Maternal metabolic, immune, and microbial systems in late pregnancy vary with malnutrition in mice

Malnutrition is a global threat to pregnancy health and impacts offspring development. Establishing an optimal pregnancy environment requires the coordination of maternal metabolic and immune pathways, which converge at the gut. Diet, metabolic, and immune dysfunctions have been associated with gut dysbiosis in the nonpregnant individual. In pregnancy, these states are associated with poor pregnancy outcomes and offspring development. However, the impact of malnutrition on maternal gut microbes, and their relationships with maternal metabolic and immune status, has been largely underexplored. To determine the impact of undernutrition and overnutrition on maternal metabolic status, inflammation, and the microbiome, and whether relationships exist between these systems, pregnant mice were fed either a normal, calorically restricted (CR), or a high fat (HF) diet. In late pregnancy, maternal inflammatory and metabolic biomarkers were measured and the cecal microbiome was characterized. Microbial richness was reduced in HF mothers although they did not gain more weight than controls. First trimester weight gain was associated with differences in the microbiome. Microbial abundance was associated with altered plasma and gut inflammatory phenotypes and peripheral leptin levels. Taxa potentially protective against elevated maternal leptin, without the requirement of a CR diet, were identified. Suboptimal dietary conditions common during pregnancy adversely impact maternal metabolic and immune status and the microbiome. HF nutrition exerts the greatest pressures on maternal microbial dynamics and inflammation. Key gut bacteria may mediate local and peripheral inflammatory events in response to maternal nutrient and metabolic status, with implications for maternal and offspring health. Summary Sentence Malnutrition alters immune and metabolic systems in pregnancy, and gut microbes may mediate the maternal response to these suboptimal dietary exposures.