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The%20human%20microbiome

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Title: The%20human%20microbiome


1
The human microbiome
  • The Forgotten Organ

2
The Forgotten Organ
  • Within body of healthy adult, microbial cells are
    estimated to outnumber human cells ten to one
    (100 trillion microbial cells)
  • Vast majority of microbial species have not been
    analyzed, because their growth is dependent upon
    a specific microenvironment
  • Human Microbiome Project is studying these
    communities at different sites on the body,
    including nasal passages, mouth, skin, GI tract
    and UG tract ( http//commonfund.nih.gov/hmp/)

3
Interaction of human and our commensural community
  • We have evolved in the context of complex
    communities
  • Microbes play an important part of an organisms
    phenotype, beyond just symbiosis
  • We cannot separate our genes from the context of
    our microbes

4
Human microbiome
  • Provide a wide range of metabolic functions that
    humans lack
  • Microbes include bacteria, eukaryotes and viruses
  • DNA based studies to identify and understand the
    functions of the community

5
Human Microbiome, contd
  • Gut microbiota of humans is dissimilar between
    individuals
  • Populations of different countries are similar,
    with the US having fewer species of gut microbes

6
Gut flora
  • Consists of microorganisms that live in the
    digestive tracts
  • Largest reservoir of human flora
  • Estimated to have a hundred times as many genes
    as there are in the human genome
  • 300 and 1000 different species of bacteria
  • Fungi and protozoa make up part

7
Escherichia coli, one of the many species of
bacteria present in our gut
8
Candida albicans, a fungus that grows as a yeast
in the gut
9
Gut flora, contd
  • Commensal (non-harmful) but also mutualistic
    relationship.
  • Microbes perform a host of useful functions such
    as
  • Fermenting unused energy
  • Training the immune system
  • Preventing growth of pathogenic bacteria
  • Regulating the development of the gut
  • Producing vitamins, such as biotin and Vit K
  • Producing hormones to direct the hose to store
    fats

10
Diet and Gut Flora
  • Gut micro flora mainly composed of 3 enterotypes,
    are necessary for the the digestion of
    carbohydrates, animal proteins, and fats.
  • They will vary, depending on diet, and as your
    diet changes, their percentages will change

11
Gut flora in human infants
  • GI tract of human fetus is sterile
  • During birth and shortly thereafter, bacteria
    from the mother and the environment colonize the
    infants gut.
  • Immediately after vaginal delivery, babies may
    have bacterial strains derived from the mothers
    feces
  • Vaginally born infants take up to one month for
    their intestinal microflora to be well
    established caesarian section babies may take 6
    months

12
Functions of gut bacteria
  • Have enzymes that human cells lack for breaking
    down carbs, turning them into SCFAs
  • SCFAs increase growth of gut epithelial cells,
    and may increase growth of lymph tissue
  • Rats raised in sterile environment have to eat
    30 more calories to remain the same weight

13
More functions
  • Repress microbial growth through the barrier
    effect
  • Harmful yeasts and bacteria like Clostridium
    difficile are unable to grow excessively due to
    competition from the helpful gut flora
  • Process of fermentation lowers the pH in colon,
    preventing proliferation of bad bacteria

14
Functions regarding Immunity
  • Bacteria promote early development of guts
    mucosal immune system
  • Stimulate lymph tissue to produce antibodies to
    pathogens
  • Immune system recognizes and fights harmful
    bacteria, but leaves the helpful species alone

15
More immune functions
  • Play a role in toll-like receptors molecules
    that help repair damage due to injury, like
    radiation
  • Allow gut ability to discriminate between
    pathogenic and helpful bacteria
  • Activate inflammatory cytokines
  • Create oral tolerance, which help IS be less
    sensitive to antigen once its been ingested.

16
Help to prevent allergies
  • Children who have allergies have more harmful
    species of of bacteria, and lower helpful species
  • Since helpful gut flora stimulate the IS and
    train it to respond properly to antigens, lack of
    these bacteria leads to an inadequately trained
    IS.

17
Prevent IBS
  • Some bacteria can prevent inflammation
  • Disease linked to good hygiene in children, lack
    of breast feeding, consumption of large amounts
    of sucrose and animal fat and use of antibiotics
    in early life.
  • Inversely linked with poor sanitation in early
    years of life and consumption of fruits, veggies,
    and unprocessed foods.

