microbiome and breastmilk and breastfeeding and advantages and disadvantages and benefitsptx

microbiome

1. Breastmilk microbiome: a meal worth having for a lifetime of health!

2. Name: Academic Degrees: Institutional Affiliation: Address: Publications / Achievements: Dr. Asha Benakappa FIAP, MD,DNB, DCH,DHHM,LMC,AH). HOD of Pediatrics Dr. Chandramma Dayananda Sagar Institute of Medical Education and Research, DEVARAKAGGALAHALLI, HAROHALLI, Kanakapura Rd, Kanakapura, Karnataka 562112 ACHIEVEMENTS ,PUBLICATIONS & WABA-HCP- Task force member. Founder trustee lactation helpline. Many new innovation Director IGICH Deccan Chronicle July 1st on Doctor’s Day 2009 selected as one of the five Best Doctors of the City. Listed in “Who’s Who” of WABA General Assembly

3. Publications / Achievements: AWARDS AND RECOGNITION: FIAP award Two gold medals in MBBS and recipience of Second rank WBW award from BPNI more then 10 times Doordarshan Chandana Award 2012 on 16.11.2012 for significant contribution rendered in Health (One of the Navaratna’s) Harivu Film won the 62nd Best Regional Film Award 2015 is based on The Story written by Dr. Asha Benakappa Received over 30+ awards and felicitation. PUBLICATIONS AND PRESENTATIONS International 16 , National 25 , and State 30 Presented Guest Lectures/ webinars: 200+ at International/National/ State and IAP district. Books: NICU Companion, Breastfeeding “The Basic Instinct”, Kannada book on Bf, Flip charts on BF in Kannada and English, FAQs on Bf in English and Kannada, IGICH Pediatric: Generic Drug Pharmacopeia

4. hello! I am the MICROBIOME! 4

5. Introduction A mother is gifted with breastmilk,a natural source of nutrition for her infant. It has a wealth of macro and micronutrients. It has micro-organisms-few of which originate from the mother, while others are acquired from the mouth of the infant and the surroundings. These microorganisms initiate and help the development of the milk microbiota as well as the microbiota of the GIT in infants and contribute to developing immune regulatory factors such as cytokines,growth factors,lactoferrin etc 5

6. Cont.. These factors play an important role in reducing chronic diseases like T2Diabetes,asthma and others later in life. Breastmilk microbiota has a cross talk with the immune system in breastfed babies during the early years of life. Breastmilk is a dynamic and complex microsystem that contains a microbial signature that is transmitted to the newborn baby and is essential for immune system development and education 6

7. The Amazing Microbiome Approximately 100 trillion micro-organisms (mostly bacteria, but also viruses, fungi &protozoa)exist in human GIT. Microbiome is the virtual organ of the body Human genome consists of about 23,000 genes. Microbiome encodes for three million genes producing thousands of metabolites which replace many of the functions of the host influencing the hosts fitness, phenotype &health 7

8. Good starter kit! Rupture of the membranes during labor contributes to the early microbial seeding of the newborn. Transfer of microbes from mother to her baby during delivery, is like a starter kit that will help expand the infant’s microbiota .

9. Definition of microbiome The term microbiome was first used by Joshua Lederberg for the ‘ecological community of commensal,symbiotic and pathogenic micro-organisms that literally share the human body’ Microbiome : collective genomes of the microorganisms in a particular environment Microbiota : community of microorganisms themselves

10. Probiotics: live bacteria &yeast that when adminstered in a viable form &in adequate amounts are beneficial to human health.eg yoghurt &food supplements. Prebiotics: substrate that is selectively used by host microorganisms conferring a health benefit Symbiotic: contain a mixture of prebiotic &probiotic

11. Dysbiosis Microbiota changes associated in diseased states. Diseased states can lead to changes to the Gut microbiome through various mechanisms, including changes in eating habits, bowel functions well as through the addition of medications such as antibiotics.

