<i>B. adolescentis</i> ameliorates chronic colitis by regulating Treg/Th2 response and gut microbiota remodeling

Abstract

Inflammatory bowel disease (IBD) is defined as an immune dysregulation disease with poor prognosis. Various therapies based on gut microbe modulation have been proposed. In this study, we aim to explore the therapeutic effect of <i>B. adolescentis</i> on IBD, as well as the immune and microecology mechanism of <i>B. adolescentis</i> in IBD. The fecal level of <i>B. adolescentis</i> was decreased in the IBD patients compared with the normal people in our cohort and the GMrepo database. To further clarify the role of <i>B. adolescentis</i> in IBD, we induced chronic colitis with three cycles of dextran sulfate sodium (DSS). We found <i>B. adolescentis</i> gavage exhibited protective effects as evidenced by the significantly decreased diarrhea score, spleen weight, and increased colon length. Accordingly, the cumulative histological grading was decreased in the <i>B. adolescentis</i> administration group. In addition, tight junction protein and mucin family were enhanced after <i>B. adolescentis</i> treatment. Furthermore, distinct effects were found with decreased pro-inflammatory cytokines such as TNF-α, IL-6, IL-1β, IL-18, IL-22, IL-9 and increased anti-inflammatory cytokines IL-10, IL-4, IL-5. Importantly, the colon lamina propria in the <i>B. adolescentis</i> group consisted of more Treg and Th2 cells, which inhibited extreme gut inflammation. Additionally, 16srRNA sequencing showed an evident increase in the B:F ratio in the <i>B. adolescentis</i> group. In particular, <i>B. adolescentis</i> application inhibited the excessive growth of <i>Akkermansia</i> and <i>Escherichia-Shigella</i> in genus level. In conclusion, <i>B. adolescentis</i> refined the DSS-induced chronic colitis by stimulating protective Treg/Th2 response and gut microbiota remodeling. <i>B. adolescentis</i> regularly treatment might improve the therapeutic effects for inflammatory bowel disease.