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Figure 1. Gut microbiota dysbiosis-associated signaling pathways in muscle wasting and heart failure. Signaling pathways involved in skeletal muscle protein synthesis include androgen/testosterone, insulin and growth factors related pathways. Testosterone binds to its androgen receptor (AR) then together enter to nucleus to activate its downstream genes associated with muscle protein synthesis. It can also directly or indirectly influence mitogen-activated protein kinases (MAPK) and mammalian target of rapamycin (mTOR) pathways to control protein synthesis. IGF-1 and insulin elicit their protein sythesis function by binding to their receptors on cell membrane. Signaling pathways invovled in skeletal muscle wasting/atrophy include myostein-mediated transformation growth factor β signaling pathway, inflammation-assocaited signaling pathways. The ceullar mechamis asscoaited with skeletal muscle wasting/atrophy include the UPS proteiolsys pathway, autophage-lysome (ALP) and apopotsis. Dysregulation of mitochondria can trigger UPS, ALP and apoptosis leading muscle wasting/astrophy. Some gut microbial metabolites (GMM) and pathogens have anti-inflammation effect, such Short-chain fatty acids (SCFAs) and Urolithin A (UroA) and thus prevent muscle degredation. A variety of GMM and pathogens can trigger myostatin-mediated SMAD2/3 signaling pathway and inflammatory signaling pathways. One potential GMM that causes muscle wasting in the elderly have not been evulatued is TMAO. Background color in pink indicates cellular events and signaling pathways associated with muscle wasting, and background color in blue indicates those related to chronic heart failure. Please see the text for detail description. Please note that several signaling pathways such as MAPK, mTOR and SMAD2/3 are also involved in heart failure. However, the ligands trigger these signaling pathways leading to heart failure are different from those activate the pathways in muscle wasting. (Created with BioRender).