Maternal helminth infection protects offspring from high-fat-diet-induced obesity through altered microbiota and SCFAs

Abstract

Helminth-induced Th2 immunity and gut microbiota have been recently shown to be highly effective in modulating metabolic syndromes in animal models. This study aimed to determine whether maternal immunity and microbial factors affect the induction and development of obesity in offspring. Here, Heligomosomoides polygyrus (Hp)-infected or control female C57BL/6J mice mated with normal males and their offspring were fed a high-fat diet (HFD) for 9 weeks after weaning. Our results showed that Hp-induced maternal outcomes during gestation and lactation significantly impacted offspring metabolic phenotypes. This was evidenced by results showing that offspring from helminth-infected mothers on an HFD (Hp-offspring + HFD) gained significantly less body weight than those from uninfected mothers (Cont-offspring + HFD). Hp-offspring + HFD exhibited no Th2 phenotype but displayed a pattern of gut microbiota composition similar to that of Hp-infected mothers. Cross-fostering experiments confirmed that the helminth-induced maternal attenuation of offspring obesity was mediated through both prenatal and postnatal effects. Our results further showed that helminth-infected dams and their offspring had a markedly altered gut microbiome composition, with increased production of short-chain fatty acids (SCFAs). Intriguingly, Hp-infected mothers and Hp-offspring + HFD showed increased SCFA receptor (GPR) expression in adipose and colonic tissues compared to noninfected mothers and Cont-offspring + HFD, respectively. Moreover, SCFA supplementation to the pups of uninfected control mothers during lactation protected against HFD-induced weight gain, which corresponded with changes in gut bacterial colonization. Collectively, our findings provide new insights into the complex interaction of maternal immune status and gut microbiome, Hp infection, and the immunity and gut microbiome in obese-prone offspring in infant life.

Keywords: Helminth; Maternal; Microbiota; Obesity; Offspring; SCFAs; Th2 immunity.