G. lucidum has anti-diabetic properties and has been used in conventional Chinese medicine. In mice following a high-fat diet (HFD), administration of water concentrate of G. lucidum mycelium (WEGL) reduced bodyweight, irritation, and insulin obstruction ^[37][40]. Along with reducing HFD-induced gut dysbiosis (as seen by lower Firmicutes-to-Bacteroidetes ratio and increased abundance of endotoxin producing proteobacteria), WEGL administration alleviates metabolic endotoxemia ^[38][41]. The weight-reducing and microbiota-regulatory effects can be passed on from WEGL-treated mice to HFD-administered ones by faecal exchange. In addition, high molecular weight polysaccharides (>300 kDa) present in the WEGL have shown anti-obesity and microbiota-regulating properties. G. lucidum and its high atomic weight polysaccharides can be used as prebiotics in overweight individuals to treat gut dysbiosis and metabolic disorders ^[37][40].

Pleurotus citrinopileatus is another potential source of bioactive mixtures and therefore, can be used in anti-obesity treatment ^[39][40][41][42,43,44]. One study assessed the anti-obesity and hypolipidemic effects of P. citrinopileatus water extract (PWE) in high-fat diet-induced obese (DIO) C57BL/6J mice. They were administered with PWE in gradually increasing concentrations (400 to 800 mg/kg of body weight, independently) along with a high-fat diet for 12 weeks ^[42][45]. Within 12 weeks, the weight gain, fat build-up, and food utilisation of DIO mice were drastically reduced in mice administered with PWE. PWE also decreased fatty acid, cholesterol, and low-density lipoprotein levels in the blood, simultaneously increasing the activity of aspartate transaminase, non-esterified unsaturated fats, creatinine levels, and high-density lipoprotein levels. Moreover, PWE also enhanced glucose tolerance in HFD mice and showed a high potential for managing obesity and other metabolic diseases ^[42][45].

2. Effect of Mushroom Consumption on Gut Microbiota

The beneficial effects of edible mushrooms and their polysaccharides on the gut microbiota, which are closely linked with the body weight, are currently a major focus in the field. A study in mice reported that administering the concentrates of G. lucidum reduced the body weight by modifying the microbiota, suggesting that mushrooms might be used as a potential probiotic for weight reduction ^[37][40]. The effect of HFD on gut microflora is more pronounced than the effect on energy balance. HFD-induced changes in the gut microbiota have been shown to reduce Firmicutes to Bacteroides ratio, which is related to high energy accumulation, fat storage, and intestinal homeostasis over time. Through the provocative rundown and platelet markers, obesity negatively affects the immunity. Several studies have examined the anti-obesity effects of polysaccharides from various mushrooms in vitro and in vivo ^[43][44][45][87,103,111]. Polysaccharides from Coriolus versicolor initiated an immunomodulatory effect in mice splenocytes through the MAPK-NF-B pathway ^[46][112]. A polysaccharide from Tremella fuciformis hindered the differentiation of 3T3-L1 adipocytes by reducing the mRNA expression, suggesting that this polysaccharide could be a potential prebiotic for obesity ^[47][74]. Cure of adipocytes with G. lucidum diminished adipogenic record factor articulation, which increases glucose and lipid transport and activates AMPK pathway, suggesting its potential as an anti-obesity drug ^[48][113]. Being overweight could cause several other illnesses and result in a reduced lifespan. A recent study suggests that changes in the gut microbiota are associated with obesity and other related metabolic syndromes ^[49][50][51][114,115,116]. The gut microbiota comprises trillions of microorganisms that perform several functions, including nutrient metabolism, maintaining the gastrointestinal cells, modulating the immune system, protecting against the invasion of pathogens, and balancing the endotoxins. The gut microbiota generate energy from food and can cause overweight and type 2 diabetes mellitus (T2DM). It has been observed that in overweight mice, the gut microbiota draws out more energy from food than lean mice ^[52][117]. In healthy people, vancomycin treatment for one week modifies the gut microbiota, which results in reduced insulin sensitivity ^[53][118]. Additionally, the transfer of gut microbiota of any lean person to an overweight person leads to the development of insulin sensitivity in the recipient. These results suggest that changes in gut microbiota could cause obesity and T2DM. In HFD animals, the levels of proteins that play a role in maintaining tight junctions of the intestine are lower than those in chow-fed animals. Administration of G. lucidum extract could recover the levels of those proteins, which resulted in the maintenance of the integrity of the intestine and prevention of the translocation of pro-inflammatory endotoxins from gut bacteria to blood (for example, lipopolysaccharides) ^[37][40]. Using a mouse obese model, it has been observed that feeding of high-fat diet for eight weeks increased the body weight, liver weight, fat accumulation, and lipid deposition in hepatocytes and adipocytes compared to the control group that were fed with chow. Supplementation with the water extract of G. lucidum reduced the weight gain and accumulation of fats in HFD mice. G. lucidum also improved glucose tolerance and insulin sensitivity. Compounds in G. lucidum that reduce obesity are high molecular weight polysaccharides (greater than 300 kDa). Fungal polysaccharides cannot be digested in the stomach or small intestine. However, the large intestine can digest them and produces short-chain fatty acids, consequently secreting GLP-1. GLP-1 and short-chain fatty acids ultimately enter the blood and affect the brain, muscles, adipose tissues, and liver. Additionally, GLP-1 reduces gastric emptying and thereby, the appetite. It also reduces the deposition of fats, resistance to insulin, and inflammation. It also upregulates the proliferation and downregulates apoptosis in β-cells ^[37][40]. This suggests that Escherichia coli in the large intestine releases proteins that enhance or aid in the production of GLP-1 and peptide YY, which increases satiety ^[44][103]. These results indicate that the water extract of G. lucidum could be a potential prebiotic agent that can be used for the treatment of obesity and related complications ^[37][40]. Button mushrooms (A. bisporus) and L. edodes contain several polysaccharides, indicating their potential to stimulate the growth of beneficial bacteria in the gut. Hirsutella sinensis is the asexual form of Ophiocordyceps sinensis. It modifies the composition of the gut microbiota and is beneficial in reducing obesity, inflammation, and diabetes in HFD mice. Table 12 presents the effects of various mushrooms on gut microbiota.

