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Pediatrics

Childhood body mass index and associations with infant gut metabolites and secretory IgA: findings from a prospective cohort study

International Journal of Obesity volume 46, pages 1712–1719 (2022)Cite this article

Subjects

Abstract

Background/Objectives

Differences in gut microbiota, metabolites and immune markers have been observed between individuals with and without obesity. Our study determined the temporal association between infant fecal gut metabolites, sIgA and body mass index (BMI) z score of preschool children, independent of pre/postnatal factors.

Subjects/Methods

The study includes a subset of 647 infants from the CHILD Cohort Study (recruited between January 1, 2009, and December 31, 2012). Fecal metabolites and sIgA were measured at 3–4 months of age, and age and sex adjusted BMI z scores at 1 and 3 years of age. Associations between the metabolites, IgA, and child BMI z scores at age 1 and 3 years were tested using linear regression adjusted for pre/postnatal factors (breastfeeding, birthweight-for-gestational age, birthmode and IAP, solid food introduction).

Results

Mean BMI z score for all infants was 0.34 (SD 1.16) at 1 year (N = 647) and 0.71 (SD 1.06) at 3 years (N = 573). High fecal formate in infancy was associated with a significantly lower BMI z score (adjusted mean difference −0.23 (95% CI −0.42, −0.04)) and high butyrate was associated with a higher BMI z score (adjusted mean difference 0.21 (95% CI 0.01, 0.41)) at age 3 years only. The influence of formate and butyrate on BMI z score at age 3 were seen only in those that were not exclusively breastfed at stool sample collection (adjusted mean difference for high formate/EBF- group: −0.33 (95%CI −0.55, −0.10) and 0.25 (95% CI 0.02, 0.47) for high butyrate/EBF- group). No associations were seen between sIgA and BMI z score at age 1 or 3 years in adjusted regression models.

Conclusion and relevance

Differences in fecal metabolite levels in early infancy were associated with childhood BMI. This study identifies an important area of future research in understanding the pathogenesis of obesity.

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Fig. 1: Difference in BMI z scores by fecal metabolites.
Fig. 2: Difference in BMI z score in infants with high fecal metabolites.
Fig. 3: Correlation between microbiota phylum and formate, butyrate and sIgA.
Fig. 4: Correlation between microbiota family and formate, butyrate and sIgA.

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Data availability

A list of variables available in the CHILD Cohort Study is available at https://childstudy.ca/for-researchers/study-data/. Researchers interested in collaborating on a project and accessing CHILD Cohort Study data should contact the Study’s National Coordinating Center (NCC) to discuss their needs before initiating a formal request. To contact the NCC, please email child@mcmaster.ca. More information about data access for the CHILD Cohort Study can be found at https://childstudy.ca/forresearchers/data-access/.

References

  1. Ogden CL, Carroll MD, Lawman HG, Fryar CD, Kruszon-Moran D, Kit BK, et al. Trends in obesity prevalence among children and adolescents in the United States, 1988–1994 Through 2013–2014. JAMA. 2016;315:2292–9.

    CAS  Google Scholar 

  2. Biro FM, Wien M. Childhood obesity and adult morbidities. Am J Clin Nutr. 2010;91:1499s–505s.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Simmonds M, Llewellyn A, Owen CG, Woolacott N. Predicting adult obesity from childhood obesity: a systematic review and meta-analysis. Obes Rev. 2016;17:95–107.

    Article  CAS  PubMed  Google Scholar 

  4. Sommer F, Backhed F. The gut microbiota–masters of host development and physiology. Nat Rev Microbiol. 2013;11:227–38.

    Article  CAS  PubMed  Google Scholar 

  5. Angelakis E, Armougom F, Million M, Raoult D. The relationship between gut microbiota and weight gain in humans. Future Microbiol. 2012;7:91–109.

    Article  PubMed  Google Scholar 

  6. Karlsson CL, Onnerfalt J, Xu J, Molin G, Ahrne S, Thorngren-Jerneck K. The microbiota of the gut in preschool children with normal and excessive body weight. Obesity. 2012;20:2257–61.

