Coprococcus eutactus, a Potent Probiotic, Alleviates Colitis via Acetate-Mediated IgA Response and Microbiota Restoration.

Inflammatory bowel disease (IBD) is a complex disease characterized by relapsing episodes of inflammation of the colonic mucosa. Research into IBD suggests that this disease condition is caused by alterations in resident mucosal bacterial populations. Our previous study showed that Coprococcus was significantly elevated during the improvement of IBD. Human metagenome database GMrepo also indicates Coprococcus, in particular, Coprococcus eutactus (C. eutactus), which was negatively associated with IBD. The current study implied the alleviated effects and mechanisms of C. eutactus on dextran sodium sulfate-induced experimental colitis mice. Gavage with C. eutactus-ameliorated acute colitis, as evidenced, relieved weight loss, decreased concentrations of proinflammatory cytokines TNF-α, IL-1β, and IL-6, and increased anti-inflammatory factors, IL-4, IL-5, and IL-10. In addition, C. eutactus enhanced the maturation of goblet cells and the expressions of mucins and restored the expressions of tight junction proteins such as claudin-1, occludin, and ZO-1. As a short-chain fatty acid-producing bacterium, C. eutactus mainly generates acetic acid. Interestingly, not only high levels of secretory immunoglobulin A (SIgA) but also increased IgA-producing plasma cells were observed in colitis mice during the administration of C. eutactus. Importantly, our data demonstrated that colonic SIgA is specifically coated on pathogens of Enterobacteriaceae. Owing to the selective binding effect of SIgA on microorganisms, the microbial diversity in the intestinal lumen and mucosa of C. eutactus-treated colitis mice was significantly restored, and the microbiota structure was remodeled. These findings provide substantial insight that C. eutactus as a promising probiotic can ameliorate colitis. In conclusion, our findings may deliver a novel approach to the prevention and biotherapy of IBD.

[1]  E. Villablanca,et al.  Type 2 immunity in intestinal homeostasis and inflammatory bowel disease , 2021, Biochemical Society transactions.

[2]  O. Ohara,et al.  Acetate differentially regulates IgA reactivity to commensal bacteria , 2021, Nature.

[3]  J. Raes,et al.  Short chain fatty acids and its producing organisms: An overlooked therapy for IBD? , 2021, EBioMedicine.

[4]  J. Si,et al.  B. adolescentis ameliorates chronic colitis by regulating Treg/Th2 response and gut microbiota remodeling , 2021, Gut microbes.

[5]  G. Hu,et al.  Angiogenin maintains gut microbe homeostasis by balancing α-Proteobacteria and Lachnospiraceae , 2020, Gut.

[6]  Xing-Ming Zhao,et al.  GMrepo: a database of curated and consistently annotated human gut metagenomes , 2019, Nucleic Acids Res..

[7]  N. Somboonna,et al.  Additional Candida albicans administration enhances the severity of dextran sulfate solution induced colitis mouse model through leaky gut-enhanced systemic inflammation and gut-dysbiosis but attenuated by Lactobacillus rhamnosus L34 , 2020, Gut microbes.

[8]  S. Vermeire,et al.  Anti-TNF therapy in IBD exerts its therapeutic effect through macrophage IL-10 signalling , 2019, Gut.

[9]  E. Blaak,et al.  The Short-Chain Fatty Acid Acetate in Body Weight Control and Insulin Sensitivity , 2019, Nutrients.

[10]  L. C. Xia,et al.  Identifying Gut Microbiota Associated With Colorectal Cancer Using a Zero-Inflated Lognormal Model , 2019, Front. Microbiol..

[11]  W. Alrefai,et al.  Pathophysiology of IBD associated diarrhea , 2018, Tissue barriers.

[12]  Nima Hamidi,et al.  Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies , 2017, The Lancet.

[13]  Y. Naito,et al.  Gut microbiota in the pathogenesis of inflammatory bowel disease , 2018, Clinical Journal of Gastroenterology.

[14]  A. Ivanov,et al.  Disruption of the epithelial barrier during intestinal inflammation: Quest for new molecules and mechanisms. , 2017, Biochimica et biophysica acta. Molecular cell research.

[15]  S. Ng,et al.  Understanding and Preventing the Global Increase of Inflammatory Bowel Disease. , 2017, Gastroenterology.

