Calorie restriction during gestation impacts maternal and offspring fecal microbiome in mice

Authors: GILLEY, STEPHANIE - University Of Colorado; Ruebel, Meghan; CHINTAPALLI, SREE - Arkansas Children'S Nutrition Research Center (ACNC); WRIGHT, CLYDE - University Of Colorado; ROZANCE, PAUL - University Of Colorado; SHANKAR, KARTIK - University Of Colorado

Submitted to: Frontiers in Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/28/2024
Publication Date: 10/4/2024
Citation: Gilley, S.P., Ruebel, M., Chintapalli, S.V., Wright, C.J., Rozance, P.J., Shankar, K. 2024. Calorie restriction during gestation impacts maternal and offspring fecal microbiome in mice. Frontiers in Endocrinology. 15(2024):1-14. https://doi.org/10.3389/fendo.2024.1423464.
DOI: https://doi.org/10.3389/fendo.2024.1423464

Interpretive Summary: Maternal undernutrition is the most common global cause of poor fetal growth which in turn leads to worse outcomes for babies. We used a mouse model of maternal caloric restriction during pregnancy to test the role of the maternal and early life fecal microbiome in offspring growth. Our results showed that caloric restricted moms and their offspring had reduce levels of beneficial gut microbes. We also found associations with different microbes from the mother and/or offspring gut microbiome with weight gain during pregnancy, litter size, and offspring weight outcomes. Future studies are still needed for a more complete understanding of the role of gut bacteria in pregnancy and infancy and how they impact offspring growth outcomes and long-term health.

Technical Abstract: Background: Maternal undernutrition is the most common cause of fetal growth restriction (FGR) worldwide. FGR increases morbidity and mortality during infancy, as well as contributes to adult-onset diseases including obesity and type 2 diabetes. The role of the maternal or offspring microbiome in growth outcomes following FGR is not well understood. Methods: FGR was induced by 30% maternal calorie restriction (CR) during the second half of gestation in C57BL/6 mice. Pup weights were obtained on day of life 0, 1, and 7 and ages 3, 4 and 16 weeks. Fecal pellets were collected from pregnant dams at gestational day 18.5 and from offspring at ages 3 and 4 weeks of age. Bacterial genomic DNA was used for amplification of the V4 variable region of the 16S rRNA gene. Multivariable associations between maternal CR and taxonomic abundance were assessed using the MaAsLin2 package. Associations between microbial taxa and offspring outcomes were performed using Pearson correlations Results: FGR pups weighed about 20% less than controls. Beta but not alpha diversity differed between control and CR dam microbiomes. CR dams had lower relative abundance of Turicibacter, Flexispira, and Rikenella, and increased relative abundance of Parabacteriodes and Prevotella. In control dams there was a negative correlation between Alistipes abundance and offspring weight at day 0. Control and FGR offspring microbiota differed by beta diversity at ages 3 and 4 weeks. At 3 weeks, FGR offspring had decreased relative abundance of Akkermansia and Sutterella and increased relative abundance of Anaerostipes and Paraprevotella. At 4 weeks, FGR animals had decreased relative abundance of Allobaculum, Sutterella, Bifidobacterium, and Lactobacillus, among others, and increased relative abundance of Turcibacter, Dorea, and Roseburia. There were no associations between taxa abundance and offspring growth outcomes in FGR animals. Conclusions: We demonstrate gut microbial dysbiosis in pregnant dams and offspring at two timepoints following maternal calorie restriction. Additional research is needed to test a functional role of the microbiome in offspring growth outcomes and long-term health.