6. GUT MICROBIOTA
1013 -1014 microbes
1000- 35000 of species (most of them are still to be identified)
Weight – 3 to 5 lbs
Genome – 150 fold of our Genome
Bacteroides,
Prevotella,
Fusobacterium,
Eubacterium, Ruminococcus, Peptococcus,
Peptostreptococcus, Bifidobacterium.
Escherichia and Lactobacillus.
Bacteroides alone constitute about 30% of all bacteria in
the gut.....
7. Carbohydrate fermentation and absorption
Digest starch, plant fiber, pectin into SCFAs (short chain fatty acids) viz.
acetic acid, propionic acid, butyric acid. Digest proteins like collagen,
elastin.
Repression of pathogenic microbial growth
Competition for nutrition, attachment. Produce bacteriocins , Lactic
acid.
Metabolic function
HCA (heterocyclic amines)
Preventing inflammatory bowel disease
SCFAs prevent IBD
Preventing allergy
Allegies = C. difficile and S. aureus > Bacteroides and Bifidobacteria
8. Ecology.....
Babies delivered Normally are dominated
by Lactobacillus, Prevotella, and
Atopobium ....
Babies delivered by Cesarian section have
microbiota that of the maternal skin
community like Staphylococcus.
Prevotella is related with carbohydrates and simple sugars.
Bacteroides enterotypes is associated with animal proteins, amino acids and
saturated fats.
11. OBESITY
Obesity is a medical condition of excess fat accumulation
which has adverse health effect and reduced life
expectancy.
Obesity increases the likelihood of various diseases,
particularly heart disease, type 2 diabetes, obstructive
sleep apnea, certain types of cancer, and osteoarthritis.
one of the most serious public health problems of the
21st century.
In 2013, the American Medical Association classified
obesity as a disease
12. BIOLOGY OF OBESITY
Pgc 1a
Regulation of fatty acid uptake by suppression of fasting-induced adipose factor
(Fiaf)….. is a protein secreted by adipose tissues, liver and intestine that inhibits the
activity of Lipoprotein Lipase (LPL), a key enzyme in the hydrolysis of the release of
fatty acids for transport into cells.
J.L, Nature, 2013,;JCL, 2012.
13. Metabolic regulation by suppression of AMP-activated protein kinase (AMPK)
AMPK is an enzyme expressed in liver, brain and skeletal muscle that functions as a cellular
energy sensor and metabolic regulator. It is activated by phosphorylation at Thr-172 of the
catalytic a subunit, when intracellular AMP:ATP or NAD:NADH ratios increase in response to
metabolic stress such as exercise or glucose deprivation. AMPK activation increases cellular
energy levels by stimulating catabolic pathways (e.g., glucose transport, fat oxidation) and by
inhibiting anabolic pathways (e.g., fatty acid, protein and glycogen synthesis), in part through
inhibition of mammalian Target of Rapamycin (mTOR).
14. Endocannabinoid (eCB) signaling
Dysbiosis … Increased Gram Negative Bacteria (Enterobacteriaceae spp.) less Gram Positive
bacteria (Bifidobacteria)
endocannabinoid (eCB) system consists of the neuromodulatory lipids anandamide (AEA)
and 2-arachidonoylglycerol (2-AG)
Upregulate
Ghrelin
FAAH
CB1
receptor
Lipogenesis
Down-regulate
Fiaf, Ampk and
PYY
LPS
Restore Gut
Microbiota
17. Gut Microbiota: Stress, Anxiety and
Depression
Biology of
Stress
Stress is a person's response to
a
stressor
such
as
an
environmental condition or a
stimulus. Stress is a body's way to
react to a challenge in a flight or
fight situation.
1.
2.
3.
4.
5.
6.
7.
