146] <Analysis of Results> For statistical analysis, the numerical values ​​of the test results were compiled into a cumulative table using Microsoft Office Excel 2016 (Microsoft Corp.), and the mean and standard deviation were calculated as basic statistics. Statistical analysis was performed using appropriate statistical analysis software such as SAS (SAS 9.4) or SPSS (Statistics26), and for all tests, a two-tailed 5% significance level was used, and a 10% trend level. In the group comparisons between each group in Figures 1-5 and 13-14, the data treated as parametrics were subjected to independent t-tests. Specifically, Student's t-test (hereinafter abbreviated as "T-test") was used for the group comparisons in Figures 2, 13, and 14, while Tukey's multiple comparison test (hereinafter abbreviated as "Tukey"), assuming equal variances, was used for the group comparisons in Figures 1, 3, 4, and 5. In Figures 1-5 and 13-14, an asterisk (*) indicates that the p-value for these statistical tests was less than 0.05.

[0147] [Table 1] JPEG2026115009000002.jpg224149

[0148] [Table 2]

[0149] [Glutathione solution] Glutathione manufactured by Kyowa Hakko Bio Co., Ltd. was used. Glutathione was diluted with phosphate buffered saline (manufactured by Nacalai Tesque, hereinafter abbreviated as "PBS") to a concentration of 50 mM to obtain a 50 mM glutathione solution.

[0150] [BSO solution] All DL-buthionine-(S,R)-sulfoximine (BSO) was manufactured by Sigma. BSO was diluted with PBS to a concentration of 40 mM to obtain a 40 mM BSO solution.

[0151] [N-ethylmorpholine solution] N-ethylmorpholine (manufactured by Fujifilm Wako Pure Chemical Corporation, 055-02113) (hereinafter abbreviated as NEM) was diluted with MilliQ water to a concentration of 50 mM and adjusted to pH 8.0 using 1 M hydrochloric acid (manufactured by Wako Pure Chemical Industries, 083-01095). This solution was used as the NEM solution. Hereinafter, this solution will also be referred to as the 50 mM NEM solution.

[0152] [Monobromobimane solution] Monobromobimane (manufactured by Tokyo Chemical Industry, B4220) (hereinafter abbreviated as mBBr) was dissolved by adding 500 μL of acetonitrile (manufactured by Nacalai Tesque, 00430-83), and then diluted with 50 mM NEM solution to a concentration of 8 mM. This solution was used as the mBBr solution. Hereinafter, this solution will also be referred to as the 8 mM mBBr solution.

[0153] [Example 1: Evaluation of the effect of intracellular glutathione concentration on the number of immune cells] In this example, we investigated whether intracellular glutathione (hereinafter also referred to as "GSH") concentration affects the reduction of immune cells. The effect on the reduction of immune cells was measured using cell viability as an indicator. In this example, LC-Plasma was used as the lactic acid bacterium.

[0154] [Evaluation of the contribution of LC-Plasma to intracellular glutathione concentration and cell viability in CAL-1 cells] Using serum-free medium, CAL-1 cells were raised to 3.7 × 10⁶ 5 Cell suspensions containing cells / mL were prepared. In the BSO-added group (labeled "BSO(+)" in Figures 1 and 3), 62.5 μL / well of 40 mM BSO solution (final BSO concentration 0.25 mM) was added to a 10 cm diameter culture dish, followed by seeding with 10 mL / well of the cell suspension, and the cells were cultured for 16 hours. In the BSO-free group (labeled "BSO(-)" in Figures 1 and 3), the same amount of cell suspension was seeded in a 10 cm diameter culture dish without any prior additives and cultured for the same amount of time. After culture, CAL-1 cells were harvested by pipetting.

[0155] The harvested CAL-1 cells were placed in serum-free medium in a 4.0 × 10⁶ layer. 5 The cells were resuspended at a concentration of cells / mL and seeded at 200 μL / well in each well of a 96-well microplate. In the LC-Plasma-added group (labeled "LC-Plasma(+)" in Figures 1 and 3, and "LC-Plasma" in Figure 2), LC-Plasma suspension suspended in PBS was added to the cell suspension in each well to a final concentration of 10 μg / mL. In the LC-Plasma-free group (labeled "LC-Plasma(-)" in Figures 1 and 3, and "No Addition" in Figure 2), the above addition was not performed. In the GSH-added group (labeled "GSH(+)" in Figure 1), 50 mM glutathione solution was added to a final concentration of 0.25 mM. In the GSH-free group (labeled "GSH(-)" in Figure 1), the above addition was not performed. After adding each solution, the cells were cultured for 22 hours, and then the culture supernatant from each well was collected.

