Deciphering natural alkaline water-induced human molecular homeostatic regulation via non-invasive sweat metabolic profiling

Natural alkaline water, a weakly alkaline NaHCO 3 ‐enriched solution, has been postulated to modulate systemic metabolic homeostasis, but its clinical metabolic effects remain poorly characterized due to the scarcity of non-invasive, longitudinal molecular evidence. Conventional flexible microneedles for sweat analysis are limited to single‐analyte detection, failing to meet the need for simultaneous profiling of multiple biomarkers required to assess systemic homeostasis. To address these challenges, we engineered a hierarchical metal‐carbide (MXene)‐based flexible microneedle array integrated with high‐performance mass spectrometry, establishing a non‐invasive, high‐throughput sweat metabolic profiling platform. Here, we show that the hierarchical architecture, featuring a petal‐like AgNWs@MXene heterostructure, creates synergistic hotspots that enhance laser desorption/ionization mass spectrometry (LDI‐MS) signal intensity by more than twofold compared with pristine MXene, allowing robust detection of 77 ± 8 metabolic features from a single sweat‐patch sample. In a cohort study (n = 107), this platform enabled simultaneous dynamic monitoring of key metabolic features associated with uric acid, lactate, and glutamine (p < 0.001). Overall, this work reveals the regulatory effects of natural alkaline water on metabolic homeostasis and provides a scalable, high‐throughput strategy for non‐invasive multi‐feature sweat metabolic profiling.