Gut microbiota

Gut MicrobiotaA healthy gut is the sign of healthy life

Saurav DasDepartment of Agricultural Biotechnology

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We Are Really More Bug than Man.......

LCA (Lowest Common Ancestor) of Human Microbiome

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.....

Carbohydrate fermentation and absorptionDigest 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 growthCompetition for nutrition, attachment. Produce bacteriocins , Lactic acid.

Metabolic functionHCA (heterocyclic amines)

Preventing inflammatory bowel diseaseSCFAs prevent IBD

Preventing allergy Allegies = C. difficile and S. aureus > Bacteroides and Bifidobacteria

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.

J.K. Nickolson, sci-mag, 2012

A.OBESITY B.MIND ALTERATION

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

BIOLOGY OF OBESITY

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 theactivity of Lipoprotein Lipase (LPL), a key enzyme in the hydrolysis of the release of fatty acids for transport into cells.

Pgc 1a

J.L, Nature, 2013,;JCL, 2012.

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).

Metabolic regulation by suppression of AMP-activated protein kinase (AMPK)

Endocannabinoid (eCB) signaling

Restore Gut Microbiota

LPSCB1

receptor

Lipogenesis

Upregulate Ghrelin

Down-regulate Fiaf, Ampk and

PYY

FAAH

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)

Alan W Walker, Sci-Mag, Sept, 2013

Obese twin

Microbiotatransplant Recipient mice Increased adiposity

Low-fat,high-fiber diet

Lean twin Lean

High Fat, Low Fiber

Low fat, High FiberIneffective transplant

Ineffective transplant

Low-fat,high-fiber diet

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. Blood pressure rises2. Breathing becomes more rapid3. Digestive system slows down4. Heart rate (pulse) rises5. Immune system goes down6. Muscles become tense7. We do not sleep (heightened

state of alertness)

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)

Lactobacillus spp. and Bifidobacterium spp. produce GABA

J F Cryan, Nature reviews, Neuroscience, october,2012

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.

ANXIETY &DEPRESSION

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

Parkinson's disease, a degenerative condition causing tremor and motor impairment, is caused by loss of dopamine-secreting neurons

Bacillus spp. produce dopamine

JF Cryan - 2012, Nature review Neuroscience

Mice conventionalised with Lactobacillus rhamnosus showed less anxiety and depression like behaviour when tested elevated plus maze and light and dark conditions with swim test.

J. Bravo, Nature, 2013

Conventionally grown

GF + GABA inducedGerm Free

L.R

Autism

Dae-Wook Kang, PLOS One, July , 2013

Dr. Dae-Wook Kang, Arizona State UniversityAutistic 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.

Second Genome

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.

2008

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.

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……