Research ArticleMICROBIOTA

Increasing breast milk betaine modulates Akkermansia abundance in mammalian neonates and improves long-term metabolic health

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Science Translational Medicine  31 Mar 2021:
Vol. 13, Issue 587, eabb0322
DOI: 10.1126/scitranslmed.abb0322

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Supplementing mother’s milk

Metabolites from the one-carbon metabolism pool are critical nutrients during mammalian early growth and development. Ribo et al. now identify an inverse relationship between maternal breast milk betaine content and infant growth in two independent cohorts. Given that accelerated postnatal growth is a risk factor for future obesity, the authors tested whether maternal betaine supplementation during lactation in mice could affect the metabolic health of mouse offspring. Supplementation increased breast milk betaine content, induced a transient increase in offspring intestinal Akkermansia abundance, and reduced early weight gain. Furthermore, maternal betaine supplementation decreased adiposity and improved glucose metabolism throughout adulthood, demonstrating a link between breast milk betaine content and long-term metabolic health.

Abstract

Accelerated postnatal growth is a 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 breast milk and found an inverse association between milk betaine content and infant growth. This association was replicated in an independent and geographically distinct cohort. To determine the potential role of milk betaine in modulating offspring obesity risk, we performed maternal betaine supplementation experiments in mice. Higher betaine intake during lactation increased milk betaine content in dams and led to lower adiposity and improved glucose homeostasis throughout adulthood in mouse offspring. These effects were accompanied by a transient increase in Akkermansia spp. abundance in the gut during early life and a long-lasting increase in intestinal goblet cell number. The link between breast milk betaine and Akkermansia abundance in the gut was also observed in humans, as infants exposed to higher milk betaine content during breastfeeding showed higher fecal Akkermansia muciniphila abundance. Furthermore, administration of A. muciniphila to mouse pups during the lactation period partially replicated the effects of maternal breast milk betaine, including increased intestinal goblet cell number, lower adiposity, and improved glucose homeostasis during adulthood. These data demonstrate a link between breast milk betaine content and long-term metabolic health of offspring.

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