Health & Microbiome Transmission & Development of Microbiota PDF

HEALTH & MICROBIOME TRANSMISSION AND DEVELOPMENT OF MICROBIOTA Deniz SERTEL, PhD FORMATION OF MICROBIOTA  When do humans first encounter microbes?  Sterile womb hypothesis  In utero colonization hypothesis  STERILE WOMB HYPOTHESIS  The human fetus lives in a protected,...

HEALTH & MICROBIOME TRANSMISSION AND DEVELOPMENT OF MICROBIOTA Deniz SERTEL, PhD FORMATION OF MICROBIOTA  When do humans first encounter microbes?  Sterile womb hypothesis  In utero colonization hypothesis  STERILE WOMB HYPOTHESIS  The human fetus lives in a protected, sterile environment, so until birth fetus is sterile, unless there is an intrauterine infection during pregnancy.  Most of the placenta and amniotic fluid samples from healthy pregnancies are reported to be sterile  Most meconium samples have been reported to be free of viable microbes  Most of these studies have used traditional culture based methods and microscopy techniques. INUTERO COLONIZATION HYPOTHESIS  Several recent studies suggests that the placenta is not a sterile organ, but rather has its own endogenous microbiome.  Microorganisms have been detected in meconium, fetal membranes and amniotic fluid of uncomplicated pregnancies  Most of these studies have used molecular assays, that detected microbial nucleic acids Is «sterile womb» hypothesis refuted Does «in utero colonization» hypothesis have a solid background Most of the placenta, Plasental microbiome amniotic fluid and could not be detected to meconium samples date because of the acquired from healthy limitations of pregnancies have been conventional methods shown to be free of viable microbes Presence of microbes Sensitivity of culture have been associated based methods are low. with prenatal infections Non culturable microbes and/or contamination exist Perez-Muñoz et al. Microbiome (2017) 5:48 Perez-Muñoz et al. Microbiome (2017) 5:48  Microbial products rather than the microbe itself can be transmitted to fetal tissues and this may contribute to the priming of the fetal immune system.  Microbial antigens can be transported to fetal tissues via immune cells  Microbial metabolites derived from the maternal microbiota can be vertically transmitted NEONATAL MİCROBİOTA  During and immeadiately after birth infant is exposed to  Maternal vaginal microbes  Maternal and other peoples’ skin microbes  Microbes from environment  After initial colonization considerable temporal fluctations occur in the first years of life Hill et al.: The neonatal microbiome in utero and beyond  NEONATAL GUT MİCROBİOTA  Full-term neonate  First days: Aerobic and facultative anaerobic bacteria dominate  (Proteobacteria- Enterobacteriaceae-, Firmicutes- streptococci-)  First weeks: Anaerobic bacteria becomes abundant  Actinobacteria (including Bifidobacterium), Bacteroides M. Tanaka, J. Nakayama / Allergology International 66 (2017) 515e522  FACTORS THAT INFLUENCE NEONATAL MICROBIOTA  Gestational age  Mode of delivery  Nutrition  Antibiotics  Microbiota and health status of the mother  Microorganisms present in the environment Hill et al.: The neonatal microbiome in utero and beyond GESTATIONAL AGE Premature birth: delay in microbial colonization, decreased microbial diversity, higher relative abundance of potential pathogens Preterm delivery is associated with complicated pregnancies Initial differences in the neonatal period may have major impact on neonatal health and survival Intestinal microbiota is similar in term and preterm babies by the age of 1-3 years.  MODE OF DELIVERY  Several studies have shown increased abundance of bacilli and Enterobacteriaceae, reduced abundance of bifidobacteria and a clear long term lack of bacteroides in c-section born infants  Vaginal delivery : higher diversity fewer Staphylococci and C. difficile  C-section: delayed bacterial colonization, reduced Proteobacteria diversity, higher rates of opportunistic pathogens (Klebsiella, Lactobacillus, Enterobacter) and  «Vaginal seeding» didnt show any benefit Prevotella, Firmicutes (Enterococcus, Bifidobacterium,  Generally differences decline by the age of 12 Staphylococcus, Escherichia and months Clostridium, Bacteroides Streptococcus)  ANTIBIOTIC USE  Microbial diversity and bifidobacterial population decreased and clostiridia increased in antibiotic treated infants  Microbiota was found to rrecover by the first year of life  Continiuous use of antibiotics in the early life has been associated with increased risk of overweight and allergy. NUTRITION  Breast milk contains bioactive compaounds (IgA, lactoferrin, growth factos) and maternal microbiota (esp Bifidobacterium and Lactobacillus spp)  Formula fed infants have a more diverse microbiota with higher relative abundance of Firmicutes, Bacteroidetes and Proteobacteria  Introduction of solid foods: bifidobacteria decrease, clostridia increase MATERNAL FACTORS Maternal BMI Maternal diet Maternal antibiotic use Maternal stres Maternal microbiota Early life exposures and impact on microbiome (Hill et al.: The neonatal microbiome in utero and beyond)  ABOUT THE ORIGINS OF NEONATAL GUT MICROBIOTA  Bacterial taxa present in infant fecal samples are rarely seen in maternal vaginal samples1  Several studies have shown that same species and strains are present in faecal samples of infants and their mothers2-4  Maternal gut is probably the main source of microbes colonising the infant gut but not for all5,6  Bifidobacteria and bacteroides spp seems to be transmitted vertically  Same bifidobacterial strains (and bifidophages) have been detected in the infants gut and maternal gut and breast milk  Most of the clostridia that colonize childeren are not of maternal origin  (1- Benef Microbes 2017, 8:763-778; 2- Cell Host Microb 2015 17:690-703; 3- Genome Res 2016, 26:1612-1625; 4- Systems 2017, 2:e00164-16; 5- Microbiome 2017 5:66; 6- Genome Res 2018, 28:561-568) DIVERSITY OF MICROBIOTA  The microbiota is specific to the host  Major factors affecting the composition of microbiota:  Genetics  First exposure  Diet  Age  Hormones  Health status and drug use  Environment…..  The microbial flora in and on the human body is in a continual state of flux  The composition of the microbiota differs significantly between body sites  FACTORS THAT AFFECT MICROBIAL COMPOSITION AND LOAD ❑Water content ❑Temperature ❑Oxygen content ❑pH ❑Available nutrients ❑Antimicrobial defences