From Birth to Overweight and Atopic Disease: Multiple and Common Pathways of the Infant Gut Microbiome

Gastroenterology. 2021 Jan;160(1):128-144.e10. doi: 10.1053/j.gastro.2020.08.053. Epub 2020 Sep 16.


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.

Keywords: Cesarean Birth; Gut Microbiota; Labor; Metabolites.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Birth Weight*
  • Body Mass Index
  • Canada
  • Cesarean Section
  • Child, Preschool
  • Cohort Studies
  • Female
  • Gastrointestinal Microbiome / physiology*
  • Humans
  • Hypersensitivity / epidemiology*
  • Immunoglobulin A / metabolism
  • Infant
  • Infant, Newborn
  • Male
  • Overweight / epidemiology*
  • Pregnancy
  • Pregnancy Complications / epidemiology*


  • Immunoglobulin A

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