[0156] For cell viability evaluation, after removing the culture supernatant, the cells were washed with PBS (Nacalai Task, 14249-24), and then resuspended in a medium containing Cell Counting Kit-8 (Dojin Chemical Research Institute, CK04) in a volume ratio of 20:1 to serum-free medium. The cells were then cultured for 1 hour. Subsequently, the absorbance of the suspension at 450 nm was measured using a microplate reader (PerkinElmer Launches VICTOR® Nivo® Multimode Plate Reader or Promega GloMax® Discover).

[0157] For the evaluation of intracellular glutathione concentration, the 96-well plates, after supernatant collection, were washed with PBS. Then, 100 μL / well each of 50 mM NEM solution and 8 mM mBBr solution were added, and the mixture was allowed to stand at room temperature in the dark for 10 minutes. After standing, 10 μL of trichloroacetic acid was added to the solution, and the supernatant was collected after centrifugation. The supernatant was passed through a 0.20 μm filter (ADVATEC, 13HP020AN05), and the glutathione concentration in the collected supernatant was measured using HPLC (instrument: HITACHI chromaster, column: Nacalai Tesque COSMOSIL Packed Column 5C18-MS-2 4.6 mm I.D. × 100 mm).

[0158] [Evaluation of the contribution of LC-Plasma to intracellular glutathione concentration in bone marrow cells derived from female BALB / c mice] (i) Female BALB / c mouse bone marrow cells (hereinafter also referred to as "BMDC") are placed in RPMI medium (Sigma-A) prepared to the respective final concentrations described below, in a 1 × 10⁻¹⁶ medium. 6 The cells were suspended to a concentration of cells / mL to prepare a cell suspension. (Composition of culture medium) • 10% volume FBS • 100 U / mL Penicillin / Streptomycin 1 mM sodium pyruvate 2.5mM HEPES ·1 mass% non-essential amino acids (NEAA) for MEM 50 μM β-mercaptoethanol • 100 ng / mL Flt-3L

[0159] (ii) The prepared cell suspension was seeded in 1 mL portions and cultured in a CO2 incubator at 37°C and 5% CO2 for 1 week to induce dendritic cells including mDCs and pDCs.

[0160] (iii) Bone marrow cells containing induced mDCs and pDCs, 2 × 10 5 The LC-Plasma suspension was adjusted to a concentration of 10 μg / mL, and 200 μL was seeded into each 96-well plate. LC-Plasma suspension in PBS was then added to a final concentration of 10 μg / mL. After 22 hours of incubation, the supernatant was collected from each well. The 96-well plate was washed with PBS (Nacalai Task, 14249-24) after supernatant collection. 100 μL each of 50 mM NEM solution and 8 mM mBBr solution were added to each well, and the plate was allowed to stand in the dark at room temperature for 10 minutes. 10 μL of trichloroacetic acid was added, and the supernatant was collected after centrifugation. The solution was passed through a 0.20 μm filter (ADVATEC, 13HP020AN05), and the glutathione concentration in the recovered supernatant was measured using HPLC (instrument: HITACHI chromaster, column: Nacalai Tesque COSMOSIL Packed Column 5C18-MS-2 4.6 mm I.D. × 100 mm).

[0161] Figure 1 shows the results of evaluating intracellular GSH concentration using CAL-1 cells (N=6). Figure 2 shows the results of evaluating intracellular GSH concentration using BMDC cells (N=3). Figure 3 shows the results of evaluating the effect of changes in intracellular GSH concentration on cell number using CAL-1 cells (N=6). According to the results in Figures 1-3, intracellular glutathione concentration in CAL-1 cells increased with the addition of LC-Plasma, similar to the case with GSH addition. In addition, the addition of LC-Plasma also increased intracellular glutathione concentration in BMDC cells and suppressed the decrease in CAL-1 cell number caused by BSO addition (the number of cells with BSO added decreased by 6.6% compared to the number of cells without BSO addition, but after BSO treatment, the number of cells increased by 14.2% compared to the number of cells with BSO alone). This revealed that LC-Plasma protects immune cells and enhances their survival rate by increasing intracellular glutathione concentration.

[0162] <Example 2: Relationship between exposure to lactic acid bacteria and increased intracellular glutathione levels in immune cells> In this example, the relationship between exposure to lactic acid bacteria and the increase in intracellular glutathione in immune cells was investigated. In this example, LC-Plasma and L-137 (manufactured by House Wellness Foods Co., Ltd.) were used as lactic acid bacteria.

