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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
human gastrointestinal
tract harbors one of the
highest densities
of microorganisms
on earth

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

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

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

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
indigestible plant polysaccharides
, biotransformation of conjugated bile acids,
of oxalates, &
of vitamins
(Xu & Gordon, 2003)
Microbial fermentation
of plant polysaccharides provides
10-30% of daily energy
from a Western diet (Raj et al. 2008)
, particularly butyrate, provide
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
of over
genes for the
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
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
older females
of underground storage units for
plant roots
, bulbs and tubers
essential for the nourishment of children
, allowed more pregnancies in
and thus greater
reproductive fitness
(O’Connell et al. 1999)
Importance of Microbial Fermentation of Plant Polysaccharides in Human Evolution
larger body & brain
of modern human ancestors (genus
) was likely facilitated by acquisition of
PP-fermenting microbes
, as additional energy from plants would

animal protein
consumed from being metabolized for energy,
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
between the
current diet
and our
Palaeolithic genome
(Kuipers et al. 2012)
Past & Present Mismatch
milk glycans
by mammalian gut but known to s
elecively promote
the growth of
, preventing colonization by
C. diff
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)


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


important in promoting neonate health
Importance of Microbiota-Human Coevolution
I suggest that the
extends to our
current lifestyle
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
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
(Biasucci et al. 2010)

stability of gut microbiota largely based on
of the
infant-acquired microbiota
by the gut immune system, which identifies these as
, by
to- and sampling of their microbial antigens
(Krajmalnik-Brown et al. 2012)
Fiber-rich diets
shown to
of the
microbiota population
& their
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
abundance of
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
effort joining multiple projects launched
concurrently worldwide
, including in the US, Europe and Asia.
Main goal:
the human
and the

the distribution and evolution of the
constituent microorganisms
Anticipated outcome:
a deeper
of human
nutritional requirements
, which may lead to new
for food production, distribution & consumption, formulated
based on knowledge of the microbiome.
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
), are
less abundant
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
with the
of either
mice or
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' (
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
metabolic syndrome
with gut microbiota from
lean healthy donors
(Vrieze et al. 2012)
Fecal Transplants:
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


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Microbiota of the Human Body
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