3. Mushrooms as Potential Anti-Obesity Agents

Numerous clinical studies have reported the anti-obesity effects of mushrooms. A clinical trial was conducted on 73 obese adults in which mushrooms were substituted for red meat as a part of the regular diet. At the end of one year, less energy intake, reduced body weight, low body mass index, low waist circumference, and low systolic and diastolic blood pressure was reported in the subjects on mushroom diet ^[72][136]. Few animal studies have also reported the anti-obesity effects of mushrooms. One study showed the anti-obesogenic effect of mushroom (Grifola gargal- 2%) after its administration in mice for 42 days. IThis study observed a reduction in blood glucose, triglyceride, and adipose tissue ^[73][105]. In another study, six weeks mice were divided into six groups: (1) low-fat diet control group, (2) low dose of mushroom (G. lucidum)- 100 mg/kg in the low-fat diet group, (3) high dose of mushroom (G. lucidum)- 300 mg/kg in the low-fat diet group, (4) high-fat diet control group, (5) low dose of mushroom (G. lucidum)- 100 mg/kg in the high-fat diet group, (6) high dose of mushroom (G. lucidum)- 300 mg/kg in the high-fat diet group. Mice in each group were divided into two cages, with three mice in each cage. The temperature was maintained at 25–28 °C. G. lucidum was administered once a day to each mouse for 12 weeks, and weight and food intake were monitored regularly. Weight was significantly reduced in the low-fat diet group ^[74][137].

4. Recommendations and Implications for the Future

Different clinical trials have been conducted on mushrooms in various forms and their beneficial effects on health have been analysed. They include fresh, cooked, and powdered forms. HereThin concluds manuscript reviewed in vitro and in vivo studied on the anti-obesity effects of edible mushrooms by modulating gut microflora. The findings of the clinical trials suggest that edible mushrooms can be used as alternative to vegetables; they contain several bioactive compounds and could be used as nutraceuticals. They also contain essential nutrients such as vitamins and minerals and have low sodium and cholesterol contents. Therefore, it is an excellent alternative food source for patients with hypertension. They also contain trace elements such as selenium which aids in improving human health. Therefore, edible mushrooms are potential candidates for preventing obesity and several other chronic ailments.