Smoking-Related Multi-Metal Exposure Associated with Hierarchical Gut Microbiota Alterations in Colorectal Polyp Patients

Smoking-related metal exposure involves complex mixtures, yet its combined effects on gut microbiota and colorectal polyp progression remain unclear. We constructed a multi-metal disruption index integrating urinary arsenic, cadmium, and zinc concentrations that differed significantly between smokers and non-smokers in 196 colorectal polyp patients in 2023-2024 and examined its associations with gut microbiota and colorectal polyp progression. The index showed dose-dependent increases in detection rates of Limosilactobacillus, Methylovirgula and Peptoclostridium, with the most robust association observed for Limosilactobacillus after adjusting for covariates (OR = 3.39, 95%CI: 1.49-7.76, p = 0.004). Its detection rate was broadly negatively associated with the predicted abundance of pathways such as metabolism and organismal systems. In stratified analyses, the number of pathways with decreased predicted abundance among Limosilactobacillus-positive samples increased significantly as index levels rose (low: 0/27; medium: 15/27; high: 19/27), with 10 pathways significant at both medium and high levels. This dose-dependent genus-level response was observed alongside population-level relative stability, as no significant associations were found between the index and colorectal polyp progression. This multi-Metal Index approach provides a practical framework for assessing the health effects of smoking-related multi-metal mixtures. The dose-dependent increase in Limosilactobacillus colonization, occurring together with the decreased predicted abundance of specific metabolic pathways, suggests a possible association with metal-related stress.