Acetate produced by the interaction between Houttuynia pectin and Phocaeicola vulgatus alleviated H1N1-induced acute lung injury in mice through the GPR43/JAK2/STAT3 pathway.

Short-chain fatty acids (SCFAs) are widely recognized as important microbial metabolites of polysaccharides, playing crucial roles in modulating the intestinal immune system and protecting the intestinal barrier. This study investigated the effects of HCPM, a heteropolysaccharide from medicinal Houttuynia cordata, on the SCFAs production in mice infected with H1N1, and elucidated the potential mechanism underlying the therapy of H1N1-induced acute lung injury (ALI) through comparison with inactive Artemisia annua polysaccharide (AAP01-1). Our findings revealed that HCPM effectively alleviated ALI in H1N1-infected mice and specifically promoted acetate production in the feces rather than the serum acetate levels. In comparison, the inactive polysaccharide AAP01-1 had no significant impact on fecal acetate content. This evidence suggests that the therapeutic effects of HCPM could be mediated by intestinal acetate rather than serum acetate. The correlation analysis demonstrated that the abundance of Phocaeicola vulgatus specifically regulated by HCPM exhibited a strong correlation with the inflammatory indicators or the acetate levels in feces. In vitro, HCPM significantly enhanced acetate production by P. vulgatus. Acetate by enema restored the balance of Th17/Treg cells by activating GPR43 and inhibiting the JAK2/STAT3 pathway in the intestine. These findings suggest that acetate produced by the interaction between P. vulgatus and HCPM alleviates H1N1-induced ALI in mice through the GPR43/JAK2/STAT3 pathway in the intestine.