Lactobacillus T3L Inhibits High-fat-diet Mice's Bone Mass Loss Via Gut Microbiota

Lactobacillus is widely used in food and health as a safe and non-toxic probiotic preparation.Studies have found that long-term consumption of fermented dairy products can reduce intestinal inflammatory reactions,benefit the intestinal health,increase bone density,and reduce bone loss.These effects can be exerted by the probiotic itself and its metabolites.However,the specific relationship between probiotics and intestinal immune system and bone health remains to be further studied.Previous studies have found that L.coryniformis(T3L),which is isolated from the traditional Tibetan yak fermented milk,has probiotic functions and can inhibit the bone loss in mice caused by high-fat diet.We speculate that this function may be through gut microbiota.Therefore,in this study,the colony colonies of the T3 Ltreated mice were transplanted into high-fat diet mice for 10 weeks.To investigate the changes of gut microbiota in mice after transplantation and its related effects on intestinal immunity,osteoclast differentiation and bone performance.The results showed that T3 L faecal transplantation significantly reduced body weight,body fat ratio,serum triglyceride and total cholesterol levels.At the same time,the result of the femoral mechanics and morphology showed that T3 L faecal transplantation protected high-fat diet mice from bone loss and bone resorption.The qPCR analysis of bone-related expression factors in femur tissue showed that the ratio of RANKL/OPG and CTSK was significantly decreased by T3 L faecal transplantation.High-throughput sequencing of intestinal bacteria in feces showed that T3 L influenced intestinal microbiota structure,improved high-fat diet-induced structural imbalance and enhanced abundance of SCFA-producing bacteria.qPCR analysis of histone acetylation-related expression factors in the colon revealed that the expression of Ffar2 was increased after T3 L faecal transplantation.And the expression of HDAC2 and HDAC7 was significantly decreased.The expression of P300,CREBBP and PCAF was significantly increased,indicating that histidine acetyltransferase was affected by SCFAs.Intestinal IL-10,TGF-?,Foxp3 colonic immunity and gene expression results suggest that probiotics may affect the immune system.Splenic T lymphocytes can inhibit the differentiation of osteoclasts by secreting IL-10 and TGF-?.These results indicate that T3 L faecal transplantation can alter the diversity of the intestinal flora and the immune status of the host,thereby reducing the obesity and bone loss induced by high-fat diet.