[16]  J. Turner,et al.  The intestinal epithelial barrier: a therapeutic target? , 2017, Nature Reviews Gastroenterology &Hepatology.

[17]  F. Liew,et al.  Interleukin-33 in health and disease , 2016, Nature Reviews Immunology.

[18]  T. Vatanen,et al.  Dysbiosis, inflammation, and response to treatment: a longitudinal study of pediatric subjects with newly diagnosed inflammatory bowel disease , 2016, Genome Medicine.

[19]  A. Hart,et al.  Tight junctions in inflammatory bowel diseases and inflammatory bowel disease associated colorectal cancer. , 2016, World journal of gastroenterology.

[20]  C. Fiocchi,et al.  Immunopathogenesis of IBD: current state of the art , 2016, Nature Reviews Gastroenterology &Hepatology.

[21]  J. Ravel,et al.  The vocabulary of microbiome research: a proposal , 2015, Microbiome.

[22]  Rustem F. Ismagilov,et al.  Indigenous Bacteria from the Gut Microbiota Regulate Host Serotonin Biosynthesis , 2015, Cell.

[23]  Judy H. Cho,et al.  Immunoglobulin A Coating Identifies Colitogenic Bacteria in Inflammatory Bowel Disease , 2014, Cell.

[24]  M. Hattori,et al.  Multiple Omics Uncovers Host–Gut Microbial Mutualism During Prebiotic Fructooligosaccharide Supplementation , 2014, DNA research : an international journal for rapid publication of reports on genes and genomes.

[25]  M. Johansson,et al.  The gastrointestinal mucus system in health and disease , 2013, Nature Reviews Gastroenterology &Hepatology.

[26]  M. Blaser,et al.  Antibiotics in early life alter the murine colonic microbiome and adiposity , 2012, Nature.

[27]  Richard Hansen,et al.  IBD—what role do Proteobacteria play? , 2012, Nature Reviews Gastroenterology &Hepatology.

[28]  F. Bäckhed,et al.  Tissue factor and PAR1 promote microbiota-induced intestinal vascular remodelling , 2012, Nature.

[29]  W. Khan,et al.  Investigating intestinal inflammation in DSS-induced model of IBD. , 2012, Journal of visualized experiments : JoVE.

[30]  Wei Sun,et al.  The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon. , 2011, Cell metabolism.

[31]  Julian Parkhill,et al.  High-throughput clone library analysis of the mucosa-associated microbiota reveals dysbiosis and differences between inflamed and non-inflamed regions of the intestine in inflammatory bowel disease , 2011, BMC Microbiology.

[32]  Zaid Abdo,et al.  Molecular characterization of mucosal adherent bacteria and associations with colorectal adenomas , 2010, Gut microbes.

[33]  Keiichiro Suzuki,et al.  Adaptive immune regulation in the gut: T cell-dependent and T cell-independent IgA synthesis. , 2010, Annual review of immunology.

[34]  R. Xavier,et al.  Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43 , 2009, Nature.

[35]  Ian R. Holzman,et al.  Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers. , 2009, The Journal of nutrition.

[36]  Janet K. Jansson,et al.  Twin studies reveal specific imbalances in the mucosa‐associated microbiota of patients with ileal Crohn's disease , 2009, Inflammatory bowel diseases.

[37]  Harry J. Flint,et al.  Diversity, metabolism and microbial ecology of butyrate-producing bacteria from the human large intestine. , 2009, FEMS microbiology letters.

[38]  A. Cerutti The regulation of IgA class switching , 2008, Nature Reviews Immunology.

[39]  B. Finlay,et al.  Host-mediated inflammation disrupts the intestinal microbiota and promotes the overgrowth of Enterobacteriaceae. , 2007, Cell host & microbe.

[40]  D. Connolly,et al.  (d)-β-Hydroxybutyrate Inhibits Adipocyte Lipolysis via the Nicotinic Acid Receptor PUMA-G* , 2005, Journal of Biological Chemistry.

[41]  S. Dowell,et al.  The Orphan G Protein-coupled Receptors GPR41 and GPR43 Are Activated by Propionate and Other Short Chain Carboxylic Acids* , 2003, The Journal of Biological Chemistry.

[42]  Domschke,et al.  IL‐4, IL‐10 and IL‐13 down‐regulate monocyte‐chemoattracting protein‐1 (MCP‐1) production in activated intestinal epithelial cells , 1998, Clinical and experimental immunology.