Blood pressure rises
Breathing becomes more rapid
Digestive system slows down
Heart rate (pulse) rises
Immune system goes down
Muscles become tense
We do not sleep (heightened
state of alertness)
18. Lactobacillus spp. and Bifidobacterium spp. produce GABA
GABA’s natural function is to reduce the activity of the neurons to which it binds. GABA
neutralizes the overexcited neurons. (anti-stress drug : Benzodiazepine)
19. ANXIETY &DEPRESSION
Serotonin
•Contributor to feelings of well-being
and happiness.
•80% of the human body's total serotonin is
located in the enterochromaffin cells in the
gut
•Aggression, anxiety, appetite, cognition,
learning, memory, mood, nausea, sleep,
and thermoregulation.
Anti-Depressive Drugs (Venlafaxine
Levomilnacipran) (SSRI : Selective Serotonin
Reuptake inhibitor)
Weak bone mass in elderly and increased risk
for osteoporosis.
J F Cryan, Nature reviews, Neuroscience, october,2012
20. Bifidobacteria spp. can increase
the concentration of tryptophan
in blood plasma (the precursor
of sreotonin) so act as a
antidepressent.
Which
was
tested by Desbonnet L in 2008
by infecting Germ Free mice with
specific
pathogen
viz.
Bifidobacterium infantis and let
them take the swim test
forcefully.
Desbonnet L, Journal of psychiatric research, 2008
21.
22. Bacillus spp. produce
dopamine
Parkinson's disease, a degenerative condition
causing tremor and motor impairment, is caused
by loss of dopamine-secreting neurons
JF Cryan - 2012, Nature review Neuroscience
24. Autism
Dr. Dae-Wook Kang, Arizona State University
Autistic Children significantly have fewer types of gut bacteria and significantly lower
amounts of three critical bacteria prevotella, coprococcus and veillonellaceae. These three
bacterial groups represent important strains of carbohydrate degrading and fermenting
microbes. So, In may cases the autistic children have IBD symptoms and they have found
that when they tried to manage the IBD with application of probiotics the child seems to
recover a fewer percent.
Dae-Wook Kang, PLOS One, July , 2013
25. Second Genome
2008
Researchers in the HMP are sampling and
analyzing the genome of microbes from
five sites on the human body: nasal
passages,
oral
cavities,
skin,
gastrointestinal tract, and urogenital
tract. (NIH)
1. Microbes
contribute
more
genes
responsible for human survival than
humans' own genes. It is estimated that
bacterial protein-coding genes are 360
times more abundant than human genes.
2. Microbial metabolic activities; for example,
digestion of fats; are not always provided
by the same bacterial species. The
presence of the activities seems to matter
more.
3. Components of the human microbiome
change over time, affected by a patient
disease state and medication. However, the
microbiome eventually returns to a state of
equilibrium, even the composition of
bacterial types has changed.
26. CONCLUSION AND FUTURE PROSPECT
1. We need an improved understanding of the dynamics and impact of maternal Microbiota
transfer and the influence of infant nutrition on development of the gut Microbiota in early
childhood. We also need to elucidate the influence of host genome variations and the fetal
environment on the future gut Microbiota.
2. It will be important to map the impact of early antibiotic use on the developmental ecology,
function, and resilience of the Microbiota during childhood. As the Microbiota develops over the
first few years of life, there may be greater potential for disruption of the long-term microbial
state than would be encountered in adults.
3. A deeper knowledge is required regarding how variation in the gut Microbiota influences drug
metabolism, drug bioavailability, and drug toxicity with repercussions for patient stratification
and personalized health care.
4. Strategies should be developed for the in vitro culture of the complete Microbiota in order to
elucidate bacterial species biology and microbial interactions in engineered ecological
constructs and synthetic ecosystems.
5. Comprehensive top-down systems biology analyses should be applied to the changing
immunological and metabolic interactions between the host and its gut Microbiota to elucidate
how these changing interactions affect gut, liver, and brain function.
27. Thank you for your Kind Attention………..
From Next time Don’t feel
Lonely….cause you have some
friends inside you to take care
of yourself……