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Mg2+ in drinking water boosts Salmonella infection risk by rewiring gut ecology and virulence

Nature Water (2026)Cite this article

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Abstract

The mineral content in drinking water is an emerging regulator of intestinal health. While certain mineral waters are generally considered beneficial, their health effects under enteric infection conditions remain unclear. Here we show that Mg2+ in drinking water exacerbates inflammation caused by enteric pathogen Salmonella Typhimurium via two interlinked mechanisms: direct activation of its key bacterial competition machinery type VI secretion system (T6SS) and indirect amplification through inflammation-driven dysbiosis. Mg2+ depletes beneficial Akkermansia and enriches Bacteroides, elevating pro-inflammatory bile acids and arginine that enhance T6SS-mediated competitive fitness. These effects vary with host health and water sources. Our findings support the use of low-mineral water for vulnerable groups during infection risk periods, establishing Mg2+ in drinking water as a modifiable risk factor for infectious enteritis.

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Fig. 1: Impact of drinking water cationic composition on S. Tm infection kinetics and visceral colonization in C57BL/6N mice.
Fig. 2: Development of chronic enteritis in C57BL/6N mice following low-dose S. Tm infection under varying drinking water conditions.
Fig. 3: Impact of Mg2+ supplementation in drinking water on gut microbiota composition in S. Tm-infected mice.
Fig. 4: Modulation of bile acid metabolism by Mg2+ concentration in drinking water during S. Tm infection.
Fig. 5: Modulation of intestinal arginine metabolism by magnesium-enriched water during S. Tm infection.
Fig. 6: Gut microbiota-dependent enhancement of S. Tm colonization by drinking high-magnesium water (HMW).
Fig. 7: Mechanism of Mg2+ in drinking water regulating S. Tm gut colonization and infection.

Data availability

16S rRNA sequencing data are publicly accessible via NCBI SRA (BioProject, PRJNA1284006). Untargeted metabolomics data are deposited in MetaboLights (study ID MTBLS12690). All other data supporting the findings of this study are available within this article and its Supplementary Information. Source data are provided with this paper.

References

  1. Barnich, N. et al. Beneficial effects of natural mineral waters on intestinal inflammation and the mucosa-associated microbiota. Int. J. Mol. Sci. 22, 4336 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Böhmer, H., Müller, H. & Resch, K. L. Calcium supplementation with calcium-rich mineral waters: a systematic review and meta-analysis of its bioavailability. Osteoporos. Int. 11, 938–943 (2000).

    Article  PubMed  Google Scholar 

  3. Peng, H., Lu, T. T., Xiong, S., Ferrer, A. S. N. & Wang, Y. X. Calcium and magnesium in China’s public drinking water and their daily estimated average requirements. Environ. Geochem. Health 45, 3447–3464 (2023).

    Article  CAS  PubMed  Google Scholar 

  4. Willis, J. R. et al. Citizen science charts two major ‘stomatotypes’ in the oral microbiome of adolescents and reveals links with habits and drinking water composition. Microbiome 6, 218 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  5. Guo, H. et al. High-efficiency capture and recovery of anionic perfluoroalkyl substances from water using PVA/PDDA nanofibrous membranes with near-zero energy consumption. Environ. Sci. Technol. Lett. 8, 350–355 (2021).

    Article  CAS  Google Scholar 

  6. Chen, Y. et al. Protective effects of selenium nanoparticle-enriched Lactococcus lactis NZ9000 against enterotoxigenic Escherichia coli K88-induced intestinal barrier damage in mice. Appl. Environ. Microbiol. 87, e01636-21 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  7. Liu, X. et al. Mendelian randomization analyses support causal relationships between blood metabolites and the gut microbiome. Nat. Genet. 54, 52–61 (2022).

    Article  CAS  PubMed  Google Scholar 

  8. Chen, J. et al. Metasilicate-based alkaline mineral water confers diarrhea resistance in maternally separated piglets via the microbiota-gut interaction. Pharmacol. Res. 187, 106580 (2023).

    Article  CAS  PubMed  Google Scholar 

  9. Bowyer, R. C. E. et al. Associations between UK tap water and gut microbiota composition suggest the gut microbiome as a potential mediator of health differences linked to water quality. Sci. Total Environ. 739, 139697 (2020).

    Article  CAS  PubMed  Google Scholar 

  10. Vanhaecke, T., Bretin, O., Poirel, M. & Tap, J. Drinking water source and intake are associated with distinct gut microbiota signatures in US and UK populations. J. Nutr. 152, 171–182 (2022).

    Article  CAS  PubMed  Google Scholar 

  11. Wotzka, S. Y., Nguyen, B. D. & Hardt, W. D. Salmonella Typhimurium diarrhea reveals basic principles of enteropathogen infection and disease-promoted DNA exchange. Cell Host Microbe 21, 443–454 (2017).

