Akkermansia muciniphila Alleviates Dextran Sulfate Sodium (DSS)-Induced Acute Colitis by NLRP3 Activation

Qu, Siwen; Fan, Li; Qi, Yadong; Xu, Chaochao; Hu, Yingying; Chen, Shujie; Liu, Wei; Liu, Weili; Si, Jianmin

doi:10.1128/spectrum.00730-21

Cited by 147 publications

(102 citation statements)

References 47 publications

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“…After combing and analyzing the existing literature, we found that a large number of studies induced animal models of UC with 2.5% or higher concentration of DSS and carried out relevant basic studies on gut microbiome and immune inflammation. 36–39 Other studies have found that the relative abundance of some bacteria ( Bacteroides , norank_f_Muribaculaceae, Turicibacter , Romboutsia , Clostridium_sensu_stricto_1) in the intestinal tract of DSS-induced UC model changed significantly. 40–43 In addition, the altered bacteria could trigger changes in levels of relevant inflammatory factors.…”

Section: Introductionmentioning

confidence: 95%

Dynamic Changes in Gut Microbiome of Ulcerative Colitis: Initial Study from Animal Model

Gu¹,

Zhang²,

Han³

et al. 2022

JIR

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Background An animal model of DSS-induced UC has been widely used in basic research, and the dysbiosis of gut microbiome is one of the important pathogenetic mechanisms of DSS-induced UC, but its dynamic changes and correlation with inflammatory factors are not clear yet. Methods Clinical signs and tissue damage degree of C57BL/6 ulcerative colitis mice model induced by different concentrations of DSS were compared with that of normal mice, and finally the optimal concentration of DSS was determined. Then we analyzed the sequencing results of gut microbiome and inflammatory factors to determine the dynamic patterns of gut microbiome and their correlation with the inflammatory factors. Results DSS at 2.5% and 3.0% concentration could cause intestinal injury and induce colitis. However, 3.0% DSS resulted in higher mortality. In addition, there were dynamic changes of gut microbiome in DSS-induced UC model: the relative abundance of intestinal flora increased first and then decreased in Bacteroides , Parabacteroides , Romboutsia , Clostridium_sensu_stricto_1, Lachnospiraceae_NK4A136_group, norank_f_norank_o_Clostridia_UCG-014, Parasutterella , and decreased first and then increased in Lactobacillus , Muribaculum , norank_f_Muribaculaceae, in addition, Bifidobacterium , Coriobacteriaceae_UCG-002 and Enterorhabdus did not change in the first 14 days but increased significantly on day 21. Moreover, inflammatory cytokines were closely associated with the imbalance of the intestinal microbiota in mice with UC: most pathogenic bacteria in the intestinal tract of the UC animal model were positively correlated with pro-inflammatory factors and negatively correlated with anti-inflammatory factors, while beneficial bacteria were the opposite. Conclusion Intestinal microecology plays an important role in DSS-induced UC model, and the relative abundance of gut microbiome changes dynamically in the occurrence and development of ulcerative colitis.

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Section: Introductionmentioning

confidence: 95%

Dynamic Changes in Gut Microbiome of Ulcerative Colitis: Initial Study from Animal Model

Gu¹,

Zhang²,

Han³

et al. 2022

JIR

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“…It has been reported that antibiotic use during childhood alters the gut microbiota and increases susceptibility to IBD, suggesting an important role of gut microbiota in the maintenance of intestinal homeostasis ( 26 ). Several studies have found differences in the composition of the gut microbiota between healthy people and patients with IBD, with a remarkable reduction in A. muciniphila in patients with UC ( 16 , 27 ). Furthermore, it has been reported that A. muciniphila or Amuc_1100 (an outer membrane protein of A. muciniphila ) can attenuate DSS-induced colitis in mice.…”

Section: Role Of a Muciniphila In Protecting Again...mentioning

confidence: 99%

“…A recent study has shown that Amuc_2109, an enzyme secreted by A. muciniphila , also attenuated DSS-induced colitis in mice, increasing the expression of TJs and reducing the expression of the NLRP3 inflammasome ( 30 ). However, the protective effect of viable A. muciniphila against DSS-induced colitis was shown to be dependent of NLRP3 activation ( 27 ). Indeed, the role of NLRP3 in the regulation of intestinal homeostasis was previously elucidated, since NLRP3 -/- mice are more susceptible to the development of experimentally induced colitis ( 31 ).Additionally, it was demonstrated that the administration of A. muciniphila induced the proliferation of intestinal stem cells and boosted the differentiation of Paneth and goblet cells in the small intestine and colon of healthy mice or mice with gut damage caused by radiation and methotrexate.…”

