Early-life gut microbial reconstitution with Lactobacillus johnsonii during lactation mitigates high-fat diet-induced obesity in adult mice

Abstract

Epidemiological and animal studies have suggested that early-life overfeeding (ELOF) triggers lasting metabolic dysfunction. However, the role of gut microbiota in this process remains largely unelucidated. Here, we established a mouse model of ELOF through reducing litter size and revealed that ELOF accelerated growth during lactation, induced obesity at weaning, and left a lasting obesity imprinting and gut microbiota dysbiosis. Notably, a detailed analysis of gut microbiota revealed that a pivotal differential species, Lactobacillus johnsonii, demonstrated significant depletion exclusively in weaned ELOF mice, with no analogous reduction observed in adult ELOF mice. Furthermore, while post-weaning microbiota reconstitution proved insufficient to reverse diet-induced obesity in adult ELOF mice, early supplementation with Lactobacillus johnsonii during the lactation period substantially mitigated these programmed metabolic alterations. Our findings causally link ELOF, early-life gut microbial imbalance, and late-onset obesity in mice, and suggest that probiotic intervention during critical developmental periods may serve as an effective strategy to mitigate the obesity imprint in infants and young children.