Moderate-intensity continuous training and high-intensity interval training modulate gut microbes, and weaken leaky gut-immune activation reduces systemic inflammation in high-fat diet APOE-KO mice

Abstract

Abstract Atherosclerosis is a common disease typically associated with the dysregulation of inflammatory pathways and lipid metabolism. Regular exercise can prevent and delay atherosclerosis-related dysfunctions; however the effects of different types of exercise on atherosclerosis and their underlying molecular mechanisms remain unclear. Based on the evidence of intestinal microbiota dysbiosis and impaired intestine-liver-brain axis in APOE-knockout (KO) mice, we found plasma lipid profile abnormalities, intestinal microbiota imbalance, intestinal inflammation, liver inflammation, bacterial lipopolysaccharide displacement, and neuroinflammation in APOE-KO mice fed a high-fat diet. Our experimental findings indicate that following a twelve-week intervention of moderate-intensity continuous training and high-intensity interval training interventions, alterations in the gut microbiota and improvements in the damaged gut-liver-brain axis were partially associated with the beneficial effects of exercise. demonstrating that both forms of exercise effectively reduce body weight and lipid profiles associated with hyperlipidemia in APOE-KO mice, while promoting stability in the gut microbiota of these mice, thereby inhibiting the expression of inflammatory signaling pathways. It is noteworthy that exercise downregulates LPS, retards intestinal leakage and brain leakage in mice, thereby alleviating systemic inflammation linked closely with the TLR4/MyD88/NF-KB inflammatory signaling pathway. The mechanism involves MICT and HIIT reinforcing the gut-liver and gut-brain barriers against LPS interception, weakening LPS translocation to the internal milieu, inhibiting the liver and brain TLR4/MyD88/NF-κB inflammatory signaling pathways, and alleviating systemic inflammation in APOE-KO mice. Particularly, HIIT demonstrates superior improvement in plasma lipid profiles in APOE-KO mice compared to MICT.