GUT HEALTH IN THE FIRST 1000 DAYS

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1 GUT HEALTH IN THE FIRST 1000 DAYS Welcome note The first 1000 days period, from the day of conception to the 24th month of life, is critical for the future health, well being and success of the child. It is a critical window of opportunity to impact the lifelong health of the child. It is not unfounded that the instinct of every mother is to nourish, nurture and protect her child from the moment she becomes aware of the baby s existence. There is a scientific basis for this. It is a period of rapid growth and development and healthy development of the gut is of great importance. The child moves from a protected environment to a challenging extra uterine world. An imbalanced intake of nutrients in terms of quality and quantity may alter the intestinal microbiota. This can have profound effects on the development of the child allowing an increased risk of non communicable diseases such as intestinal bowel diseases, allergy, asthma, obesity, diabetes and heart disease. It is our hope that you will find this article,by Dr.Oduwole, insightful and relevant to your practice. Please write to us at nutrinews@danone.co.ke with your feedback. Have a splendid month! Nutrinews desk Dr. Oduwole

2 Associate professor/consultant paediatrician Lagos University Teaching Hospital,Idi Araba Criteria for Defining Gut Health 5 major criteria for a healthy gut Specific signs of gut health Normal nutritional status Effective digestion & absorption of food Regular bowel movement, normal transit time & no abdominal pain Normal stool consistency, rare constipation & bloating Rare nausea, vomiting & diarrhea Absence of GI illness No gastro esophageal reflux or inflammatory disease and cancer No carbohydrate intolerance & enzyme deficiencies Stable gut or intestinal microbiota No bacteria overgrowth Normal composition & vitality of gut microbiome No GI infection or antibiotic associated disease Effective GI barrier function, normal mucus Effective immune status production Normal levels of IgA, normal number & activity of immune cells Immuntolerance,no allergy or mucosal hypersensitivity Normal quality of life Status of well being Positive gut feeling Balanced serotonin production & normal function of enteric nervous system Gut Microbiota in the first 1000 days The gut bacteria consist of commensal (resident) and transiently introduced bacteria. The human colon is haven to approximately bacterial cells. This complex array of commensal bacteria in the gut is known as gut microbiota. It is now also known as microbiome.

3 The development of the intestinal microbiota in the first 1000 days is a dynamic process that is influenced greatly by early life nutrition. The bacteria that initially colonize the infant neonatal intestinal tract and the gradual diversification to a mature ecosystem play an important role in establishing host microbe interactions essential for optimal symbiosis. The intestinal microbiota exist in a homeostatic relationship with the host. This host microbial relationship is maintained in a bi directional manner with the host immune system. The increased understanding at the molecular level and improvement in the sequencing technology has identified four key players in the development of the intestinal microbiota; these are the Actinobacteria (Bifidobacterium and Colinsella), the Bacteroides (Bacteroides and Prevotella), Firmicutes (Lactobacillus, Clostridium, Eubacterium and Ruminicoccus), and the Proteobacteria (Enterobacter species). There is also Verumicrobia that is seen throughout life. The composition of the gut microbiota is influenced by a complex interaction of factors such as physiological, cultural and environmental. Hence the composition of species comprising the microbiota varies among individuals and is personalized. For instance identical twins only share 50 80% of the species in their gut microbiota. Overtime the composition also varies due to environmental factors. Also after a short time disruption such as following use of antibiotics, it reverts back to the original composition. Role of Gut Microbiota Metabolic role Improves digestion Produces Short Chain Fatty acids(scfa) & vitamins. Supplies micronutrients Metabolizes bile acids Degrades fibre/mucus Trophic effects Protective role Colonization resistance Immune homeostasis Improve barrier effects Detoxification Dysbiosis Dysbiosis is the disturbance or imbalance in the gut microorganism communities. It increases the risk of developing a range of diseases such as allergy, food intolerance, infection, and long term conditions like obesity. There is increasing literature to support these associations. During infancy associated medical conditions include: Necrotizing enterocolitis (NEC) Colic GI infections Constipation/diarrhea Celiac disease Antibiotic associated diarrhea Allergy

