PROBIOTA ASIA 2019

2019.10.24Dr. Bejit Ideas

Epigenetics based AI technology as platform to develop personalized health solutions

Version 5

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SUMMARY

1.WHAT IS SECRET OF HEALTH AND LONGEVITY?

a)Importance of gut health

b)Study on centenarian microbiota

2.AI technology to develop smart health solution

1.METABOLITES AS A SOLUTION TO TARGET EPIGENETICS

2.Personalized Care using biomimetic Fermentation technology

3.Successful examples

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1. WHAT IS THE SECRET OF JAPANESE WOMEN HEALTH AND LONGEVITY?

Okinawa has 740 centenarians, 592 are women

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HOW DO MICROBIOTA AFFECT GENE EXPRESSION?

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2. PROBIOTICS AND METABOLITES AS A SOLUTION TO TARGETS EPIGENETIC

• Epigenetic: genetic control by factors other than an individual's

DNA sequence.

• Epigenetic changes can switch genes on or off

• influenced of our lifestyle, diet, and environment

• Epigenetic changes are hereditary

• But reversible

• Can activate gene expression of coronary artery disease, chronic

obstructive pulmonary disease, Type 2 Diabetes and obesity

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CLINICAL TRIAL OF EVALUATION OF THE GUT MICROBIOTA COMMUNITY OF CENTENARIANS

STUDY DESIGN: Total 24 subjects divided as Group 1) healthy centenarians between age of 100 to 109or above years and Group 2) Elderly adults between the age group of 70-90 years, without any knowndisease, and antibiotic/Probiotic intake before one month of start of experiment.

METHOD:

1. Faecal sample of subjects collected in sterile containers

2. Gut bacteria are isolated by nutrient plate culture method and

3. Genus and Species are identified by 16S rDNA isolation and PCR techniques.

Study on centenarian microbiota

Collection of stools Extraction of metabolites in stools

Mass Spectrometry

Metabolism mappingDetection of metabolites

AI TECHNOLOGY TO DEVELOP SMART HEALTH SOLUTION

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CENTENARIAN UNIQUE MICROBIOTA:ALPHA GROUP

• Bacteroidetes• Firmicutes• Proteobacteria

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RESULTS:Results indicated that Centenarians have higher microbial diversity compared to elderly adults

Study on centenarian microbiota

RESULTS: Results indicated that Centenarians have higher amount of set of metabolites likep-cresol-sulfate (PAG) and phenylacetylglutamine (PCS) and 2–hydrdroxybenzoate (2-HB).

✓ Centenarians Metabolism Pattern- Gut microbiota metabolise protein and amino acids to form p-cresol-sulfate (PAG) and phenylacetylglutamine (PCS).

✓ Centenarians- Increased concentration of 2–hydrdroxybenzoate (2-HB). Which has anti-inflammatory activity., inhibit cyclooxygenase activity (COX-2) which produces proinflammatorycytokines.

✓ PAG, PCS and 2-HB are called metabolic markers of Longevity.

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Elderly Centenarians

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PAG p-cresol-sulfate

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Elderly Centenarians

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PCS, Phenylacetylgluatmine

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Elderly Centenarians

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2-HB, 2-hydroxybenzoate

3. MITOCHONDRIA GENE EXPRESSION BY MICROBIOTA METABOLITES

Gene expression mechanisms of action

Fermentation of centenarian bacteria provides a large variety of active metabolites thattarget mitochondria gene expression:

Microbiota metabolites promotes mitochondria biogenesis through gene expression

• PGC1-α (Peroxisome proliferator-activated receptor gamma coactivator) central inducer of

mitochondrial biogenesis

• NRF-1 (Nuclear Respiratory factor-1), key regulation of respiration process

• mt TFAM (Mitochondrial transcription factor A), mitochondrial key transcription activator

through activating CytC oxidase, SIRT-1, AMPK signalling pathways.

IMPROVEMENT OF MITOCHONDRIA HEALTH WHICH PRODUCE INCREASE LEVEL OF ATP

Total cellular ATP mtDNA content

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*+135%

MITOCHONDRIA SOLUTION

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• Short chain fatty acids induce gene expression

• Increase of fat oxidation by mitochondria

• Decrease of lipids storage

Metabolites promote mitochondria activity and fat

burning

Activity of metabolites on mitochondria

For lactose sensitivity induced acne

Proteins in milk whey and casein release a hormone IGF-1 during metabolism. This hormone triggers acne breakouts and increase P. acnes microbiota in the skin

ACNE HEALTHY

Firmicutes -Bacteroidia +

Clostridia +Lachnospiraceae +Ruminococcaceae genera +

People with acne vulgaris have dysbiosis and imbalanced gut microbiota

5. Successful applications to reprogram gene expression

BENEFICIAL EFFECT

QUERCETIN –

Anti-inflammation: Prevents TNF-α, IL-6, MAPK and NFkβ mediated skin inflammation

Anti-aging: Potential antioxidant

Anti-acne: Inhibits Propionibacterium growth

β –SITOSTEROL-

Anti-dermatitis: Down regulates TSLP (thymic stromal lympopoietin) through blocking caspase-1 and NFkβ

Anti-sarcopenia: Diminish expression of cytokines, improve collagen synthesis

RUTIN

Anti-Psoriasis: Inhibit inflammatory molecules involved in psoriasis.

Anti-glycation: Inhibits the skin collagen glycation, and glycation end product formation

SCFA (Short Chain Fatty Acids)

Balance microbiota: skin commensal bacteria are promoted, pathogens selectively inhibited.

Immune regulation: regulate immune cell function

4. HOW MICROBIOTA ACTIVATE GENE EXPRESSION

For lactose sensitivity induced acne

100%metabolites

Microbiota inoculation

Pomegranate

- Pomegranate fruits are left to decompose under the pomegranate plant to enrich the microbiota of the pomegranate

- Discovery of a specific bacteria strain on the pomegranate fruit which is used to ferment the whole pomegranate fruit in order to obtain unique metabolites

5. Successful applications to reprogram gene expression

For lactose sensitivity induced acne

Reduction of 25% of P. acne

Increased of Bacteroides levels by 174.88%

A randomized double-blind, placebo-controlled, evaluation of the efficacy of pomegranate metabolites to modulate skin microbiota, administered orally for 4 weeks

5. Successful applications to reprogram gene expression

WHAT IS NEXT?

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HUMAN MICROBIOME ECOSYSTEM

METABOLITES BED SPRAY

• -90% nosocomial infections• +60% recovery time• -40% length of stay in hospital

Double-blind, placebo controlled study conducted on 240 patients during 6 month

PLANT MICROBIOME

• In plants, microbiomes and metabolites can stimulate the genomic and metabolic capabilities of their hosts

• Plant microbiome, the new platform for next green revolution