High-altitude exposure, characterized by hypobaric hypoxia, cold, and intense radiation, profoundly remodels the gut microbiota, triggering a cascade of physiological and pathological changes that extend far beyond the gastrointestinal tract. As millions travel to or reside in regions above 2500 meters, understanding this gut-centric axis has become critical for managing health risks. Hypoxia disrupts the delicate balance of the gut ecosystem, leading to dysbiosis, impaired barrier function, and increased intestinal permeability. This allows bacterial translocation and systemic inflammation, which underpin conditions like acute and chronic mountain sickness. Crucially, the gut microbiome acts as a dynamic environmental sensor; its altered production of metabolites—particularly short-chain fatty acids (SCFAs) and bile acids—directly influences host energy metabolism, immune responses, and acclimatization capacity. These changes are increasingly implicated in a spectrum of diseases, from metabolic disorders to colorectal cancer, positioning the gut as a central mediator of high-altitude health. This review synthesizes evidence from human and animal studies to elucidate how high-altitude stress reshapes the microbial landscape, explores the mechanisms linking microbiota to disease, and evaluates emerging microbiome-based interventions for promoting resilience.

The ERASur (Evaluation of Resection or Ablation for Limited Metastatic Colorectal Cancer) clinical trial has reached a major enrollment milestone, with more than one-third of its targeted patients now accrued, signaling strong momentum for this national study. ERASur (Alliance A022101) is investigating whether adding total ablative therapy—including ablative radiation, surgery, or thermal ablation of all metastatic sites—to standard chemotherapy can improve overall survival compared with chemotherapy alone in patients with newly diagnosed, limited metastatic colorectal cancer.

Colorectal cancer (CRC) is one of the most prevalent and lethal malignancies globally, with long-term survival heavily hindered by tumor recurrence, metastasis, and therapy resistance driven by a subpopulation of cancer stem cells (CSCs). While immune checkpoint blockade has revolutionized cancer treatment, its efficacy as a monotherapy in CRC remains limited, largely due to CSC-mediated immune evasion and adaptive resistance.