Standardized Complex Gut Microbiomes Influence Fetal Growth, Food Intake, and Adult Body Weight in Outbred Mice

Abstract

Obesity places a tremendous burden on individual health and the healthcare system. The gut microbiome (GM) influences host metabolism and behaviors affecting body weight (BW) such as feeding. The GM of mice varies between suppliers and significantly influences BW. We sought to determine whether GM-associated differences in BW are associated with differences in intake, fecal energy loss, or fetal growth. Pair-housed mice colonized with a low or high microbial richness GM were weighed, and the total and BW-adjusted intake were measured at weaning and adulthood. Pups were weighed at birth to determine the effects of the maternal microbiome on fetal growth. Fecal samples were collected to assess the fecal energy loss and to characterize differences in the microbiome. The results showed that supplier-origin microbiomes were associated with profound differences in fetal growth and excessive BW-adjusted differences in intake during adulthood, with no detected difference in fecal energy loss. Agreement between the features of the maternal microbiome associated with increased birth weight here and in recent human studies supports the value of this model to investigate the mechanisms by which the maternal microbiome regulates offspring growth and food intake.

Fetal programming by the maternal microbiome of offspring behavior, and DNA methylation and gene expression within the hippocampus

“…Compositional differences between GM Low and GM High have been described previously 32–34 , including greater richness in GM High compared to GM Low ( Fig. 2a ).…”

“…Taxonomic differences are associated with different levels of biologically relevant metabolites Compositional differences between GM Low and GM High have been described previously [32][33][34] , including greater richness in GM High compared to GM Low (Fig. 2a).…”

Supplier-origin gut microbiomes affect host body weight and select autism-related behaviors

“…The postnatal GM-mediated effects on body weight identified in this study were of particular interest. In CD-1 mice, we have historically found that animals with a Jackson-origin microbiome (GM Low ) are heavier than those with an Envigo-origin (GM High ), beginning in utero and persisting into adulthood 12,13 . The GM-dependent difference in body weight observed in CD-1 mice is likely due to an effect on overall growth, as these groups do not differ in relative body composition and GM Low CD-1 mice exhibit increased cardiac weight 12 .…”

“…While assessing the effect of supplier-origin GMs on the ASD-related behavior of BTBR mice, we collected body weights as previous work by our group using comparable GMs in CD-1 mice has revealed microbiome-dependent effects on body weight 12,13 . In the cohort of neonatal mice used for USV testing, we measured body weight at birth (D0) and after testing (D7).…”

“…Food intake was monitored using a modified protocol from Cheathem et al 13 . Food intake was monitored for four consecutive days for six consecutive weeks beginning after weaning (3 weeks old).…”