The terms “inflammatome” (holistic inflammation networks) and “inflammatomics” (a novel omics field) were proposed to decode dysbiosis-driven chronic inflammation and its disease links. Inflammatomics explores microbiota–immune crosstalk, particularly innate immune interactions, revealing how dysregulated microbial communities trigger chronic inflammation underlying disorders like inflammatory bowel disease, metabolic diseases, and neurodegeneration. This discipline transcends traditional inflammation paradigms by dissecting molecular pathways connecting dysbiosis to systemic inflammation, enabling early detection and precision interventions. It integrates evolutionary perspectives on host–microbe interactions, emphasizing the human body as a stress-sensitive “organ”. Challenges include standardizing inflammatome profiling, translating findings into clinical tools, and advancing multiomics technologies. By bridging microbial ecology, immunology, and systems medicine, inflammatomics holds a transformative potential to shift health care from reactive treatment to proactive, personalized prevention, targeting disease origins shaped by chronic inflammatome dysregulation.

High altitudes are one type of extreme environment characterized by hypobaric hypoxia, extreme cold, strong ultraviolet radiation, and low energy availabilty that present tremendous challenges to human and wildlife inhabiting these environs. These extreme environments serve as a unique natural laboratory for delving into the impact of selective pressures on species variation and adaptation. This narrative review compiles the latest research on high-altitude adaptation, with a specific focus on the crucial role of gut microbiota in this process. Evidence indicates that gut microbiota significantly impacts an organism's ability to adapt to high-altitude conditions by adjusting its composition, and hence impacting its function and ability to release microbial metabolites. We explore the link between gut microbiota and high-altitude environments, the microbial signatures, and their effects on adaptation, as well as the potential for targeted modulation of gut microbiota to enhance acclimatization to high altitudes. By examining the interaction between microbiota and host adaptation, this review aims to promote further mechanistic studies and support strategies for improving high-altitude acclimatization through gut microbiota modulation.