Download PDF
Am J Perinatol 2024; 41(S 01): e1866-e1877
DOI: 10.1055/s-0043-1769793
Original Article

Sociodemographic Factors and Intestinal Microbiome Development in Preterm, Very Low Birth Weight Infants

Katelyn Desorcy-Scherer 
1   College of Nursing, University of Florida, Gainesville, Florida
2   School of Nursing, University of Wisconsin, Madison, Wisconsin
,
Monica F. Torrez Lamberti
3   Department of Microbiology and Cell Science, Genetics Institute, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, Florida
,
Michael Weaver
1   College of Nursing, University of Florida, Gainesville, Florida
,
Graciela L. Lorca
3   Department of Microbiology and Cell Science, Genetics Institute, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, Florida
,
Leslie A. Parker
1   College of Nursing, University of Florida, Gainesville, Florida
› Author Affiliations Funding Research reported in this publication was supported by the National Institute of Nursing Research of the National Institutes of Health under award number “R01NR016964.”
› Further Information
Also available at
    Permissions and Reprints

Abstract

Objective Preterm very low birth weight (VLBW) infants are at risk for intestinal morbidities and dysbiotic development of the intestinal microbiome. Despite the influence of sociodemographic factors on premature infant health outcomes, whether they shape the intestinal microbiome early in life is not clear. The objective was to explore the associations between race, sex, and socioeconomic status and the intestinal microbiome of VLBW infants during the first 4 weeks of life.

Study Design This was a secondary analysis of data from an ongoing randomized trial of 79 infants ≤30 weeks' gestation and ≤1,500 g. Stool samples were collected at week 1 through week 4, frozen to −80°C and analyzed by 16S rRNA sequencing of the V4 region using Illumina MiSeq. Reads were analyzed to measure α and β diversity as well as relative abundance of bacteria in the intestinal microbiome.

Results Of the 79 infants, 63 had at least one sample available. Twenty-three (37%) of infants were African American, 30 (48%) were male, and 44 (71%) had Medicaid insurance. There were no statistically significant (<0.05) differences in α diversity or β diversity, and the differential abundance analysis suggests limited patterns of distinction in the intestinal microbiome between non-African American and African American infants, male and female infants, and infants with maternal private or Medicaid insurance.

Conclusion Our results suggest race, sex, and socioeconomic status shape colonization of specific microorganisms to a limited extent. Future studies should confirm these findings and determine clinical relevance through further study of differentially abundant microorganisms and additional factors contributing to colonization patterns.

Key Points

  • Diversity of the gut microbiome was similar between infants of varying race, sex, and socioeconomic status.

  • We observed sociodemographic-linked differences in colonization of individual taxa.

  • Further study is required to confirm these results and the clinical relevance of these findings.

Keywords

gut microbiome - premature - race - sex - socioeconomic status - insurance

Availability of Data and Material

The data that support the findings of this study are part of an ongoing, National Institutes of Health–funded clinical trial. Data will be shared at time of publication for the parent study.