    Article  PubMed  Google Scholar 

  7. Bervoets L, Van Hoorenbeeck K, Kortleven I, Van Noten C, Hens N, Vael C, et al. Differences in gut microbiota composition between obese and lean children: a cross-sectional study. Gut Pathog. 2013;5:10.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Koleva PT, Bridgman SL, Kozyrskyj AL. The infant gut microbiome: evidence for obesity risk and dietary intervention. Nutrients. 2015;7:2237–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Payne AN, Chassard C, Zimmermann M, Muller P, Stinca S, Lacroix C. The metabolic activity of gut microbiota in obese children is increased compared with normal-weight children and exhibits more exhaustive substrate utilization. Nutr Diabetes. 2011;1:e12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Kumari M, Kozyrskyj AL. Gut microbial metabolism defines host metabolism: an emerging perspective in obesity and allergic inflammation. Obes Rev. 2017;18:18–31.

    Article  CAS  PubMed  Google Scholar 

  11. Murugesan S, Nirmalkar K, Hoyo-Vadillo C, Garcia-Espitia M, Ramirez-Sanchez D, Garcia-Mena J. Gut microbiome production of short-chain fatty acids and obesity in children. Eur J Clin Microbiol Infect Dis. 2018;37:621–5.

    Article  CAS  PubMed  Google Scholar 

  12. Gutzeit C, Magri G, Cerutti A. Intestinal IgA production and its role in host-microbe interaction. Immunol Rev. 2014;260:76–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Luck H, Khan S, Kim JH, Copeland JK, Revelo XS, Tsai S, et al. Gut-associated IgA(+) immune cells regulate obesity-related insulin resistance. Nat Commun. 2019;10:3650.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Subbarao P, Anand SS, Becker AB, Befus AD, Brauer M, Brook JR, et al. The Canadian Healthy Infant Longitudinal Development (CHILD) Study: examining developmental origins of allergy and asthma. Thorax. 2015;70:998–1000.

    Article  PubMed  Google Scholar 

  15. Tun HM, Konya T, Takaro TK, Brook JR, Chari R, Field CJ, et al. Exposure to household furry pets influences the gut microbiota of infant at 3-4 months following various birth scenarios. Microbiome. 2017;5:40.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Emwas AH. The strengths and weaknesses of NMR spectroscopy and mass spectrometry with particular focus on metabolomics research. Methods Mol Biol. 2015;1277:161–93.

    Article  CAS  PubMed  Google Scholar 

  17. Forrest BD. Effects of sample processing on the measurement of specific intestinal IgA immune responses. Vaccine. 1992;10:802–5.

    Article  CAS  PubMed  Google Scholar 

  18. WHO. Child Growth Standards based on length/height, weight and age. Acta Paediatr Suppl. 2006;450:76–85.

    Google Scholar 

  19. Kim KN, Yao Y, Ju SY. Short chain fatty acids and fecal microbiota abundance in humans with obesity: a systematic review and meta-analysis. Nutrients. 2019;11:2512.

    Article  CAS  PubMed Central  Google Scholar 

  20. Kang LJ, Koleva PT, Field CJ, Giesbrecht GF, Wine E, Becker AB, et al. Maternal depressive symptoms linked to reduced fecal Immunoglobulin A concentrations in infants. Brain Behav Immun. 2018;68:123–31.

    Article  CAS  PubMed  Google Scholar 

  21. Glickman ME, Rao SR, Schultz MR. False discovery rate control is a recommended alternative to Bonferroni-type adjustments in health studies. J Clin Epidemiol. 2014;67:850–7.

    Article  PubMed  Google Scholar 

  22. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J Royal Stat Soc Ser B. 1995;57:289–300.

    Google Scholar 

  23. Riva A, Borgo F, Lassandro C, Verduci E, Morace G, Borghi E, et al. Pediatric obesity is associated with an altered gut microbiota and discordant shifts in Firmicutes populations. Environ Microbiol. 2017;19:95–105.

