ganoderm lucidum reduces obesity in mice by modulating the composition of gut microbiota (nafisa...

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Nafisa Nawal Islam Dept. of Genetic Engineering and Biotechnology University of Dhaka

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Page 1: Ganoderm lucidum reduces obesity in mice by modulating the composition of gut microbiota (Nafisa Nawal Islam)

Nafisa Nawal IslamDept. of Genetic Engineering and Biotechnology

University of Dhaka

Page 2: Ganoderm lucidum reduces obesity in mice by modulating the composition of gut microbiota (Nafisa Nawal Islam)

Introduction• A medicinal mushroom • Used in traditional Chinese medicine to promote health and longevity • Putative anti-diabetic effects• Previous studies

- triterpenes and polysaccharides isolated from this fungus inhibit adipocyte differentiation and lower serum glucose on type 2 diabetes mellitus mice- proteoglycans isolated from its fruiting bodies induce

antidiabetic, antihyperlipidemic and antioxidant activities. • The effects on gut microbiota, inflammation and obesity-related

disorders remained unknown.

Ganoderma lucidum

Page 3: Ganoderm lucidum reduces obesity in mice by modulating the composition of gut microbiota (Nafisa Nawal Islam)

• A disease condition associated with numerous health problems and a reduced life expectancy.

• Closely linked with intestinal dysbiosis and chronic inflammation, which can lead to –

- insulin resistance - type 2 diabetes

- fatty liver disease - cardiovascular disease - obstructive sleep apnea and - cancer

• The high prevalence is currently a major threat to public health, with ~ 500 million obese people and

1.4 billion overweight individuals worldwide.

Obesity

Page 4: Ganoderm lucidum reduces obesity in mice by modulating the composition of gut microbiota (Nafisa Nawal Islam)

• To determine the effects of a water extract of G. lucidum (WEGL) on obesity, inflammation and insulin resistance in HFD-fed mice.

Objective

Page 5: Ganoderm lucidum reduces obesity in mice by modulating the composition of gut microbiota (Nafisa Nawal Islam)

MethodsMurine strain

(C57BL/6NCrl Bltw)Processing of the water extract

G. lucidum (WEGL)

Determination of energy and fat in feces

qRT-PCR

Biochemical analysis

Fecal transplantation

Oil red O staining

Oral glucose tolerance test

Cytokine measurements

Morphometry analysis of epididymal adipose tissues

Determination of bacteria by quantitative real-time PCR

Gut microbiota analysis

Statistical analysis

Western blotting

Page 6: Ganoderm lucidum reduces obesity in mice by modulating the composition of gut microbiota (Nafisa Nawal Islam)

Results: WEGL reduced body weight and fat accumulation in HFD-fed mice

Fig 1 a-d

Page 7: Ganoderm lucidum reduces obesity in mice by modulating the composition of gut microbiota (Nafisa Nawal Islam)

Results: Obesity and fat accumulation were reversed by fecal transplantation from

WEGL-treated mice to HFD-fed mice

Fig 5 a-d

Page 8: Ganoderm lucidum reduces obesity in mice by modulating the composition of gut microbiota (Nafisa Nawal Islam)

Results: WEGL reduced pro-inflammatory cytokine expression in liver and adipose

tissues of HFD-fed mice

Fig 2 a-d , 6a

Following fecal transplantation

Page 9: Ganoderm lucidum reduces obesity in mice by modulating the composition of gut microbiota (Nafisa Nawal Islam)

Results: WEGL reduced serum LPS and TLR4- related signaling pathways in HFD mice

Fig 3 a-c

Page 10: Ganoderm lucidum reduces obesity in mice by modulating the composition of gut microbiota (Nafisa Nawal Islam)

Results: WEGL may improve intestinal integrity in HFD-fed mice

Following fecal transplantation

Fig: 6 e-f, Sup. 8

Page 11: Ganoderm lucidum reduces obesity in mice by modulating the composition of gut microbiota (Nafisa Nawal Islam)

Results: WEGL altered HFD-induced gut dysbiosis and WEGL fecal transplants modulated gut

microbiota composition

Fig 4c, 7 c, sup. 9

Page 12: Ganoderm lucidum reduces obesity in mice by modulating the composition of gut microbiota (Nafisa Nawal Islam)

Fig 8 a-e

WEGL high molecular weight polysaccharides reduce body weight and fat accumulation in HFD-fed mice

Page 13: Ganoderm lucidum reduces obesity in mice by modulating the composition of gut microbiota (Nafisa Nawal Islam)

• As SCFAs are produced from fermentation of polysaccharides and some other prebiotics by gut bacteria (i.e., Bacteroides spp.) and the percentage of Bacteroides was enhanced by 8% WEGL treatment in HFD mice, it is possible that the amount of SCFAs may also increase.

• It remains to be determined - whether SCFAs are affected or not by WEGL and - whether these molecules contribute to the anti-inflammatory

effect of WEGL.

Scope for Future Research

Page 14: Ganoderm lucidum reduces obesity in mice by modulating the composition of gut microbiota (Nafisa Nawal Islam)

Summary• WEGL reduces dietary-induced obesity, body weight, fat

accumulation as well as chronic inflammation in the liver and adipose tissues of HFD-fed mice.

• WEGL alters microbiota composition in HFD-fed mice.• WEGL may improve intestinal integrity in HFD-fed mice• WEGL reduces serum LPS (therefore, endotoxemia) and TLR4-related

signaling pathways in HFD mice.

• WEGL fecal transplants reduce pro-inflammatory cytokines, obesity and fat accumulation; modulate gut microbiota composition and increase intestinal tight junction expression in HFD-mice.

• Both WEGL and its high Mw polysaccharides (>300 kDa) may be used as prebiotics to reduce gut dysbiosis, chronic inflammation and obesity-related metabolic disorders in obese individuals.

Page 15: Ganoderm lucidum reduces obesity in mice by modulating the composition of gut microbiota (Nafisa Nawal Islam)

Thank You