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Copy of Microbiology

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Rona Wilf

on 10 December 2013

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Transcript of Copy of Microbiology

The Human Gut Microbiota
The
human gastrointestinal
tract harbors one of the
highest densities
of microorganisms
on earth


10e+11 - 10e+12
organisms
per ml
of luminal content

9 Bacterial
phyla
*Firmicutes & Bacteroidetes most abundant (>96%)
1 member of Archaea
-
Ethanobrevibacter smithii

1,800 genera and 16,000 phylotypes at species level
each

person
possesses a
dynamic subset of 160 species

(Rajilic-Stojanovic et al. 2007)


Microbial Ecology of the Gut
The Role of Microbiota in Immune Function

Competing with pathogenic bacteria
(Buffie & Pamer, 2013)

Producing short chain fatty acids (SCFA) crucial for colonic epithelial cell growth and differentiation (Natividad and Verdu, 2013)

Stabilizing tight junctions of intestinal epithelium through interaction with integrins
(Segawa et al. 2011)
Buffie CG & Pamer EG (2013). Microbiota-mediated colonization resistance against intestinal pathogens. Nature Reviews Immunology 13:790–801
The Role of Microbiota in Metabolism
Provide capability of
breaking-down
otherwise
indigestible plant polysaccharides
, biotransformation of conjugated bile acids,
degradation
of oxalates, &
synthesis
of vitamins
(Xu & Gordon, 2003)
Microbial fermentation
of plant polysaccharides provides
10-30% of daily energy
from a Western diet (Raj et al. 2008)
SCFAs
, particularly butyrate, provide
most
of the large intestine
enterocyte energy requirements
(Walter & Ley, 2011)
Gut bacteria
provide humans
with metabolic traits they did
not need to evolve
on their own
Functionality
of over
9,000
genes for the
‘price’
of
~17
El Kaoutari et al. (2013) Abundance and variety of carbohydrate-active enzymes in the human gut microbiota.
Nature Reviews Microbiology
, 11, 497-504
Human-Microbiota Coevolution & Implications for Human Health
Early hominids
were
omnivorous
and, in periods of food scarcity,
relied mainly on starch
-rich roots & bulbs, especially in dry savannahs (Walter & Ley, 2011)
The grandmother hypothesis
proposed that the
foraging and sharing
by
older females
of underground storage units for
plant roots
, bulbs and tubers
essential for the nourishment of children
, allowed more pregnancies in
daughters
and thus greater
reproductive fitness
(O’Connell et al. 1999)
Importance of Microbial Fermentation of Plant Polysaccharides in Human Evolution
The
larger body & brain
of modern human ancestors (genus
Homo
) was likely facilitated by acquisition of
PP-fermenting microbes
, as additional energy from plants would
spare

animal protein
consumed from being metabolized for energy,
allowing
its use in
building tissue mass instead
(Aiello & Wells, 2002)
It has been advocated that the current pandemic of
"diseases of civilisation"
results in part from the
mismatch
between the
current diet
and our
Palaeolithic genome
(Kuipers et al. 2012)
Past & Present Mismatch
Human
milk glycans
are
indigestible
by mammalian gut but known to s
elecively promote
the growth of
bifidobacteria
&
lactobacilli
, preventing colonization by
pathogens
like
C. diff
and
S. aureus
(Milena-Marques et al. 2010)
Vertical Transmission of the Microbiota
Parent–offspring and/or kin–offspring transmission of microbiotas promotes the coevolution of whole communities with their host species by stabilizing the associations between particular host and microbial lineages
(Ley et al. 2008)
The 1st microbial communities of the newborn's gut are determined by the microbial communities of the mother’s vagina & skin, and transmitted during birth & nursing
(Matamoros et al. 2013)
Bifidobacteria