    Article  CAS  PubMed  Google Scholar 

  24. Murugesan S, Ulloa-Martinez M, Martinez-Rojano H, Galvan-Rodriguez FM, Miranda-Brito C, Romano MC, et al. Study of the diversity and short-chain fatty acids production by the bacterial community in overweight and obese Mexican children. Eur J Clin Microbiol Infect Dis. 2015;34:1337–46.

    Article  CAS  PubMed  Google Scholar 

  25. Baker JL, Olsen LW, Sørensen TI. Childhood body-mass index and the risk of coronary heart disease in adulthood. N Engl J Med. 2007;357:2329–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Meyer JF, Larsen SB, Blond K, Damsgaard CT, Bjerregaard LG, Baker JL. Associations between body mass index and height during childhood and adolescence and the risk of coronary heart disease in adulthood: a systematic review and meta-analysis. Obes Rev. 2021;22:e13276.

    Article  PubMed  Google Scholar 

  27. Guilloteau P, Martin L, Eeckhaut V, Ducatelle R, Zabielski R, Van Immerseel F. From the gut to the peripheral tissues: the multiple effects of butyrate. Nutr Res Rev. 2010;23:366–84.

    Article  CAS  PubMed  Google Scholar 

  28. Zhang L, Liu C, Jiang Q, Yin Y. Butyrate in energy metabolism: there is still more to learn. Trends Endocrinol Metab. 2021;32:159–69.

    Article  CAS  PubMed  Google Scholar 

  29. Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444:1027–31.

    Article  PubMed  Google Scholar 

  30. de la Cuesta-Zuluaga J, Mueller NT, Álvarez-Quintero R, Velásquez-Mejía EP, Sierra JA, Corrales-Agudelo V, et al. Higher fecal short-chain fatty acid levels are associated with gut microbiome dysbiosis, obesity, hypertension and cardiometabolic disease risk factors. Nutrients. 2018;11:51.

    Article  PubMed Central  CAS  Google Scholar 

  31. Ferrer-Picón E, Dotti I, Corraliza AM, Mayorgas A, Esteller M, Perales JC, et al. Intestinal inflammation modulates the epithelial response to butyrate in patients with inflammatory bowel disease. Inflamm Bowel Dis. 2020;26:43–55.

    Article  PubMed  Google Scholar 

  32. Pietzke M, Meiser J, Vazquez A. Formate metabolism in health and disease. Mol Metab. 2020;33:23–37.

    Article  CAS  PubMed  Google Scholar 

  33. Badillo-Suárez PA, Rodríguez-Cruz M, Nieves-Morales X. Impact of metabolic hormones secreted in human breast milk on nutritional programming in childhood obesity. J Mammary Gland Biol Neoplasia. 2017;22:171–91.

    Article  PubMed  Google Scholar 

  34. Savino F, Liguori SA, Fissore MF, Oggero R. Breast milk hormones and their protective effect on obesity. Int J Pediatr Endocrinol. 2009;2009:327505.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Pallaro A, Barbeito S, Taberner P, Marino P, Franchello A, Strasnoy I, et al. Total salivary IgA, serum C3c and IgA in obese school children. J Nutr Biochem. 2002;13:539.

    Article  CAS  PubMed  Google Scholar 

  36. Koh A, De Vadder F, Kovatcheva-Datchary P, Bäckhed F. From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites. Cell. 2016;165:1332–45.

    Article  CAS  PubMed  Google Scholar 

  37. Louis P, Flint HJ. Diversity, metabolism and microbial ecology of butyrate-producing bacteria from the human large intestine. FEMS Microbiol Lett. 2009;294:1–8.

    Article  CAS  PubMed  Google Scholar 

  38. Louis P, Flint HJ. Formation of propionate and butyrate by the human colonic microbiota. Environ Microbiol. 2017;19:29–41.

