Impacts of natural microbial exposure on gut lipid metabolism in mice
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Impacts of natural microbial exposure on gut lipid metabolism in mice
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2024-04-18
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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.
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This research was supported by the Undergraduate Research Opportunities Program (UROP).
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Wang, Zihao; Zhang, Yuan; Wang, Haiguang; Revelo, Xavier; Ruan, Hai-bin. (2024). Impacts of natural microbial exposure on gut lipid metabolism in mice. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/262392.
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