Pu-erh tea regulated chronic low-grade inflammation and multi-organ interaction dysfunction via the “gut microbiota-SCFAs-mitochondria” axis

• Chronic low-grade inflammation can trigger gut, liver, and brain dysfunction • Mitochondrial dysfunction is one of the key factors triggering dysfunction • Pu-erh tea improved hepatic lipid metabolism disorders and brain barrier function • Pu-erh tea reshaped gut microbes and increased production of SCFAs • Gut microbiota-SCFAs-mitochondrial axis is key mechanism for Pu-erh tea regulation Chronic low-grade inflammation (CLI) is a common pathological basis for many major diseases, whose systemic regulatory mechanism remains unclear. Based on Pu-erh tea’s potential to improve gut inflammation and dysfunction in the “gut-liver/brain” axis, this study systematically explored the multi-target regulatory mechanisms of Pu-erh tea through establishing a dextran sodium sulfate-induced CLI model. The results demonstrated that CLI triggered an inflammatory cascade in the colon, liver, and brain, accompanied by liver metabolism disorders (downregulation of FXR/SREBP-1c) and gut-brain barrier damage (downregulation of ZO-1/Occludin). Pu-erh tea significantly reversed these pathological changes by reshaping the gut microbiota (increased levels of norank_f__Muribaculaceae, Lactobacillus, Akkermansia , and Dubosiella ) and promoting the biosynthesis of short-chain fatty acids (SCFAs, butyric acid and isobutyric acid), which stemmed from improved mitochondrial dysfunction. The “gut microbes-SCFAs-mitochondria” axis may hold promise as a potential strategy for phytochemicals to improve body inflammation.