A maternal higher-complex carbohydrate diet increases bifidobacteria and alters early life acquisition of the infant microbiome in women with gestational diabetes mellitus

There is a rich and diverse community of microbes in the human gut, which play an important role in maintaining host health. A substantial body of evidence indicates that the gut microbiome plays a pivotal role in the regulation of metabolic, endocrine, and immune functions. Gestational diabetes mellitus (GDM) is a common condition during pregnancy that impairs the health of several million women worldwide. Development of common diseases in the offspring—including diabetes, allergy and atopic disease, cardiovascular disease, and obesity—are influenced by early life exposures throughout pregnancy and lactation, such as maternal obesity and GDM. Recent studies suggest gut microbiota abnormalities linked to GDM lead to further health problems in both mothers and babies.

Dietary intervention is a major form of treatment for GDM, and the dynamic interactions between GDM, maternal diet, and the gut flora of the mother and baby are important considerations which impact pregnancy outcomes and long-term health of the infant. Despite the knowledge that diet is a significant predictor of microbiota composition and activity, the effect of maternal diet treatment in women with GDM on the maternal and newborn microbiome have not yet been thoroughly examined. Conventional GDM diet therapy involves lowering carbohydrate intake to blunt postprandial glucose excursion at the cost of increasing dietary fats, which may promote insulin resistance and predispose the offspring to developing metabolic syndrome due to excess lipid exposure in utero. Thus, alternate diets are needed to improve maternal/infant health in women with GDM without the unintended consequences that may arise from administering a high-fat GDM diet.

In a new study published in the Frontiers in endocrinology, researchers at the University of Oklahoma Health Science Center: Dr. Kameron Sugino and Professor Jacob Friedman together with Associate Professor Teri Hernandez, Dr. Linda Barbour, Ms. Jennifer Kofonow, and Associate Professor Daniel Frank from the University of Colorado examined the maternal and infant gut microbiome using a shotgun metagenomic analysis of a subset of stool samples from a randomized, controlled dietary trial in women with GDM in order to more precisely identify these changes. In their randomized controlled dietary trial, pregnant women with GDM were placed on a conventional GDM diet treatment (CONV) or a diet comparably higher in complex carbohydrates and lower in fat (CHOICE, Choosing Healthy Options in Carbohydrate Energy). The participant characteristics in each study arm were well matched, the diets were well-controlled (matched in fibre, calories, simple sugars, and all meals provided), and gestational weight gain was virtually equal, which are all key strengths of the current study. The authors also accounted for antibiotic exposure by excluding any maternal or newborn specimen when antibiotics were indicated within 4 weeks of collection of samples. Importantly, they took samples of both the mother’s and the child’s stool at various intervals, which allowed them to investigate how the mother’s diet group relates to changes in the microbiome throughout gestation (30 and 37 weeks’ gestation) and newborn age (2 weeks, 2 months, and 4-5 months of age).

Under these study conditions, the researchers determined how the diets affected the maternal gut microbiota and associations with maternal metabolic traits and the newborn microbiome. Surprisingly, they found that the probiotic family Bifidobacteriaceae, particularly B. adolescentis, had increased in the microbiome of women on the CHOICE diet. The maternal microbiome, specifically Alistipes species from the family Rikenellaceae, was also strongly associated with fasting levels of free fatty acids, glycerol, and glucose AUC measured by oral glucose tolerance test. In particular, they discovered a negative correlation between Rikenellaceae and fasting free-fatty acids (FFAs) and Alistipes finegoldii and Alistipes putredinis were negatively associated with fasting glycerol levels. Together, their findings suggest that bacteria in the family Rikenellaceae may aid in the reduction of FFAs, although different species are associated with other elements of the same metabolic pathway, most notably fasting glucose and glycerol levels.

Within the infant microbiome, maternal diet significantly impacted infant gut colonization, where CHOICE infants showed an increase in microbiota richness as well as an increase in Clostridiaceae, and decreased Enterococcaceae abundance. In healthy infants, members of Enterococcaceae are known to influence normal development of the intestinal immune system, but can also act as opportunistic pathogens. Thus, the authors suggest that early Enterococcaceae colonization is important for early immune programming but an overabundance in the early life could increase the risk of infection and other microbiota-related pathologies. Maternal diet also impacted colonization patterns of the infant gut as they aged. For example, C. perfringens was enriched in the gut of CONV infants, which has been associated with maternal obesity, cesarean delivery, and is a known pathogen. This may suggest the higher fat CONV diet exacerbated obesity-associated microbiome signals within a population that is already at risk for adverse health events due to maternal GDM status.

In conclusion, these findings suggest that an isocaloric GDM diet with more complex carbohydrates and less fat has a supposedly positive effect on the maternal microbiome, improves the diversity of the infant gut microbiome, and reduces opportunistic pathogens that affect immune system development and obesity. These findings underline how important a mother’s diet is in influencing the microbiota of her child and herself in GDM patients.