Gestational diabetes linked to altered gut microbiome and larger head circumference in male offspring

Gestational diabetes mellitus (GDM) not only disrupts the gut microbiome of mothers and their infants, but is also linked to increased head circumference in male offspring, researchers from the Chinese University of Hong Kong (CUHK) have shown.

“Current understanding of the mother-to-infant microbiome is largely skewed by European and American birth cohorts, which are demographically distinct from Asian populations,” said Professor Francis Chan, Director of the Microbiota I-Center (MagIC), CUHK. “Owing to lifestyle, diet, and geographical factors, those findings may lack generalizability and translation of those findings to Asian populations may be imprecise.”

The researchers therefore used data from the MOMmy study to assess how early life exposure to GDM impacts gut microbiota and head circumference growth in Chinese offspring. A total of 269 mothers (90 with GDM and 179 without GDM) in Hong Kong and their babies (n=266; 90 born to mothers with GDM; 176 born to mothers without GDM) were analyzed for gut microbiota (using serial stool samples), extensive exposure metadata, and growth (for babies only). [Cell Host Microbe 2024;32:1192-1206.e5]

Altered gut microbiome

For the first time, the research team showcased the gut microbiome trajectory of mothers with GDM throughout pregnancy and that of their infants from meconium (the first poop) to 1 year of age.

“GDM mothers exhibited reduced gut microbiome diversity, characterized by lower abundance of Akkermansia muciniphila, Coprococcus eutactus, and Enterorhabdus caecimuris, along with an increased abundance of Fusobacterium mortiferum vs mothers without GDM,” reported Professor Lin Zhang of the Department of Medicine & Therapeutics, CUHK. Additionally, infants of GDM mothers had a higher abundance of Clostridium during the first year of life, confirming deep GDM fingerprints on the infant’s gut microbiome.

Abnormal head circumference growth

The head circumference growth rate was significantly higher at 2, 6 and 12 months in infants born to GDM mothers vs those born to non-GDM mothers (all p<0.05). After categorizing the data based on infants’ gender, only male infants exposed to GDM exhibited accelerated head growth within the first year of life, suggesting a gender-dependent effect.

“The abnormal growth in head circumference in male offspring of mothers with GDM may be an important indicator of neurodevelopmental disorders early in life,” commented Professor Siew Ng, Director of MagIC, CUHK. “Future research is necessary to understand the long-term consequences of overgrowth of head circumference in these male infants, and whether microbiota modulation serves as a potential approach to mitigate and prevent these risks.”

Looking at the bigger picture

Participants in the current study were selected from the MOMmy study, a longitudinal cohort project involving 100,000 mother-baby pairs with a follow-up period of 7 years. [NCT04117321]

“The MOMmy study will outline the development trajectory of the gut microbiome in healthy infants and young children in China. It aims to establish early noninvasive screening methods for common diseases in infants, and enable early intervention in the course of disease and alleviate symptoms by improving gut microbiome,” said Chan.