Fetal programming of overweight through the microbiome: boys are disproportionately affected

Abstract

Maternal and childhood obesity in pregnancy are worrisome public health issues facing our world today. New gene sequencing methods have advanced our knowledge of the disruptive effect of birth interventions and postnatal exposures on the maturation of gut microbiota and immunity during infancy. Yet, little is known about the impact of maternal pregnancy overweight on gut microbes and related processes, and how this may affect overweight risk in offspring. To address this gap in knowledge, we surveyed human studies for evidence in children, infants and pregnant women to piece together the limited literature and generate hypotheses for future investigation. From this literature, we learned that higher Lactobacillus yet lower Bacteroides spp. colonization of gut microbiota within 3 months of birth predicted risk for infant and child overweight. The abundance of bifidobacteria and staphylococci also appeared to play a role in the association with overweight, as did infant fecal immunoglobulin A levels, glycoproteins of the gut immune system that are acquired from breast milk and produced by the infant. We proposed that pregnancy overweight influences the compositional structure of gut microbiota in infants through vertical transfer of microbiota and/or their metabolites during pregnancy, delivery and breastfeeding. Finally, we brought forward emerging evidence on sex dimorphism, as well as ethnic and geographic variation, in reported associations between maternal overweight-induced gut microbiota dysbiosis and overweight risk.

Impact of maternal pre‐pregnancy overweight on infant overweight at 1 year of age: associations and sex‐specific differences

“…In our study, postnatal (with or without maternal intrapartum) antibiotic use by 3 months of age was the sole factor in female infants to raise the likelihood of the extreme overweight phenotype. This association was absent in male infants, inconsistent with the disproportionate influence of antibiotic treatment on overweight among male children in later life (16). As noted earlier, breastfeeding or caesarean section associations with overweight were not independent of maternal overweight in our male infants.…”

“…Both hormones are elevated with pregnancy overweight . Finally, obesity‐related microbes, metabolites or hormones that preferentially affect the weight of male fetuses, may also influence postnatal gut microbial composition . This finding offers an explanation for why pregnancy and postnatal microbiota risk factors for overweight might be inter‐related in male infants and why adjustment with microbiota‐affecting variables reduced the crude fivefold risk associated with maternal obesity.…”

Maternal and early‐life area‐level characteristics and childhood adiposity: A systematic review

“…The composition of the antenatal microbiome is influenced by maternal exposure to environmental pollutants, with particular combinations being associated with susceptibility to NCDs . For example, high counts of Lactobacillius bacteria in the antenatal microbiome are associated with high risk of offspring being affected by overweight and obesity during infancy and childhood …”

“…20 For example, high counts of Lactobacillius bacteria in the antenatal microbiome are associated with high risk of offspring being affected by overweight and obesity during infancy and childhood. 21 The environment and diet children are exposed to in their first year of life may also affect their weight during childhood. The diversity of gut microbiota is formed in the first few hours of human life as a response to the antenatal microbiome 22 and rapidly evolves as a result of exposure to environmental pollutants, 20 and the microbiome is associated with weight in childhood.…”

The microbiota–gut–brain axis: A promising avenue to foster healthy developmental outcomes

“…In humans, associations between early microbiota composition and child health are well documented and growing. Studies examining the correlates of antibiotic use, probiotic use, and microbiota composition suggest that imbalances in the gut microbiota in infancy and childhood are implicated in: increased risk for child obesity (e.g., Dogra et al, ; Kozyrskyj, Kalu, Koleva, & Bridgman, ), irritable bowel syndrome (e.g., Saulnier et al, ), allergies (e.g., Noverr & Huffnagle, ), atopic disorders (Penders et al, ), and asthma (e.g., Kummeling et al, ). Research continues to emerge illustrating the gut microbiota's importance in establishing and maintaining physical health beginning in the earliest days of life.…”