    Article  CAS  PubMed  Google Scholar 

  12. Liou, M. J. et al. Host cells subdivide nutrient niches into discrete biogeographical microhabitats for gut microbes. Cell Host Microbe 30, 836–847 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Bratburd, J. R. et al. Gut microbial and metabolic responses to Salmonella enterica serovar Typhimurium and Candida albicans. mBio 9, 02032–18 (2018).

    Article  Google Scholar 

  14. von Strempel, A. et al. Bacteriophages targeting protective commensals impair resistance against Salmonella Typhimurium infection in gnotobiotic mice. PLoS Pathog. 19, e1011600 (2023).

    Article  Google Scholar 

  15. Cianfanelli, F. R., Monlezun, L. & Coulthurst, S. J. Aim, load, fire: the type VI secretion system, a bacterial nanoweapon. Trends Microbiol. 24, 51–62 (2016).

    Article  CAS  PubMed  Google Scholar 

  16. Sana, T. G. et al. Salmonella Typhimurium utilizes a T6SS-mediated antibacterial weapon to establish in the host gut. Proc. Natl Acad. Sci. USA 113, E5044–E5051 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Weiss, A. S. et al. In vitro interaction network of a synthetic gut bacterial community. ISME J. 16, 1095–1109 (2022).

    Article  CAS  PubMed  Google Scholar 

  18. Zhang, J. et al. SecReT6 update: a comprehensive resource of bacterial type VI secretion systems. Sci. China Life Sci. 66, 626–634 (2023).

    Article  CAS  PubMed  Google Scholar 

  19. Lories, B. et al. Biofilm bacteria use stress responses to detect and respond to competitors. Curr. Biol. 30, 1231–1244 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Lories, B., Belpaire, T. E. R., Smeets, B. & Steenackers, H. P. Competition quenching strategies reduce antibiotic tolerance in polymicrobial biofilms. npj Biofilms Microbiomes 10, 23 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Speare, L., Jackson, A. & Septer, A. N. Calcium promotes T6SS-mediated killing and aggregation between competing symbionts. Microbiol. Spectr. 10, e01397-22 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  22. Tang, M.-X. et al. Abiotic factors modulate interspecies competition mediated by the type VI secretion system effectors in Vibrio cholerae. ISME J. 16, 1765–1775 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Yang, J. et al. Xylooligosaccharides ameliorate insulin resistance by increasing Akkermansia muciniphila and improving intestinal barrier dysfunction in gestational diabetes mellitus mice. Food Funct. 15, 3122–3129 (2024).

    Article  CAS  PubMed  Google Scholar 

  24. Yoo, W. et al. Salmonella Typhimurium expansion in the inflamed murine gut is dependent on aspartate derived from ROS-mediated microbiota lysis. Cell Host Microbe 32, 887–899 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Jacobson, A. et al. A gut commensal-produced metabolite mediates colonization resistance to Salmonella infection. Cell Host Microbe 24, 296–307 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Jaeggi, T. et al. Iron fortification adversely affects the gut microbiome, increases pathogen abundance and induces intestinal inflammation in Kenyan infants. Gut 64, 731–742 (2015).

    Article  CAS  PubMed  Google Scholar 

  27. Bachmann, V. et al. Bile salts modulate the mucin-activated type VI secretion system of pandemic Vibrio cholerae. PLoS Negl. Trop. Dis. 9, e0004031 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  28. Li, S. et al. c-di-GMP inhibits the DNA binding activity of H-NS in Salmonella. Nat. Commun. 14, 7502 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Li, S. et al. Autoinducer-2 and bile salts induce c-di-GMP synthesis to repress the T3SS via a T3SS chaperone. Nat. Commun. 13, 6684 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  30. Pontes, M. H., Lee, E.-J., Choi, J. & Groisman, E. A. Salmonella promotes virulence by repressing cellulose production. Proc. Natl Acad. Sci. USA 112, 5183–5188 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Ferreira, R. M. et al. Gastric microbial community profiling reveals a dysbiotic cancer-associated microbiota. Gut 67, 226–236 (2018).

    Article  CAS  PubMed  Google Scholar 

  32. Wotzka, S. Y. et al. Escherichia coli limits Salmonella Typhimurium infections after diet shifts and fat-mediated microbiota perturbation in mice. Nat. Microbiol. 4, 2164–2174 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  33. Walker, G. T. & Raffatellu, M. Salmonella respiration turns the tables on propionate. Trends Microbiol. 30, 206–208 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Corte-Real, J. & Bohn, T. Interaction of divalent minerals with liposoluble nutrients and phytochemicals during digestion and influences on their bioavailability – a review. Food Chem. 252, 285–293 (2018).

    Article  CAS  PubMed  Google Scholar 

  35. Funabashi, M. et al. A metabolic pathway for bile acid dehydroxylation by the gut microbiome. Nature 582, 566–570 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Wu, Q. et al. Intestinal hypoxia-inducible factor 2α regulates lactate levels to shape the gut microbiome and alter thermogenesis. Cell Metab. 33, 1988–2003 (2021).

