ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: Endocrinology vol. 161,2 (2020): bqz041. doi: https://academic.oup.com/endo/article/161/2/bqz041/5698115

This mouse study demonstrates the influence of maternal nutrition during lactation on offspring gut microbiota and its consequences on metabolism and puberty timing.

Childhood obesity is a risk factor for the development of precocious puberty in girls, and the metabolic state of children also depends on maternal nutrition (1). Increasing evidence shows that maternal high-fat diet (MHFD) induces gut microbial dysbiosis in offspring (2), and breastfeeding also has a critical role on gut microbiota maturation (3). In addition, MHFD has been shown to induce precocious puberty in animal offspring (4), but little is known about the role of the gut microbiota (GM) in pubertal development.

This mouse study investigated whether MHFD during lactation alters GM in offspring and influences the risk of obesity and early pubertal development. The authors observed that MHFD-exposed pups developed juvenile obesity, early puberty, irregular estrous cycles and signs of disrupted glucose metabolism. Offspring metabolic abnormalities induced by MHFD were linked to reduced GM diversity and richness, with an increase of Streptococcaceae and Peptostreptococcaceae families, which are strongly correlated with adiposity (5). It was recently shown that co-housing obese mice with lean mice restored a lean phenotype (6), as mice are coprophagic, so co-housed family members share gut microbiota through the fecal–oral route. The authors found that co-housing offspring of MHFD with those of normally-fed mothers increased GM richness, reversed early puberty, and improved insulin sensitivity.

This study provides novel potential therapeutic targets and a specific window to treat metabolic and reproductive diseases. Acting on microbial reconstitution during lactation may prevent early puberty associated with insulin resistance.

References:

1. Cnattingius S, Villamor E, LagerrosYT, WikstroömAK,Granath F. (2012) High birth weight and obesity: a vicious circle across generations. Int J Obes (Lond). 36(10):1320–1324.

2. Ma J, Prince AL, Bader D, et al. (2014) High-fat maternal diet during pregnancy persistently alters the offspring microbiome in a pri- mate model. Nat Commun. 5:3889.

3. Stewart CJ, Ajami NJ, O’Brien JL, et al. (2018) Temporal development of the gut microbiome in early childhood from the TEDDY study. Nature. 562(7728):583–588.

4. Takumi K, Shimada K, Iijima N, Ozawa H. (2015) Maternal high-fat diet during lactation increases Kiss1 mRNA expression in the arcuate nucleus at weaning and advances puberty onset in female rats. Neurosci Res. 100:21–28.

5. Sanguinetti E, Guzzardi MA, Tripodi M, et al. (2019) Microbiota signatures relating to murine model. Sci Rep. 9(1):12609.

6. Ridaura VK, Faith JJ, Rey FE, et al. (2013) Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science. 341(6150):1241214.