Gut microbiota and immunometabolic response to Choline and Betaine supplementation in a Mouse Model of Diet-Induced Obesity

Abstract

Obesity is a chronic, recurring and multifactorial disease characterized by systemic inflammation, visceral adipose tissue dysfunction and gut microbiota dysbiosis. While Omega-3 fatty acids have shown beneficial effects in this context, the potential of other dietary modulators remains underexplored.Our aim was to investigate the effects of dietary supplementation with choline and betaine on weight gain, gut microbiota composition and visceral immunometabolic profiles in a mouse model of diet-induced obesity.Mice fed with choline and betaine supplemented diets, exhibited significantly reduced weight gain compared to obesity fat diet, at weeks 4, 12 and 24 after differential feeding was started. Beta-diversity analyses revealed sustained divergence in microbial communities between diet groups. Fat diet supplemented with choline and betaine feeding generated enrichment of SCFA-producing taxa such as Parabacteroides, Oscillospira, Flavonifractor, Harryflintia and Christensenellaceae R7 group while Fat diet feeding promoted the expansion of pro-inflammatory genera such as Helicobacter and Negativibacillus. In parallel, in the choline and betaine supplementation group immune data point toward an anti-inflammatory visceral adipose tissue phenotype, with IL-10?skewed T regulatory cell signatures producing high levels of IL-10.Choline and betaine supplementation modulates the gut?adipose?immune axis by reshaping gut microbial community and enhancing host immunometabolic homeostasis. These findings support the potential of methyl-donor nutrients as dietary strategy to mitigate obesity-related inflammation and metabolic dysfunction.Multiblock analysis with DIABLO identified a coordinated microbial?immune?metabolic signature that distinguished diet groups, linking Fat diet supplemented with choline and betaine-enriched taxa with IL-10?producing Tregs and adiponectin levels. These findings highlight the systemic impact of choline and betaine supplementation.