[0163] [Evaluation of the contributions of LC-Plasma and L-137 to intracellular glutathione concentration in CAL-1 cells] Using serum-free medium, CAL-1 cells were raised to 3.7 × 10⁶ 5 A cell suspension containing cells / mL was prepared. The cell suspension was seeded at 10 mL / well in a 10 cm diameter culture dish and cultured for 16 hours. CAL-1 cells were harvested by pipetting. The harvested CAL-1 cells were placed in serum-free medium in a 4.0 × 10⁶ layer. 5 The cells were resuspended at a concentration of cells / mL and seeded at 200 μL / well in each well of a 96-well microplate. The suspension of each lactic acid bacterium was added to the cell suspension in each well. In the LC-Plasma group (labeled "LC-Plasma" in Figure 4), an LC-Plasma suspension suspended in PBS was added to a final concentration of 10 μg / mL. In the L-137 group (labeled "L-137" in Figure 4), an L-137 suspension suspended in PBS was added to a final concentration of 650 μg / mL. In the no-addition group (labeled "No Addition" in Figure 4), no lactic acid bacteria were added. After culturing the CAL-1 cells for 22 hours, the culture supernatant was collected from each well. The 96-well plate, after supernatant collection, was washed with PBS (Nacalai Tesque, 14249-24), and then 100 μL / well each of 50 mM NEM solution and 8 mM mBBr solution were added, and the plate was allowed to stand in the dark at room temperature for 10 minutes. 10 μL of trichloroacetic acid was added, and the supernatant was collected after centrifugation. The supernatant was passed through a 0.20 μm filter (ADVATEC, 13HP020AN05), and the glutathione concentration in the collected supernatant was measured using HPLC (instrument: HITACHI chromaster, column: Nacalai Tesque COSMOSIL Packed Column 5C18-MS-2 4.6 mm I.D. × 100 mm).

[0164] [Evaluation of the contributions of LC-Plasma and L-137 to intracellular glutathione concentration in bone marrow cells derived from female BALB / c mice] (i) Female BALB / c mouse bone marrow cells (hereinafter also referred to as "BMDC") are placed in RPMI medium (Sigma-A) prepared to the respective final concentrations described below, in a 1 × 10⁻¹⁶ medium. 6 The cells were suspended to a concentration of cells / mL to prepare a cell suspension. (Composition of culture medium) • 10% volume FBS • 100 U / mL Penicillin / Streptomycin 1 mM sodium pyruvate 2.5mM HEPES ·1 mass% non-essential amino acids (NEAA) for MEM 50 μM β-mercaptoethanol • 100 ng / mL Flt-3L

[0165] (ii) The prepared cell suspension was seeded in 1 mL portions and cultured in a CO2 incubator at 37°C and 5% CO2 for 1 week to induce dendritic cells including mDCs and pDCs.

[0166] (iii) Bone marrow cells containing induced mDCs and pDCs, 2 × 10 5 The cells were suspended to a concentration of 1 / mL and seeded in 200 μL portions into 96-well plates. The suspension of each lactic acid bacterium was then added. For the LC-Plasma group (labeled "LC-Plasma" in Figure 5), LC-Plasma suspension suspended in PBS was added to a final concentration of 10 μg / mL. For the L-137 group (labeled "L-137" in Figure 5), L-137 suspension suspended in PBS was added to a final concentration of 650 μg / mL. In the unadded group (labeled "Unadded" in Figure 5), no lactic acid bacteria were added. After culturing these CAL-1 cells for 22 hours, the culture supernatant was collected from each well. After collecting the supernatant, the 96-well plates were washed with PBS (Nacalai Task, 14249-24), and then 100 μL / well each of 50 mM NEM solution and 8 mM mBBr solution were added. The plates were then allowed to stand in the dark at room temperature for 10 minutes. 10 μL of trichloroacetic acid was added, and the supernatant was collected after centrifugation. The supernatant was passed through a 0.20 μm filter (ADVATEC, 13HP020AN05), and the glutathione concentration in the collected supernatant was measured using HPLC (instrument: HITACHI chromaster, column: Nacalai Tesque COSMOSIL Packed Column 5C18-MS-2 4.6 mm I.D. × 100 mm).

[0167] Figure 4 shows the results of evaluating intracellular GSH concentration in CAL-1 cells depending on whether or not they were exposed to lactic acid bacteria (N=3). Figure 5 shows the results of evaluating intracellular GSH concentration in BMDC cells depending on whether or not they were exposed to lactic acid bacteria (N=3). These results confirm that the increase in intracellular GSH concentration in immune cells due to exposure to LC-Plasma, as observed in Example 1, also occurs when exposed to lactic acid bacteria other than LC-Plasma.

