The human microbiome
“The Forgotten Organ”
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/)
Interaction of human and our
commensural community
We have evolved in the context of
complex communities
Microbes play an important part of an
organism’s phenotype, beyond just
symbiosis
We cannot separate our genes from
the context of our microbes
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
Human Microbiome, cont’d
Gut microbiota of humans is dissimilar
between individuals
Populations of different countries are
similar, with the US having fewer
species of gut microbes
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
Escherichia coli, one of the many species of
bacteria present in our gut
QuickTime™ and a
decompressor
are needed to see this picture.
Candida albicans, a fungus that grows as a
yeast in the gut
QuickTime™ and a
decompressor
are needed to see this picture.
Gut flora, cont’d
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
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
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 infant’s 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
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
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
Functions regarding
Immunity
Bacteria promote early development
of gut’s mucosal immune system
Stimulate lymph tissue to produce
antibodies to pathogens
Immune system recognizes and fights
harmful bacteria, but leaves the
helpful species alone
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.
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.
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.
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;
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, Crohn’s,
Ulcerative Colitis
Balance is critical: harmful if numbers
are too high or too low
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))
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
potential…could lead to an increase
in weight despite decrease in food
Role in disease, cont’d
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
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
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, Crohn’s
Autism spectrum disorders being
investigated
Specific bacteria direct their differentiation
in the mucosa of the gut
How does body differentiate
good and bad
SI function of sorter, teaching IS to
separate self from non-self
Oral tolerance:gut flora train innate IS to
recognize self
If not “self” IL-12 in Peyer’s Patches
inducing inflammation
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
Appendix, cont;d
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
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.
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.
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.
Electron micrograph of phages attached to
bacterial cell
QuickTime™ and a
decompressor
are needed to see this picture.
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”