12. Breast milk microbiota and health Breastmilk is home to diverse microbiome: human milk microbiome(HMM) Early life environmental exposure can affect fetal and infant programming, resulting in change in health status(DOHaD) Early life microbiota is a key participant in DOHaD contributing to infant health status in short and long term.

13. Origin and sources of the human milk microbiota. Breastmilk is a source of microbes for the establishment of oral and gut microbiota in breastfed infants. ‘Retrograde transfer’: external bacteria could enter mammary gland from sources such as areola skin, infant oral cavity, and /or breast pumps. ‘Enteromammary pathway’: bacteria from mother’s gut are translocated to the mammary gland via immune cells and colonize the available niche. ‘Oro –mammary translocation’ : microbes in the mother’s oral cavity will translocate to the mammary gland.

14. Where do bacteria come from mother’s milk Externally from baby’s mouth to mammary gland via mammary duct Streptococcus(saliva) Staphylococcus(skin) Corynbacterium(skin) Internally via entero-mammary pathways: translocation of bacteria from mother’s gut to mammary gland through dendrite cells and macrophages

15. Sources of micro biota Amniotic fluid Meconium :MB originates from uterus of the mother Maternal vagina Maternal feaces Skin Breast milk Surroundings –as clean as possible 10000000 cells /ml of breastmilk 7-8 billion bacterial cells formed each day.

16. Factors influencing the composition of human milk microbiota Stage of lactation: colostrum is abundant with BMM Method of BM expression: DBF is associated with higher abundance of oral cavity genera. Indirect BF is associated with increased prevalence of potential opportunistic pathogenic families. Direct BF allows the acquisition of oral associated micro-organisms. Indirect BF favour the colonization with environment related organisms that could compromise infant’s immune system and increased risk of diseases.

17. Child cohort study: direct breast feeding and pumped milk.

18. Factors influencing the composition of human milk microbiota contd.. 3. Lifestyle and diet of Mother: mother’s diet effect on BMM via enteromammary pathway. During pregnancy and lactation bacteria from maternal gut translocate into the mammary gland ,altering the mammary and BMM. 4. Maternal factors: link between BMM changes and women’s BMI, mothers with high BMI have a more homogenous bacterial composition.

19. Implications of microbiome on health Infections, Allergic sensitization, asthma Necrotizing enter colitis Celiac disease Inflammatory bowel disease Autoimmune disease Irritable bowel syndrome Obesity Type1 diabetes Kwashiorkor Mastitis Cancer Autism(decreased conversion of glutamine to GABA) Stress, Depression, Schizophrenia, Parkinson’s, other neurodegenerative diseases

20. Function of gut micro biome Metabolize barely digestible polysaccharides results in the synthesis of short chain fatty acids(SFA)which are rich source of energy for the host Synthesis of vitamin K, other components of vitamin B, conversion of glutamine to GABA,breakdown of various polyphenols (fruits, vegetables and green tea) Detoxifying toxic products and has an effect on drug metabolism Maintenance of structural integrity of the gut mucosal barrier Serves as a barrier against pathogens Development of host immune system.

21. Development and maintenance of immune function Born with TH2 bias to protect them from intrauterine rejection, when baby is in womb Bacteria stimulate dendritic cells It allows naïve helper cells(THO) to create balanced subclass of TH cells Bacteria is taken up by dendritic cells to mesenteric lymph nodes & presented to B cells resulting in polymeric Iga which is shuttled across the epithelium to help contain bacterial attachment and penetration.

22. Development of immune tolerance Antigens taken up by dendritic cell to the lymph nodes stimulates TGF(transforming growth factor)induces differentation of naïve T cells to T reg. Production of IL-22 by gp 3 innate lymphoid cells(ILC3) IL-22 induces antimicrobial peptide production by paneth cells & mucus production by goblet cells thereby strengthening gut barrier This prevents transfer of dietary antigen across the barrier and therefore allergic sensitization.

