Dataset Information

Lactobacillus pentosus Increases the Abundance of Akkermansia and Affects the Serum Metabolome to Alleviate DSS-Induced Colitis in a Murine Model.

ABSTRACT: Lactobacillus pentosus has the beneficial function of regulating the host's immune system and plays an indispensable role in intestinal health. The purpose of this study was to investigate the specific mechanism by which L. pentosus relieves dextran sulfate sodium (DSS) induced ulcerative colon inflammation. We randomly divided 24 mice into three groups, which were administered either a basic diet, drinking water with 2.5% DSS (DSS), or drinking water with 2.5% DSS and intragastric administration of L. pentosus (DSS + L. pentosus). DSS was added to the drinking water on days 8 to 12, and L. pentosus was administered on days 12 to 19. Serum was collected for metabolomic analysis, colon length and weight were measured, and colon contents were collected to detect microbial structural composition. Compared with the DSS group, the DSS + L. pentosus group had significantly higher levels of indolepyruvate and pantothenic acid in the serum and significantly lower levels of 3,4-dimethyl-5-pentyl-2-furannonanoic acid and 5-oxo-6-trans-leukotriene B4. Moreover, compared with the other two groups, the DSS + L. pentosus group had a significantly greater abundance of Akkermansia. The abundance of Akkermansia was positively correlated with indolepyruvate and pantothenic acid levels. Therefore, L. pentosus can interact with Akkermansia to increase its abundance in the intestinal tract. This results in the production of metabolites that are beneficial for the regulation of intestinal immunity, thereby alleviating DSS-induced ulcerative colon inflammation.

SUBMITTER: Ma Y

PROVIDER: S-EPMC7609924 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Lactobacillus pentosus Increases the Abundance of Akkermansia and Affects the Serum Metabolome to Alleviate DSS-Induced Colitis in a Murine Model.

Ma Yong Y Hu Chao C Yan Wenxin W Jiang Hongmei H Liu Gang G

Frontiers in cell and developmental biology 20201021

Lactobacillus pentosus has the beneficial function of regulating the host's immune system and plays an indispensable role in intestinal health. The purpose of this study was to investigate the specific mechanism by which L. pentosus relieves dextran sulfate sodium (DSS) induced ulcerative colon inflammation. We randomly divided 24 mice into three groups, which were administered either a basic diet, drinking water with 2.5% DSS (DSS), or drinking water with 2.5% DSS and intragastric ...[more]

PMID: 33195257

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Project description:Akkermansia muciniphila has been proved to play a crucial role in the progression of colitis, but its underlying mechanism remains inconclusive. In this study, we aim to investigate the effect of A. muciniphila on the development of acute colitis and explore the underlying mechanism. We found that the fecal level of A. muciniphila was decreased in ulcerative colitis (UC) patients compared to the healthy people in the GMrepo database. Oral administration of A. muciniphila strain BAA-835 significantly ameliorated the symptoms in dextran sulfate sodium (DSS)-induced acute colitis, evidenced by decreased body weight loss, colon length shortening, and colon histological inflammatory score. In addition, the number of goblet cells and the mucin family were enhanced after A. muciniphila treatment. Furthermore, proinflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and monocyte chemoattractant protein 1 (MCP-1) had a downward trend. Mechanistically, the expression of NLRP3, caspase-1 p20, and IL-1β p17 were upregulated in A. muciniphila-treated mice. Additionally, the colon tissues from high-A. muciniphila UC patients had a higher NLRP3 expression than that from low-A. muciniphila UC patients. Moreover, the upregulation of NLRP3 was observed in mouse macrophage Raw264.7 cells and bone marrow-derived macrophage (BMDM) cells after incubation with A. muciniphila. To clarify whether the protective effect of A. muciniphila in colitis depends on NLRP3, we performed the NLRP3-deficient assay in NLRP3-/- mice in vivo. The evidence showed that NLRP3 deficiency eliminated the protective effects of A. muciniphila in acute colitis. In conclusion, A. muciniphila alleviates DSS-induced acute colitis by NLRP3 activation, which enriches the mechanism and provides a new prospect for the probiotic-based treatment of colitis. IMPORTANCE The gut microbiota and host immune response interaction influences the progression of intestinal inflammatory disease. As a well-recognized next-generation probiotic, Akkermansia muciniphila has been proved to play a crucial role in the progression of colitis, but its underlying mechanism remains inconclusive. We found that oral administration of A. muciniphila strain BAA-835 significantly ameliorated the symptoms of acute colitis. Mechanistically, the expression of NLRP3 was upregulated in the A. muciniphila group, and the protective effect of A. muciniphila in colitis depends on NLRP3 activation. This enriches the mechanism and provides a new prospect for the probiotic-based treatment of colitis, which would promote a deeper understanding of the complex characteristics of A. muciniphila and provide guidance for the treatment of human colitis in the future.

Project description:Akkermansia muciniphila is a commensal bacterium of the gut mucus layer. Although both in vitro and in vivo data have shown that A. muciniphila strains exhibit strain-specific modulation of gut functions, its ability to moderate immunity to ulcerative colitis have not been verified. We selected three isolated human A. muciniphila strains (FSDLZ39M14, FSDLZ36M5 and FSDLZ20M4) and the A. muciniphila type strain ATCC BAA-835 to examine the effects of different A. muciniphila strains on dextran sulfate sodium-induced colitis. All of the A. muciniphila strains were cultured anaerobically in brain heart infusion medium supplemented with 0.25% type II mucin from porcine stomach. To create animal models, colitis was established in C57BL/6 mice which randomly divided into six groups with 10 mice in each group by adding 3% dextran sulfate sodium to drinking water for 7 days. A. muciniphila strains were orally administered to the mice at a dose of 1 × 109 CFU. Only A. muciniphila FSDLZ36M5 exerted significant protection against ulcerative colitis (UC) by increasing the colon length, restoring body weight, decreasing gut permeability and promoting anti-inflammatory cytokine expression. However, the other strains (FSDLZ39M14, ATCC BAA-835 and FSDLZ20M4) failed to provide these effects. Notably, A. muciniphila FSDLZ20M4 showed a tendency to exacerbate inflammation according to several indicators. Gut microbiota sequencing showed that A. muciniphila FSDLZ36M5 supplementation recovered the gut microbiota of mice to a similar state to that of the control group. A comparative genomic analysis demonstrated that the positive effects of A. muciniphila FSDLZ36M5 compared with the FSDLZ20M4 strain may be associated with specific functional genes that are involved in immune defense mechanisms and protein synthesis. Our results verify the efficacy of A. muciniphila in improving UC and provide gene targets for the efficient and rapid screening of A. muciniphila strains with UC-alleviating effects.

Dataset Information

Lactobacillus pentosus Increases the Abundance of Akkermansia and Affects the Serum Metabolome to Alleviate DSS-Induced Colitis in a Murine Model.

Publications

<i>Lactobacillus pentosus</i> Increases the Abundance of <i>Akkermansia</i> and Affects the Serum Metabolome to Alleviate DSS-Induced Colitis in a Murine Model.

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