Human Genetics
Mariam55The Human Microbiome
microbiome
90% of cells in human body are microorganisms
communities of microbes
genes interact with microbiome
environmental factors affect most traits
co-evolution in specific environments
community biology
diversity, stability, resilience
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The Human Microbiome
site-specific biomes
e.g., skin microbiome
intra-individual variation
inter-individual variation
interactions
microbe-microbe
microbe-host
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The Human Microbiome
functional core microbiome
species diversity, functional uniformity
i.e., same species does not necessarily provide same function
co-evolved in a particular habitat
convergent evolution of function
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protein-, small molecule-, or transcript-based
symbiotic host-microbial relationship
resilient to external or internal changes
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The Human Microbiome
changes due to environmental changes
contributes to development and aging
contributes to chronic disease
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The Human Microbiome
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host-microbiome interaction
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The Human Microbiome
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study of microbiome
earliest culture studies
E.coli grows well in labs
assumed to be most abundant
later anaerobic culture techniques in 1970’s
>300 other bacterial species
subculturing serial dilutions to quantify
Bacteroides and anaerobic cocci in high abundance
Clostridium in lower abundance
Bifidobacterium, Eubacterium, Lactobacillus, Streptococcus, Escherichia in much lower abundance
difficult to distinguish species
viruses or eukaryotes not culturable
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The Human Microbiome
study of microbiome
culture-independent techniques
DNA sequencing
FISH targeting 16S ribosomal gene
2/3 of human microbiome due to
2 species of Bacteroides
2 species of Clostridium
Streptococcus/ Lactococcus
Eubacterium rectale
large variability between samples
unknown species? 75-80% of sequences
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The Human Microbiome
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study of microbiome
culture-independent techniques
massive parallel shotgun sequencing
up to 50% still uncharacterized
implies set of genes common to all microbiomes
functional rather than taxonomic
Metagenomes of the Human Intestinal Tract (MetaHIT)
Human Microbiome Project (HMP)
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The Human Microbiome
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typical microbiome
1000-1150 bacterial species of gut microbiome
overlapping and redundant functions
each person carries subset of ~160 species
dominated by Bacteroidetes and Firmicutes phyla
ratio may differ within the population
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The Human Microbiome
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typical microbiome
oral mucosa microbiome
dominated by Streptococcus spp.
skin mucosa microbiome
depends on skin condition (dry, moist, waxy)
colonized by Cornyebacterium, Propionibacterium, Staphylococcus
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The Human Microbiome
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non-bacterial microbiome
archaea: Methanobrevibacter smithii
aids digestion of dietary polysaccharides by other microbes
virome: mostly bacteriophages (unique)
provide horizontal gene transfer through transduction
fungi: Candida, Malassezia, Saccharomyces
trans-kingdom interactions to control growth
Saccharomyces boulardii combats cholera
multi-celled: helminths (flatworms)
immunomodulatory, educator of immune system
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The Human Microbiome
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geographic variation
environmental differences, coevolution
North vs. South America
Europe vs. Africa
Korea vs. Japan
rural vs. urban Russia
rural vs. urban China
diet, geography, early-life exposure, genetics?
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The Human Microbiome
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The Human Microbiome
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microbiome establishment
enrichment of infant gut
Bacteroides, Parabacteroides, Clostridium, Lactobacillus, Bifidobacterium, and Faecalibacterium prausnitzii
produce short-chain fatty acids (SCFAs)
energy from nondigestible carbohydrates
immunomodulatory, educates immune system
inhibit pathogens
tumor-suppressive?
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The Human Microbiome
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Functional core microbiome
housekeeping functions
transcription/translation
energy production
cell division
specific to host-microbiome interaction
cell to cell adhesion
production of compounds for host
essential vitamins (K) and immunostimulatory compounds
specialized core functions for body habitat
e.g., in gut: glycosaminoglycan degradation and essential amino acids
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The Human Microbiome
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healthy community ecology
diversity, richness and evenness
overlapping functions, redundancy
associated with health and stability
lack of diversity in gut microbiome and disease:
inflammatory bowel disease
obesity
diabetes (types 1 and 2)
too much diversity in vaginal microbiome and disease:
bacterial vaginosis
cervical polyps
pre-term birth
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The Human Microbiome
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healthy community ecology
diversity, richness and evenness
lack of diversity in developed countries
higher chronic disease rates
linked to diet? high fat, high refined sugar, low fiber
mouse studies show it is reversible with high fiber diet
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