23. Development of immune tolerance contd. IDO (indolamine dioxygenase) gets activated in response to allergen induced immune activation IDO: metabolize tryptophan to kynurenine which exhibit tolerogenic effect by causing T cell anergy(absence of normal immune response) &adoption This also induces T reg leading to attenuation of allergic response

24. Human milk oligosaccharides HMO’s are lactose based unconjugated carbhohydrates . Food for bacteria. Bacteria here are microbiome. Colostrum in the golden hour is the source of gut microbiome

25. Human milk oligosaccharides

26. Human milk oligosaccharides(HMO’S) Group of structurally diverse unconjugated short chain as well as long chain glycans found uniquely & abundently in breast milk 20-23gm/ml in colostrum &5-20gm/ml in mature milk Preterm milk has higher amount HMO’S are resistent to gastric acidity,hydrolysis by host enzymes &GI absorption

27. Human milk oligosaccharides(HMO’S) HMO’S reach the distal small intestine &colon intact and at high concentration Bifidobacterium longum,sub species infantis grows well compared to B.infantis These bacteria produce SCFA and other metabolites that favour the growth of commensals over potential pathogens

28. Functions of HMO : food for microbiota Prebiotic bifidus factor that serves as a metabolic substrate for desired bacteria Shapes an intestinal microbiota composition by keeping harmful bacteria in check as they compete for limited nutrient supply Prevents pathogen attachment to infant mucosal surfaces and lower the risk of Viral e.g., rota virus noro virus, HIV ,Bacterial E.coli, H.pylori , C.jejuni Protozoan infection E.histolytica etc

29. HMO ….. contd Modulate epithelial cell and immune cell response thereby modulating gene expression Reduce rolling of leucocytes on endothelial cells decreasing extensive leucocyte infilteration &activation Lower the risk of NEC Provide infant sialic acid as a potential essential nutrient for brain development and cognition

30. human milk oligosaccharides : prebiotics

31. Gut brain axis

32. Gut brain axis Refers to bidirectional biochemical communications between GI and brain. It influences production, expression and turnover of neurotransmitters such as serotinin,GABA,brain derived neurotrophic factor(BDNF) It contributes to intestinal barrier, tight junction integrity, there by attenuating Hypothalamo-Pituitary adrenal axis and ANS function Metabolite of some gut microfilmed like SCFA,serotonin,kynurinine,can exert effect on brain Immunological pathway both systemic and mucosal immune play in regulation of gut brain axis.

33. Gut brain axis … The concept of micro biome-gut –brain axis is emerging It is involved in diverse form of neuroimmune conditions like multiple sclerosis Neural, endocrinal and metabolic mechanisms are critical mediators of the micro biome-CNS signaling which are involved in neuropsychiatric disorders like autism,anxiety,depression and stress.

34. Summaries: Microbiome:ecological community of commensal,symbiotic and pathogenic microorganisms that literally share the human body. microbiome refers to the collective genomes of the microorganisms in a particular environment and microbiota is the community of organisms themselves The breastmilk(BM)is a dynamic and complex microecosystem that contains a microbial signature that is transmitted to the newborn baby and is essential for immune system development and eduction 46

35. Cont … Breastmilk is a natural source of nutrition for the infant. In addition to the wealth of macro/micro nutrients,human milk contains many micro- organisms,few of which originate from the mother,while others are acquired from the mouth of the infant and the surroundings. Delivery mode appears to be an important factor in the development of the infant gut microbiota. These microbes initiate and help the development of the milk microbiota as well as the microbiota of the GIT and contribute to developing immune regulatory factors. 47

36. Objectives of microbiome research Predict the risk of disease development. Develop newer techniques to diagnose related diseases. Evolve therapeutic approaches for manipulation of the human microbiome for betterment of mankind 48

37. acknowledgments Dr Rupal Dalal MD,IBCLC Adjunct professor IIT Mumbai Dr Sharadadevi Mannur Y. HOD microbiology CDSIMER.

38. thanks! Any questions? 50