Gestational diabetes mellitus alters neonatal gut microbiota and increases infection susceptibility

Yifei Hu¹Shunjie Zheng²Jing Xu²Fangyu Zhao¹Jianbao Wang³Zenghui Fang¹Lanfang Zhou^1*

• ¹Jinhua Municipal Central Hospital, Jinhua, China
• ²Jinhua Maternity and Child Health Care Hospital, Jinhua, Zhejiang Province, China
• ³Jindong District Maternal and Child Health Care Hospital, Jinhua, China

Gestational diabetes mellitus (GDM) affects up to 27.6% of pregnancies in certain regions and is associated with a two-to threefold increased risk of neonatal infections. Although maternal gut microbiota undergoes significant remodeling during pregnancy, the specific mechanisms governing GDM-induced microbial reprogramming in offspring and its implications for susceptibility to infections remain unclear. This study aimed to investigate the impact of GDM on the composition of neonatal gut microbiota, metabolomic profiles, and susceptibility to infections using a translational approach.We recruited pregnant women with and without GDM at the JinHua Municipal Central Hospital in China. Meconium and blood samples were collected from newborns within 24 hours of birth. The composition of the gut microbiota was analyzed using 16S rDNA amplicon sequencing, and short-chain fatty acids (SCFAs) were quantified using gas chromatography-mass spectrometry.Serum inflammatory markers, including interleukin-6 (IL-6), C-reactive protein (CRP), lipopolysaccharides (LPS), and procalcitonin (PCT), were measured by enzyme-linked immunosorbent assay. To establish causality, fecal microbiota transplantation (FMT) was conducted in antibiotic-treated mice using pooled samples from healthy and GDM-exposed neonates, followed by assessment of inflammatory markers and intestinal barrier integrity.Results and discussion: GDM significantly reduced the diversity of neonatal gut microbiota and altered its composition, characterized by a depletion of beneficial taxa (Bifidobacterium, Blautia, Faecalibacterium) and an enrichment of potential pathogens (Stenotrophomonas, Chryseobacterium). These alterations were accompanied by significant reductions in fecal SCFAs, particularly acetate (49.30%), butyrate (41.00%), and propionate (17.83%). GDM-exposed neonates exhibited elevated serum inflammatory markers, including IL-6, CRP, LPS, and PCT, which correlated negatively with beneficial bacteria and positively with opportunistic pathogens. FMT experiments demonstrated that mice receiving GDM-associated microbiota developed increased systemic inflammation and compromised intestinal barrier function, as evidenced by the downregulation of tight junction proteins (ZO-1, occludin, claudin-1, mucin1). These findings suggest that GDM-induced alterations in neonatal gut microbiota composition and metabolite production may compromise intestinal barrier function and increase susceptibility to infections, highlighting the potential for microbiome-targeted interventions to mitigate infection risk in GDMexposed neonates.