We have previously shown that the high molecular weight polysaccharides of Ganoderma lucidum ameliorates obesity through gut microbiota (Nature Communication 2015). In the present presentation, we show that a water extract of the medicinal mushroom Hirsutella sinensis also reduces obesity, inflammation and insulin resistance in high-fat diet (HFD)-fed mice (GUT 2018). A high molecular weight polysaccharide fraction (>300 kDa) isolated from the water extract not only lowers body weight by 50 to 70% but it also reduces intestinal permeability, metabolic endotoxemia, inflammation and insulin resistance. Horizontal fecal transfer combined with antibiotic-induced depletion of specific gut bacteria shows that the effects of H. sinensis polysaccharides are dependent on neomycin-sensitive bacteria. Gut microbiota analysis reveals that the Gram-negative bacterium Parabacteroides goldsteinii is highly reduced in the microbiota of HFD-fed mice, while this bacterium is enriched in polysaccharide-treated mice. Notably, oral administration of live, but not heat-killed, P. goldsteinii bacteria to HFD-fed mice considerably reduces weight gain and obesity-associated metabolic disorders. These results indicate that the anti-obesity, anti-inflammatory and insulin-sensitizing effects of mushroom polysaccharides are mediated by the gut microbiota and involve the newly identified probiotic P. goldsteinii. Bacterial metabolites and structure components are being identified to show the effects of anti-obsogenicity.