An international team of researchers led by the University of North Carolina at Chapel Hill, the University of Massachusetts Amherst and Hong Kong Baptist University identified the bacteria, and even specific enzymes, that trigger triclosan’s harmful effects. Moreover, studies in mice suggest these bacterial enzymes can be blocked from driving intestinal damage.
The findings were published in Nature Communications.
“By identifying the culprit bacteria, new approaches could be developed for the diagnoses, prevention and treatment of inflammatory bowel diseases,” said study author Matthew Redinbo, a chemistry and microbiology professor at the UNC-Chapel Hill College of Arts & Sciences and UNC School of Medicine.
Researchers connected specific gut microbial enzymes, notably gut microbial beta-glucuronidase (GUS) proteins, with triclosan and showed these enzymes drive triclosan to wreak havoc in the gut.
Knowing which bacterial proteins were the culprits, the team used a microbiome-targeted inhibitor to block triclosan processing in the gut. Blocking this process in mice prevented damage to the colon and symptoms of colitis, a form of inflammatory bowel disease.
The study provides new clues about management of IBD among the growing number of people diagnosed with the disease. IBD can be managed for long periods of time only to flare up out of seemingly nowhere.
Study authors suggest the need for better understanding of the impact of environmental chemicals on gut health.
Triclosan used to be widely available in antibacterial soaps marketed to consumers. But in 2016, the Food and Drug Administration ordered it removed from handwashing products used in homes and hospital settings because of concerns it contributed to more resistant bacteria.
But triclosan remains ubiquitous as an ingredient added to cosmetics, yoga mats and other athletic clothes and gear to reduce bacterial contamination. It’s also routinely used in many toothpastes – with FDA approval – since it has been found to prevent gingivitis.
Triclosan appears to be readily absorbed in the gastrointestinal tract, leading study authors to write, “the safety of triclosan and related compounds should be reconsidered given their potential for intestinal damage.”
The National Institutes of Health, through grants to several authors, the Hong Kong Research Grants Council and the National Science Foundation funded the study, “Microbial enzymes induce colitis by reactivating triclosan in the mouse gastrointestinal tract.”
Triclosan (TCS) is an antimicrobial compound incorporated into more than 2,000 consumer products, such as toothpaste, mouthwash, clothes, kitchenware, and toys.1,2 This compound is frequently detected in the human body: the National Health and Nutrition Examination Survey showed that TCS was detected in ~ 75% of the urine samples of individuals tested in the United States.3
Also, TCS causes ubiquitous contamination in the environment and is listed among the top-ten pollutants found in the rivers of the United States.1 Previous studies have shown that exposure to TCS could cause some adverse effects, such as endocrine disruption, antibiotic resistance, liver fibrosis, and liver tumorigenesis.4
Our recent study showed that exposure to low-dose TCS exaggerates colonic inflammation and exacerbates the development of colitis-associated colon tumorigenesis in mouse models, suggesting that TCS could have adverse effects on gut health.5
Exposure to TCS alters the gut microbiome and fails to induce colonic inflammation in mice lacking a gut microbiome (germ-free mice) or mice lacking Toll-like receptor 4 (Tlr4-/- mice), a critical regulator of host-microbiome interactions, supporting that the gut microbiome contributes to the pro-inflammatory effect of TCS.5
Because TCS is so widely used in our daily lives, the research from us and other investigators supports that it is of critical importance to further evaluate its impact on gut health, in order to provide science-based regulatory policies. In this essay, we will discuss the importance of studying the effects of TCS, as well as other consumer antimicrobials, on the gut microbiome and gut health.
Effects of TCS exposure on the gut microbiome
Our study showed that a 3-week treatment of TCS via diet reduced the diversity and altered the composition of the gut microbiome in C57BL/6 mice, demonstrating that TCS can disrupt the gut microbiome.5 This finding is largely in agreement with previous studies which showed that TCS exposure disturbs gut microbiota in various animal model systems, including fathead minnows,6 zebrafish,7 rats,8 and mice.9
Notably, previous studies demonstrated that TCS had an extremely potent effect to disturb the gut microbiome. Treatment with TCS, at environmentally relevant concentrations (0.1–1 ppb, equivalent to ~ 0.35–3.45 nM), reduced the diversity of the gut microbiome in fathead minnows (Pimephales promelas).6 Considering that TCS is found to be among the top-ten most abundant pollutants in the rivers of the United States,1 this study suggest that TCS could have potential adverse effects on aquatic ecosystems.
In addition, to put the concentrations in perspective, previous studies showed that after routine usage of TCS-containing consumer products such as toothpastes, the plasma concentration of TCS can reach ~ 90–1000 nM,10,11 which is several magnitudes higher than the concentration used in the fish study.6
These results suggest that routine exposure to TCS could also alter the gut microbiome in humans. Indeed, recent human studies support that routine exposure to TCS alters the gut microbiome in humans. Bever et al. reported that the gut microbiomes of infants who received breast milk containing TCS had significantly lower alpha diversity compared with the infants who received breast milk with non-detectable levels of TCS.12
In addition, the relative abundances of certain bacteria were also modulated in the infants who were fed TCS-containing breast milk.12 In another human study, Ribado et al. reported that routine usage of TCS-containing toothpaste increased the relative abundance of broadly antibiotic-resistant Proteobacteria species in adults, as well as in the infants with high urinal concentrations of TCS.13
We need to acknowledge that there are also inconsistent results, which failed to demonstrate that TCS exposure has significant impact on the gut microbiome in humans.14
reference link: https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC6546352/
More information: Microbial enzymes induce colitis by reactivating triclosan in the mouse gastrointestinal tract, Nature Communications (2022). DOI: 10.1038/s41467-021-27762-y