Khanh Vu1, Wendy Lou2, Hein M Tun3, Theodore B Konya2, Nadia Morales-Lizcano2, Radha S Chari4, Catherine J Field5, David S Guttman6, Rupasri Mandal7, David S Wishart7, Meghan B Azad8, Allan B Becker8, Piush J Mandhane1, Theo J Moraes9, Diana L Lefebvre10, Malcolm R Sears10, Stuart E Turvey11, Padmaja Subbarao9, James A Scott2, Anita L Kozyrskyj12. 1. Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada. 2. Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada. 3. School of Public Health, University of Hong Kong, Hong Kong. 4. Department of Obstetrics and Gynecology, University of Alberta, Edmonton, Alberta, Canada. 5. Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada. 6. Centre for the Analysis of Genome Evolution and Function, University of Toronto, Toronto, Ontario, Canada. 7. The Metabolomics Innovation Centre, Edmonton, Alberta, Canada. 8. Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada. 9. Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada. 10. Department of Medicine, McMaster University, Hamilton, Ontario, Canada. 11. Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada. 12. Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada; Department of Obstetrics and Gynecology, University of Alberta, Edmonton, Alberta, Canada; School of Public Health, University of Alberta, Edmonton, Alberta, Canada. Electronic address: kozyrsky@ualberta.ca.
Abstract
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.
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.
Authors: Rachael G Horne; Stephen B Freedman; Kathene C Johnson-Henry; Xiao-Li Pang; Bonita E Lee; Ken J Farion; Serge Gouin; Suzanne Schuh; Naveen Poonai; Katrina F Hurley; Yaron Finkelstein; Jianling Xie; Sarah Williamson-Urquhart; Linda Chui; Laura Rossi; Michael G Surette; Philip M Sherman Journal: Front Cell Infect Microbiol Date: 2022-06-14 Impact factor: 6.073
Authors: Monica Gio-Batta; Karin Spetz; Malin Barman; Lennart Bråbäck; Elisabeth Norin; Bengt Björkstén; Agnes E Wold; Anna Sandin Journal: Int Arch Allergy Immunol Date: 2021-11-26 Impact factor: 3.767
Authors: Candace R Lewis; Kevin S Bonham; Shelley Hoeft McCann; Alexandra R Volpe; Viren D'Sa; Marcus Naymik; Matt D De Both; Matthew J Huentelman; Kathryn Lemery-Chalfant; Sarah K Highlander; Sean C L Deoni; Vanja Klepac-Ceraj Journal: Microorganisms Date: 2021-07-28
Authors: Silvia Saturio; Alicja M Nogacka; Guadalupe M Alvarado-Jasso; Nuria Salazar; Clara G de Los Reyes-Gavilán; Miguel Gueimonde; Silvia Arboleya Journal: Microorganisms Date: 2021-11-23