Publication History

Received: 04 November 2022

Accepted: 02 May 2023

Article published online:
28 August 2023

© 2023. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 Huda S, Chaudhery S, Ibrahim H, Pramanik A. Neonatal necrotizing enterocolitis: clinical challenges, pathophysiology and management. Pathophysiology 2014; 21 (01) 3-12
    CrossrefPubMedSearch in Google Scholar
  • 2 Groer MW, Miller EM, D'Agata A. et al. Contributors to dysbiosis in very-low-birth-weight infants. J Obstet Gynecol Neonatal Nurs 2020; 49 (03) 232-242
    CrossrefPubMedSearch in Google Scholar
  • 3 Underwood MA, Umberger E, Patel RM. Safety and efficacy of probiotic administration to preterm infants: ten common questions. Pediatr Res 2020; 88 (1, suppl 1): 48-55
    CrossrefPubMedSearch in Google Scholar
  • 4 Hull MA, Fisher JG, Gutierrez IM. et al. Mortality and management of surgical necrotizing enterocolitis in very low birth weight neonates: a prospective cohort study. J Am Coll Surg 2014; 218 (06) 1148-1155
    CrossrefPubMedSearch in Google Scholar
  • 5 Rich BS, Dolgin SE. Necrotizing enterocolitis. Pediatr Rev 2017; 38 (12) 552-559
    CrossrefPubMedSearch in Google Scholar
  • 6 Rozé JC, Ancel PY, Lepage P. et al; Nutrition EPIPAGE 2 study group, EPIFLORE Study Group. Nutritional strategies and gut microbiota composition as risk factors for necrotizing enterocolitis in very-preterm infants. Am J Clin Nutr 2017; 106 (03) 821-830
    CrossrefPubMedSearch in Google Scholar
  • 7 Rackaityte E, Halkias J, Fukui EM. et al. Viable bacterial colonization is highly limited in the human intestine in utero. Nat Med 2020; 26 (04) 599-607
    CrossrefPubMedSearch in Google Scholar
  • 8 Ardissone AN, de la Cruz DM, Davis-Richardson AG. et al. Meconium microbiome analysis identifies bacteria correlated with premature birth. PLoS One 2014; 9 (03) e90784
    CrossrefPubMedSearch in Google Scholar
  • 9 Dardas M, Gill SR, Grier A. et al. The impact of postnatal antibiotics on the preterm intestinal microbiome. Pediatr Res 2014; 76 (02) 150-158
    CrossrefPubMedSearch in Google Scholar
  • 10 Greenwood C, Morrow AL, Lagomarcino AJ. et al. Early empiric antibiotic use in preterm infants is associated with lower bacterial diversity and higher relative abundance of Enterobacter. J Pediatr 2014; 165 (01) 23-29
    CrossrefPubMedSearch in Google Scholar
  • 11 Patel AL, Mutlu EA, Sun Y. et al. Longitudinal survey of microbiota in hospitalized preterm very-low-birth-weight infants. J Pediatr Gastroenterol Nutr 2016; 62 (02) 292-303
    CrossrefPubMedSearch in Google Scholar
  • 12 Chernikova DA, Koestler DC, Hoen AG. et al. Fetal exposures and perinatal influences on the stool microbiota of premature infants. J Matern Fetal Neonatal Med 2016; 29 (01) 99-105
    CrossrefPubMedSearch in Google Scholar
  • 13 Gupta RW, Tran L, Norori J. et al. Histamine-2 receptor blockers alter the fecal microbiota in premature infants. J Pediatr Gastroenterol Nutr 2013; 56 (04) 397-400
    CrossrefPubMedSearch in Google Scholar
  • 14 Ho TTB, Groer MW, Kane B. et al. Dichotomous development of the gut microbiome in preterm infants. Microbiome 2018; 6 (01) 157
    CrossrefPubMedSearch in Google Scholar
  • 15 Gregory KE, Samuel BS, Houghteling P. et al. Influence of maternal breast milk ingestion on acquisition of the intestinal microbiome in preterm infants. Microbiome 2016; 4 (01) 68
    CrossrefPubMedSearch in Google Scholar
  • 16 Ford SL, Lohmann P, Preidis GA. et al. Improved feeding tolerance and growth are linked to increased gut microbial community diversity in very-low-birth-weight infants fed mother's own milk compared with donor breast milk. Am J Clin Nutr 2019; 109 (04) 1088-1097
    CrossrefPubMedSearch in Google Scholar
  • 17 Yee AL, Miller E, Dishaw LJ. et al. Longitudinal microbiome composition and stability correlate with increased weight and length of very-low-birth-weight infants. mSystems 2019; 4 (01) e00229-18
    CrossrefPubMedSearch in Google Scholar
  • 18 Parra-Llorca A, Gormaz M, Alcántara C. et al. Preterm gut microbiome depending on feeding type: significance of donor human milk. Front Microbiol 2018; 9: 1376