[0168] <Example 3: Relationship between phagocytosis of lactic acid bacteria by immune cells and intracellular glutathione concentration> Using serum-free medium, CAL-1 cells were raised to 3.7 × 10⁶ 5 A cell suspension containing cells / mL was prepared. This cell suspension was seeded at 10 mL / well in a 10 cm diameter culture dish, and the cells were cultured for 16 hours. CAL-1 cells were harvested by pipetting. The harvested CAL-1 cells were then placed in serum-free medium in a 4.0 × 10⁶ cubic meter. 5 The cells were resuspended at a concentration of cells / mL and seeded at 200 μL / well in each well of a 96-well microplate. A 400 μM cytochalasin D solution (hereinafter abbreviated as "Cyt-D", Fujifilm Wako, 037-17561) was prepared by dissolving it in 4 vol% dimethyl sulfoxide (DMSO). In the LC-Plasma+Cyt-D group ("LC-Plasma+Cyt-D" in Figure 6), Cyt-D and DMSO were added to the cell suspension in each well to a final concentration of 1 μM and 0.1 vol% respectively, and incubated for 30 minutes. In the Medium group ("Medium" in Figure 6) and the LC-Plasma group ("LC-Plasma" in Figure 6), 4 vol% DMSO was added to a final concentration of 0.1 vol%, and incubated similarly for 30 minutes. In the LC-Plasma group and the LC-Plasma+Cyt-D group, LC-Plasma suspension suspended in PBS was added to each well after incubation to a final concentration of 10 μg / mL. This addition procedure was not performed in the Medium group. The culture supernatant was collected from each well. After collecting the supernatant, the 96-well plate was washed with PBS (Nacalai Task, 14249-24), and then 100 μL / well each of 50 mM NEM solution and 8 mM mBBr solution were added, and the plate was allowed to stand in the dark at room temperature for 10 minutes. 10 μL of trichloroacetic acid was added, and the supernatant was collected after centrifugation. The solution was passed through a 0.20 μm filter (ADVATEC, 13HP020AN05), and the glutathione concentration in the recovered supernatant was measured using HPLC (instrument: HITACHI chromaster, column: Nacalai Tesque COSMOSIL Packed Column 5C18-MS-2 4.6 mm I.D. × 100 mm). Furthermore, Cyt-D is an actin polymerization inhibitor, and it is known that phagocytosis is suppressed in cells to which Cyt-D has been added.

[0169] Figure 6 shows the change in GSH concentration in immune cells caused by exposure to LC-Plasma, with and without phagocytosis inhibition using Cyt-D (N=3). According to these results, the increase in glutathione concentration caused by exposure to LC-Plasma was not observed in the LC-Plasma + Cyt-D group, where actin polymerization was inhibited by blocking with Cyt-D. These results indicate that phagocytosis of lactic acid bacteria by immune cells is one of the stages that determines the extent to which lactic acid bacteria cause an increase in glutathione concentration within immune cells.

[0170] <Example 4: Relationship between phagocytosis of various lactic acid bacteria and intracellular glutathione concentration in immune cells> Using serum-free medium, CAL-1 cells were raised to 5.0 × 10⁶ 5 A cell suspension containing cells / mL was prepared. This cell suspension was seeded at 10 mL / well in a 10 cm diameter culture dish, and the cells were cultured for 16 hours. CAL-1 cells were harvested by pipetting. The harvested CAL-1 cells were then placed in serum-free medium in a 2.0 × 10⁶ layer. 5 Resuspended at a concentration of cells / mL and seeded at 200 μL / well in each well of a 96-well microplate. Various lactic acid bacteria stained with pH rodo Red SE (Invitrogen, P36600) by the following <Method for staining bacteria with pHrodo Red SE> were added to the cell suspension in each well to a final concentration of 10 μg / mL (「LC-Plasma」「ATCC 15577」「JCM11340」「JCM1021」「JCM1055」「JCM1165」「JCM1120」「JCM1003」「JCM1112」「JCM1053」「JCM1134」「JCM2120」「JCM2014」「JCM1185」「JCM2012」「JCM8797」「JCM5890」「JCM1132」「JCM1136」「JCM1149」 in Figures 7, 8, 9 and 10). A group without adding bacteria (「Medium」 in Figures 7, 8, 9 and 10) was also prepared as a negative group. Then, the fluorescence of pHrodo Red SE in each well was measured over time using an Incucyte® SX5 Live-Cell Analysis System (Sartorius). The fluorescence intensity analysis conditions of the Incucyte® SX5 Live-Cell Analysis System (Sartorius) were as described in the following <Incucyte fluorescence intensity analysis>. The field area per Image was 0.572 mm 2 It was. The intracellular glutathione concentration was measured as follows. First, 22 hours after the start of culture, the culture supernatant of CAL-1 cells was collected. After washing the 96-well plate after supernatant collection with PBS, 100 μL / well of 50 mM NEM solution and 8 mM mBBr solution were added and left standing at room temperature in the dark for 10 minutes. 10 μL of trichloroacetic acid was added, and the supernatant was collected after centrifugation. It was passed through using a 0.20 μm filter (ADVATEC, 13HP020AN05), and the glutathione concentration in the collected supernatant was measured using HPLC (equipment: Hitachi chromaster, column: Nacalai Tesque COSMOSIL Packed Column 5C18-MS-2 4.6 mm I.D.×100 mm).

