Early lifestyle intestinal microbiome

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1 Session 4A Dietitians ensuring a healthy start in life 29/9/ Early lifestyle intestinal microbiome Dr Emilia Vassilopoulou Assistant Professor of Diet and Nutrition Clinical Dietitian-Psychologist

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3 MET Museum NYC

4 Microbiota synthesis/ aging Nagpal R., et al. Nutrition and Healthy Aging, vol 4, pp , 2018

5 Development of human gut microbiota: Who s born first, baby or it s microbiome? Tanaka, J. Nakayama. Allergology International 66 (2017)

6 Pregnancy: dramatic change of gut microbiota inflammation & energy content

7 Gut microbiota impacts metabolism in pregnancy similarly to metabolic syndrome Meital Nuriel-Ohayon et al. Front Microbiol. 2016; 7: 1031.

8 Fetus colonization Dogma challenged: fetus resides in a sterile environment Microbes that colonize fetus: pregnancy outcome, future health status of neonate Prevotella, Gardnerella vs Lactobacillus Genetically labeled Enterococcus faecium Fichorova RN, et al. MBio 2011; 2: e Stout MJ, et al. Am J Obstet Gynecol 2013; 208: 226.e1 7

9 Oral microbiota composition: Actinomynes naselundi vs Lactobacili Pregnancy outcome: o birth weight o earlier delivery Angela et al. Seminars in Fetal and Neonatal Medicine. Volume 21, Issue 2, April 2016, Pages Dasanayake AP, et al.. J Periodontol 2005; 76:

10 Birth (mode of delivery) Aagaard K, et al. The placenta harbors a unique microbiome. Sci Transl Med 2014; 6: 237ra65. Funkhouser LJ, et al. PLoS Biol 2013; 11: e Lactobacillus, Prevotella, Sneathia (vaginal microbiotas) Vs Staphylococcus, Corynebacterium, and Propionibacterium (skin microbiotas)

11 1 month of age o Delayed colonization by Bacteroides, Bifidobacterium o Abundant Clostridium difficile o Low diversity in C-section (3months) o risk of immune disorders (asthma, allergic rhinitis, celiac disease)

12 Vaginal seeding Dominguez Bello MG, De Jesus Laboy KM, Shen N, Cox LM, Amir A, Gonzalez A, Bokulich NA, Song SJ, Hoashi M, Rivera Vinas JI et al (2016) Partial restoration of the microbiota of Cesarean born infants via vaginal microbial transfer. Nat Med 22:

13 Mode of feeding greatly affects development of gut microbiota in early life Breast milk contains immunoglobulins (IgA, IgG) antimicrobial compounds (lysozyme, lactoferrin) immune regulatory cytokines (TGF-b, IL-10) lymphocytes that express gut homing markers

14 Breastfeeding Macronutrients Immunoglobulins, endocannabinoids Human Milk Oligosaccharides (such as galactooligosaccharide (GOS)) partial digestion in small intestine & mostly reach the colon, where they are fermented, mainly by Bifidobacterium, to SCFA Bifido- bacterium spp. enzyme lacto-nbiosidase facilitita assimilation of GOS 1month: Bifidobacterium feces HMOs acetic acid - lactic acid Formula-feeding Milk formula inclusion of some oligosaccharides: possible Bifidobacterium-rich microbiota Still distinct features of microbiotas: C. difficile, enriched with anaerobic organisms such as Bacteroides and Clostridium Pasteurized donor human milk : partially successful microbial community similar to breastfed infants rapid increases in bacterial diversity HMOs have a clear probiotic effect by selectively stimulating the development of a Bifidobacterium-rich microbiota