    CrossrefPubMedSearch in Google Scholar
  • 19 Brooks B, Firek BA, Miller CS. et al. Microbes in the neonatal intensive care unit resemble those found in the gut of premature infants. Microbiome 2014; 2 (01) 1
    CrossrefPubMedSearch in Google Scholar
  • 20 Brooks B, Olm MR, Firek BA. et al. The developing premature infant gut microbiome is a major factor shaping the microbiome of neonatal intensive care unit rooms. Microbiome 2018; 6 (01) 112
    CrossrefPubMedSearch in Google Scholar
  • 21 Drell T, Lutsar I, Stšepetova J. et al. The development of gut microbiota in critically ill extremely low birth weight infants assessed with 16S rRNA gene based sequencing. Gut Microbes 2014; 5 (03) 304-312
    CrossrefPubMedSearch in Google Scholar
  • 22 D'Agata AL, Wu J, Welandawe MKV, Dutra SVO, Kane B, Groer MW. Effects of early life NICU stress on the developing gut microbiome. Dev Psychobiol 2019; 61 (05) 650-660
    CrossrefPubMedSearch in Google Scholar
  • 23 Gephart SM, Spitzer AR, Effken JA, Dodd E, Halpern M, McGrath JM. Discrimination of GutCheck(NEC): a clinical risk index for necrotizing enterocolitis. J Perinatol 2014; 34 (06) 468-475
    CrossrefPubMedSearch in Google Scholar
  • 24 Jammeh ML, Adibe OO, Tracy ET. et al. Racial/ethnic differences in necrotizing enterocolitis incidence and outcomes in premature very low birth weight infants. J Perinatol 2018; 38 (10) 1386-1390
    CrossrefPubMedSearch in Google Scholar
  • 25 Morse SB, Wu SS, Ma C, Ariet M, Resnick M, Roth J. Racial and gender differences in the viability of extremely low birth weight infants: a population-based study. Pediatrics 2006; 117 (01) e106-e112
    CrossrefPubMedSearch in Google Scholar
  • 26 Anderson JG, Baer RJ, Partridge JC. et al. Survival and major morbidity of extremely preterm infants: a population-based study. Pediatrics 2016; 138 (01) e20154434
    CrossrefPubMedSearch in Google Scholar
  • 27 Bowyer RCE, Jackson MA, Le Roy CI. et al. Socioeconomic status and the gut microbiome: a TwinsUK cohort study. Microorganisms 2019; 7 (01) 17
    CrossrefPubMedSearch in Google Scholar
  • 28 Miller GE, Engen PA, Gillevet PM. et al. Lower neighborhood socioeconomic status associated with reduced diversity of the colonic microbiota in healthy adults. PLoS One 2016; 11 (02) e0148952
    CrossrefPubMedSearch in Google Scholar
  • 29 Levin AM, Sitarik AR, Havstad SL. et al. Joint effects of pregnancy, sociocultural, and environmental factors on early life gut microbiome structure and diversity. Sci Rep 2016; 6: 31775
    CrossrefPubMedSearch in Google Scholar
  • 30 Gschwendtner S, Kang H, Thiering E. et al. Early life determinants induce sustainable changes in the gut microbiome of six-year-old children. Sci Rep 2019; 9 (01) 12675
    CrossrefPubMedSearch in Google Scholar
  • 31 Xu J, Lawley B, Wong G. et al. Ethnic diversity in infant gut microbiota is apparent before the introduction of complementary diets. Gut Microbes 2020; 11 (05) 1362-1373
    CrossrefPubMedSearch in Google Scholar
  • 32 Lewis CR, Bonham KS, McCann SH. et al. Family SES is associated with the gut microbiome in infants and children. Microorganisms 2021; 9 (08) 1608
    CrossrefPubMedSearch in Google Scholar
  • 33 Mello CS, Carmo-Rodrigues MS, Filho HB. et al. Gut microbiota differences in children from distinct socioeconomic levels living in the same urban area in Brazil. J Pediatr Gastroenterol Nutr 2016; 63 (05) 460-465
    CrossrefPubMedSearch in Google Scholar
  • 34 Neu J, Pammi M. Necrotizing enterocolitis: the intestinal microbiome, metabolome and inflammatory mediators. Semin Fetal Neonatal Med 2018; 23 (06) 400-405
    CrossrefPubMedSearch in Google Scholar
  • 35 Cong X, Xu W, Janton S. et al. Gut microbiome developmental patterns in early life of preterm infants: impacts of feeding and gender. PLoS One 2016; 11 (04) e0152751
    CrossrefPubMedSearch in Google Scholar
  • 36 Chen J, Li H, Hird SM. et al. Sex differences in gut microbial development of preterm infant twins in early life: a longitudinal analysis. Front Cell Infect Microbiol 2021; 11: 671074
    CrossrefPubMedSearch in Google Scholar
