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

Silvia Ribo, David Sánchez-Infantes, Laura Martinez-Guino, Izaskun García-Mantrana, Marta Ramon-Krauel, Mireia Tondo, Erland Arning, Miquel Nofrarías, Óscar Osorio-Conles, Antonio Fernández-Pérez, Pedro González-Torres, Judith Cebrià, Aleix Gavaldà-Navarro, Empar Chenoll, Elvira Isganaitis, Francesc Villarroya, Mario Vallejo, Joaquim Segalés, Josep C. Jiménez-Chillarón, Teodoro BottiglieriEllen W. Demerath, David A. Fields, María Carmen Collado, Carles Lerin

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article numbereabb0322
JournalScience Translational Medicine
Volume13
Issue number587
DOIs
StatePublished - Mar 31 2021

Bibliographical note

Publisher Copyright:
Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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