Restoring Mitochondrial Function and Remodeling Gut Microbiota by Low-Molecular-Weight β-Glucan of <i>Hericium erinaceus</i> in Alcohol-Induced Gastrointestinal Injury

Excessive alcohol consumption poses significant risks for gastrointestinal injury; β-glucans from <i>Hericium erinaceus</i> are known for gastroprotective properties; however, the efficacy of its high-molecular-weight β-glucan is often limited by poor solubility and bioavailability, leaving its protective mechanisms against alcohol-induced gastroenteropathy incompletely understood. This study obtained a low-molecular-weight β-glucan (LHEP) from <i>H. erinaceus</i> and demonstrated its superior protective effects in a mouse model of ethanol-induced gastroenteropathy. LHEP significantly alleviated oxidative stress and inflammatory responses, enhanced gastroprotective factors, and preserved mucosal barrier integrity compared to its high-molecular-weight counterpart. Integrated proteomic and metabolomic analyses revealed that the core mechanism involves the rescue of alcohol-impaired mitochondrial function, as LHEP restored respiratory capacity and mitochondrial biogenesis by normalizing the expression of key mitochondrial complex proteins (e.g., SDHA, COX1, ATP6) and regulators (NRF1, TFAM), mediated through activation of the CREB/PGC-1α signaling pathway. Additionally, LHEP modulated the gut microbiota composition, notably increasing the abundance of beneficial bacteria such as <i>Lachnospiraceae_NK4A136_group</i>, thereby counteracting alcohol-induced dysbiosis and contributing to intestinal health restoration.