Administration of Akkermansia muciniphila Ameliorates Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice

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.

Pediococcus pentosaceus LI05 alleviates DSS‐induced colitis by modulating immunological profiles, the gut microbiota and short‐chain fatty acid levels in a mouse model

“…Remarkably, compelling evidence has shown that the level of the anti‐inflammatory cytokine IL10 is increased after probiotic treatments (e.g. Lactobacillus GG, VSL#3, and Akkermansia ) in animal models of colitis (Dieleman et al , 2003; Lammers et al , 2003; Bian et al , 2019), consistent with our findings.…”

“…Notably, an increased abundance of the genus Akkermansia was observed in mice treated with P. pentosaceus LI05 in our study. Multiple studies have reported a reduced abundance of Akkermansia in both patients with IBD and animals with colitis (Png et al , 2010; Bian et al , 2019). Akkermansia, a mucin‐degrading bacterium, has been shown to degrade mucin into multiple metabolites, such as SCFAs, subsequently regulating host immune responses and biological functions, including glucose and lipid metabolism (Derrien et al , 2004).…”

“…A permeability probe, fluorescein isothiocyanate‐conjugated (FITC)–dextran (3–5 kDa, Sigma‐Aldrich), was applied for the intestinal permeability analysis, as previously described (Bian et al , 2019). Animals were treated with FITC–dextran (12 mg per 20 g body weight) by gavage after an overnight fast.…”

Fish Oil, Cannabidiol and the Gut Microbiota: An Investigation in a Murine Model of Colitis

“…A. muciniphila , a species that plays a beneficial role in inflammation and was previously reported to be increased in murine models of IBDs and to mediate the anti-inflammatory effects of several treatments on these models ( Bian et al, 2019 ; Li et al, 2019 ; Zhai R. et al, 2019 ; Zhang et al, 2019 ), was increased by DSS only at d14, suggesting that this effect might represent a potentially adaptive and protective mechanism intervening the resolution of inflammation. Importantly, this effect was rendered statistically significant also at d8 by a combination of per se ineffective doses of FO and CBD, but also by the single treatments.…”

Latexin deficiency in mice up-regulates inflammation and aggravates colitis through HECTD1/Rps3/NF-κB pathway

“…Data are representative of three independent experiments. (2020) 10:9868 | https://doi.org/10.1038/s41598-020-66789-x www.nature.com/scientificreports www.nature.com/scientificreports/ colitis model is the most widely used 23,[30][31][32] . In animal model, we found that LXN deficiency leads to severity of DSS colitis, which can be demonstrated by a number of clinicopathological indicators, including more severe weight loss, hematochezia, shortening of the colon and rectum, damage to the mucosa and loss of goblet cells, increased proinflammatory cytokines and increased STAT3 activity.…”