[0171] <Bacterial staining with pHrodo Red SE> pHrodo Red SE (Invitrogen, P36600) was dissolved in DMSO to prepare a 10.2 mM solution. Bacterial powder was weighed into a 2 mL tube, and a 0.1 M aqueous sodium hydrogen carbonate solution adjusted to pH 9.0 was added to prepare a bacterial suspension of 20 mg / mL. Then, 95 μL was transferred to a new 2 mL tube, and 5 μL of the prepared 10.2 mM pHrodo Red SE was added. After dispersion by stirring with a vortex mixer, it was shielded from light with aluminum foil and incubated at room temperature for 60 minutes. Then, 1.5 mL of methanol (Wako Pure Chemical Industries, 131 - 01826) was added, stirred using a vortex mixer, and centrifuged at 20,000×g for 2 minutes at room temperature. After discarding 1.55 mL of the supernatant, 1.5 mL of PBS was added, and the precipitate mass was completely suspended by stirring with a vortex mixer. After centrifuging again at 20,000×g for 2 minutes at room temperature, 1.5 mL of the supernatant was discarded. 140 μL of PBS was added and suspended to prepare a bacterial solution of 10 mg / mL of stained lactic acid bacteria, which was shielded from light with aluminum foil and stored at 4°C until use. Immediately before use, it was diluted 10-fold with PBS and used as a bacterial solution of 1 mg / mL of bacteria. Note that the stained bacterial solution was used within 24 hours after preparation.

[0172] <Incucyte fluorescence intensity analysis> In the Incucyte fluorescence intensity analysis, two channels, the "Phase channel" and the "Orange channel", were set. In the Phase channel, CAL-1 cells were detected based on the phase difference. In the Orange channel, the fluorescence of pHrodo Red SE was detected. The detailed detection conditions are as shown in the following Scan Setteings and Analysis Settings. ·Scan Settings ·Scan Type:Non-Adherent Cell-by-Cell ·Vessel Type:96-well Corning ·Image Channels: Phase, Orange (Acquisition Time: 400 ms) Objective: Multiply by 20 Images per Well: 9 Analysis Settings ·Analysis Type: Basic Analyzer Phase Channel Segmentation: AI Confluence • Cleanup: - Hole Fill (μm 2 ):0.000 - Adjust Size (pixels): 0 Filters: - Area (μm) 2 ): 60,000 or more - Eccentricity: Not set Orange Channel Segmentation: Surface Fit - Threshold (OCU): 5.000 - Edge Split: On - Edge Sensitivity: 0 • Cleanup: - Hole Fill (micrometers): 0.000 - Adjust Size (pixels): 0 Filters: - Area (μm) 2 ):20 - Eccentricity: Not set - Mean Intensity: Not set - Mean Intensity: Not set

[0173] <Evaluation of phagocytic intake> The entire field of view (0.572 mm) to be evaluated was obtained from each well of the plate. 2 The amount of bacterial phagocytosis by CAL-1 cells was quantified using the total area (fluorescence detection area) where fluorescence of pHrodo Red SE was detected as an indicator. An Incucyte® SX 5 Live-Cell Analysis System (Sartorius) was used to evaluate the number of images, with one image (0.572 mm²) being used depending on the number of images to be evaluated. 2 ) fluorescence detection area per unit (e.g., μm) 2 The image ( / image) was analyzed to evaluate the amount of phagocytosis. At this time, stained bacteria fluoresce slightly even if they are not phagocytosed, so the threshold value of OrangeChannel was set to 5.0 to eliminate the effect of fluorescence not due to phagocytosis. In addition, depending on the type of bacteria, the bacterial cells may form aggregates and fluoresce beyond the threshold value even if they are not phagocytosed, so the area of ​​the Filters in OrangeChannel was set to 20 to eliminate the effect of excessively large aggregates.

[0174] Figures 7 and 8 show the results of evaluating intracellular GSH concentration when CAL-1 cells were exposed to various lactic acid bacteria (N=3). Figures 9 and 10 show the results of evaluating the amount of phagocytosis of various lactic acid bacteria by CAL-1 cells (N=3). Figure 11 shows the correlation between intracellular GSH concentration and phagocytosis amount in CAL-1 cells exposed to various lactic acid bacteria, based on Figures 7 and 9. Figure 12 shows the correlation between intracellular GSH concentration and phagocytosis amount in CAL-1 cells exposed to various lactic acid bacteria, based on Figures 8 and 10. According to these results, a strong positive correlation was observed between the amount of phagocytosis for each bacterium and the increase in glutathione concentration in immune cells. From this, it became clear that the effect of increasing glutathione concentration in immune cells is determined by the phagocytosis of lactic acid bacteria by immune cells.

