Examining the Microbiome Changes with Fecal Microbiota Transplantation (FMT) for Children with Recurrent Clostridium Difficile Infection

Clostridium difficile infection is an intestinal infection that can be life threatening. The incidence is increasing in children, and there is resistance to standard treatment with rising rates of recurrence. In resistant and recurrent cases, manipulation of the microbiome by FMT is an effective treatment. We are examining the intestinal microbiome in children before and after FMT. The goal is to gain a better understanding of why this treatment is effective and also to improve FMT treatment for children in the future.

The contribution of antibiotic exposure in the prenatal, peripartum and infancy period to intestinal microbiome perturbations and association with early childhood obesity.

There is accumulating evidence that early life exposure to antibiotics increases the risk for obesity. It is hypothesized, but has never been shown, that this is due to antibiotics causing detrimental gut microbiota disturbances that “program” the host to an obesity-prone metabolism. This research study aims to determine the relative contributions of antibiotic exposure in the prenatal, peripartum and infancy period to intestinal microbiome disturbances and association with early childhood obesity. Babies are followed from birth until 2 years of age with serial stool collections and survey assessments of their health. The results of this study, with identification of the critical time period of antibiotic exposure as a risk for obesity, would allow for several strategies for reducing the risk of obesity later in life.

This research is funded in part by the National Institute of Child Health and Human Development under award number K23HD099240.

Pediatric Specialists of Virginia
3023 Hamaker Court
Suite 600
Fairfax, VA  22031

Inova Children's Hospital
Inova Fairfax Medical Campus
3300 Gallows Road
Falls Church, VA  22042 

• Children who have had at least 3 recurrences of Clostridium difficile infection and are clinically undergoing fecal microbiota transplantation. These can be children both with and without inflammatory bowel disease (IBD).

More Information

Hourigan SK, Oliva-Hemker M. Fecal Microbiota Transplantation in Children - A Brief Review. Pediatr Res. 2016 Mar 16. [Epub ahead of print]. http://www.ncbi.nlm.nih.gov/pubmed/26982451

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.