MICROBIOME AND GROWTH: AN OVERVIEW

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1 5/27/2016 MICROBIOME AND GROWTH: AN OVERVIEW Judd Walson, MD, MPH University of Washington Departments of Global Health, Medicine (Infectious Disease), Pediatrics and Epidemiology

2 Different environments lead to different growth 2

translocation Metabolic/Energy balance Appetite/satiety Growth hormone axis regulation Immune function/responsiveness Vaccine response

3 Maternal BMI Weight gain in pregnancy Infant weight Gestational age Linear Growth Cognitive Function Robust Immune Protection Anemia due to blood loss/chronic disease, Fe, ferritin Micronutrient status (Zn, Vit A, Vit D) Systemic activation/inflammation Bacterial translocation Metabolic/Energy balance Appetite/satiety Growth hormone axis regulation Immune function/responsiveness Vaccine response Functional immunology/antigen challenge Pathogen carriage Nutritional Enteric Failure/EED Intestinal Permeability (L:M) Microbiome maturity

4 Children live in environments where contamination of food and water is common 4 5/27/2016 4

5 Dirty chicken hypothesis Poor health and impaired growth among chicks raised in filthy conditions Antibiotics reversed changes associated with dirty conditions 5

Dirty environments + undernutrition lead to changes in the gut Environmental Enteric Dysfunction: A subclinical disorder of the small intestine observed among children living in settings of poor

6 Dirty environments + undernutrition lead to changes in the gut Environmental Enteric Dysfunction: A subclinical disorder of the small intestine observed among children living in settings of poor hygiene and sanitation, marked by: Villous atrophy ( absorption) Villus crypt proliferation barrier integrity Mucosal inflammation SOURCE: Kolling G, et al. Frontiers in cellular and infection microbiology Alterations in the gut microbiome may link EED to growth faltering 6

7 Microbiome maturity is linked to normal child growth 7

8 Microbiome maturity & physical growth Composition of gut microbiome changes with age in healthy children Bangladesh Malawi SOURCE: Subramanian S, et al. Nature 2014 SOURCE: Blanton LV, et al. Science

9 Microbiome maturity & physical growth Microbiome maturity is linked to growth status Bangladesh Malawi SOURCE: Subramanian S, et al. Nature

10 Microbiome maturity & physical growth Microbiome transfer results in growth deficit Kwashiorkor discordant twins SOURCE: Blanton LV, et al. Science 2016 SOURCE: Smith MI, et al. Science

11 Microbiome maturity & physical growth Microbiome transfer results in growth deficit Kwashiorkor discordant twins SOURCE: Blanton LV, et al. Science 2016 ADAPTED from Smith MI, et al. Science

Childhood Acute Illness & Nutrition Network A multi-country, multi-site collaboration which will identify mechanisms and modifiable factors

12 Childhood Acute Illness & Nutrition Network A multi-country, multi-site collaboration which will identify mechanisms and modifiable factors involved in death and treatment failure of acutely ill malnourished children, and establish a platform for pilot studies and definitive trials 12

13 Sites & Investigators Karachi Dhak amatlab Migori Nairobi Kampala Kilifi Blantyre

Samples 1 st set 2 nd set 3 rd set 4 th set 5 th set 6 th set 7 th set Key CRFS

14 Cohort Overview ADMISSION OBSERVATION & SAMPLE COLLECTION DISCHARGE POST-DISCHARGE FOLLOW UP First 24 hours Day 2 Day 5 Day 7 Day 45 Day 90 Day 180 Samples 1 st set 2 nd set 3 rd set 4 th set 5 th set 6 th set 7 th set Key CRFS Admission Form Daily Review Form Household Survey Verbal Autopsy & Study Conclusion Forms 14

15 Acknowledgements Funding Bill and Melinda Gates Foundation: CHAIN, EED planning grant, BEED grant NIH U19 AI NIH R01 HD A1 Center for AIDS Research (CFAR) Kenya Research Program International Centre for Diarrhoeal Disease Research, Bangladesh Collaborators Michael Arndt Tahmeed Ahmed Mustafa Mahfuz Baitun Nahar Donna Denno Patricia Pavlinac Emily Mosites Guy Palmer Peter Rabinowitz Grace John-Stewart UW Global Center for Integrated Health of Women, Adolescents, and Children 15

16 References References Blanton, L. V., Charbonneau, M. R., Salih, T., Barratt, M. J., Venkatesh, S., Ilkaveya, O.,... Gordon, J. I. (2016). Gut bacteria that prevent growth impairments transmitted by microbiota from malnourished children. Science, 351(6275), aad3311. doi: /science.aad3311 Brown, E. M., Wlodarska, M., Willing, B. P., Vonaesch, P., Han, J., Reynolds, L. A.,... Finlay, B. B. (2015). Diet and specific microbial exposure trigger features of environmental enteropathy in a novel murine model. Nature Communications, 6, doi: /ncomms8806 Charbonneau, M. R., O Donnell, D., Blanton, L. V., Totten, S. M., Davis, J. C. C., Barratt, M. J.,... Gordon, J. I. Sialylated Milk Oligosaccharides Promote Microbiota-Dependent Growth in Models of Infant Undernutrition. doi: /j.cell Dewey, K. G., & Adu-Afarwuah, S. (2008). Systematic review of the efficacy and effectiveness of complementary feeding interventions in developing countries. Matern Child Nutr, 4 Suppl 1, doi: /j x Kelly, C. R., Kahn, S., Kashyap, P., Laine, L., Rubin, D., Atreja, A.,... Wu, G. (2015). Update on Fecal Microbiota Transplantation 2015: Indications, Methodologies, Mechanisms, and Outlook. Gastroenterology, 149(1), doi: /j.gastro Kolling, G., Wu, M., & Guerrant, R. L. (2012). Enteric pathogens through life stages. Front Cell Infect Microbiol, 2, 114. doi: /fcimb Schwarzer, M., Makki, K., Storelli, G., Machuca-Gayet, I., Srutkova, D., Hermanova, P.,... Leulier, F. (2016). Lactobacillus plantarum strain maintains growth of infant mice during chronic undernutrition. Science, 351(6275), 854. doi: /science.aad8588 Smith, M. I., Yatsunenko, T., Manary, M. J., Trehan, I., Mkakosya, R., Cheng, J.,... Gordon, J. I. (2013). Gut microbiomes of Malawian twin pairs discordant for kwashiorkor. Science (New York, N.Y.), 339(6119), doi: /science Subramanian, S., Huq, S., Yatsunenko, T., Haque, R., Mahfuz, M., Alam, M. A.,... Gordon, J. I. (2014). Persistent gut microbiota immaturity in malnourished Bangladeshi children. Nature. doi: /nature

Biomarkers for Environmental Enteric Dysfunction (EED) Donna M. Denno, MD, MPH Nutrition Symposium October 16, 2014

Biomarkers for Environmental Enteric Dysfunction (EED) Donna M. Denno, MD, MPH Nutrition Symposium October 16, 2014 What is EED? Expats in Barbados Hillary 1700s Sprouw Manson 1880 Tropical sprue 2 Photo: