Ganoderma lucidum reduces obesity in mice by modulating the composition of the gut microbiota

Obesity is associated with low-grade chronic inflammation and intestinal dysbiosis. Ganoderma lucidum is a medicinal mushroom used in traditional Chinese medicine with putative anti-diabetic effects. Here, we show that a water extract of Ganoderma lucidum mycelium (WEGL) reduces body weight, inflammation and insulin resistance in mice fed a high-fat diet (HFD). Our data indicate that WEGL not only reverses HFD-induced gut dysbiosis-as indicated by the decreased Firmicutes-to-Bacteroidetes ratios and endotoxin-bearing Proteobacteria levels-but also maintains intestinal barrier integrity and reduces metabolic endotoxemia. The anti-obesity and microbiota-modulating effects are transmissible via horizontal faeces transfer from WEGL-treated mice to HFD-fed mice. We further show that high molecular weight polysaccharides (>300 kDa) isolated from the WEGL extract produce similar anti-obesity and microbiota-modulating effects. Our results indicate that Ganoderma lucidum and its high molecular weight polysaccharides may be used as prebiotic agents to prevent gut dysbiosis and obesity-related metabolic disorders in obese individuals. 

Traditional Chinese Medicine has a long history in Asian countries dating back several thousands of years. One class of traditional remedies commonly in use consists of medicinal mushrooms such as Ophiocordyceps sinensis, Antrodia cinnamomea and Agaricus blazei Murrill, which contain a wide range of immuno-modulatory and bioactive compounds. One of the most intriguing medicinal mushrooms is the Basidiomycete fungus Ganoderma lucidum, which has been used for centuries to promote health and longevity. Previous studies have shown that triterpenes and polysaccharides isolated from Ganoderma lucidum inhibit adipocyte differentiation and produce hypoglycaemia effects in diabetic mice. In addition, proteoglycans isolated from Ganoderma lucidum fruiting bodies induce antidiabetic, antihyperlipidemic and antioxidant activities. However, it remained unknown whether Ganoderma lucidum produces any effect on body weight and obesity-related disorders.

Obesity is defined as a disease condition associated with numerous health problems and a reduced life expectancy. Growing evidence indicates that obesity is closely linked with chronic, low-grade inflammation, which can lead to insulin resistance, type 2 diabetes, fatty liver disease, cardiovascular disease, obstructive sleep apnoea and cancer. The high prevalence of obesity is currently a major threat to public health, with ~500 million obese people and 1.4 billion overweight individuals worldwide. Prevention of obesity thus represents a major challenge for modern societies.

A recent study indicates that changes in the composition of the gut microbiota are associated with the development of obesity and its associated metabolic disorders. The gut microbiota comprises trillions of bacteria that contribute to nutrient acquisition and energy regulation. An increased ratio of the major phyla Firmicutes/Bacteroidetes and changes in several bacterial species can promote the development of obesity in both dietary and genetic models of obesity in mice. Other studies in obese animals suggest that obesity-induced gut dysbiosis caused by either environmental or genetic factors impairs intestinal integrity. This process leads to the release of the endotoxin lipopolysaccaride (LPS) from intestinal Gram-negative bacteria into the bloodstream, in turn, leading to metabolic inflammation and insulin resistance in obese mice due to stimulation of Toll-like receptor 4 (TLR4)-mediated inflammation. Moreover, chronic injection of LPS in mice leads to mild obesity and insulin resistance, highlighting a possible role for microbiota-derived LPS in obesity-induced inflammation.

A number of treatments, including antibiotics and prebiotics, are being evaluated for the management of obesity and its related metabolic disorders. For example, antibiotic treatment alters the gut microbiota, reduces blood endotoxemia and improves glucose tolerance in mice lacking the leptin gene (ob/ob mice) or in mice fed with a HFD. In addition, prebiotics are non-digestible, fermentable carbohydrates and fibres, which reduce body weight and exert anti-inflammatory effects mainly by enhancing the growth of specific beneficial bacteria found in the gut. Prebiotics not only alter the intestinal microbiota but also improve intestinal tight junction integrity and decrease blood endotoxemia caused by LPS. Prebiotics may, therefore, protect animals against obesity-induced inflammation.

In the present study, we examined whether a water extract of Ganoderma lucidum mycelium (WEGL) can decrease obesity in HFD-fed mice. Our results indicate that WEGL reduces obesity and inflammation in the treated mice. These effects are transmissible to HFD-fed mice through horizontal faeces transplantation, indicating that the effects of WEGL involve the gut microbiota. Characterization of WEGL showed that polysaccharides of molecular weight >300 kDa exerted similar ameliorative effects as WEGL. These results implied that the high molecular weight polysaccharides may be the active components of WEGL. Our data thus demonstrate that WEGL represents a potential prebiotic agent that may be used for the treatment of obesity and its complications.