Abstract
Inflammatory bowel diseases (IBDs) develop as a result of complex interactions among genes, innate immunity and environmental factors, which are related to the gut microbiota. Multiple clinical and animal data have shown that Akkermansia muciniphila is associated with a healthy mucosa. However, its precise role in colitis is currently unknown. Our study aimed to determine its protective effects and underlying mechanisms in a dextran sulfate sodium (DSS)-induced colitis mouse model. Twenty-four C57BL/6 male mice were administered A. muciniphila MucT or phosphate-buffered saline (PBS) once daily by oral gavage for 14 days. Colitis was induced by drinking 2% DSS from days 0 to 6, followed by 2 days of drinking normal water. Mice were weighed daily and then sacrificed on day 8. We found that A. muciniphila improved DSS-induced colitis, which was evidenced by reduced weight loss, colon length shortening and histopathology scores and enhanced barrier function. Serum and tissue levels of inflammatory cytokines and chemokines (TNF-α, IL1α, IL6, IL12A, MIP-1A, G-CSF, and KC) decreased as a result of A. muciniphila administration. Analysis of 16S rDNA sequences showed that A. muciniphila induced significant gut microbiota alterations. Furthermore, correlation analysis indicated that pro-inflammatory cytokines and other injury factors were negatively associated with Verrucomicrobia, Akkermansia, Ruminococcaceae, and Rikenellaceae, which were prominently abundant in A. muciniphila-treated mice. We confirmed that A. muciniphila treatment could ameliorate mucosal inflammation either via microbe-host interactions, which protect the gut barrier function and reduce the levels of inflammatory cytokines, or by improving the microbial community. Our findings suggest that A. muciniphila may be a potential probiotic agent for ameliorating colitis.
Highlights
Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn’s disease (CD), have developed into a global scourge with an increasing incidence and prevalence worldwide in the last 50 years (Kaplan, 2015; Parada Venegas et al, 2019)
Png et al (2010) observed that the abundance of A. muciniphila was markedly reduced in patients with IBD compared with the abundance in controls, indicating that A. muciniphila may be related to the health of the intestinal mucosa. These findings indicate that A. muciniphila might play a crucial role in protecting against intestinal injury, which occurs in IBD
Our results demonstrated that A. muciniphila treatment exerted a protective effect against mouse colitis by inhibiting some critical components associated with the inflammatory response, including pro-inflammatory cytokines (TNF-α, IL6, IL12A, INF-γ, and IL1α), anti-inflammatory cytokines (IL10), and chemokines (MIP-1α, granulocyte colony-stimulating factor (G-CSF), and keratinocyte-derived chemokine (KC))
Summary
Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn’s disease (CD), have developed into a global scourge with an increasing incidence and prevalence worldwide in the last 50 years (Kaplan, 2015; Parada Venegas et al, 2019). IBDs were convincingly shown to develop as a result of complex interactions among genes, innate immunity and environmental factors. Gut microbiota, relevant to the mucosal immunity and host metabolism, is likely the most crucial environmental factors in IBD pathogenesis. Multiple studies have confirmed that gut microbiota plays an key role in the severity and progression of colitis in IBD patients (Marion-Letellier et al, 2016). Dextran sulfate sodium (DSS) administration is a chemical method to induce colitis, which results in similar key clinical and pathological features of IBDs to those in humans (Okayasu et al, 1990). DSS administration is believed to impair intestinal epithelial cells due to its toxicity. Based on the properties of colitis, this method is suitable to investigate the impacts of the intestinal microbiota on colitis progression (Hudcovic et al, 2001; Hernandez-Chirlaque et al, 2016). DSS-induced colitis has been broadly applied as a model for its simplicity and reproducibility
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