Diet can affect health directly or by altering the gut microbiota; thus, there are strong interrelationships between the gut immune system, gut microbiota, and diet. This study examined the effects of ingesting AIN-93M purified diet on gut immune function and gut microbiota in DO11.10 mice, in which T cell–dependent and –independent IgA can be analysed separately. Ingestion of the purified diet for 2 weeks reduced both T cell–dependent and –independent secretory IgA in the faeces compared with non-purified diet, whereas the diet did not affect T cell–dependent and –independent serum IgA. Ingestion of the purified diet had no effect on systemic immune system splenocyte responses. Ingestion of the purified diet reduced intestinal tissue expression levels of BAFF and APRIL, cytokines involved in T cell–independent IgA production, and pIgR, which transports IgA into the intestinal lumen. Co-abundance group analysis of the intestinal microbiota was conducted based on correlations between changes in the abundance of bacterial genera, and the correlations between co-abundance groups and IgA were determined. The Allobaculum-dominated co-abundance group expanded following ingestion of the purified diet, accompanied by an inverse correlation with the decrease in faecal IgA, whereas the Lactobacillus-dominated co-abundance group shrank relative to the Allobaculum-dominated co-abundance group. These results suggest that T cell–independent IgA suppresses the expansion of some intestinal bacteria and that ingestion of the purified diet induces dysbiosis via impaired IgA secretion into the intestinal lumen.

The nutritional environment during fetal and early postnatal life has a long-term impact on growth, development, and metabolic health of the offspring, a process termed “nutritional programming.” Rodent models studying programming effects of nutritional interventions use either purified or grain-based rodent diets as background diets. However, the impact of these diets on phenotypic outcomes in these models has not been comprehensively investigated. We used a previously validated (C57BL/6J) mouse model to investigate the effects of infant milk formula (IMF) interventions on nutritional programming. Specifically, we investigated the effects of maternal diet type (i.e., grain-based vs purified) during early lactation and prior to the intervention on offspring growth, metabolic phenotype, and gut microbiota profile. Maternal exposure to purified diet led to an increased post-weaning growth velocity in the offspring and reduced adult diet-induced obesity. Further, maternal exposure to purified diet reduced the offspring gut microbiota diversity and modified its composition post-weaning. These data not only reinforce the notion that maternal nutrition significantly influences the programming of offspring vulnerability to an obesogenic diet in adulthood but emphasizes the importance of careful selection of standard background diet type when designing any preclinical study with (early life) nutritional interventions.