Microbiome study. 16S Mus musculus cecum. Increasing breast milk betaine content modulates offspring Akkermansia abundance during early life and improves long-term metabolic health. mouse gut metagenome Taxonomy ID: 410661 ( NCBI:txid410661)

Accelerated postnatal growth is a strong and potentially modifiable risk factor for future obesity. To study how specific breast milk components contribute to early growth and obesity risk, we quantified one-carbon metabolism-related metabolites in human milk and found an inverse association between milk betaine content and infant growth. Notably, this association was replicated in an independent and geographically distinct cohort. To determine the potential role of milk betaine in programming offspring obesity risk, we performed maternal betaine supplementation experiments in mice. Higher betaine intake during lactation increased milk betaine content and led to lower offspring adiposity and improved glucose homeostasis throughout adulthood. These effects were accompanied by a transient increase of Akkermansia spp. abundance during early life and a long-lasting increase in intestinal goblet cell number. Akkermansia muciniphila levels in infants were also linked to milk betaine content in the human cohort. Furthermore, administration of Akkermansia muciniphila to pups during the lactation period partially replicated maternal betaine effects, including long-term improvements in adiposity and glucose homeostasis. Together, our data demonstrate a link between breast milk betaine content and offspring long-term metabolic health, and indicate that betaine may be a target for early interventions aimed at childhood obesity prevention.