High ambient temperature exposure during late gestation disrupts glycolipid metabolism and hepatic mitochondrial function tightly related to gut microbial dysbiosis in pregnant mice

As global warming intensifies, emerging evidence has demonstrated high ambient temperature during pregnancy negatively affects maternal physiology with compromised pregnant outcomes; however, little is known about the roles of gut microbiota and its underlying mechanisms in this process. Here, for the first time, we explored the potential mechanisms of gut microbiota involved in the disrupted glycolipid metabolism via hepatic mitochondrial function. Our results indicate heat stress (HS) reduces fat and protein contents and serum levels of insulin and triglyceride (TG), while increases that of non-esterified fatty acid (NEFA), β-hydroxybutyric acid (B-HBA), creatinine and blood urea nitrogen (BUN) (P < 0.05). Additionally, HS downregulates both mitochondrial genes (mtDNA) and nuclear encoding mitochondrial functional genes with increasing serum levels of malondialdehyde (MDA) and 8-hydroxydeoxyguanosine (8-OHdG) (P < 0.05). Regarding microbial response, HS boosts serum levels of lipopolysaccharide (LPS) (P < 0.05) and alters β-diversity (ANOSIM, P < 0.01), increasing the proportions of Escherichia–Shigella, Acinetobacter and Klebsiella (q < 0.05), while reducing that of Ruminiclostridium, Blautia, Lachnospiraceae_NK4A136_group, Clostridium VadinBB60 and Muribaculaceae (q < 0.05). PICRUSt analysis predicts that HS upregulates 11 KEGG pathways, mainly including bile secretion and bacterial invasion of epithelial cells. The collective results suggest that microbial dysbiosis due to late gestational HS has strong associations with damaged hepatic mitochondrial function and disrupted metabolic profiles.