Pediatric Gastroenterology, Hepatology & Nutrition

The Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition (대한소아소화기영양학회)
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A Pilot Study Exploring Temporal Development of Gut Microbiome/Metabolome in Breastfed Neonates during the First Week of Life

  • Imad Awan (Department of Medicine, Loma Linda University Medical Center) ;
  • Emily Schultz (Department of Biomedical Sciences, Cooper Medical School of Rowan University) ;
  • John D. Sterrett (Department of Integrative Physiology, University of Colorado Boulder) ;
  • Lamya'a M. Dawud (Department of Integrative Physiology, University of Colorado Boulder) ;
  • Lyanna R. Kessler (Department of Integrative Physiology, University of Colorado Boulder) ;
  • Deborah Schoch (Cooper Medical School of Rowan University and Cooper University Hospital) ;
  • Christopher A. Lowry (Department of Integrative Physiology, University of Colorado Boulder) ;
  • Lori Feldman-Winter (Cooper Medical School of Rowan University and Cooper University Hospital) ;
  • Sangita Phadtare (Department of Biomedical Sciences, Cooper Medical School of Rowan University)
  • Received : 2022.08.04
  • Accepted : 2023.01.07
  • Published : 2023.03.15
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Abstract

Purpose: Exclusive breastfeeding promotes gut microbial compositions associated with lower rates of metabolic and autoimmune diseases. Its cessation is implicated in increased microbiome-metabolome discordance, suggesting a vulnerability to dietary changes. Formula supplementation is common within our low-income, ethnic-minority community. We studied exclusively breastfed (EBF) neonates' early microbiome-metabolome coupling in efforts to build foundational knowledge needed to target this inequality. Methods: Maternal surveys and stool samples from seven EBF neonates at first transitional stool (0-24 hours), discharge (30-48 hours), and at first appointment (days 3-5) were collected. Survey included demographics, feeding method, medications, medical history and tobacco and alcohol use. Stool samples were processed for 16S rRNA gene sequencing and lipid analysis by gas chromatography-mass spectrometry. Alpha and beta diversity analyses and Procrustes randomization for associations were carried out. Results: Firmicutes, Proteobacteria, Bacteroidetes and Actinobacteria were the most abundant taxa. Variation in microbiome composition was greater between individuals than within (p=0.001). Palmitic, oleic, stearic, and linoleic acids were the most abundant lipids. Variation in lipid composition was greater between individuals than within (p=0.040). Multivariate composition of the metabolome, but not microbiome, correlated with time (p=0.030). Total lipids, saturated lipids, and unsaturated lipids concentrations increased over time (p=0.012, p=0.008, p=0.023). Alpha diversity did not correlate with time (p=0.403). Microbiome composition was not associated with each samples' metabolome (p=0.450). Conclusion: Neonate gut microbiomes were unique to each neonate; respective metabolome profiles demonstrated generalizable temporal developments. The overall variability suggests potential interplay between influences including maternal breastmilk composition, amount consumed and living environment.

