Akkermansia muciniphilaandHelicobacter typhloniusmodulate intestinal tumor development in mice

Abstract

Gastrointestinal tumor growth is thought to be promoted by gastrointestinal bacteria and their inflammatory products. We observed that intestine-specific conditional Apc mutant mice (FabplCre;Apc (15lox/+)) developed many more colorectal tumors under conventional than under pathogen-low housing conditions. Shotgun metagenomic sequencing plus quantitative PCR analysis of feces DNA revealed the presence of two bacterial species in conventional mice, absent from pathogen-low mice. One, Helicobacter typhlonius, has not been associated with cancer in man, nor in immune-competent mice. The other species, mucin-degrading Akkermansia muciniphila, is abundantly present in healthy humans, but reduced in patients with inflammatory gastrointestinal diseases and in obese and type 2 diabetic mice. Eradication of H.typhlonius in young conventional mice by antibiotics decreased the number of intestinal tumors. Additional presence of A.muciniphila prior to the antibiotic treatment reduced the tumor number even further. Colonization of pathogen-low FabplCre;Apc (15lox/+) mice with H.typhlonius or A.muciniphila increased the number of intestinal tumors, the thickness of the intestinal mucus layer and A.muciniphila colonization without H.typhlonius increased the density of mucin-producing goblet cells. However, dual colonization with H.typhlonius and A.muciniphila significantly reduced the number of intestinal tumors, the mucus layer thickness and goblet cell density to that of control mice. By global microbiota composition analysis, we found a positive association of A.muciniphila, and of H.typhlonius, and a negative association of unclassified Clostridiales with increased tumor burden. We conclude that A.muciniphila and H.typhlonius can modulate gut microbiota composition and intestinal tumor development in mice.

IL-33 regulates the IgA-microbiota axis to restrain IL-1α–dependent colitis and tumorigenesis

“…As a consequence, experimental Akkermansia colonization weakens the mucus barrier and promotes epithelial injury after administration of the cytotoxic agent heme (43). Repeated dosing with Akkermansia also leads to increased severity of DSS-induced colitis in WT mice (44) and promotes colon tumorigenesis in a mouse model of aberrant Wnt signaling in the epithelium (58). In line with these studies, we found that depletion of Akkermansia by metronidazole treatment protected Il33-deficient mice from DSS-induced colitis and associated epithelial hyperplasia.…”

Dysbiosis Contributes to Chronic Constipation Development via Regulation of Serotonin Transporter in the Intestine

“…In our study, pyrosequencing analysis showed that the mice in FMT-C group were rich in the Akkmermansia, and Akkmermansia can degrade intestinal mucin leading to dry stool and finally the impairment of intestinal mucosal barrier, but the mechanisms still need further study. This finding was in accordance with the role of Akkermansia in colorectal cancer in the mice 46 . Moreover, the proportion of Verrucomicrobia increased in colon cancer patients, and the level of Akkermansia increased about 4 times compared with the control group 47 .…”

Alterations of Urinary Microbiota in Type 2 Diabetes Mellitus with Hypertension and/or Hyperlipidemia

“…Notably, Akkermansia and Bifidobacterium , which are considered probiotic bacteria, were detected in all four cohorts. In a previous intestinal microbiota study, the relative abundance of Akkermansia was lower in patients with inflammatory diseases compared to healthy humans, and was also lower in diabetic mice (Dingemanse et al, 2015). Bifidobacterium has been shown to be able to reduce levels of intestinal endotoxins and improve the mucosal barrier, which results in reduced systemic inflammation (Cani et al, 2008).…”