Neonatal Intestinal Microbiome: Impact on Infant and Early Childhood Health and Disease

The first few months and years of a child’s life are essential in shaping the intestinal microbiome, which rapidly develops during this time. An individual’s intestinal microbiome reaches a relative stability by toddlerhood that generally lasts into adulthood. Hence, this early period may be critical for shaping future health and preventing the development of many diseases.

Premature infants are at increased risk of an imbalance in gut bacteria and delayed or disturbed gut colonization for many reasons, including an immature gut and immune system, increased exposure to antibiotics, and delayed feeding. They are also at increased risk of many disorders associated with gut bacteria imbalance compared to infants who are born full term.

At Inova Children’s Hospital, we are conducting a microbiome study of babies born prematurely who spend time in the neonatal intensive care unit (NICU). We follow them into early childhood to examine why and how disturbances in gut bacteria develop and how they may lead to early childhood health problems such as necrotizing enterocolitis, obesity and allergies. Using the latest technology, we hope to gain better insight into how disturbances of the microbiota are associated with disease. This knowledge is essential to enable future possible microbiota manipulation in childhood, which could help prevent disease.

Neonatal Intensive Care Unit (NICU)
Inova Fairfax Hospital
3300 Gallows Road
Falls Church, VA  22042

• Admitted to the NICU with anticipated stay of more than 5 days

Key Publications

1. Hourigan SK, Chirumamilla SR, Ross T, Golub JE, Rabizadeh S, Saeed SA, Elson CO, Kelly CP, Carroll KC, Oliva-Hemker M, Sears C. Clostridium difficile carriage and serum antitoxin responses in children with inflammatory bowel disease. Inflamm Bowel Dis. 2013 Dec;19(13):2744-52.

2. Hourigan SK, Hutfless S, Oliva-Hemker M. The Prevalence of Clostridium difficile Infection in Hospitalized Pediatric and Adult Patients with Inflammatory Bowel Disease. Dig Dis Sci. 2014 Sep;59(9):2222-7.

3. Hourigan SK, Chen LA, Grigoryan Z, Laroche G, Weidner M, Sears CL, Oliva-Hemker M. Microbiome changes associated with sustained eradication of Clostridium difficile after single faecal microbiota transplantation in children with and without inflammatory bowel disease. Aliment Pharmacol Ther. 2015 Sep;42(6):741-52.

4. Hourigan SK, Sears CL, Oliva-Hemker M .Clostridium difficile Infection in Pediatric Inflammatory Bowel Disease. Inflamm Bowel Dis. 2016 Apr;22(4):1020-5.

5. Hourigan SK, Oliva-Hemker M. Fecal Microbiota Transplantation in Children - A Brief Review. Pediatr Res. 2016. Pediatr Res. 2016 Jul;80(1):2-6.

6. Hourigan SK, Ta A, Wong SW, Clemency N, Provenzano MG, Baveja R, Iyer R, Klein E, Niederhuber JE. .The microbiome in necrotizing enterocolitis: A case report in twins and mini-review. Clin Ther. 2016 Apr;38(4):747-53.

7. Mueller NT, Mao G, Bennet W, Hourigan S, Dominguez-Bello MG, Appel LJ, Wang X. Does vaginal delivery mitigate or strengthen the intergenerational association of overweight and obesity? Findings from the boston birth cohort. Int J Obes (Lond). 2017 Apr;41(4):497-501. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5380521/

8. Wong WSW, Clemency N, Klein E, Provenzano M, Iyer R, Niederhuber JE, Hourigan SK. Collection of non-meconium stool on fecal occult blood cards is an effective method for fecal microbiota studies in infants.Microbiome. 2017 Sep 5;5(1):114. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5583988/

9. Hazrati S, Yui Y, Prem N, Sahel Hazrati, Wong SW, Huddleston K, Niederhuber JE, Hourigan SK. Clinical, Social and Genomic Factors Associated with Obesity at 12 Months of Age. J Pediatr. 2018 May;196:175-181.e7.