18
Effects of antibiotics
  • Can alter the numbers of gut bacteria, which can
    reduce ability to digest
  • Can cause diarrhea by irritating the bowel
    directly, changing the levels of gut flora, and
    allowing pathogenic bacteria to grow
  • Creates antibiotic resistant bacteria in gut
  • Probiotics rely on a few strains of good
    bacteria

19
Role in disease
  • Bacteria in digestive tract have pathogenic and
    health promoting roles
  • Can produce toxins and carcinogens
  • Bacteria have been related to sepsis and colon
    cancer, IBD, Crohns, Ulcerative Colitis
  • Balance is critical harmful if numbers are too
    high or too low

20
Gut bacteria may affect arteries
  • Different mixes of gut microbes help determine
    whether people will have heart attacks or strokes
    brought on by plaque
  • HT disease patients carry fewer microbes that
    make anti-inflammatory and anti-oxidant compounds
    and more inflammation-producing bacteria (Dec 4
    Nature Communications/Science News 1/12/2013,p
    24))

21
Obesity
  • Obese mice lacking leptin have distinct gut flora
    population
  • Microbe colonies are different between obese and
    lean humans
  • Different species of flora have different energy
    reabsorbing potentialcould lead to an increase
    in weight despite decrease in food

22
Role in disease, contd
  • Some bacteria are associated with tumor growth
    and others prevent tumors
  • Helpful bacteria can be harmful if they get
    outside of intestinal tract
  • Increased gut lining permeability can occur in
    leaky gut syndrome, or cirrhosis

23
Leaky Gut Syndrome
  • Means increased intestinal wall permeability
  • Just now being investigated not recognized as a
    diagnosis
  • Hypothesized to be caused by increased
    permeability of the gut wall resulting from
    toxins, poor diet, parasites, infection or
    medications
  • Leaky gut allows toxins, microbes, indigested
    food, waste to leak through gut
  • Could cause immune reactions (rheumatoid
    arthritis, lupus, asthma, Type I diabeties, etc.)

24
T helper 17 cells
  • Recently discovered to play role in inflammatory
    process
  • Important anti-microbial barrier
  • Excessive amounts hypothesized to play role in
    autoimmune diseases such as MS, psoriasis, Type I
    diabetes, rheumatoid arthritis, Crohns
  • Autism spectrum disorders being investigated
  • Specific bacteria direct their differentiation in
    the mucosa of the gut

25
How does body differentiate good and bad
  • SI function of sorter, teaching IS to separate
    self from non-self
  • Oral tolerancegut flora train innate IS to
    recognize self
  • If not self IL-12 in Peyers Patches inducing
    inflammation

26
Appendix
  • Immune tissue and antibodies are concentrated
  • Houses large numbers of bacteria in biofilms that
    offer services to our gut
  • Serves as an incubator, allowing for regeneration
  • When severe illness wipes out good bacteria,
    appendix can regenerate

27
Appendix, contd
  • Appendix in developed countries is infrequently
    challenged by pathogens and appendicitis is more
    common
  • In developing countries, humans get very sick
    from intestinal parasites
  • Perhaps appendix, through its role of
    replenishing the gut, is being kept healthy

28
Because nearly 70 of the immune system is
localized to the digestive tract, a state of
controlled physiologic inflammation,along with
environmental contact with commensal bacteria, is
essential for proper development of the immune
system.
29
Fecal Transplants
  • Transplanting fecal matter directly into gut of
    someone suffering from a number of intestinal
    illnesses, including various inflammatory
    diseases, C Diff overpopulation, etc,has shown
    great promise
  • Still in experimental stage.

30
Bacteriophage
  • A virus that infects and replicates within
    bacteria, killing them.
  • Phages are all over - in soil, sea water,
    intestines, etc.
  • Use for over 90 years in the Eastern Europe
    against bacterial infections
  • Possible therapy against multi-drug resistant
    strains of bacteria.

31
Electron micrograph of phages attached to
bacterial cell
32
Resources
  • Integrative Gastroenterology, by Gerard E.
    Mullin
  • The Wild Life of our Bodies Predators,
    Parasites, and Partners That Shape Who We Are
    Today, by Rob Dunn
  • Ted.com Meet Your Microbes Jonathan Eisen, 2012
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