Section: Role Of a Muciniphila In Protecting Again...mentioning

confidence: 99%

Akkermansia muciniphila and Gut Immune System: A Good Friendship That Attenuates Inflammatory Bowel Disease, Obesity, and Diabetes

et al. 2022

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Akkermansia muciniphila is a Gram-negative anaerobic mucus-layer-degrading bacterium that colonizes the intestinal mucosa of humans and rodents. Metagenomic data have shown an inverse correlation between the abundance of A. muciniphila and diseases such as inflammatory bowel disease (IBD), obesity, and diabetes. Thus, in recent decades, the potential of this bacterium as an immunomodulatory probiotic for autoimmune and chronic inflammatory diseases has been explored in experimental models. Corroborating these human correlation data, it has been reported that A. muciniphila slows down the development and progression of diabetes, obesity, and IBD in mice. Consequently, clinical studies with obese and diabetic patients are being performed, and the preliminary results are very promising. Therefore, this mini review highlights the main findings regarding the beneficial roles of A. muciniphila and its action mechanisms in autoimmune and chronic inflammatory diseases.

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“…Intestinal dysbiosis exacerbates colitis by promoting ubiquitination and accumulation of the innate immune adaptor stimulator of interferon genes (STING) in myeloid cells [ 40 ]. Olu et al confirmed that oral administration of Akkermansia muciniphila strain BAA-835 considerably ameliorated colitis by modulating intestinal microecology [ 45 ]. Larsen et al reported that lysozyme leveraged gut microbiota to inhibit DSS-induced colitis [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Sex-Biased Immune Responses to Antibiotics during Anti-PD-L1 Treatment in Mice with Colon Cancer

Jing

Wang

Zhuang

et al. 2022

Journal of Immunology Research

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Colitis is a frequently occurred side effect of immune checkpoint inhibitors (ICIs), which are increasingly used in cancer treatment, whereas antibiotics are widely used to treat colitis, their effectiveness in ICI-associated colitis remains controversial. In this study, we firstly assessed the effectiveness of several commonly used antibiotics and antibiotic cocktails in alleviating of dextran sulfate sodium- (DSS-) induced colitis. We observed that two narrow-spectrum antibiotics, neomycin and metronidazole, were more effective in alleviating colitis, as evidenced by the remission of loss of the body weight, enlargement of the spleen, shortening of the colon, secretion of proinflammatory cytokines, and histological score of the colon tissue. Moreover, these two antibiotics resulted in better relief of colitis symptoms in the MC38 tumor-bearing male mice receiving the anti-PD-L1 mAb (αPD-L1) treatment, compared to the females. In the meantime, an enhanced response to αPD-L1 efficiency against mice colon cancer was observed in the male mouse group upon the application of these two antibiotics. In contrast, both neomycin and metronidazole showed destructive effects on the antitumor efficiency of αPD-L1 in female mice, despite relief from colitis. We found that antibiotic treatment attenuated the increased infiltration of granulocytes and myeloid cells in colon tissue induced by DSS in female mice, while reducing the proportion of Th17 cells in male mice. These differences were further associated with the sex-biased differences in the gut microbiota. These findings indicated that sex-dependent alterations in the gut microbiota should be considered when applying antibiotics for the treatment of ICI-associated colitis.

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Akkermansia muciniphila Alleviates Dextran Sulfate Sodium (DSS)-Induced Acute Colitis by NLRP3 Activation

Cited by 147 publications

References 47 publications

Dynamic Changes in Gut Microbiome of Ulcerative Colitis: Initial Study from Animal Model

Dynamic Changes in Gut Microbiome of Ulcerative Colitis: Initial Study from Animal Model

Akkermansia muciniphila and Gut Immune System: A Good Friendship That Attenuates Inflammatory Bowel Disease, Obesity, and Diabetes

Sex-Biased Immune Responses to Antibiotics during Anti-PD-L1 Treatment in Mice with Colon Cancer

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