Impacts of natural microbial exposure on gut lipid metabolism in mice

Abstract

Microbial exposure to the host influences various factors. Current murine research predominantly occurs in specific pathogen-free (SPF) environments. However, humans are exposed to pathogenic and commensal microbes on a daily basis from birth. How natural microbial exposure (NME) influences metabolic and immune responses in hosts remains unclear. Our hypothesis is that laboratory mice models housed at SPF conditions are missing essential components of the natural microbiome that impact the host response under normal diet and protect mice from diet-induced obesity. In this study, C57BL/6 mice under normal chow were divided into two groups: SPF group and NME group. Both cohorts were initiated at the age of 6 weeks, NME group involved mice cohabitation with pet store mice for another 4 weeks. Mice were sacrificed in week 10, small intestine and gonadal white adipose tissue (gWAT) were collected. To establish an obesity model, 8-week old C57BL/6 male mice were housed in SPF and NME facilities under western diet for 16 weeks. Mice were sacrificed in week 24 and inguinal white adipose tissue (iWAT) was collected. qRT-PCR was performed to measure the key genes in lipid uptake in small intestine and fluorescence bead-based antibody systems (Luminex platform) was applied to determine cytokine levels in the small intestine. Mice in the NME group exhibited a significant reduction in body weight compared to the SPF group under normal chow condition. Furthermore, a notable decrease in iWAT mass was observed in NME mice under western diet. qRT-PCR analysis revealed a down-regulation of lipid uptake genes, including CD36 and FATP4, in the NME group. NME led to more robust changes in chemokine level rather than pro-inflammatory cytokine level in the small intestine. Our results provided compelling evidence that NME exerted a protective role from diet-induced obesity and caused perturbation of cytokine levels in small intestine, thereby underscoring the pivotal role of microbiota exposure in modulating host metabolism. This revelation highlighted the critical role gut microbes play in orchestrating metabolic and immunological interactions in mammalian systems.