Keywords

References

  1. Oddy WH, Mori TA, Huang RC, Marsh JA, Pennell CE, Chivers PT, et al. Early infant feeding and adiposity risk: from infancy to adulthood. Ann Nutr Metab 2014;64:262-70.  https://doi.org/10.1159/000365031
  2. Koleva PT, Bridgman SL, Kozyrskyj AL. The infant gut microbiome: evidence for obesity risk and dietary intervention. Nutrients 2015;7:2237-60.  https://doi.org/10.3390/nu7042237
  3. Feldman-Winter L, Burnham L, Grossman X, Matlak S, Chen N, Merewood A. Weight gain in the first week of life predicts overweight at 2 years: a prospective cohort study. Matern Child Nutr 2018;14:e12472. 
  4. Hildebrand JS, Ferguson PL, Sciscione AC, Grobman WA, Newman RB, Tita AT, et al. Breastfeeding associations with childhood obesity and body composition: findings from a racially diverse maternalchild cohort. Child Obes 2022;18:178-87.  https://doi.org/10.1089/chi.2021.0138
  5. Zhang T, Song Y, Teng H, Zhang Y, Lu J, Tao L, et al. BMI trajectories during the first 2 years, and their associations with infant overweight/obesity: a registered based cohort study in Taizhou, China. Front Pediatr 2021;9:665655. 
  6. Nguyen QP, Karagas MR, Madan JC, Dade E, Palys TJ, Morrison HG, et al. Associations between the gut microbiome and metabolome in early life. BMC Microbiol 2021;21:238. 
  7. Kisuse J, La-Ongkham O, Nakphaichit M, Therdtatha P, Momoda R, Tanaka M, et al. Urban diets linked to gut microbiome and metabolome alterations in children: a comparative cross-sectional study in Thailand. Front Microbiol 2018;9:1345. 
  8. Ayeni FA, Biagi E, Rampelli S, Fiori J, Soverini M, Audu HJ, et al. Infant and adult gut microbiome and metabolome in rural Bassa and urban settlers from Nigeria. Cell Rep 2018;23:3056-67.  https://doi.org/10.1016/j.celrep.2018.05.018
  9. Nelson JM, Grossniklaus DA, Galuska DA, Perrine CG. The mPINC survey: impacting US maternity care practices. Matern Child Nutr 2021;17:e13092. 
  10. Stewart CJ, Embleton ND, Marrs ECL, Smith DP, Fofanova T, Nelson A, et al. Longitudinal development of the gut microbiome and metabolome in preterm neonates with late onset sepsis and healthy controls. Microbiome 2017;5:75. 
  11. Younge NE, Newgard CB, Cotten CM, Goldberg RN, Muehlbauer MJ, Bain JR, et al. Disrupted maturation of the microbiota and metabolome among extremely preterm infants with postnatal growth failure. Sci Rep 2019;9:8167. 
  12. Brink LR, Mercer KE, Piccolo BD, Chintapalli SV, Elolimy A, Bowlin AK, et al. Neonatal diet alters fecal microbiota and metabolome profiles at different ages in infants fed breast milk or formula. Am J Clin Nutr 2020;111:1190-202.  https://doi.org/10.1093/ajcn/nqaa076
  13. O'Neill L, Pandya V, Grigoryan Z, Patel R, DeSipio J, Judge T, et al. Effects of milkfat on the gut microbiome of patients after bariatric surgery, a pilot study. Obes Surg 2022;32:480-8.  https://doi.org/10.1007/s11695-021-05805-z
  14. Caporaso JG, Lauber CL, Walters WA, Berg-Lyons D, Huntley J, Fierer N, et al. Ultra-high-throughput microbial community analysis on the Illumina HiSeq and MiSeq platforms. ISME J 2012;6:1621-4.  https://doi.org/10.1038/ismej.2012.8
  15. Callahan BJ, McMurdie PJ, Rosen MJ, Han AW, Johnson AJ, Holmes SP. DADA2: high-resolution sample inference from Illumina amplicon data. Nat Methods 2016;13:581-3.  https://doi.org/10.1038/nmeth.3869
  16. Janssen S, McDonald D, Gonzalez A, Navas-Molina JA, Jiang L, Xu ZZ, et al. Phylogenetic placement of exact amplicon sequences improves associations with clinical information. mSystems 2018;3:e00021-18. 
  17. Weiss S, Xu ZZ, Peddada S, Amir A, Bittinger K, Gonzalez A, et al. Normalization and microbial differential abundance strategies depend upon data characteristics. Microbiome 2017;5:27.
  18. Peres-Neto PR, Jackson DA. How well do multivariate data sets match? The advantages of a Procrustean superimposition approach over the Mantel test. Oecologia 2001;129:169-78.  https://doi.org/10.1007/s004420100720
  19. Marques TM, Wall R, Ross RP, Fitzgerald GF, Ryan CA, Stanton C. Programming infant gut microbiota: influence of dietary and environmental factors. Curr Opin Biotechnol 2010;21:149-56.  https://doi.org/10.1016/j.copbio.2010.03.020
  20. Gomez-Llorente C, Plaza-Diaz J, Aguilera M, Munoz-Quezada S, Bermudez-Brito M, Peso-Echarri P, et al. Three main factors define changes in fecal microbiota associated with feeding modality in infants. J Pediatr Gastroenterol Nutr 2013;57:461-6.  https://doi.org/10.1097/MPG.0b013e31829d519a
