Vaginal Seeding and Other Strategies Suchi Hourigan, M.D. Director - - PowerPoint PPT Presentation
RESTORING A CHILD'S MICROBIOME TO IMPROVE FUTURE HEALTH: Vaginal Seeding and Other Strategies Suchi Hourigan, M.D. Director of Pediatric Research, Inova Childrens Hospital Pediatric Gastroenterologist, Pediatric Specialists of Virginia
Suchi Hourigan, M.D. Director of Pediatric Research, Inova Children’s Hospital Pediatric Gastroenterologist, Pediatric Specialists of Virginia
Nature Cover. June 2012
– 1000-2000 species – Highly variable between individuals
– Fungi – Protozoa – Viruses – Bacteriophages
Image from Medscape 2017
– Immune and metabolic system: Development and maturation – Synthesis: Vitamins – Fermentation: Dietary carbohydrates – Pathogens: Competitive exclusion
GI Illnesses Non – GI Illnesses
Colorectal Cancer Autoimmune diseases Necrotizing Enterocolitis Asthma/Eczema/Atopy Inflammatory bowel disease Autism Irritable Bowel syndrome Type 2 diabetes Clostridium difficile infection Obesity Hepatic Encephalopathy Mood disorders Gastric carcinoma/lymphoma Chronic Fatigue Syndrome Idiopathic Constipation Fibromyalgia
Adapted from Brandt . AJG. 2013
Yatsunenko T. Nature. 2012
Yatsunenko T. Nature. 2012
Dominguez-Bello . PNAS. 2010
Dominguez-Bello . PNAS. 2010
– Breast milk contains unique oligosaccharides – 700 species bacteria breast milk and colostrum – Different dominating species gut microbiome breast fed vs. formula fed infants
Bezirtzoglou E. Anerobe. 2011
– Profound effect gut microbiome – Childhood anti-anaerobe antibiotic → IBD development – Association with childhood obesity
– Infectious agents/microbiome → Development immune system – Older siblings →increased diversity and richness of gut microbiome in early childhood – Amish vs Hutterite Farming
enterocolitis (NEC)
Syndrome
Early Life antibiotics: Prenatal Peripartum First years of life
“Viable microorganisms, sufficient amounts of which reach the intestine in an active state and thus exert positive health effects”
antibiotics
“A selectively fermented ingredient (non-digestible carbohydrates) that allows specific changes, both in the composition and/or activity in the gastrointestinal microflora that confers benefits upon host well being and health”
– Liber et al, RCT, no difference BMI for age z-score. – Nicolucci et al, RCT, significant decrease body weight z score
Image from Borody et al Nature 2012
Donate Deliver Restore
adults
treatment (abx)
Role for FMT
Now in IDSA guidelines
Ge Hong. 4th Century. Li Shizhen. 16th Century.
Image from Borody et al. Nature reviews. 2012
Image from Borody et al. Nature reviews. 2012
Image from Borody et al. Nature reviews. 2012
Image from Borody et al. Nature reviews. 2012
Van Nood. NEJM. 2013
Van Nood. NEJM. 2013
Van Nood. NEJM. 2013
– 2 RCT, 28 case series and 5 case reports – Overall resolution 85% of cases
– Recurring or relapsing CDI – Moderate-severe CDI unresponsive to standard therapy
Drekonja et al. Ann Intern Med. 2015
– Donor known to recipient – Universal Donors
Hamilton MJ. Am J Gastroenterol 2012.
Courtesy of awkwardfamilyphotos.com
Image adapted from openbiome.org
Blood & Stool Tests Questionnaire, H&P
Youngster et al. JAMA. 2014
All routes effective for treatment of recurrent CDI
Brandt L. Am J Gastroenterol. 2013
microbiome changes
– Abdominal discomfort/cramping – Diarrhea – Constipation – Belching
Brandt L. Am J Gastroenterol. 2013
MDRO.
– Potential pathogens: low level in “healthy” microbiome – Asymptomatic carriage – Pathogenic in different host??
Human Microbiome Project Consortium. Nature. 2012
– Inadvertent transfer of disease propensity associated with intestinal microbiome
– Few patients developed autoimmune disease – No clear association with FMT – Predisposing factors
– Rapidly developing gut microbiome in first few years of life – ↑ risk of immune ageing and immune related diseases? – Use of age matched donors?
Image from Arrieta. Frontiers in Immunology. 2014
FMT
implications for GI & non-GI sites
clinical and microbiome follow up
Future: Lab grown “stool”, e.g. “RePOOPulate”
– Obesity
– Asthma – Allergies
Vaginal C-section Dominguez-Bello et al. PNAS 2010
C-section impairs transmission of the early maternal microbiome
infants
– ↓Lactobacillus, ↑ Staphylococcus and Acinetobacter
– Differences last into childhood
– Associated with microbiome imbalance
C-section infants do not receive first “bolus” of healthy bacteria from Mom’s vagina
– Different pioneering gut microbes – Different colonization of GI tract – Aberrant immune and metabolic development
Salminen, Gut. 2004 Dominguez-Bello. Proc Natl Acad Sci. 2010.
vaginally, 11 CS – 4 born by CS exposed to maternal vaginal fluid – Gut, oral and skin microbiome in first 30 days – Those exposed, had microbiome closer to vaginally delivered babies
Dominguez-Bello. Nat Med. 2016
amongst mothers and in press
large scale studies
– Risk of infection including GBS – Caution from ACOG – Trials needed
600 Infants born by scheduled CS Vaginal Seeding Sham Seeding 3 year follow up with serial health assessment and microbiome samples ClinicalTrials.gov Identifier: NCT03298334
INCLUSION CRITERIA EXCLUSION CRITERIA
Scheduled cesarean delivery ≥ 37 weeks Hospital other than Inova Mother: single fetus, in good general health, age 18 years or older Current immunosuppressive medication within three months of cesarean delivery Negative maternal testing for infections as standard of care tests in pregnancy CD scheduled for active infection such as genital herpetic lesions Negative testing for GBS after 35 weeks gestation Onset of labor or rupture of membranes Vaginal pH < 4.5, Lactobacillus-dominated vaginal microbiota Bacterial vaginosis No maternal or fetal complications that may inhibit the ability to perform seeding Symptomatic urinary tract infection Infant condition after delivery requires only standard neonatal resuscitation Antibiotic therapy within 30 days of cesarean delivery English or Spanish speaking Symptoms on admission suggesting Chorioamnionitis Negative maternal testing for gonorrhea, chlamydia, hepatitis B, hepatitis C, syphilis, and HIV at 35 weeks gestation or later Symptoms on delivery admission of possible vaginal infection such as genital herpetic lesions History positive testing for GBS infection History of a child with GBS sepsis Normal Pap smear within 3 years Maternal history of HPV
Suchitra Hourigan, MD Rajiv Baveja, MD Shukwan Wendy Wong Ph.D Shira Levy, MA, CCRP Varsha Deopujari, MD Wei Zhu, Ph. D Ankit Shah, MD Marina Provenzana, MS Lopa Mehta, DMLT Noel Mueller, PhD MariaDominguez-Bello, PhD Ketroya Oliver, MD
What if we could give every child the chance to grow up as healthy as possible?