15 Fernandez L, Langa S, Martin V, Maldonado A, Jimenez E, Martin R et al,. Pharmacol Res 2013; 69: 1 10 Hunt KM, Foster JA, Forney LJ, Schiitte UME, Beck DL, Abdo Z et al,. PLoS One 2011; 6: e Palmer C, Bik EM, DiGiulio DB, Relman DA, Brown PO. PLoS Biol 2007; 5: e177. Why breastfeeding is so important? IL-10, TGF-b: tolerance of host immune system to intestinal bacteria & promote IL-10 production Bifidobacterium (Bifidobacterium infantis) promoted by HMO IgA & anti- inflammatory effects Breast milk is not sterile (bacterial species & bacteria cells) lactic acid bacteria (Lactobacillus, Leuconostoc, Streptococcus, etc) & beneficial Bifidobacterium sp. gram (-) bacteria: Serratia, Pseudomonas oral cavity typical inhabitants: Veillonella, Leptotrichia & Prevotella Fatty acids (FA) host health and development of immune system TGF-b levels (+)PUFA (-) SFA cohort studies: ratio PUFA atopic dermatitis Variability of microbiotas & FA profiles in milk in EU (Spain vs Finland), Africa (South Africa), Asia (China)

16 Solids introduction From Bifidobacteriumdominant to Bacteroidetes & Firmicutes 2.5-3yrs: Increased bacterial loads & SCFA levels Codominance Bacteroidetes, Firmicitus Enrichment fuctional genes (adult gut microbiome) Breakdown of xenobiotic compounds, vitamin biosynthesis, plant derived polysaccharides Disease-associated dysbiosis, antibiotics Proc Natl Acad Sci U S A Mar 15;108 Suppl 1: doi: /pnas Epub 2010 Jul 28. Succession of microbial consortia in the developing infant gut microbiome. Koenig JE1, Spor A, Scalfone N, Fricker AD, Stombaugh J, Knight R, Angenent LT, Ley RE

17 Exposure to antibiotics during pregnancy or early life exposure Highly dynamic developing infant gut microbiota (IGM) prone to disruption by external factors, including antibiotic exposure Proteobacteria Actinobacteria diversity of gut microbiota drug-resistant bacteria Epidemiological surveys: risk of developing allergic diseases & type 1 diabetes

18 Environmental factors Siblings: Bifidobacterium Geographical location: Northern EU Bifidobacterium spp., some Clostridium spp. & Atopobium spp. Southern infants Eubacteria, Lactobacillus, Bacteroides Penders J, Thijs C, Vink C, Stelma FF, Snijders B, Kummeling I et al,. Pediatrics 2006; 118: Fallani M, Young D, Scott J, Norin E, Amarri S, Adam R et al. J Pediatr Gastroenterol Nutr 2010; 51: 77 84

19 Childhood microbiomes Stable; less variability Geography & food culture Asian: Bacteroides-Bifidobacterium (BB- type) & Prevotella-dominated microbiotas (P-type) USA: Bacteroides, Firmicitus Venezulea, Malawi, Bangladesh: Prevotella Urban: BB-type Rural: P-type High-fat diets (modern food) BB-type bacteria genes encoding bile acids that aid lipid absorption Traditional food (developing areas) P-type bacteria encoding oligosaccharide-degrading enzymes

20 Early life microbiome: implications in human health Excess host adiposity Protect against Type-I diabetes Induce colitis Metabolic syndrome Therapeutic intervention for chronic disease

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22 Dietary modifications pre-, during- pregnancy & early life Probiotics in Pregnancy Study (PiP Study): Early pregnancy probiotic supplementation with Lactobacillus rhamnosus: gestational diabetes, atopic eczema & rhinoconjunctivitis Νo association with asthma at 36months No reduction at blood glucose in obese mothers Further studies on probiotics (live organisms) & prebiotics (non digestible CHO) with antibiotics n-3 PUFA reverse stress in early life Bertelsen RJ, Brantsæter AL, Magnus MC, Haugen M, Myhre R, Jacobsson B, Longnecker MP, Meltzer HM, London SJ. J Allergy Clin Immunol Jan;133(1): e1-8

23 Strategies for microbiota modulation: early changing eating & lifestyle habits Fermented product & symbiotics before, during pregnancy & breastfeeding Exclusive breastfeeding Hygiene hypothesis Solid food introduction with parallel breastfeeding not after 7months of age Avoidance of long use antibiotics Supplement of symbiotics when under drug therapy/stress/.. Mediterranean diet model + fermented products through life

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