    Article  CAS  PubMed  Google Scholar 

  39. Barcenilla A, Pryde SE, Martin JC, Duncan SH, Stewart CS, Henderson C, et al. Phylogenetic relationships of butyrate-producing bacteria from the human gut. Appl Environ Microbiol. 2000;66:1654–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Forbes JD, Azad MB, Vehling L, Tun HM, Konya TB, Guttman DS, et al. Association of exposure to formula in the hospital and subsequent infant feeding practices with gut microbiota and risk of overweight in the first year of life. JAMA Pediatr. 2018;172:e181161.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Xu Y, Wang N, Tan HY, Li S, Zhang C, Feng Y. Function of Akkermansia muciniphila in obesity: interactions with lipid metabolism, immune response and gut systems. Front Microbiol. 2020;11:219.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Tsukuda N, Yahagi K, Hara T, Watanabe Y, Matsumoto H, Mori H, et al. Key bacterial taxa and metabolic pathways affecting gut short-chain fatty acid profiles in early life. Isme j. 2021;15:2574–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Korpela K, Zijlmans MA, Kuitunen M, Kukkonen K, Savilahti E, Salonen A, et al. Childhood BMI in relation to microbiota in infancy and lifetime antibiotic use. Microbiome. 2017;5:26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Kalliomaki M, Collado MC, Salminen S, Isolauri E. Early differences in fecal microbiota composition in children may predict overweight. Am J Clin Nutr. 2008;87:534–8.

    Article  CAS  PubMed  Google Scholar 

  45. Belzer C, Chia LW, Aalvink S, Chamlagain B, Piironen V, Knol J, et al. Microbial metabolic networks at the mucus layer lead to diet- independent butyrate and vitamin B(12) production by intestinal symbionts. mBio. 2017;8:e00770–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Karav S, Casaburi G, Frese SA. Reduced colonic mucin degradation in breastfed infants colonized by Bifidobacterium longum subsp. infantis EVC001. FEBS Open Bio. 2018;8:1649–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank the CHILD Cohort Study (CHILD) participant families for their dedication and commitment to advancing health research as well as the whole CHILD study team, which includes interviewers, nurses, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, and receptionists. We also thank Susan Goruk for her assistance in sIgA analysis, Theodore Konya for his work on the microbiota sample processing and analysis and Jennifer Petrie for her assistance in data entry. The Canadian Institutes of Health Research (CIHR) and the Allergy, Genes and Environment Network of Centers of Excellence provided core funding for the Canadian Healthy Infant Longitudinal Development (CHILD) Study. This research was specifically funded by CIHR Microbiome Initiative team grant 227312 and the Women and Children’s Health Research Institute at the University of Alberta.

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Authors and Affiliations

  1. Department of Pediatrics, University of Alberta, Edmonton, AB, Canada

    Sarah L. Bridgman, Andrea M. Haqq, Piushkumar J. Mandhane & Anita L. Kozyrskyj

  2. Agriculture Agri-Food Canada, Lethbridge Research and Development Centre, Lethbridge, AB, Canada

    Nilusha Malmuthuge

  3. Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada

    Rupasri Mandal & David S. Wishart

  4. Department of Agriculture, Food and Nutritional Sciences, University of Alberta, Edmonton, AB, Canada

    Catherine J. Field & Andrea M. Haqq

  5. Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada

    Theo J. Moraes

  6. Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada

    Stuart E. Turvey

  7. BC Children’s Hospital, Vancouver, BC, Canada

    Stuart E. Turvey

  8. Developmental Origins of Chronic Diseases in Children Network (DEVOTION), Department of Pediatrics and Child Health, Children’s Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, MB, Canada

    Elinor Simons

  9. Department of Pediatrics and Physiology, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada

    Padmaja Subbarao

  10. Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada

    James A. Scott

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Contributions

ALK, SLB, CJF, AMH, PJM, ES, PS, SET, JAS were involved in the study concept and design. CJF, RM, PJM, TJM, ES, SET, JAS and DSW were involved in the acquisition of data. SLB conducted the data cleaning and statistical analysis and SLB and ALK drafted of the manuscript. All authors provided critical revision of the manuscript for important intellectual content and approved the final submitted manuscript.

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Correspondence to Anita L. Kozyrskyj.

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Bridgman, S.L., Malmuthuge, N., Mandal, R. et al. Childhood body mass index and associations with infant gut metabolites and secretory IgA: findings from a prospective cohort study. Int J Obes 46, 1712–1719 (2022). https://doi.org/10.1038/s41366-022-01183-3

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