[0175] <Example 5: Evaluation of the effect of lactic acid bacteria on NRF-2 expression within immune cells> In this example, we investigated whether the addition of lactic acid bacteria to immune cells affects NRF2 (NFE2-Related Factor 2, also known as NFE2L2) expression. The effect on NRF2 expression was assessed using the expression level of the Nfe2l2 gene (Nfe2l2 mRNA) within the cell as an indicator. In this example, LC-Plasma was used as the lactic acid bacteria.

[0176] [Evaluation of the contribution of LC-Plasma to the expression level of the Nfe2l2 gene in CAL-1 cells] Using serum-free medium, CAL-1 cells were raised to 3.7 × 10⁶ 5 A cell suspension containing cells / mL was prepared. Then, 10 mL of the cell suspension was seeded into 10 cm dishes and cultured for 16 hours. After culturing, CAL-1 cells were harvested by pipetting.

[0177] The harvested CAL-1 cells were placed in serum-free medium in a 4.0 × 10⁶ layer. 5 The cells were resuspended at a concentration of cells / mL and seeded at 1000 μL / well in each well of a 24-well microplate. In the LC-Plasma-added group (labeled "LC-Plasma" in Figures 13 and 14), LC-Plasma suspension suspended in PBS was added to the cell suspension in each well to a final concentration of 10 μg / mL. In the non-LC-Plasma-added group (control group, labeled "CT" in Figures 13 and 14), the above addition was not performed. After adding each solution, the cells were cultured for 24 hours, and then the culture supernatant was removed from each well.

[0178] For the evaluation of Nfe2l2 gene expression levels, cells were washed with PBS (Nacalai Task, 14249-24) after removing the culture supernatant, and then RNA was extracted using the RNeasy mini kit (Qiagen, 74104). The extracted RNA was then processed using SuperScript. TM IV VILO TM Master Mix with ezDNase TM cDNA was synthesized using the enzyme (Invitrogen, 1176605), and qPCR was performed using Taqman Fast Advanced Master Mix (Thermo Scientific, 4444557). The gene evaluated was Nfe2l2, and Gapdh was used as the housekeeping gene. The qPCR conditions are shown in Table 3. The primer information used for amplification of each gene is shown in Table 4. [Table 3] [Table 4]

[0179] [Evaluation of the contribution of LC-Plasma to glutathione concentration in bone marrow cells derived from female BALB / c mice] (i) Female BALB / c mouse bone marrow cells (hereinafter also referred to as "BMDC") are placed in RPMI medium (Sigma-A) prepared to the respective final concentrations described below, in a 1 × 10⁻¹⁶ medium. 6 The cells were suspended to a concentration of cells / mL to prepare a cell suspension. (Composition of culture medium) • 10% volume FBS • 100 U / mL Penicillin / Streptomycin 1 mM sodium pyruvate 2.5mM HEPES ·1 mass% non-essential amino acids (NEAA) for MEM 50 μM β-mercaptoethanol • 100 ng / mL Flt-3L

[0180] (ii) The prepared cell suspension was seeded in 1 mL portions and cultured in a CO2 incubator at 37°C and 5% CO2 for 1 week to induce dendritic cells including mDCs and pDCs.

[0181] (iii) Bone marrow cells containing induced mDCs and pDCs, 3.5 × 10 5 The cells were suspended to a concentration of 1 / mL and seeded into 24-well plates in 500 μL portions. LC-Plasma suspension in PBS was added to a final concentration of 10 μg / mL. After 3 hours of incubation, the culture supernatant was removed from each well. The 24-well plates were washed with PBS (Nacalai Task, 14249-24). After removing the culture supernatant, the cells were washed with PBS (Nacalai Task, 14249-24), and RNA was extracted using the RNeasy mini kit (Qiagen, 74104). The extracted RNA was then processed using SuperScript. TM IV VILO TM Master Mix with ezDNase TM cDNA was synthesized using the enzyme (Invitrogen, 1176605), and qPCR was performed using Taqman Fast Advanced Master Mix (Thermo Scientific, 4444557). The gene evaluated was Nfe2l2, and Gapdh was used as the housekeeping gene. The qPCR conditions are shown in Table 5. The primer information used for amplification of each gene is shown in Table 6. [Table 5] [Table 6]

