The%20human%20microbiome

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The human microbiome

• The Forgotten Organ

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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/)

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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

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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

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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

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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

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Escherichia coli, one of the many species of
bacteria present in our gut
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Candida albicans, a fungus that grows as a yeast
in the gut
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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

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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

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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

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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

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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

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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

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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.

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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.

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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.

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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

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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

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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))

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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

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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

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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.)

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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

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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

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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

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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

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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.
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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.

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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.

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Electron micrograph of phages attached to
bacterial cell
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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