  21. Backhed F, Roswall J, Peng Y, Feng Q, Jia H, Kovatcheva-Datchary P, et al. Dynamics and stabilization of the human gut microbiome during the first year of life. Cell Host Microbe 2015;17:852. 
  22. Kok CR, Brabec B, Chichlowski M, Harris CL, Moore N, Wampler JL, et al. Stool microbiome, pH and short/branched chain fatty acids in infants receiving extensively hydrolyzed formula, amino acid formula, or human milk through two months of age. BMC Microbiol 2020;20:337. 
  23. Li N, Yan F, Wang N, Song Y, Yue Y, Guan J, et al. Distinct gut microbiota and metabolite profiles induced by different feeding methods in healthy Chinese infants. Front Microbiol 2020;11:714. 
  24. Palmer C, Bik EM, DiGiulio DB, Relman DA, Brown PO. Development of the human infant intestinal microbiota. PLoS Biol 2007;5:e177. 
  25. Bazanella M, Maier TV, Clavel T, Lagkouvardos I, Lucio M, Maldonado-Gomez MX, et al. Randomized controlled trial on the impact of early-life intervention with bifidobacteria on the healthy infant fecal microbiota and metabolome. Am J Clin Nutr 2017;106:1274-86.  https://doi.org/10.3945/ajcn.117.157529
  26. Hoen AG, Coker MO, Madan JC, Pathmasiri W, McRitchie S, Dade EF, et al. Association of cesarean delivery and formula supplementation with the stool metabolome of 6-week-old infants. Metabolites 2021;11:702. 
  27. Madan JC, Hoen AG, Lundgren SN, Farzan SF, Cottingham KL, Morrison HG, et al. Association of cesarean delivery and formula supplementation with the intestinal microbiome of 6-week-old infants. JAMA Pediatr 2016;170:212-9.  https://doi.org/10.1001/jamapediatrics.2015.3732
  28. Cukrowska B, Bierla JB, Zakrzewska M, Klukowski M, Maciorkowska E. The relationship between the infant gut microbiota and allergy. The role of Bifidobacterium breve and prebiotic oligosaccharides in the activation of anti-allergic mechanisms in early life. Nutrients 2020;12:946. 
  29. Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello MG, Contreras M, et al. Human gut microbiome viewed across age and geography. Nature 2012;486:222-7.  https://doi.org/10.1038/nature11053
  30. Wandro S, Osborne S, Enriquez C, Bixby C, Arrieta A, Whiteson K. The microbiome and metabolome of preterm infant stool are personalized and not driven by health outcomes, including necrotizing enterocolitis and late-onset sepsis. mSphere 2018;3:e00104-18.  https://doi.org/10.1128/mSphere.00104-18
  31. Zhou W, Sailani MR, Contrepois K, Zhou Y, Ahadi S, Leopold SR, et al. Longitudinal multi-omics of hostmicrobe dynamics in prediabetes. Nature 2019;569:663-71.  https://doi.org/10.1038/s41586-019-1236-x
  32. Gilley SP, Ruebel ML, Sims C, Zhong Y, Turner D, Lan RS, et al. Associations between maternal obesity and offspring gut microbiome in the first year of life. Pediatr Obes 2022;17:e12921. 
  33. Cheema AS, Gridneva Z, Furst AJ, Roman AS, Trevenen ML, Turlach BA, et al. Human milk oligosaccharides and bacterial profile modulate infant body composition during exclusive breastfeeding. Int J Mol Sci 2022;23:2865. 
  34. McOrist AL, Miller RB, Bird AR, Keogh JB, Noakes M, Topping DL, et al. Fecal butyrate levels vary widely among individuals but are usually increased by a diet high in resistant starch. J Nutr 2011;141:883-9. https://doi.org/10.3945/jn.110.128504
  35. Sillner N, Walker A, Lucio M, Maier TV, Bazanella M, Rychlik M, et al. Longitudinal profiles of dietary and microbial metabolites in formula- and breastfed infants. Front Mol Biosci 2021;8:660456. 
  36. German JB, Dillard CJ. Saturated fats: a perspective from lactation and milk composition. Lipids 2010;45:915-23.  https://doi.org/10.1007/s11745-010-3445-9
  37. Giuffrida F, Fleith M, Goyer A, Samuel TM, Elmelegy-Masserey I, Fontannaz P, et al. Human milk fatty acid composition and its association with maternal blood and adipose tissue fatty acid content in a cohort of women from Europe. Eur J Nutr 2022;61:2167-82.  https://doi.org/10.1007/s00394-021-02788-6
  38. Sanchez-Hernandez S, Esteban-Munoz A, Gimenez-Martinez R, Aguilar-Cordero MJ, Miralles-Buraglia B, Olalla-Herrera M. A comparison of changes in the fatty acid profile of human milk of Spanish lactating women during the first month of lactation using gas chromatography-mass spectrometry. A comparison with infant formulas. Nutrients 2019;11:3055. 
  39. Lin C, Wan J, Su Y, Zhu W. Effects of early intervention with maternal fecal microbiota and antibiotics on the gut microbiota and metabolite profiles of piglets. Metabolites 2018;8:89.