Discussion
Our findings suggest that alterations in the early growth environment may prevent fetal-programmed glucose metabolic disorder via modulation of the microbiota-gut-brain axis. These findings offer direction for development of translational solutions for adult diseases associated with aberrant microbial communities in early life.
Methods
We performed a surrogate fostering experiment in mice and examined the relationship between the metabolic markers associated to insulin resistance and the composition of the gut microbiota.
Results
HE pups raised by HE foster dams (HE-HE) developed insulin resistance, but HE pups fostered by negative control dams (NC-HE) did not. The gut microbiota composition of HE-HE mice differed from that of NC mice raised by NC foster dams (NC-NC), whereas the composition in NC-HE mice was similar to that of NC-NC mice. Compared with NC-NC mice, HE-HE mice had decreased levels of fecal short-chain fatty acids and serum intestinal hormones, increased food intake, and increased hypothalamic neuropeptide Y expression. In contrast, none of these indices differed between NC-HE and NC-NC mice. Spearman correlation analysis revealed a significant correlation between the altered gut microbiota composition and the insulin resistance-related metabolic indicators, indicating involvement of the microbiota-gut-brain axis.