A nucleus accumbens-projecting prefrontal cortex circuit underlies chronic social stress-induced depression-like behaviors.

Body composition represents an important aspect of physical fitness and has gained increasing attention in recent years. Exposure to high altitude might cause the body to adapt with negative energy and fluid balance that compromise body composition and physical performance. Systematic review and meta-analysis studies have reported significant reductions in body weight, body fat mass (BFM), fat free mass (FFM), and lean body mass (LBM) of individuals exposed to high altitude, and these components play distinct roles in the weight loss caused by the plateau environment [, ]. Furthermore, it has been observed at high altitude that the decline of FFM, total body water (TBW), and ECW might be related to the severity of acute mountain sickness (AMS), and fatigue was the AMS relevant symptom which was closely related to the decline of FFM, TBW, intracellular water (ICW) and extracellular water (ECW) []. In the healthy indigenous populations living on the Qinghai-Tibet Plateau, protein mass, bone mass, fat mass and body water values decrease with increasing altitude []. Additionally, exposure to high-altitude hypobaric environment can lead to serious loss of muscle mass, which results in skeletal muscle trophy. Muscle loss and decreased protein reserves likely contribute to the decreased physical performance and the increased infection rate and slow wound healing reported with chronic hypoxic exposure. Therefore, it is of great significance to investigate the changes of body composition and physiological and environmental factors associated with high-altitude exposure. Body composition changes induced by high-altitude exposure are not only regulated by direct physiological adaptations to hypoxia but also potentially modulated by gut microbiota, a key factor involved in human metabolic and immune homeostasis. Notably, gut microbiota is also significantly influenced by altitude, although the dynamics of gut microbiota in relation to altitude remains undisclosed. The roles played by the gut microbiota in human health have been increasingly recognized, including the gut-muscle axis between the gut microbiome and skeletal muscles []. It has been found that the gut microbiota and its metabolites impact the muscles in various ways by influencing nutrient absorption, immune inflammation, and energy metabolism. Our previous study observed that curcumin supplementation modulated gut microbiota by increasing the abundance of butyrate-producing bacteria including , , and to accelerate high-altitude acclimatization []. Gut butyrate is considered to attribute to an increase in LBM and/or FFM and a reduction in BFM []. In addition, butyrate derivative b-hydroxy-b methyl butyrate has been demonstrated that enhances the synthesis of muscle proteins, reduces the breakdown of muscle proteins and improves the stability of muscle membranes, resulting in improvement of muscle quality []. Given the close association between gut microbiota, body composition, and high-altitude adaptation, and the known regulatory effects of curcumin on gut microbiota, curcumin may further exert a protective role in mitigating high-altitude-induced adverse changes in body composition by modulating the gut-muscle axis. Previous studies have clearly shown that chronic hypobaric hypoxia induced muscle atrophy results in decreased physical performance at high altitude []. Prolonged and severe hypoxia menaces human function and survival, and also associated with profound loss of muscle mass which results into a debilitating critical illness of skeletal muscle atrophy []. Curcumin has a significant protective effect on relieving exercise fatigue and skeletal muscle injury [, ]. Curcuminoid degradants supplementation effectively promoted protein synthesis and inhibit degradation in muscle tissue by activating the PI3K/Akt/mTOR pathway, potentially through modulation of gut microbiota []. Recent clinical trials reported curcumin show significant effects on improve body composition by decreasing fat mass or inhibiting FFM loss []. Furthermore, curcumin administration significantly enhanced muscle mass under hypobaric hypoxia resulting in improved physical performance of the rats at high altitude []. Despite these promising findings, the specific mechanism by which curcumin regulates body composition in high-altitude environments, particularly its interplay with gut microbiota and the gut-muscle axis-remains unclear, and limited studies have directly investigated the effects of curcumin on body composition among populations exposed to high-altitude environments. In the present study, body composition and gut microbiota were evaluated from the plains to the plateau for male Han population, and the changes of them were assessed during high-altitude exposure. This study also investigated the potential role of gut microbiota on the changes of body composition induced by high-altitude exposure.