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Early life is a critical window for preventing the intergenerational transmission of metabolic diseases. Betaine has been proven to play a role in improving glucose and lipid metabolism disorders in animal models. However, whether maternal betaine supplementation plays a role in regulating gut microbiota in both dams and offspring remains unclear. In this study, C57BL/6 female mice were fed with control diet (Ctr), high-fat diet (HF), and high-fat with betaine supplementation (0.3% betaine in the diet, HFB) from 3 weeks prior to mating and lasted throughout pregnancy and lactation. After weaning, the offspring got free access to normal chow diet until 20 weeks of age. We found that maternal dietary betaine supplementation significantly improved glucose and insulin resistance, as well as reduced free fatty acid (FFA) concentration in dams and offspring from young to adult. When compared to the HF group,  Intestinimonas  and  Acetatifactor  were reduced by betaine supplementation in dams;  Desulfovibrio  was reduced in 4-week-old offspring of the HFB group; and  Lachnoclostridium  was enriched in 20-week-old offspring of the HFB group. Moreover, the persistent elevated genus  Romboutsia  in both dams and offspring in the HFB group was reported for the first time. Overall, maternal betaine could dramatically alleviate the detrimental effects of maternal overnutrition on metabolism in both dams and offspring. The persistent alterations in gut microbiota might play critical roles in uncovering the intergenerational metabolic benefits of maternal betaine, which highlights evidence for combating generational metabolic diseases.

frontiers in microbiology

Maternal Dietary Betaine Prevents High-Fat Diet-Induced Metabolic Disorders and Gut Microbiota Alterations in Mouse Dams and Offspring From Young to Adult