The Enigma of the Infant Microbiome

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1 The Enigma of the Infant Microbiome 3 rd Microbiome R&D and Business Collaboration Forum Europe London, April 2016 David J. Kyle, CEO, Evolve Biosystems Inc

2 Microbiome diversity is a good thing. Modern medicine is the best practice. The infant gut microbiome is seeded by vaginal microflora.

3 Mother Mom and Baby are Different composition and diversity Bifidobacterium longum subsp. infantis Cho & Blaser (2012) Nature Rev Gen 13, 260 Huda et al (2014) Pediatrics 134:

4 Infant Microbiomes from Around the World Observational Data from Ours and Other Studies

5 Discrepancies with Formula Feeding Bifidobacteria Bifidobacteria were more prevalent in the gut of breast fed neonates E.coli and Enterococci sp. were more prevalent in the gut of formula fed neonates. Cooke, G. et al. (2005) Microb. Ecol. Health Dis. 17,

6 Breast-fed Babies are Hi Bif and Formula-fed Babies are Lo Bif Avg = 1.2 Million/g Avg = 2.0 Billion/g Lewis et al Microbiome 3:13.

7 The enigma about human milk HMOs are not food for the baby Undigestible by the infant Carlito Lebrilla Daniela Barile

8 Only B. infantis grows on HMO Vaginal Microflora (no growth)

9 B. infantis has unique genes to consume HMOs - HMOs are utilized by large gene cassette in B. longum subsp. infantis - Three basic functions capturing, transporting and consuming HMOs permease Outside the Bacterial Cell Internal Cytoplasm Glycolytic enzymes Dr. David Mills Professor in Food Science and Technology and Endowed Chair in Dairy Food Science ATP ADP ATPase

10 The Little Big Discovery There are two consumers of Human Milk 85% WHAT??? 15% Universal Baby Bif B. Infantis Not vaginal microflora

11 What is the Baby Bif doing? Competitive exclusion of all other bacteria (inc. pathogens) Anti-inflammatory environment (SCFA production) Facilitation of closing of gap junctions Hi Bif - improved vaccine response Review: Underwood et al (2015) B. longum subsp infantis: Champion Colonizer of the Gut. Pediatr Res 77: 229

12 How does the Baby Bif get there? All gut microbes are acquired at parturition. Microbes from environment, mom, food. Rapidly introduced, but only very few colonize.

13 Cesarean - Section Disparity Vag-D C-Sect Lewis et al Microbiome 3:13

14 First Corollary We have been practicing internal microbial farming for thousands of years to improve the survival of our babies. Seeding and Selective Feeding + C-Section Infant Formula Dysbiosis

15 Clinical Observations with Formula Feeding Bartick M, Reinhold A. Pediatrics. 2010;125(5):e Increased incidence of colic, atopy Increased doctors visits and use of antibiotics Increased risk of general metabolic disorders later in life Obesity Diabetes IBD Dysbiotic Microbiome (Low in B. infantis)

16 Clinical Observations with C-Section 1.3 Million C-sections USA (32.7%) 29% increase in risk for IBD (0-14 yr) 18-32% increase in risk for food allergy/atopy/allergic rhinitis and asthma (0-31 yr) 68% increase in risk of early childhood obesity (2 yr) Dysbiotic Microbiome (Low in B. infantis)

17 Evolve s Solution to Baby Dysbiosis? follow the evolutionary recommendation HMO + Bif-based Microbiome

18 Summary Problem: Worldwide pandemic of obesity Increasing incidence of allergies in children Increasing incidence of IBD, asthma, JD, Strong correlation with early gut dysbiosis Good News/Solution: Early gut microbiome is shaped by diet (BM v. IF) Gut microbes from mom by oral/fecal transfer Moms cannot give what they don t already have Baby Bif (Imprint) can restore the natural infant microbiome to improve lifetime health trajectory

19 Thank You

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