Increased mucin‐degrading bacteria by high protein diet leads to thinner mucus layer and aggravates experimental colitis

Background and aim Westernized high-fat diet increases the risk for inflammatory bowel diseases (IBDs), yet with insufficient understanding of the role of high-protein diet. We aimed to identify the effect of high-protein diets from different dietary proteins (casein, whey protein, soy protein) on experimental colitis and its impact on microbiota, structure and function of colonic mucus layer. Methods Female BALB/c mice were fed by standard diet, high-casein diet (HCD), high whey protein diet or high soy protein diet for 4 weeks. The susceptibility of dextran sulfate sodium (DSS)-induced colitis in mice and thickness of colonic mucus layer were compared after different dietary interventions, associated with the identification of the reversal effect of broad-spectrum antibiotic intervention (0.5 g/L of vancomycin and 1 g/L of neomycin sulfate, metronidazole and ampicillin in drinking water). Further analysis was performed on the synthesis of mucin, microbiota and sialidase involved in degradation of mucus layer. Results High-protein diets aggravated acute DSS-induced colitis independent of protein composition, while broad-spectrum antibiotics reversed this effect. HCD significantly altered the composition of bacteria in the colonic mucus layer, especially Bacteroides thetaiotaomicron and total mucin-degrading bacteria; besides, it increased sialidase concentration and reduced the thickness of mucus layer. However, it exhibited no significant effect on the synthesis of Muc2. Broad-spectrum antibiotics decreased the abundance of mucin-degrading bacteria and sialidase concentration while increased the thickness of mucus layer. Conclusion High-protein diet shifts microbial composition and thickness of colonic mucus layer, leading to the aggravation of acute DSS-induced colitis.