Maternal prebiotic supplementation impacts colitis development in offspring mice

Abstract

Background and aimsMaternal diet plays a key role in preventing or contributing to the development of chronic diseases, such as obesity, allergy, and brain disorders. Supplementation of maternal diet with prebiotics has been shown to reduce the risk of food allergies and affect the intestinal permeability in offspring later in life. However, its role in modulating the development of other intestinal disorders, such as colitis, remains unknown. Therefore, we investigated the effects of prebiotic supplementation in pregnant mice on the occurrence of colitis in their offspring.Materials and methodsOffspring from mothers, who were administered prebiotic galacto-oligosaccharides and inulin during gestation or fed a control diet, were subjected to three cycles of dextran sulphate sodium (DSS) treatment to induce chronic colitis, and their intestinal function and disease activity were evaluated. Colonic remodelling, gut microbiota composition, and lipidomic and transcriptomic profiles were also assessed.ResultsDSS-treated offspring from prebiotic-fed mothers presented a higher disease score, increased weight loss, and increased faecal humidity than those from standard diet-fed mothers. DSS-treated offspring from prebiotic-fed mothers also showed increased number of colonic mucosal lymphocytes and macrophages than the control group, associated with the increased colonic concentrations of resolvin D5, protectin DX, and 14-hydroxydocosahexaenoic acid, and modulation of colonic gene expression. In addition, maternal prebiotic supplementation induced an overabundance of eight bacterial families and a decrease in the butyrate caecal concentration in DSS-treated offspring.ConclusionMaternal prebiotic exposure modified the microbiota composition and function, lipid content, and transcriptome of the colon of the offspring. These modifications did not protect against colitis, but rather sensitised the mice to colitis development.

Immunomodulatory effects of inulin and its intestinal metabolites

“…For example, Armstrong and colleagues found that unfermented inulin induced secretion of pro-inflammatory cytokines in a subset of IBD intestinal biopsies cultured ex vivo ( 150 ). In several other animal studies, researchers have found that dietary supplementation with inulin may be beneficial for low-grade inflammation and associated metabolic disease, but that it also exacerbates the severity of DSS-induced acute colitis ( 151 – 153 ). Furthermore, treatment with an “antibiotic cocktail” led to intestinal ecological dysregulation and induced colitis in mice, whereas supplementation with inulin-type fructans delayed the recovery of this antibiotic-induced intestinal inflammation and decreased the recovery of T reg and B cells in the lamina propria.…”