Akkermansia muciniphila Exerts Strain-Specific Effects on DSS-Induced Ulcerative Colitis in Mice

Abstract

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.

Variation in the Efficacy of Anti-Ulcerative Colitis Treatments Reveals the Conflict Between Precipitating Compatibility of Traditional Chinese Medicine and Modern Technology: A Case of Scutellaria-Coptis

“…The diversity and composition of intestinal flora were rich, which was conducive to the production of anti-inflammatory factors and changes in antioxidant stress levels of colon tissues, in turn, alleviating UC symptoms after treatment of UC mice with combined decoction of Scutellaria-Coptis (Liu et al, 2020). Furthermore, ABX and FMT models confirmed that Scutellaria-Coptis alleviated UC in mice based on the composition of the gut microbiota (Liu et al, 2020; Benech and Sokol, 2020 ; Liu et al, 2021 ; Draper et al, 2018 ). Therefore, we inferred that the traditional method of extracting Scutellaria-Coptis decoction exerts a superior effect to that of separate decoction, which mainly treats UC by regulating intestinal flora, inflammation, and oxidative stress ( Figure 8 ).…”

“…The abundances of Bacteroides , Akkermansia , and Lactobacillus also changed, although the difference was not significant. The results suggest that Bacteroides was the key species of intestinal flora in DSS group, whereas Akkermansia could influence the treatment of DSS-induced colitis with Scutellaria-Coptis decoction ( Chen et al, 2017 ; Liu et al, 2021 ).…”

“…Previous studies have reported that Blautia is a key flora associated with UC ( Gough et al, 2015 ; Lan et al, 2017 ; Wei et al, 2020 ). Notably, two typical bacterial groups, including Akkermansia and Lactobacillus , which facilitate the synthesis of intestinal microbial metabolites, such as short chain fatty acids, were relatively enriched in SD and DT groups ( Liu et al, 2021 ). In addition, Akkermansia as a novel anticancer “star bacterium”, provides nutrients to the intestinal mucosa, promotes intestinal barrier function, generates certain molecular signals, stimulates and strengthens the intestinal wall, in addition to exhibiting anti-cancer, anti-aging, and anti-diabetic effects.…”

“…Furthermore, 16S rRNA sequencing was used to analyze the structure and diversity of intestinal flora, and the effect of Scutellaria-Coptis decoction on the intestinal flora of DSS-induced UC in mice was investigated ( Li et al, 2015 ; Liu et al, 2020; Singh et al, 2019 ; Zhang et al, 2020 ). The effect of Scutellaria-Coptis decoction on UC and its correlation with intestinal flora were determined using a pseudo-sterile mouse model and a flora transplantation test ( Armstrong et al, 2019 ; Liu et al, 2020; Liu et al, 2021 ). The scientific extraction technology of Scutellaria-Coptis extract employed in the present study was preliminarily described, providing reference for its clinical use and scientific basis for the preparation process design of Proprietary Chinese Medicine.…”

How Microbes Affect Depression: Underlying Mechanisms via the Gut–Brain Axis and the Modulating Role of Probiotics

“…Before the MGB axis gained research attention, extensive research sought to elucidate the relationship between the gut microbiota and inflammation and immune response, and numerous studies have shown that the gut microbiota directly affects the balance between pro-and anti-inflammatory responses in the gut [70][71][72][73]. Butyrate is also known to exert anti-inflammatory effects on immune cells.…”