  • 37 Aguilar-Lopez M, Dinsmoor AM, Ho TTB, Donovan SM. A systematic review of the factors influencing microbial colonization of the preterm infant gut. Gut Microbes 2021; 13 (01) 1-33
    CrossrefPubMedSearch in Google Scholar
  • 38 Zhou Y, Shan G, Sodergren E, Weinstock G, Walker WA, Gregory KE. Longitudinal analysis of the premature infant intestinal microbiome prior to necrotizing enterocolitis: a case-control study. PLoS One 2015; 10 (03) e0118632
    CrossrefPubMedSearch in Google Scholar
  • 39 Zwittink RD, Renes IB, van Lingen RA. et al. Association between duration of intravenous antibiotic administration and early-life microbiota development in late-preterm infants. Eur J Clin Microbiol Infect Dis 2018; 37 (03) 475-483
    CrossrefPubMedSearch in Google Scholar
  • 40 Chong CYL, Vatanen T, Alexander T, Bloomfield FH, O'Sullivan JM. Factors associated with the microbiome in moderate-late preterm babies: a cohort study from the DIAMOND randomized controlled trial. Front Cell Infect Microbiol 2021; 11: 595323
    CrossrefPubMedSearch in Google Scholar
  • 41 Marcial GE, Ford AL, Haller MJ. et al. Lactobacillus johnsonii N6.2 modulates the host immune responses: a double-blind, randomized trial in healthy adults. Front Immunol 2017; 8: 655
    CrossrefPubMedSearch in Google Scholar
  • 42 Caporaso JG, Lauber CL, Walters WA. et al. Ultra-high-throughput microbial community analysis on the Illumina HiSeq and MiSeq platforms. ISME J 2012; 6 (08) 1621-1624
    CrossrefPubMedSearch in Google Scholar
  • 43 Callahan BJ, McMurdie PJ, Rosen MJ, Han AW, Johnson AJA, Holmes SP. DADA2: high-resolution sample inference from Illumina amplicon data. Nat Methods 2016; 13 (07) 581-583
    CrossrefPubMedSearch in Google Scholar
  • 44 Callahan BJ, McMurdie PJ, Holmes SP. Exact sequence variants should replace operational taxonomic units in marker-gene data analysis. ISME J 2017; 11 (12) 2639-2643
    CrossrefPubMedSearch in Google Scholar
  • 45 McMurdie PJ, Holmes S. phyloseq: an R package for reproducible interactive analysis and graphics of microbiome census data. PLoS One 2013; 8 (04) e61217
    CrossrefPubMedSearch in Google Scholar
  • 46 Martin BD, Witten D, Willis AD. Modeling microbial abundances and dysbiosis with beta-binomial regression. Ann Appl Stat 2020; 14 (01) 94-115
    CrossrefPubMedSearch in Google Scholar
  • 47 Wickham H. ggplot2: Elegant Graphics for Data Analysis. New York, NY: Springer; 2016
    CrossrefSearch in Google Scholar
  • 48 Gasparrini AJ, Wang B, Sun X. et al. Persistent metagenomic signatures of early-life hospitalization and antibiotic treatment in the infant gut microbiota and resistome. Nat Microbiol 2019; 4 (12) 2285-2297
    CrossrefPubMedSearch in Google Scholar
  • 49 Devanga Ragupathi NK, Muthuirulandi Sethuvel DP, Inbanathan FY, Veeraraghavan B. Accurate differentiation of Escherichia coli and Shigella serogroups: challenges and strategies. New Microbes New Infect 2017; 21: 58-62
    CrossrefPubMedSearch in Google Scholar
  • 50 Hackam DJ, Sodhi CP. Bench to bedside - new insights into the pathogenesis of necrotizing enterocolitis. Nat Rev Gastroenterol Hepatol 2022; 19 (07) 468-479
    CrossrefPubMedSearch in Google Scholar
  • 51 Sodhi CP, Wipf P, Yamaguchi Y. et al. The human milk oligosaccharides 2′-fucosyllactose and 6′-sialyllactose protect against the development of necrotizing enterocolitis by inhibiting toll-like receptor 4 signaling. Pediatr Res 2021; 89 (01) 91-101
    CrossrefPubMedSearch in Google Scholar
  • 52 Korpela K, Blakstad EW, Moltu SJ. et al. Intestinal microbiota development and gestational age in preterm neonates. Sci Rep 2018; 8 (01) 2453
    CrossrefPubMedSearch in Google Scholar
  • 53 Desorcy-Scherer K, Bendixen MM, Parker LA. Determinants of the very low-birth-weight infant's intestinal microbiome: a systematic review. J Perinat Neonatal Nurs 2020; 34 (03) 257-275
    CrossrefPubMedSearch in Google Scholar
  • 54 La Rosa PS, Warner BB, Zhou Y. et al. Patterned progression of bacterial populations in the premature infant gut. Proc Natl Acad Sci U S A 2014; 111 (34) 12522-12527
    CrossrefPubMedSearch in Google Scholar