Dietary Fiber Shapes Peritoneal Inflammation Through Microbiota-Derived SCFAs and Epigenetic Reprogramming

The current dietary pattern of the Brazilian population is characterized by a low intake of fiber-rich natural foods, which may disrupt gut microbiota homeostasis and promote inflammation. In this context, dietary fiber plays an important role in intestinal homeostasis by promoting bacterial fermentation and the production of metabolites such as short-chain fatty acids (SCFAs). Peritonitis, characterized by the leakage of intestinal contents into the peritoneal cavity, triggers a robust inflammatory response. Here, we investigated the impact of dietary fiber and SCFAs on the inflammatory response during experimental peritonitis. Mice were fed for 14 days with either 10% inulin (high-fiber; HF) or a fiber-depleted diet (zero-fiber; ZF). Fecal microbiota composition was analyzed by 16S rRNA sequencing at baseline and after 14 days of dietary intervention. SCFAs were quantified in fecal samples by gas chromatography, revealing higher levels of acetate and butyrate in HF-fed mice. Peritonitis was induced by intraperitoneal inoculation of Bacteroides fragilis combined with sterile cecal contents. Seven days later, ZF-fed mice exhibited higher inflammatory abscess scores than HF-fed animals. Oral administration of an SCFA mixture (acetate:butyrate:propionate; 3:1:1) to ZF mice reversed this susceptibility, resulting in a phenotype similar to HF mice. Resident peritoneal cells from HF mice showed increased levels of histone H3 lysine 27 acetylation (H3K27ac), suggesting diet-associated epigenetic reprogramming. Remarkably, adoptive transfer of resident peritoneal cells from HF donors to ZF recipients rescued the susceptible phenotype, markedly reducing abscess formation. Collectively, our findings indicate that dietary fiber modulates inflammation during experimental peritonitis through mechanisms associated with microbiota-derived SCFAs and epigenetic reprogramming of resident peritoneal cells.