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The microbiome : An introduction. Dr Christine K. Chege Microbiome Symposium Kenya Paediatric Association Annual Conference 10 th April 2019. Definition of microbiome. The collective genomes of microbes that live in and on the human body
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The microbiome: An introduction Dr Christine K. Chege Microbiome Symposium Kenya Paediatric Association Annual Conference 10thApril 2019
Definition of microbiome The collective genomes of microbes that live in and on the human body “ the ecological community of commensal, symbiotic and pathogenic microorganisms that literary share our body space and have long been ignored as determinants of health and disease” Molecular biologist and Nobel laureate Joshua Lederberg 2001 So what is microbiota? Community of microbes living in harmony with human cells We have evolved together!
Most found here In and on you!...and even around you: “the microbial cloud”
Important role in health and disease • Linked to : • Obesity • Malnutrition • Heart disease • Diabetes • Some cancers • Coeliac disease • Eczema • Asthma • Autoimmune disease • Autism And more………
Influence on the immune system • Particularly important in adaptive immune system development in early childhood • helps in development of tolerance • implications on future allergic, inflammatory and autoimmune disorders
Influence on behavior? Lets blame lactobacillus • Gut brain axis via the vagus nerve • Association of functional gut disorders with psychiatric disorders • Study done on cowardly vs risk-taking mice Read about it here https://www.ncbi.nlm.nih.gov/pubmed/21683077
How much of us is microbiota? • Previously thought -10 X more microbes than human cells; recently closer to 1:1(39 vs 30 trillion) • 100X more genomic content than human genome • 1-3% of body’s mass • 1-2kg (like your brain….or more )
BRAIN BUGS
Terminologies we need to know • Flora: old name; forget it • Diversity: measure of how many different species and how evenly distributed in a microbiome • Dysbiosis: imbalance in the microbial communities; associated with disease – this is the rest of the track… • Phenotype: observable trait(appearance or behaviour)determined by genes • Enterotype: collection of species of microbes in the gut microbiome
The -omes, -omics New suffix in biology – describes large scale data Metabolome Collection of metabolites from metabolic reactions in a cell, tissue or organism Metatranscriptome Collection of mRNA molecules expressed from genes in the microbiota Proteome Complete set of proteins expressed by an organism
The father of microbiome • compared his faecal and oral microbiota I then most always saw, with great wonder, that in the said matter there were many very little living animalcules, very prettily a-moving
Other key milestones • 1885: E. coli from stools of newborns in Germany; Theodor Escherich(yeah…of course) • 1908: Russian Zoologist, Elie Metchnikoff – posited that health could be enhanced by friendly bacteria in yoghurt • 1959: rearing of germ free lab animals in ‘gnobiotic facilities’ to study effect of microbe free living • 1970: Thomas Lucky estimated 100 billion microbes per gram of faeces • 1995: sequencing of the H. influenza genome • 1996: 16S rRNA sequencing of first human faecal sample
More recent Advances • 2005: bacteria in amniotic fluid of babies born via CS • 2007: Human microbiome project(HMP) launched • 2009: study showing association between gut microbiome and disease is launched • 2012: HMP unveils first map of microbes inhabiting health humans 2018: American Gut Project publishes largest study on microbiome; over 11000 participants; over 40 diverse countries Fast forward……
A sample of the key players • Bacteroidetes: most prevalent bacteria in gut; produce favourable metabolites that have anti-inflammatory effects • Bifidobacterium: early life colonizer;found in gut, mouth, vagina; modulate immune functions; reduced levels in IBD • Lactobacillus: mouth, gut, vagina; antidiarrhoeal properties • Prevotella: mouth, gut; metabolic processing • Potential pathogens: pseudomonas, streptococcus
metagenomics Study of the complete genome of every microbe in a sample • Allows study of unculturable microbes • Genetic analysis and functional expression screening of microbial communities – microbes are interdependent • Gives broader description than just species identification • Cataloging of microbiome from people of different geographical regions, body systems – microbial diversity studies • Sequencing technology using known DNA markers • 16S rRNA example – all microbes have this gene but unique DNA sequence; closely related microbes show more similarities
Microbial community DNA sample Sequence 16S genes WHO’S THERE? WHAT ARE THEY DOING? Compare to databases of known 16S genes Sequence all genes Classify as new species Compare to database of genes with known functions or Identify known species https://learn.genetics.utah.edu/content/microbiome/study/
When do we get colonized? • Possibly before birth – diverse intracellular bacteria found in 27% of placentas in crossectional study suggesting maternal fetal1 • Meconium from CS and vaginally delivered babies did not differ in bacterial composition – gut colonization occurs before delivery2 • Bacteria also present in cord blood and amniotic fluid even in elected CSections3 1.Kjersti A et al(2014) 2.Martin R et al (2016) 3. Bearfield C et al(2002)
Does it matter how we are born? C-section Vaginal birth • Colonised by mother’s skin biome • Greater risk of obesity, allergy • Mother’s vaginal and gut biome • Less risk of obesity, allergy
Gut microbiome progression in early childhood Developmental phase(3-14mo) Transitional phase(15-30mo) Stable phase(31-46mo)
Temporal development of the gut microbiome early childhood from the TEDDY study Christopher J. Stewart1,2,18*, Nadim J. Ajami1,18, Jacqueline L. O’Brien1, Diane S. Hutchinson1, Daniel P. Smith1, Matthew C. Wong1, Matthew C. ross1, richard e. Lloyd1, HarshaVardhan Doddapaneni3, Ginger A. Metcalf3, Donna Muzny3, richard A. Gibbs3, tommi Vatanen4, Curtis Huttenhower4, ramnik J. Xavier4, Marian rewers5, William Hagopian6, Jorma toppari7,8, Anette-G. Ziegler9,10,11, Jin-Xiong She12, Beena Akolkar13, Ake Lernmark14, Heikki Hyoty15,16, Kendra Vehik17, Jeffrey P. Krischer17 & Joseph F. Petrosino1* • TEDDY – The Environmental Determinants of Diabetes in the Young • 903 children Europe and US • 12500 stool samples • Aged 3-46 mo
Conclusions from TEDDY study • With increasing age,the bacterial diversity of the microbiome expanded • Bifidobacterium predominated the developmental stage and was higher in breastfed infants. • The Firmicutes dominated the third stage and were noted to increase with the introduction of solids • Vaginally born infants had higher levels of Bacteroides and a higher diversity overall