[0182] Figure 13 shows the results of evaluating the expression level of the Nfe2l2 gene using CAL-1 cells (N=3). Figure 14 shows the results of evaluating the expression level of the Nfe2l2 gene using BMDCs (N=3). According to the results in Figures 13 and 14, the expression level of the Nfe2l2 gene increased in both CAL-1 cells and BMDCs when LC-Plasma was added. This revealed that LC-Plasma increases the expression level of the Nfe2l2 gene in immune cells. < / h1> < / h13> < / h13> < / h13> < / h13> < / h13> < / h13> < / h13> < / h13> < / h13> < / h1> < / h1> < / h1> < / h7> < / h1> < / h6> < / h7> < / h5> < / g1> < / g1> < / g1> < / g13> < / g13> < / g13> < / g13> < / g13> < / g13> < / g13> < / g13> < / g13> < / g1> < / g1> < / g1> < / g1> < / g1> < / g1> < / g1> < / g1> < / f1> < / f1> < / f1> < / f13> < / f13> < / f13> < / f13> < / f13> < / f13> < / f13> < / f13> < / f13> < / f1> < / f1> < / f1> < / f1> < / f1> < / f1> < / f1> < / f1> < / e1> < / e1> < / e13> < / e13> < / e13> < / e13> < / e13> < / e13> < / e13> < / e13> < / e13> < / e1> < / e1> < / e1> < / e1> < / e1> < / e1> < / e1> < / e1> < / d1> < / d1> < / d13> < / d13> < / d13> < / d13> < / d13> < / d13> < / d13> < / d13> < / d13> < / d1> < / d1> < / d1> < / d1> < / d1> < / d1> < / d1> < / d1> < / c1> < / c1> < / c13> < / c13> < / c13> < / c13> < / c13> < / c13> < / c13> < / c13> < / c13> < / c13> < / c1> < / c1> < / c1> < / c1> < / c1> < / c1> < / c1> < / c1> < / b1> < / b1> < / b1> < / b13> < / b13> < / b13> < / b13> < / b13> < / b13> < / b13> < / b13> < / b13> < / b1> < / b1> < / b1> < / b1> < / b1> < / b1> < / b1> < / b1> < / a1> < / a13> < / a13> < / a13> < / a13> < / a13> < / a13> < / a13> < / a13> < / a13> < / a1> < / a1> < / a1> < / a1> < / a1> < / a1> < / a1> < / a1>

Claims

1. A composition for increasing the glutathione concentration in immune cells, comprising lactic acid bacteria that are phagocytosed by immune cells.

2. The composition according to claim 1, wherein the immune cells are immune cells having phagocytic ability.

3. The composition according to claim 1, wherein the immune cells are at least one selected from the group consisting of plasmacytoid dendritic cells and myeloid dendritic cells.

4. The composition according to claim 1, wherein the immune cells are peripheral blood mononuclear cells.

5. The composition according to claim 1, wherein the lactic acid bacteria is at least one selected from the group consisting of Lactococcus, Bifidobacterium, Lactobacillus, Rimosilactobacillus, Lacticaseibacillus, Pediococcus, and Lactiplantibacillus.

6. The aforementioned lactic acid bacteria include Lactococcus lactis, Lactococcus lactis subspecies lactis, Bifidobacterium longum, Bifidobacterium longum subspecies longum, Lactobacillus acidophilus, and Lactobacillus helveticus. Helveticus), Limosilactobacillus reuteri, Limosilactobacillus reuteri subsp. reuteri, Lacticaseibacillus paracasei, Lacticaseibacillus paracasei subsp. paracasei, Lacticaseibacillus casei Lactobacillus crispatus, Lactobacillus johnsonii, Pediococcus acidilactici, Pediococcus pentosaceus, Lacticaseibacillus rhamnosus, Lactiplantibacillus plantarum Lactobacillus plantarum, Lactobacillus plantarum subspecies plantarum, and Lactobacillus plantarumThe composition according to claim 1, which is at least one selected from the group consisting of (plantarum).

7. The aforementioned lactic acid bacteria are Lactococcus lactis subspecies lactis JCM 5805, Bifidobacterium longum subspecies longum JCM 11340, Lactobacillus acidophilus JCM 1021, and Lactobacillus helveticus JCM 1003. Limosilactobacillus reuteri subspecies reuteri (JCM) 1112. Lacticaseibacillus paracasei subspecies paracasei (JCM) 1053. Lacticaseibacillus casei (JCM) 1134. Lactobacillus crispatus (JCM) 1185, Lactobacillus johnsonii JCM 2012, Pediococcus acidilactici JCM 2014, Pediococcus acidilactici JCM 8797, Pediococcus pentosaceus JCM 5890, Lactobacillus acidophilus JCM 1132. Lacticaseibacillus rhamnosus (JCM) 1136. Lactiplantibacillus plantarum subspecies plantarum (JCM) 1149 and Lactobacillus plantarumThe composition according to claim 1, wherein it is at least one selected from the group consisting of L-137.

