Short-chain fatty acid attenuates intestinal inflammation by regulation of gut microbial composition in antibiotic-associated diarrhea.

Abstract

To investigate fecal short-chain fatty acid (SCFA) levels in hematological malignancies (HMs) patient with antibiotic-associated diarrhea (AAD), and explore the impacts of SCFAs on intestinal inflammation and gut microbiota in rats with AAD. Fecal SCFA concentrations were determined by high-performance liquid chromatography. Histologic examination was conducted by hematoxylin-eosin and alcian blue-Periodic acid-Schiff. Interleukin (IL)-10 and IL-18 mRNAs were assessed by quantitative real-time polymerase chain reaction. Claudin3 (CLDN3), Zona Occludens 1 (ZO-1), and plasmalemma vesicle-associated protein (PLVAP) proteins were evaluated by immunofluorescence and western blot. Gut microbiota was assessed by 16S rRNA sequencing. SCFAs are decreased in fecal samples of HM patients with AAD. AAD incidence is correlated with serum albumin level and type/duration of antibiotics administered. SCFAs attenuate colon shortening and intestinal pathology, and reinstate functionality of intestinal barrier by upregulating CLDN3/ZO-1 and downregulating PLVAP. Control (ctrl) group harbors an increased abundance of Lactobacillus, AAD group exhibits an enrichment of Enterorhabdus, AAD + low (L)-SCFAs group displays a predominance of Turicibacter, and AAD + high (H)-SCFAs group exerts an enrichment of Clostridium IV. Altogether, SCFAs alleviate colonic inflammation by regulating gut microbial composition, and provide insight into enhancing intestinal SCFAs content to alleviate AAD-induced symptoms in HM patients by modifying dietary structure.