Presented by: Yue Sandra Yin
Background: The serum amyloid A (SAA) proteins, mostly produced in the liver, are acute-phase reactants. SAA also is expressed in the intestinal epithelium, which is an interface between gut microbes and host immunity. SAA stimulates TH17 cells and functions as an inflammatory marker in infectious disease and metabolic disorders. Here, using two murine models, we investigated the role of SAA in mediating host responses and metabolism and the intestinal microbiota.
Methods: In germ-free (GF) and conventional (CONV) C57BL/6 mice, we assessed ileal and colonic SAA expression over time. Then we examined microbiota perturbation and microbiota-mediated phenotypes comparing wildtype (WT) and SAA1/2-/- (KO) mice derived from Het/Het crosses to ensure common ancestry. WT and KO mice were either reared separately or co-housed post-weaning. Dextran sodium sulfate (DSS) colitis was induced in a separate cohort of WT and KO mice. We monitored body weight and colitis development, characterized the fecal microbiome, and measured lipid levels and expression of inflammatory marker genes.
Results: GF and CONV mice expressed differential microbiota-dependent regulation of SAA subtypes in the ileum and colon. SAA expression was depressed in the absence of microbes in the ileum but increased in the colon. SAA KO led to significantly higher post-weaning weight gain (with effects in females>males), and cohousing diminished this effect, suggesting a critical role of gut microbes. Microbial community structure differed in the WT and KO mice, with specific taxonomic differences. In the KO mice, expression of genes indicative of adipocyte differentiation and inflammation was increased in white adipose tissues. DSS treatment led to increased colonic shortening and slower recovery in the KO mice.
Conclusion: Our results suggest that intestinal SAAs have major effects on local inflammation and microbiome characteristics, and mediate microbiota-dependent effects on host metabolism through alterations of inflammatory cytokines, adipogenesis, and lipid cycling.
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