8. The composition according to claim 1, wherein the lactic acid bacterium is Lactococcus lactis subspecies lactis JCM 5805.

9. The composition according to claim 1, for administration to or ingestion to a subject in which the glutathione concentration in the immune cells has decreased.

10. The composition according to claim 9, wherein the subject in which the glutathione concentration in the immune cells is reduced is a human being 40 years of age or older.

11. The composition according to claim 1, which increases the expression level of the NRF2 protein and / or mRNA encoding it within the immune cells.

12. The composition according to any one of claims 1 to 11, wherein the composition is used for at least one selected from the group consisting of protecting the immune cells and suppressing the decrease of the immune cells.

13. The composition according to any one of claims 1 to 11, wherein the composition is used for at least one selected from the group consisting of antioxidant and intracellular oxidative stress suppression.

14. A composition for protecting immune cells and / or a composition for suppressing the decrease of immune cells, comprising lactic acid bacteria that are phagocytosed by immune cells.

15. An antioxidant composition and / or a composition for suppressing intracellular oxidative stress, containing lactic acid bacteria that are phagocytosed by immune cells.

16. The composition according to claim 14 or 15, which increases the expression level of NRF2 protein and / or mRNA encoding it in the immune cells.

17. A composition for increasing the expression level of the NRF2 protein and / or the mRNA encoding it of immune cells, comprising lactic acid bacteria that are phagocytosed by immune cells.

18. The composition according to claim 14, 15, or 17, wherein the composition is used to increase the glutathione concentration in the immune cells.

19. The composition according to claim 14, 15, or 17, wherein the immune cells are immune cells having phagocytic ability.

20. The composition according to claim 14, 15, or 17, wherein the immune cells are at least one selected from the group consisting of plasmacytoid dendritic cells and myeloid dendritic cells.

21. The composition according to claim 14, 15, or 17, wherein the immune cells are peripheral blood mononuclear cells.

22. The composition according to claim 14, 15, or 17, wherein the lactic acid bacteria is at least one selected from the group consisting of Lactococcus, Bifidobacterium, Lactobacillus, Rimosilactobacillus, Lacticaseibacillus, Pediococcus, and Lactiplantibacillus.

23. The aforementioned lactic acid bacteria include Lactococcus lactis, Lactococcus lactis subspecies lactis, Bifidobacterium longum, Bifidobacterium longum subspecies longum, Lactobacillus acidophilus, and Lactobacillus helveticus. Helveticus), Limosilactobacillus reuteri, Limosilactobacillus reuteri subsp. reuteri, Lacticaseibacillus paracasei, Lacticaseibacillus paracasei subsp. paracasei, Lacticaseibacillus casei Lactobacillus crispatus, Lactobacillus johnsonii, Pediococcus acidilactici, Pediococcus pentosaceus, Lacticaseibacillus rhamnosus, Lactiplantibacillus plantarum Lactobacillus plantarum, Lactobacillus plantarum subspecies plantarum, and Lactobacillus plantarumThe composition according to claim 14, 15, or 17, wherein it is at least one selected from the group consisting of (plantarum).

24. The aforementioned lactic acid bacteria are Lactococcus lactis subspecies lactis JCM 5805, Bifidobacterium longum subspecies longum JCM 11340, Lactobacillus acidophilus JCM 1021, and Lactobacillus helveticus JCM 1003. Limosilactobacillus reuteri subspecies reuteri (JCM) 1112. Lacticaseibacillus paracasei subspecies paracasei (JCM) 1053. Lacticaseibacillus casei (JCM) 1134. Lactobacillus crispatus (JCM) 1185, Lactobacillus johnsonii JCM 2012, Pediococcus acidilactici JCM 2014, Pediococcus acidilactici JCM 8797, Pediococcus pentosaceus JCM 5890, Lactobacillus acidophilus JCM 1132. Lacticaseibacillus rhamnosus (JCM) 1136. Lactiplantibacillus plantarum subspecies plantarum (JCM) 1149 and Lactobacillus plantarumThe composition according to claim 14, 15, or 17, wherein it is at least one selected from the group consisting of L-137.

25. The composition according to claim 14, 15, or 17, wherein the lactic acid bacterium is Lactococcus lactis subspecies lactis JCM 5805.

26. The composition according to claim 14, 15, or 17, for administration to or ingestion to a subject in which the glutathione concentration in the immune cells has decreased.

27. The composition according to claim 26, wherein the subject in which the glutathione concentration in the immune cells is reduced is a human being 40 years of age or older.

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