10. Hourigan SK, Subramanian P, Hasan NA, Ta A, Klein E, Chettout N, Huddleston K, Deopujari V, Levy S, Baveja R, Clemency NC, Baker RL, Niederhuber JE, Colwell RR. Comparison of Infant Gut and Skin Microbiota, Resistome and Virulome Between Neonatal Intensive Care Unit (NICU) Environments. Front Microbiol. 2018 Jun 25;9:1361. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6026636/

11. Chen LA*, Hourigan SK*, Grigoryan Z, Gao Z, Clemente JC, Rideout JR, Chirumamilla S, Rabidazeh S, Saeed S, Elson CO, Oliva-Hemker M, Blaser MJ, Sears CL. Decreased Fecal Bacterial Diversity and Altered Microbiome in Children Colonized With Clostridium difficile. J Pediatr Gastroenterol Nutr. 2019 Apr;68(4):502-508

12. Hazrati S, Khan F, Huddleston K, De La Cruz F, Deeken JF, Fuller A, Wong WSW, Niederhuber JE, Hourigan SK. Clinical and social factors associated with excess weight in Hispanic and non-Hispanic White children. Pediatr Res. 2019 Feb;85(3):256-261.

13. Nicholson MR, Mitchell PD, Alexander E, Ballal S, Bartlett M, Becker P, Davidovics Z, Docktor M, Dole M, Felix G, Gisser J, Hourigan SK, Jensen MK, Kaplan JL, Kelsen J, Kennedy M, Khanna S, Knackstedt E, Leier M, Lewis J, Lodarek A, Michail S, Oliva-Hemker M, Patton T, Queliza K, Russell GH, Singh N, Solomon A, Suskind DL, Werlin S, Kellermayer R, Kahn SA. Efficacy of Fecal Microbiota Transplantation for Clostridium difficile Infection in Children. Clin Gastroenterol Hepatol. 2019 Apr 19. pii: S1542-3565(19)30427-6.

14. Hourigan SK, Ahn M, Gibson KM, Pérez-Losada M, Felix G, Weidner M, Leibowitz I, Niederhuber JE, Sears CL, Crandall KA, Oliva-Hemker M. Fecal Transplant in Children With Clostridioides difficile Gives Sustained Reduction in Antimicrobial Resistance and Potential Pathogen Burden. Open Forum Infect Dis. 2019 Aug 26;6(10):ofz379. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6790402/

15. Drewes JL, Corona A, Sanchez U, Fan Y, Hourigan SK, Weidner M, Sidhu SD, Simner PJ, Wang H, Timp W, Oliva-Hemker M, Sears CL. Transmission and clearance of potential procarcinogenic bacteria during fecal microbiota transplantation for recurrent Clostridioides difficile. JCI Insight. 2019 Oct 3;4(19). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6795395/

16. Hazrati S, Huddleston K, Sadat-Hossieny S, Tilman LW, Fuller A, Deeken JF, Wong WSW, Niederhuber JE, Hourigan SK. Association of Ancestral Genetic Admixture and Excess Weight at Twelve Months of Age. Child Obes. Jan 2020.

17. Mueller NT, Dominguez-Bello MG, Appel LJ, Hourigan SK. 'Vaginal seeding' after a caesarean section provides benefits to newborn children: FOR: Does exposing caesarean-delivered newborns to the vaginal microbiome affect their chronic disease risk? The critical need for trials of 'vaginal seeding' during caesarean section. BJOG. 2020 Jan;127(2):301.

18. Hourigan SK, Moutihno T, Berenz A, Guha P, Papin J, Oliphant S, Baveja R, Baker , Vilboux T, Levy S, Deopujari, V, Nataro J, Niederhuber J, Moore S. Gram-negative microbiota blooms in premature twins discordant for parenteral nutrition associated cholestasis. J Pediatr Gastroenterol Nutr. Jan 2020.

19. Sabu P, Chettout N, Clemency N, Wong SW, Ta A, Hazrati S, Provenzano M, Deopujari V, Mueller N, Dominguez-Bello MG, Huddleston K, Klein E, Niederhuber JE, Hourigan SK. Prenatal and peripartum exposure to antibiotics and Cesarean Section delivery alters the infant meconium microbiome. Accepted, Microorganisms, Jan 2020. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7074690/

20. Mueller NT, Hourigan SK, Hoffman DE, Levy L, von Rosenvinge E, Chou B, Dominguez-Bello MG. Bacterial Baptism: Scientific, Medical and Regulatory Issues Raised by Vaginal Seeding of C-Section-Born Babies. Accepted, Journal of Law, Medicine and Ethics Jan 2020.