Abstract
Obesity is associated with metabolic, immunological, and infectious disease comorbidities, including an increased risk of enteric infection and inflammatory bowel disease such as Crohn's disease (CD). Expansion of intestinal pathobionts such as adherent-invasive Escherichia coli (AIEC) is a common dysbiotic feature of CD, which is amplified by prior use of oral antibiotics. Although high-fat, high-sugar diets are associated with dysbiotic expansion of E. coli, it is unknown if the content of fat or another dietary component in obesogenic diets is sufficient to promote AIEC expansion. Here, we found that administration of an antibiotic combined with feeding mice an obesogenic low-fiber, high-sucrose, high-fat diet (HFD) that is typically used in rodent-obesity studies promoted AIEC intestinal expansion. Even a short-term (i.e., 1 day) pulse of HFD feeding before infection was sufficient to promote AIEC expansion, indicating that the magnitude of obesity was not the main driver of AIEC expansion. Controlled-diet experiments demonstrated that neither dietary fat nor sugar were the key determinants of AIEC colonization, but that lowering dietary fiber from approximately 13% to 5%-6% was sufficient to promote the intestinal expansion of AIEC when combined with antibiotics in mice. When combined with antibiotics, lowering fiber promoted AIEC intestinal expansion to a similar extent as widely used HFDs in mice. However, lowering dietary fiber was sufficient to promote AIEC intestinal expansion without affecting body mass. Our results show that low dietary fiber combined with oral antibiotics are environmental factors that promote the expansion of Crohn's disease-associated pathobionts in the gut.NEW & NOTEWORTHY It is commonly thought that obesity or a high-fat diet alters pathogenic bacteria and promotes inflammatory gut diseases. We found that lower dietary fiber is a key factor that expands a gut pathobiont linked to Crohn's disease, independent of obesity status in mice.
Highlights
Obesity is associated with an increased risk of type 2 diabetes, cardiovascular disease, and nonalcoholic fatty liver disease
We found that mice fed an obesogenic high-fat diet (HFD) that contained 60% of calories from fat for 16 wk had higher blood glucose during a glucose tolerance test, higher fasting blood glucose, higher body mass, and higher adiposity compared with mice fed a standard chow diet before adherentinvasive Escherichia coli (AIEC) infection (Fig. 1, A–D)
We found that antibiotic pretreatment was required to increase AIEC intestinal expansion during an obesogenic diet since mice fed HFD for 16 wk had similar AIEC fecal burdens to chow-fed mice if mice were not given antibiotics (Fig. 1H)
Summary
Obesity is associated with an increased risk of type 2 diabetes, cardiovascular disease, and nonalcoholic fatty liver disease. Obesity and type 2 diabetes can each increase the risk and severity of bacterial and viral infections [1,2,3]. It is not clear if an obesogenic diet is sufficient to predispose to bacterial infections. The processing of foods that are high in fat and sugar results in food that is low in fiber. It is not known which dietary factor or obesity-related factor confers the risk of severity of infection from specific pathogenic bacteria
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