Supplementing the maternal diet with betaine during lactation may reduce the risk of childhood obesity

Decreased levels of betaine in breast milk are associated with accelerated growth in babies during the first few months of life, a risk factor for childhood obesity. Study led by a research team from the Institut de Recerca Sant Joan de Déu and SJD Barcelona Children's Hospital, published in the scientific journal Science Translational Medicine.

Protecting the health of infants is key to building healthier future communities and societies. One of the biggest threats to infant health is childhood overweight and obesity, which affects approximately 41% of children between the age of six and nine in Spain. Furthermore, over 41 million children under the age of five globally are overweight or obese.

Childhood overweight and obesity are a highly significant risk factor for the development of chronic diseases during adulthood, such as type 2 diabetes, cardiovascular diseases, and certain types of cancer, among others, negatively affecting the life expectancy and quality of life of the population.

'Gestation and postnatal periods significantly determine susceptibility to develop chronic diseases in adulthood', says Dr Carles Lerín, the study coordinator, who leads the group Metabolic Diseases of Paediatric Origin of the Sant Joan de Déu Research Institute. 'Most notably, the lactation period is a window of opportunity for nutritional intervention in order to reduce the risk of childhood obesity'.

The research team analysed samples of breast milk from two different population groups, one from the United States and the other from the Valencian Community, thanks to the participation of the IATA-CSIC research group led by Dr María Carmen Collado. In both groups, the team identified a breast milk nutrient called betaine that was related to child growth during the first year of life. Specifically, they found that lower concentrations of betaine in milk were associated with accelerated growth during the first few months of life, a risk factor for the development of childhood obesity.

Betaine is a nutrient found in different foods that form our diet, such as quinoa, whole grains, spinach and beetroot. Moreover, it is naturally occurring in breast milk. Betaine is a molecule that can act as a cellular protector against osmotic stress and as a methyl group donor. Decreased levels of blood betaine in adults have been associated with obesity and metabolic problems.

To analyse whether supplementing breast milk with betaine may improve the metabolic health of infants, the working team conducted a series of studies on animal subjects. They observed that supplementing the maternal diet with betaine, only during lactation, increased the amount of this nutrient in milk and moderated the offspring's growth. Furthermore, supplementation with betaine also had long-term effects, since the offspring showed a reduction in adiposity and inflammation markers, as well as an improvement in glucose metabolism during adulthood.

The role of gut microbiota in metabolic health

The researchers observed changes in the gut microbiota of the offspring, especially an increase in the bacterium Akkermansia in those animals that had been fed milk supplemented with betaine. Akkermansia is a bacterium present in the intestines, which, according to different studies, has beneficial effects in terms of obesity and metabolic disorders.

'We also saw that if Akkermansia was administered directly to mouse offspring during lactation, the beneficial effects obtained in the long term as regards obesity and health were similar to supplementing the maternal diet with betaine', says Dr Sílvia Ribó, co-first author of the study and researcher from the Sant Joan de Déu Research Institute.

The results observed in animal subjects were also confirmed in the samples of the studied cohort. 'Intestinal abundance of Akkermansia muciniphila in one-year-old infants was directly linked to the betaine content of their mothers' milk', says Dr María Carmen Collado (IATA-CSIC).

These studies open the door for future interventions during the first period of life in order to tackle infant overweight and obesity.

'We know that the newborns of obese parents may have a greater disposition to develop metabolic diseases. Betaine supplementation during lactation may protect these infants and reduce the risk of developing obesity and related diseases once they reach adulthood', says Dr David Sánchez-Infantes, co-first author of the study and researcher from the Germans Trias i Pujol Research Institute (IGTP), now a professor at Rey Juan Carlos University.

The research group has begun a pilot clinical study to determine the effects of supplementing the maternal diet with betaine during lactation on both the growth curve of newborns and their gut microbiota.

The results, published in the scientific journal Science Translational Medicine, stem from a collaboration between researchers from the Sant Joan de Déu Research Institute (IRSJD), the Hospital Sant Joan de Déu Barcelona, the Germans Trias i Pujol Research Institute (IGTP), the Animal Health Research Centre (CreSA, IRTA-UAB), Biópolis-ADM, the Centre for Genomic Regulation (CRG) and the Spanish National Research Council (CSIC), as well as different centres in the United States such as the Joslin Diabetes Center (Harvard Medical School, Boston, MA), the University of Oklahoma Health Sciences Center (Oklahoma City, OK) and the University of Minnesota School of Public Health (Minneapolis, MN).

Paper

Ribo et al. Increasing breast milk betaine modulates Akkermansia abundance in mammalian neonates and improves long-term metabolic health. Sci. Transl. Med. 13, eabb0322 (2021)