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From Birth to Overweight and Atopic Disease: Multiple and Common Pathways of the Infant Gut Microbiome
Khanh Vu1, Wendy Lou2, Hein M Tun3
1Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
Insights
Infant gut microbiome changes, particularly Clostridioides difficile colonization, mediate risks for childhood overweight and atopy following cesarean birth or prolonged labor. These findings highlight microbial pathways influencing early-life health outcomes.
Area of Science:
- Microbiome research
- Pediatric health
- Immunology
Background:
- Few studies investigate how infant gut microbes and metabolites mediate disease onset.
- This study addresses the gap by examining these mediating effects in a cohort.
Purpose of the Study:
- To test directional relationships between early-life factors, infant gut microbiome, and child health outcomes.
- To identify specific microbial and metabolic pathways linking pregnancy and birth characteristics to childhood body mass index and atopy.
Main Methods:
- Utilized structural equation modeling path analysis in a cohort of 1667 infants.
- Examined relationships between first pregnancy, birth mode, labor duration, breastfeeding, infant gut microbiota, metabolites, IgA, and childhood BMI and atopy.
Main Results:
- Cesarean birth and prolonged labor were linked to higher Enterobacteriaceae/Bacteroidaceae ratios and Clostridioides difficile colonization, pathways to overweight and atopy.
- Depletion of Bifidobacterium and altered metabolite levels (propionate, formate) also mediated these outcomes.
- Formate was identified as a key intersecting metabolite in several pathways.
Conclusions:
- Common infant gut microbiome mediators, especially Clostridioides difficile colonization, link cesarean section and first pregnancy to child overweight and atopy.
- These findings underscore the role of the early-life gut microbiome in shaping long-term health trajectories.
Background & Aims:
Few studies, even those with cohort designs, test the mediating effects of infant gut microbes and metabolites on the onset of disease. We undertook such a study.
Methods:
Using structural equation modeling path analysis, we tested directional relationships between first pregnancy, birth mode, prolonged labor and breastfeeding; infant gut microbiota, metabolites, and IgA; and childhood body mass index and atopy in 1667 infants.
Results:
After both cesarean birth and prolonged labor with a first pregnancy, a higher Enterobacteriaceae/Bacteroidaceae ratio at 3 months was the dominant path to overweight; higher Enterobacteriaceae/Bacteroidaceae ratios and Clostridioides difficile colonization at 12 months were the main pathway to atopic sensitization. Depletion of Bifidobacterium after prolonged labor was a secondary pathway to overweight. Influenced by C difficile colonization at 3 months, metabolites propionate and formate were secondary pathways to child outcomes, with a key finding that formate was at the intersection of several paths.
Conclusions:
Pathways from cesarean section and first pregnancy to child overweight and atopy share many common mediators of the infant gut microbiome, notably C difficile colonization.
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