Impact of Water Disinfection Chemicals on the Human Gut Microbiome: A Review

Introduction

Our understanding of the human gut microbiome has greatly expanded in the last two decades (NIH, 2019). GDReBase now has over 514,000 papers on gut microbes and related diseases (Xu et al., 2019). Our expanded understanding leads us to believe that the gut microbiota is important to human health and disease and plays a role in immune function and behavior (Cresci & Bowden, 2015). Gut dysbiosis and loss of bacterial diversity may lead to a host of chronic diseases including rheumatoid arthritis, type 1 diabetes, eczema, asthma, inflammatory bowel disease, cardiovascular disease development, type 2 diabetes, non-alcoholic fatty liver disease, chronic kidney disease, and mental health disorders (Vijay & Valdes, 2022). In addition, antimicrobial agents are known to reduce and eliminate commensal flora (Bhalodi et al., 2019), and water disinfection chemicals and their byproducts may be contributing to the loss of gut bacterial diversity. Correlation studies show that drinking water plays an important role in the composition of the gut microbiome (Vanhaecke et al., 2022), and that drinking water may be an underappreciated determinant of microbiome acquisition in infants and children (Baumann-Dudenhoeffer et al., 2018). In rodent studies, drinking chlorinated water significantly altered the gut microbiome causing weight gain (Nathan, 2019) and colorectal tumors (Sasada et al,. 2015), and consuming low-concentrations of water disinfection chemical byproducts perturbed the health-associated gut microbiome (Xue et al., 2020), and disturbed the balance between pro-inflammatory and anti-inflammatory immune response by gut microbiome alterationes (Wang et al., 2022). Despite the current knowledge from rodent and correlation studies, there have been only been two small (n=130 & n=197) human clinical trials concerning the effect of water disinfection chemicals or byproducts on the human gut microbiome, but it should be noted that the chlorine levels were very low at only 0.37 to 1.1  ppm in these studies (Nadimpalli et al., 2022)(Parkin et al., 2024). Climate change and warmer temperatures may also play a role in chlorine levels and ensuing dysbiosis.  As the ambient temperature rises, bacterial counts rise while the half-life of chlorine decreases (Garcia-Avila et al., 2020) so more chlorine is added to drinking water resources.  Not surprisingly, acute gastroenteritis hospitalizations increase dramatically as the temperature rises (Ghazani et al., 2018).  Because the gut microbiome is important to human health and gut dysbiosis may be caused by the antimicrobial effect of water disinfection chemicals and their byproducts, additional research is desperately needed. The purpose of this research review is to find ways to quantify the contribution of water disinfection chemicals and their byproducts to the loss of gut bacteria species and the ensuing gut dysbiosis.

Gut Dysbiosis and Disease

Healthy gut microbiota composition with no overt signs of disease includes the dominance of Bacteroidetes and Firmicutes bacterial species with the presence of Proteobacteria and Actinobacteria species in lesser amounts (Petersen & Round, 2014) and a higher relative abundance of butyrate-producing bacteria. Gut dysbiosis is indicated by perturbations to the structure of complex commensal microbial commensal communities and loss of dominant species, with observed changes in microbial composition and signs of associated diseases. There is a strong association between gut dysbiosis and chronic diseases including inflammatory autoimmune disorders, gut inflammation-related disorders, cardiometabolic diseases, mental health disorders, and adverse neurological conditions (Vijay & Valdes, 2021). Gut dysbiosis with a disturbed balance of microbial species will create pro-inflammatory immune responses and is the driver of systemic autoimmune and bowel diseases including colorectal cancer (Mousa et al., 2022). Gut dysbiosis contributes to the development of insulin resistance and obesity (Virtue et al., 2019) and there is a causal effect of the gut microbiome on metabolic traits including insulin resistance, obesity, and other metabolic diseases (Sanna et al., 2019).

Antimicrobial Effects on the Gut Microbiome

Antimicrobial agents are generally not selective in what they eradicate. As Mondhe et al. (2014) declare in research concerning utilizing species-selective antimicrobials, “Broad-spectrum antibiotics allow empirical usage for the rapid treatment of fulminate microbial infections, but have been shown to disrupt the microbiome, which can result in colonization of pathogenic microbes.” Research has consistently confirmed that antimicrobials damage the gut microbiome, leaving the host susceptible to opportunistic pathogens, and requiring substantial recovery time (Bhalodi et al., 2019). Pesticides are another antimicrobial agent that may drastically alter the composition of the gut microbiota as they are toxic to non-target microbial species and lead to an imbalance of the microbiota composition, which can cause disease in the human host (Sharma et al., 2023).  Chlorine is also an antimicrobial agent and is widely used in drinking water disinfection.  Rodent studies indicate that water chlorination significantly alters the gut microbiome, causing weight gain (Nathan, 2019), exacerbates the growth of colorectal tumors (Sasada et al., 2015), and disturbs the balance between pro-inflammatory and anti-inflammatory immune response in rodents (Xue et al., 2020).

Drinking Water and Its Role in the Gut Microbiome Composition

There has not been significant research concerning the role of drinking water on the human gut microbiome composition. A correlation study was conducted utilizing data from the American Gut Project that associated drinking water sources with microbiota composition (Vanhaecke et al., 2022).  Drinking water sources were found to be a key contributing factor in gut microbial diversity. Study subjects who drank mostly well water had higher commensal flora diversity and lower pathogenic bacteria signatures. Baumann-Dudenhoeffer et al. (2018) analyzed the fecal metagenomes of 60 infants and found that drinking water sources played a large role in the microbiome signatures, and that there was a vast difference between the composition of the infant gut microbiome depending on the drinking water source. Another study analyzed the gut bacterial composition of people drinking spring mineral water in Bama, China, which found that they could reshape the gut composition of travelers and residents with drinking water alone (Chen et al., 2018).  Dias et al. (2018) exposed mice to various water sources and found that drinking water affects the composition of the gut microbiome.  Since it is certain that water disinfection chemicals impact microbial communities in drinking water (Dai et al., 2020), it is reasonable to conclude that disinfected drinking water would also play a role in shaping the human gut microbial communities.  Other researchers recently asserted that drinking water source, microbiota composition, and gut health are interlinked and understudied (Maghaddam, Abkar & Fowler, 2024).