&

lactobacilli
are
abundant
in the mother's vagina & breast milk, suggesting that
vaginal delivery
&

breast-feeding
are

important in promoting neonate health
Importance of Microbiota-Human Coevolution
I suggest that the
mismatch
extends to our
current lifestyle
and
past microbiome,
as well
Beyond the Hygiene Hypothesis
De Filippo, C., Cavalieri, D., Di Paola, M., Ramazzotti, M., Poullet, J.B.,Massart, S., Collini, S., Pieraccini, G., and Lionetti, P. (2010). Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa.
Proc. Natl. Acad. Sci. USA
107, 14691–14696.
Numerous studies show a
correlation
between
dysbiosis
&
auto-immune disorders
such as Type 1 diabetes, lupus, asthma, MS, rheumatoid arthritis, allergies, celiac disease, & Inflammatory Bowel Disease (IBD) including Crohn's, ulcerative colitis & irritable bowel syndrome
(Madupu et al. 2013; Clemente et al. 2012).
New methods of delivery:
Increased susceptibility
to certain pathogens, necrotizing enterocolitis and atopic diseases seen in babies delivered by
C-section
(Biasucci et al. 2010)

Long-term
stability of gut microbiota largely based on
recognition
&
tolerance
of the
infant-acquired microbiota
by the gut immune system, which identifies these as
normal
, by
exposure
to- and sampling of their microbial antigens
(Krajmalnik-Brown et al. 2012)
Fiber-rich diets
shown to
increase
overall
diversity
of the
microbiota population
& their
enzymes
that can produce a
variety of SCFAs

(De Filippo et al. 2010). The presence of SCFAs is generally associated with reduced inflammation
The Human Microbiome Project
Lower
abundance of
Bifidobacteri
a & higher abundance of aerobic bacteria in the GI of
formula-fed infants
relative to breast-fed infants correlated strongly with
childhood allergies & asthma
(Palmer et al. 2007)
Dysbiosis in Modern Societies
More reasons to eat fiber:
The HMP - an
extension of the Human Genome Project
.
An
interdisciplinary
effort joining multiple projects launched
concurrently worldwide
, including in the US, Europe and Asia.
Main goal:
“to
characterize
the human
microbiome
and the
factors

influencing
the distribution and evolution of the
constituent microorganisms
therein”.
Anticipated outcome:
a deeper
understanding
of human
nutritional requirements
, which may lead to new
recommendations
for food production, distribution & consumption, formulated
based on knowledge of the microbiome.
Applications
A
prospective
study of 49 infants showed that children who were
overweight at age 7
had higher levels of
S. aureus
(skin) and
lower levels of Bifidobacteria
(milk & vaginal birth) during infancy
(Karlsson et al. 2013)
Butyrate-producing bacteria
, known to
be
anti-inflammatory
(e.g.,
Roseburia
&
Faecalibacterium
), are
less abundant
in
T2D patients
than in healthy controls
Probiotic supplementation:
Importance of Vaginal Delivery & Breast-Feeding:
The microbiome of various anatomical locations of the human body. From: Yun Kyung Lee and Sarkis K. Mazmanian (2010). Has the Microbiota Played a Critical Role in the Evolution of the Adaptive Immune System? Science 330, 1768
Cause or Effect?
In one study published in Nature (2006),
germ-free mice
were
colonized
with the
microbiota
of either
obese
mice or
lean
mice.
They found that the
obese microbiota
, which contained more CAZ genes, appeared to
extract more energy
from the
same diet
than did the lean microbiota.
Mice that received the
'obese microbiota'
gained a
higher %

of body fat
than mice receiving the 'lean microbiota' (
47.0%
vs 0.86%), suggesting that
microbiota shifts caused obesity
in these mice.
(Qin et al. 2012)
More Applications
Insulin sensitivity
and levels of
butyrate-producing bacteria
increased in
patients
with
metabolic syndrome
after
transplantation
with gut microbiota from
lean healthy donors
(Vrieze et al. 2012)
Fecal Transplants:
Traditionally
been used to treat several
GI disorders
such as refractory
C. difficile
colitis (CDC), pseudomembranous enterocolitis and ulcerative colitis (Duplessis et al. 2012).
The Human Microbiota
BMES 571
Rona Wilf

Questions?
References

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Microbiota of the Human Body
Full transcript