4 Gut Colonization In utero the small intestine in the human fetus appears as an immature epithelial surface with prolonged cell turnover and a paucity of lymphoid elements, whereas in the newborn term baby, the small intestine appears as an active structure with a rapid turnover, expressing the subtypes of epithelial cells and displaying a plethora of lymphoid elements. The principal difference in these two situations is the intrauterine environment level of bacteria. Until recently the GI system of the fetus was thought to be germ free but several commensal bacteria have been discovered in umbilical cord blood, amniotic fluid, the placenta and infant meconium. Despite this, the level is very low compared to the extrauterine environment that consists of abundant microbiota which colonizes the gastrointestinal tract. This is an important adjustment of the newborn baby to the extra uterine environment. Several factors influence initial intestinal colonization. These include the infant s genetic signature, the nature of the delivery process, the use of excessive antibiotics during the perinatal period and whether the mother is under stress or expresses an inflammatory condition. When the infant is born full term by a vaginal delivery and is exclusively breastfed during the first 6 months of life, normal colonization is most likely to occur. Colonization of the newborn gut occurs in phases over 1 year to 18 months in the postpartum period. Phases Of Colonization Phase 1: The full term infant leaves the almost germ free intrauterine environment and passes through the birth canal where it ingests a healthy bolus of maternal vaginal and colonic microbiota. This represents the first and most important phase of colonization Phase 2: Introduction of oral feedings. The ingested bolus further stimulates the colonization of the gut. What is ingested by the baby, that is breast milk or formula feeding has a profound but short term effect. Phase 3: At the time of introducing complementary foods, e.g. after 6 months, colonization is further effected. Finally, by 1 year to 18 months of age, the infant s intestine is completely colonized with a unique signature of microorganisms. If antibiotic treatment is used during this period, the timing and nature of colonization is disrupted and prolonged. Factors that affect colonization of the infant gut Prenatal maternal factors: They include stress, diet (including dietary supplementation) postdate, maternal body mass index, smoking status and socio economic status. Mode of delivery: Affects the type of microbial that colonizes the infant s gut. Babies born vaginally have normal commensals found in the birth canal while those born by caesarian section have microbes that tend to resemble the skin and the hospital. They have less variety, lower bacterial counts with higher levels of staphylococcus Corynebacterium species and a low count of Bifidobacterium. Those born vaginally have a microbial community with varied gene like Lactobacillus, Prevotella, Escherichia, Bacteroides, Bifidobacterium and Streptococcus species. However, because this aberrant colonization takes place at an important period of immune and metabolic development, it has been shown by several studies that there are long term consequences such as increased risk for Allergy, Obesity and type 1 Diabetes. Mode of feeding (Breastmilk vs Formula): Breastmilk has long been known to contain bacterial DNA. Maternal breastmilk has been known to contain live culturable bacteria including Bifidobacterium. These bacteria are believed to