Climate Change May Exacerbate Gut Dysbiosis

Climate change and increasing ambient temperatures in summer months affect water temperatures, which may also increase the incidence of gut dysbiosis. There are strong correlations between temperature increases and bacterial gastrointestinal infections, acute gastroenteritis, and related hospitalizations (Ghazani et al., 2018).  Though bacterial counts in foods and water increase as temperature rises, the effectiveness of chlorination decreases as chlorine decay increases with temperature (Garcia-Avila et al., 2020), and thus more disinfection chemicals are required to keep bacterial pathogens low. Individuals consume more water as temperatures rise, and coupled with additional chlorination due to increasing temperatures, gut dysbiosis may be exacerbated, leaving the human host vulnerable to opportunistic pathogens. 

Additional Factors Affecting Gut Dysbiosis

Beyond antimicrobial agents that play a role in gut dysbiosis, there are other factors that may affect gut dysbiosis and ought to be considered when designing future studies. The National Institute of Health’s 10-year review of the Human Microbiome Project (NIH, 2019) indicated that dietary fiber appears to play a significant role in microbiota diversity and that low fiber diets and diet composition play a role in gut dysbiosis.  Alcohol consumption and especially alcohol use disorder has been shown to significantly alter the gut microbiota, often resulting in severe dysbiosis including an almost complete loss of the intestinal mucosal barrier, increased intestinal permeability, and may cause psychological disorders as a result (Day & Kumamoto, 2022). Stress can play a major role in gut dysbiosis.  Gao et al. (2022) reported gut dysbiosis caused by stress in COVID-19 frontline healthcare workers by analyzing fecal samples of stressed staff in a hospital in Wuhan, China. The frontline healthcare worker study was one of the few human studies concerning stress and gut dysbiosis due to ethical considerations, but stress induced gut dysbiosis has been well established in animal studies (Bailey et al., 2011). Non-antibiotic prescriptions and non-prescription medications may also induce gut dysbiosis. Proton pump inhibitors, antipsychotic medications, non-steroidal anti-inflammatory drugs, metformin, and antipsychotics are associated with changes in the overall architecture of the intestinal microbiota (Le Bastard et al., 2018). Ambient temperature and climate change may also play a role in gut dysbiosis, but as Ghazani et al. (2018) points out, “A greater in-depth understanding of the association between climate and GI infections is needed.”  Researchers ought to take into consideration these additional factors that play an important role in gut dysbiosis.

Conclusion

The purpose of this literature review is to examine our current knowledge of gut dysbiosis and disease, the agents that play a role in gut dysbiosis, and the need for future study in understudied areas, especially the role of water disinfection chemicals on the human gut microbial composition.  Given the dramatic increases in the incidence of autoimmune diseases, obesity, and colorectal cancers and the strong association between gut dysbiosis and these health conditions, further exploration of the role of antimicrobial agents, especially in drinking water resources, and its role in these diseases is necessary.  The review of the literature is certain that gut microbiome composition is an important determinant in human health and disease. However, it is uncertain as to whether water disinfection chemicals, especially chlorination, or perhaps its byproducts contribute to gut bacterial diversity loss and contribute to gut dysbiosis and associated diseases. Though we have rodent studies to quantify the loss of bacterial diversity from water chlorination and its byproducts, Dr. David Martino from the University of Western Australia (2019) indicates that there have been no studies to date of his paper that investigate the potential toxic effects of these chemicals on the human gut microbiome. A small study since Dr. Martino’s summation that was done in Bangladeshi children (Nadimpalli et al., 2022) studied very low concentrations of water chlorination of 0.37 ppm.  The Nadimpalli et al. (2022) research did indicate that some changes in bacterial genera ensued with the use of chlorinated drinking water.   Dr. Matino’s group recently investigated the impact of chlorinated water exposure on the gut microbiota development in infants in a randomized controlled trial called the TUMS study (Parkin et al., 2024). The TUMS study noted a shift in infant microbiota, and differentially abundant antibiotic-resistant species and the Firmicutes phylum in infants exposed to chlorinated water. An abundance of Firmicutes bacteria is associated with gut dysbiosis (Hou et al., 2022) and obesity (Palmas et al., 2021).  The CDC (n.d.) indicates that 4.0 ppm is safe for human consumption. However, a review of water quality reports in urban areas conducted in warmer months that have higher bacterial growth will show much higher concentrations of chlorine, which is likely because of the increased need for additional chlorination due to temperature increases (Garcia-Avila et al., 2020), but with potential toxic effects on the human gut microbiome and health. Climate change may compound these issues.  As such, additional research is needed.

Next Steps

The next steps in research would be to further test the hypothesis that chlorinated drinking water may contribute to gut dysbiosis. Quantitative survey data should first be obtained to solidify the hypothesis.  Sampling fecal matter from various communities to quantify the effects of water disinfection consumption on the human gut microbiome composition would be the next step.  In addition, randomized placebo-controlled clinical trials would solidify our understanding of the potentially toxic effects of water disinfection and help us find other ways to offer clean water that is free of toxins to the public. Study design should control for confounding factors including ambient temperature, stress, alcohol use, diet composition, non-antibiotic prescription and non-prescription medication use, and recent use of antibiotics or antiviral medications.

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