Molecular Interactions between Hsm H1 Polysaccharides, the Parabacteroides Goldsteinii and the Obese Animal Hosts

Novel anti-obesity measures that are safe, effective and available are urgently needed to combat the growing epidemics of obesity, metabolic syndromes and related diseases. Our previous studies indicate the water extract of the medicinal mushroom Hirsutella sinensis mycelium (HSM) reduces obesity, inflammation and insulin resistance in high-fat diet (HFD)-fed mice. Further studies indicate the high molecular weight polysaccharide fraction H1 (＞300 kDa.) separated from the water extract not only redued body weight by 50 to 70%, but also reduces intestinal permeability, metabolic endotoxemia, inflammation and insulin resistance. Horizontal fecal microbiota transfer combined with antibiotic-induced depletion of specific gut bacteria shows that the effects of HSM-H1 are dependent on a unique neomycin-sensitive bacterium Parabacrteroides goldsteinii (Gut, in revision). The selective gut microbial community associated with HSM-H1 and P. goldsteinii are correlated with different obesity traits, provoking us to examine detailed interplay between gut microbiome-biosynthetic gene clusters-metabolites in shaping host immune and metabolism. In this joint research proposal, we integrate cross-sectional research institutes comprising Microbiota Research Center Chang Gung University-Academia Sinica-Taipei Medical University to utilize functional multi-omics platforms, advanced structure moiety analysis and microbiological engineering in order to systemically and precisely explore the interaction network of HSM-H1-P. goldsteinii-gut microbiome-metabolites in counteracting obesity and relevant complications. The research proposal will be subdivided into six directions and stages: (1) Establishment of functional multi-omics platforms to systemically explore gut microbiome-host pathways-metabolites interaction network modulated by HSM-H1 and P. goldsteinii, (2) Elucidation of structural functional moiety of HSM-H1 and microbiome biosynthetic gene clusters underlying the anti-obesogenic favorable microbiota-metabolites network by HSM-H1 and P. glodsteinii, (3) Identification of functional chemical metabolites counteracting obesity and metabolic disorders, (4) Identification of key immune, biochemistry and metabolim pathways in intestine, liver and adipose tissue mediating the anti-obesogenic effects of HSM-H1 and P. goldsteinii and related metabolites. (5) Development of next-generation of prebiotics, probiotics and bioactive components to treat obesity and related complications. This grant proposal will shed light on the anti-obesogenic mechanism of HSM and P. goldsteinii. More importantly, the new gut microbiome bacterial species and bioactive components and metabolites will be developed as new generation of probiotics, prebiotics and compounds to modulate heathy microbiota, and prevent and treat obese individual in the future.

Project ID:PC10702-0701
External Project ID:MOST107-2321-B182-002