5 be engulfed by peripheral blood mononuclear cells and transferred intact to the mammary glands in a process known as enteromammary pathway. Maternal breastmilk contains both innate and adaptive immunity which shape the infant s microflora and protect against pathogenic infection. In addition it contains live bacteria translocated from the maternal gut and prebiotic oligosaccharides to encourage growth of commensals. There is increased colonization with Clostridium species especially C. difficile that has been associated as a risk factor for eczema in formula fed babies. Complementary Feeding: This is the next major stage is the introduction of solid foods, which is done at 6 months after exclusive breast feeding. The introduction of these more complex food increases the rate and diversity of colonization of the infant gut. From one year till after the 1000 th day, the toddler continues to establish the gut microbiota by the increased, diversified and varied solid food in the form of fibre, protein and fat intake, and increasingly resembling more closely the adult gut microbial population. Prebiotics & Probiotics The International Scientific Association of Probiotics and Prebiotics (ISAPP) defines probiotics as live microorganisms which, when administered in adequate amounts, colonize the gut and exert beneficial biological effects on the host. Prebiotics are defined as a selectively fermented ingredient that results in specific changes, in the composition and/or activity of the gut microbiota, thus conferring benefit(s) upon host health. Prebiotic supplementation of infant formula with long chain GOS (lcgos) and short chain FOS (scfos) has been shown to increase the levels of fecal Bifidobacterium in a dose dependent manner in formula fed infants, producing a similar diversity to breast fed infants, as well as producing a comparable composition of fecal SCFAs derived from the metabolic activity of Bifidobacterium. The vernix caseosa, the waxy skin coating of a fetus, is shed into the amniotic fluid as the preterm approaches term. While still in the Utero, there near term fetus swallows the amniotic fluid containing pieces of vernix. This Vernix is made up Short chain fatty acids, lipids that are unique to the vernix. This SCFAs are indigestible by human enzymes hence provide a rich medium for growth of bacteria and when the infant is born this SCFAs are present in the gut and act as initial prebiotics of the gut. Also once the infant begins to breast feed, colostrum contains high levels of Human milk oligosaccharides which are indigestible by the human enzyme. Probiotics are defined as live microorganisms, which when administered in adequate amounts, colonize the gut and exert beneficial biological effects on the host. Conclusion The importance of the microbiota to many aspects of human health and the realization that its foundation is established in early infancy are be coming increasingly recognized. Danone offers options to support optimal gut health nutrition through the Cow & Gate Nutri range with NutriStart 1containing patented unique blend of prebiotics scgos/lcfos ratio of 9:1 available in Kenya, Nigeria, Uganda and Rwanda. The company further supports Ethiopian and Sudanese mothers through the range of Bebelac infant formula with the same prebiotic blend.

6 References 1.Wopereis H, Oozeer R, Knipping K, Belzer C, Knol J. The first thousand days intestinal microbiology of early life: establishing a symbiosis. Pediatr Allergy Immunol. 2014;25: Moore, Keith L., and T. V. N. Persaud. The Developing Human: Clinically Oriented Embryology. Philadelphia, PA: W.B. Saunders Company, ISBN: Maslowski KM, Mackay CR. Diet, gut microbiota and immune Nat Immunology 2011;12: Yee Kwan Chan Mehrbod Estaki Deanna L. Gibson. Clinical Consequences of Diet Induced Dysbiosis. Ann Nutr Metab 2013;63(suppl 2):28 40 DOI: / Gut Health in Early Life: Significance of the Gut Microbiota and Nutrition for Development and Future Health. Wiley EKB Eds Raanan Shamir, Ruurd van Elburg, Jan Knol, Christophe Dupont John Wiley and Sons Ltd, The Atrium, Southern Gate, Chichester, West Sussex 6. Stephen M. Collins, Michael Surette & Premysl Bercik The interplay between the intestinal microbiota and the brain. Nature Reviews Microbiology 2012; 10: Coreen L. Johnson, PhD, and James Versalovic, The Human Microbiome and Its Potential Importance to Pediatrics. Pediatrics 2012 doi: /peds Walker AW. Initial Intestinal Colonization in the Human Infant and Immune Homeostasis. Ann Nutr Metab 2013; 63(suppl 2):8 15 DOI: / Jakaitis BM, Denning PW. Human breast milk and the gastrointestinal innate immune system. Clin Perinatol. 2014; 41: Belderbos ME, Houben ML, van Bleek GM, et al. Breastfeeding modulates neonatal innate immune responses: a prospective birth cohort study. Pediatr Allergy Immunol. 2012;23: Boehm G, Moro G. Structural and functional aspects of prebiotics used in infant nutrition. J Nutr. 2008; 138:1818S Luoto R, Collado MC, Salminen S, Isolaur E. Reshaping the Gut Microbiota at an Early Age: Functional Impact on Obesity Risk? Ann Nutr Metab 2013;63(suppl 2):17 26 DOI: / Le Huërou Luron I, Blat S, Boudry G. Breast v. formula feeding: impacts on the digestive tract and immediate and long term health effects. Nutr Res Rev. 2010; 23:23 36 FOR HCP USE ONLY

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