Obesogenic diet-induced gut barrier dysfunction and pathobiont expansion aggravate experimental colitis

Abstract

Consumption of a typical Western diet is a risk factor for several disorders. Metabolic syndrome is the most common disease associated with intake of excess fat. However, the incidence of inflammatory bowel disease is also greater in subjects consuming a Western diet, although the mechanism of this phenomenon is not clearly understood. We examined the morphological and functional changes of the intestine, the first site contacting dietary fat, in mice fed a high-fat diet (HFD) inducing obesity. Paneth cell area and production of antimicrobial peptides by Paneth cells were decreased in HFD-fed mice. Goblet cell number and secretion of mucin by goblet cells were also decreased, while intestinal permeability was increased in HFD-fed mice. HFD-fed mice were more susceptible to experimental colitis, and exhibited severe colonic inflammation, accompanied by the expansion of selected pathobionts such as Atopobium sp. and Proteobacteria. Fecal microbiota transplantation transferred the susceptibility to DSS-colitis, and antibiotic treatment abrogated colitis progression. These data suggest that an experimental HFD-induced Paneth cell dysfunction and subsequent intestinal dysbiosis characterized by pathobiont expansion can be predisposing factors to the development of inflammatory bowel disease.

OGG1 deficiency alters the intestinal microbiome and increases intestinal inflammation in a mouse model

“…In addition, while Bacteroidetes Rikenellaceae AF12 taxa were also found to be present in WT gut microbiomes (but < 0.01% compared to Ogg1 -/gut microbiomes and > 5% in Ogg1 -/-HFD), these microorganisms are of note as they have been reported to increase in the gut microbiomes of mouse models exhibiting DSSinduced or spontaneous chronic colitis in comparison to wild-type controls [87]. Finally, Proteobacteria in the Helicobacteriace and Sutterella groups have been reported to be elevated under conditions of DSS-induced colitis [74,88]. It is notable that many of these pro-inflammatory changes were present in chow-fed Ogg1 -/mice and were further exacerbated in HFDfed animals.…”

Relationship(s) between obesity and inflammatory bowel diseases: possible intertwined pathogenic mechanisms

“…Intestinal permeability was also increased. Mice transplanted with feces from high-fat fed mice were more susceptible to dextran sulfate sodium [DSS]-induced colitis [110]. These studies support (but not prove) a direct pathogenic role of dysbiosis as primary rather than secondary in disease.…”

Role of Obesity, Mesenteric Adipose Tissue, and Adipokines in Inflammatory Bowel Diseases

“…It was demonstrated that the application of an HFD or HF/HSD diets and/or the development of obesity in mice increase(s) the intestinal permeability and bacterial translocation from the intestinal lumen to mesenteric fat, as well as profound changes in the microbiota [102,108,127,181,[184][185][186][187][188][189][190][191][192][193][194][195]. HFD or HF/HSD is also associated with significantly elevated LPS levels, the reduced expression of epithelial tight junction proteins, an increased macrophage infiltration, and the increased expression of proinflammatory biomarkers in the adipose tissue [102,127,181,[184][185][186][187][188][189][190][191][192][193][196][197][198]. Both, the Paneth cell area and the release of antimicrobial factors by Paneth cells are reduced in HFD-fed mice [197].…”