    Article  CAS  PubMed  Google Scholar 

  37. Lee, E. J., Pontes, M. H. & Groisman, E. A. A bacterial virulence protein promotes pathogenicity by inhibiting the bacterium’s own F1F0 ATP synthase. Cell 154, 146–156 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Mills, E., Petersen, E., Kulasekara, B. R. & Miller, S. I. A direct screen for c-di-GMP modulators reveals a Salmonella Typhimurium periplasmic ʟ-arginine-sensing pathway. Sci. Signal 8, ra57 (2015).

    Article  PubMed  Google Scholar 

  39. Pickard, J. M. et al. Dietary amino acids regulate Salmonella colonization via microbiota-dependent mechanisms in the mouse gut. Nat. Commun. 16, 4225 (2025).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Lopes, A. A. et al. Bile-induced biofilm formation in Bacteroides thetaiotaomicron requires magnesium efflux by an RND pump. mBio 15, e03488-23 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  41. Slipko, K. et al. Removal of extracellular free DNA and antibiotic resistance genes from water and wastewater by membranes ranging from microfiltration to reverse osmosis. Water Res. 164, 114916 (2019).

    Article  CAS  PubMed  Google Scholar 

  42. Mukherjee, A. G. et al. Elimination of microplastics from the aquatic milieu: a dream to achieve. Chemosphere 303, 135232 (2022).

    Article  CAS  PubMed  Google Scholar 

  43. Li, D. P. et al. Oral magnesium prevents acetaminophen-induced acute liver injury by modulating microbial metabolism. Cell Host Microbe 32, 48–62 (2024).

    Article  PubMed  Google Scholar 

  44. McLaughlin, P. A. et al. Inflammatory monocytes provide a niche for Salmonella expansion in the lumen of the inflamed intestine. PLoS Pathog. 15, e1007847 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Ivanov, I. I. et al. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139, 485–498 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Ten Bruggencate, S. J., Bovee-Oudenhoven, I. M., Lettink-Wissink, M. L., Katan, M. B. & Van Der Meer, R. Dietary fructo-oligosaccharides and inulin decrease resistance of rats to Salmonella: protective role of calcium. Gut 53, 530–535 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  47. Miller, A. L. et al. Nitrate is an environmental cue in the gut for Salmonella enterica serovar Typhimurium biofilm dispersal through curli repression and flagellum activation via cyclic-di-GMP signaling. mBio 13, e02886-21 (2022).

    Article  CAS  PubMed Central  Google Scholar 

  48. Crawford, R. W. et al. Very long O-antigen chains enhance fitness during Salmonella-induced colitis by increasing bile resistance. PLoS Pathog. 8, e1002918 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Liu, S. J. et al. Metabolomics and proteomics reveal blocking argininosuccinate synthetase 1 alleviates colitis in mice. Nat. Commun. 16, 6983 (2025).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Datsenko, K. A. & Wanner, B. L. One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products. Proc. Natl Acad. Sci. USA 97, 6640–6645 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Chen, S. B. et al. Colonization mediated by T6SS-ClpV disrupts host gut microbiota and enhances virulence of Salmonella enterica serovar Typhimurium. J. Agric. Food Chem. 72, 19155–19166 (2024).

    Article  CAS  PubMed  Google Scholar 

  52. Yang, L. L. et al. Oligoribonuclease mediates high adaptability of P. aeruginosa through metabolic conversion. BMC Microbiol. 24, 25 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  53. Ren, Y. et al. Majorbio Cloud: a one-stop, comprehensive bioinformatic platform for multiomics analyses. iMeta 1, e12 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Wu, M. et al. Genetic determinants of in vivo fitness and diet responsiveness in multiple human gut Bacteroides. Science 350, aac5992 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  55. Wang, X. et al. Longitudinal investigation of the swine gut microbiome from birth to market reveals stage and growth performance associated bacteria. Microbiome 7, 109 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (grant no. 51878406 to X.B.) and the Natural Science Foundation of Shanghai (grant no. 25ZR1401169 to X.B.).

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Authors and Affiliations

  1. State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China

    Tanghao Liu & Xiaohui Bai

  2. School of Life Sciences, Southern University of Science and Technology, Shenzhen, China

    Tao Dong

  3. Department of Gastroenterology, Hepatology, and Nutrition, Shanghai Children’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Ting Zhang

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  1. Tanghao Liu
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  2. Tao Dong
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  3. Ting Zhang
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  4. Xiaohui Bai
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Contributions

Conceptualization, T.L., T.D., T.Z. and X.B.; methodology, T.L.; investigation, T.L. and X.B.; writing—original draft, T.L.; writing—review and editing, T.L., T.D. and X.B.; funding acquisition, X.B.; resources, X.B.; supervision, X.B. All authors read, critically revised and approved the final paper.

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Correspondence to Xiaohui Bai.

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Nature Water thanks Vanessa Speight and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Peer reviewer reports are available.

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Liu, T., Dong, T., Zhang, T. et al. Mg2+ in drinking water boosts Salmonella infection risk by rewiring gut ecology and virulence. Nat Water (2026). https://doi.org/10.1038/s44221-026-00584-2

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