The gut microbiome exerts a fundamental role in host physiology. Extrinsic factors such as lifestyle and diet are widely recognized as the main drivers of gut microbiota composition [1, 2]. While drinking water is among the food items consumed in the largest amount, little is known about its potential impact on gut microbiota structures [3-5]. Objective: We explored the associations between plain drinking water source and gut microbiota compositions in a large microbiota-based cohort. Methods: Participants in the American Gut Project database provided fecal samples and completed health, lifestyle, and food records which included plain drinking water source (bottled, tap, filtered, or well water). Associations between drinking water source and gut microbiota were evaluated using models adjusted for anthropometric, diet, and lifestyle factors in 3,413 individuals [6]. Index of intra-individual fecal microbial diversity, inter-individual differences in composition, and taxa abundance were estimated by 16S rRNA sequencing. Results: The type of drinking water was associated with fecal microbiota composition. Drinking water source ranked among the key contributing factor explaining the gut microbiota variation both in alpha and beta diversity analyses, with effect sizes comparable to that of alcohol or diet type [6] (Fig. 1). Subjects drinking different sources of water had differences in gut microbiota signatures, as revealed by beta diversity analyses (p < 0.05; Bray-Curtis dissimilarity, Weighted UniFrac distance) [6]. Subjects drinking mostly well water also had higher fecal alpha diversity than the other groups (p < 0.05; Faith’s PD, Observed OTUs) [6]. Taxonomic differences were found in well water drinkers, with clinically important taxa, such as Bacteroides, Odoribacter, and Streptococcus being depleted and Dorea being increased as compared to the other groups [6]. Conclusions: Our results reveal that drinking water may be an important factor in shaping the gut microbiome. Future research investigating the gut microbiota in relation to environmental factors may benefit from integrating drinking water source as a covariate in the analyses. CLICK TO REVIEW