(P20-024-23) Lactobacillus reuteri Alleviates Abnormal Body Fat Accumulation by Activating the Deoxycholic Acid-Angptl8 Axis

Objectives: Gut symbiotic bacteria can potentially regulate body fat accumulation, contributing to the prevention of cardiometabolic diseases, but the underlying mechanisms are largely unclear.

Methods: In the Guangzhou Nutrition and Health Study (GNHS), we used multivariable linear regression to examine the association of L. reuteri with body fat distribution and blood lipid parameters (TG, TC, LDL and HDL). Next, mouse studies and cell culture were used to the underlying mechanism of L. reuteri in reshaping abnormal body fat accumulation. Finally, we used two independent cohorts to explore the association of key metabolic molecules with body fat percentage.

Results: Here, we demonstrated that the gut symbiont Lactobacillus reuteri reshapes abnormal body fat accumulation via the deoxycholic acid (DCA)-angiopoietin-like 8 (Angptl8) axis. In a large-scale human cohort, faecal L. reuteri abundance is inversely associated with accumulated body fat across body sites. A mouse study confirmed the causal effects of L. reuteri on reducing body fat. Colonization of L. reuteri increases serum DCA levels, which in turn inhibited the transcription of Angptl8 and therefore activated adipocyte lipolysis in mice. Oral administration of DCA reduced body weight and body fat percentage in mice. In two human cohorts, serum DCA levels are inversely associated with body fat percentage.

Conclusions: This study revealed the role of the DCA-Angptl8 axis as a new potential therapeutic target for obesity.

Funding Sources: This study was funded by the National Key R&D Program of China (2022YFA1303900), National Natural Science Foundation of China (82073529, 82073546, 82103826, 82103828), Research Program (No. 202208012) of Westlake Laboratory of Life Sciences and Biomedicine, Zhejiang Ten-thousand Talents Program (2019R52039), Zhejiang Provincial Natural Science Foundation of China (LZ23H260001, LQ21H260002), Westlake Education Foundation and 5010 Program for Clinical Research (2007032) of Sun Yat-sen University (Guangzhou, China).