Toothpaste is an indispensable daily necessity in daily life, we will touch it every day, so the safety of toothpaste cannot be ignored. If a toothpaste containing harmful ingredients is chosen, it can damage our body. Recent studies have found that triclosan (TCS), an antibacterial agent contained in many toothpastes, may cause damage to the human intestine, which in turn can induce enteritis.
TCS is a broad-spectrum antibacterial agent that is widely added to daily cosmetics such as toothpaste, soap, deodorant, mouthwash, shaving cream and so on. Since TCS prevents gingivitis, many toothpastes add this substance. Previous studies have confirmed the enterotoxicity of TCS, but the associated molecular mechanisms have not been identified.
Recently, a study conducted by Cai Zongwei's team at Hong Kong Baptist University in collaboration with foreign teams explains how TCS triggers intestinal inflammation, and the results of this study reveal the metabolic activation of TCS by intestinal microbial enzymes and the mechanism of its enterotoxicity, which will help better evaluate the individual effects of TCS in different populations. The research was published in Nature Communication under the title "Microbial enzymes induce colitis by reactivating triclosan in themouse gastrointestinal tract."
Research Results (Source: Nature Communication)
In this study, the researchers linked specific gut microbial enzymes, specific gut microbial β-glucuronidase (GUS), to TCS and showed that these enzymes contribute to severe damage to TCS in the gut.
Exposure to TCS in mice and humans leads to the accumulation of free TCS in the colon (Source: Nature Communication)
To determine whether the gut exhibited different TCS metabolic signatures from other tissues, the researchers used TCS to perform a 4-week trial on mice, followed by an LC-MS/MS analysis of the concentrations of TCS and its metabolites in individual tissues in mice. They found that after exposure to TCS, the TCS metabolite in the mouse liver, bile, heart, and small intestine was the inactive conjugate metabolite TCS-G. In contrast, the TCS metabolites obtained by the mouse cecum and colon are mainly free TCS. This suggests that after exposure to TCS, there will be a generally free TCS in the colon compared to other tissues.
Next, the researchers further experimented in humans, where they analyzed the metabolic signatures of TCS in subjects after exposure to TCS. LC-MS/MS showed that in all subjects exposed to TCS, the main compound in the stool sample was free TCS and the main compound in the urine sample was TCS-G. The ratio of concentrations of TCS, TCS-G and TCS-sulfate in feces is 99.2%:0.8%:0, compared with 1.6%:98.4%:0 in urine. These results suggest that the human gut exhibits unique characteristics of TCS metabolism and contains high concentrations of TCS.
And, it is worth mentioning that the researchers found that experimental data showed that from the proximal to distal region of the intestine, the concentration of TCS was increasing, while the concentration of TCS-G was decreasing. Therefore, they believe that there may be some kind of gut microbiota that promotes the conversion of TCS-G into TCS.
Specific gut microbial glucuronidase converts TCS-G into TCS (Source: Nature Communication)
Since intestinal β-glucuronidase (GUS) has been shown to be able to convert multiple glucuronidated metabolites into corresponding glycosyl groups, the researchers hypothesized that gut microbial GUS intuitous homologs promote the conversion of TCS-G to TCS. Ultimately, based on the experimental results, they found that the Loop1 gut microbiome GUS enzyme is an important promoter of TCS-G conversion to TCS.
After identifying that gut microbial GUS enzymes can promote the conversion of TCS-G to TCS, the researchers attempted to reduce or even eliminate the cologenic effects of TCS in the human body by targeting inhibition of gut microbial GUS enzymes.
GUSi inhibits gut microbial GUS enzymes to convert TCS-G into TCS (Source: Nature Communication)
The researchers first tested the effect of the GUS inhibitor GUSi on the TCS-G conversion process in vitro and found that it inhibited the conversion of TCS-G to TCS through the purified Fp2-L1GUS enzyme and several other Loop1GUS enzymes. Notably, GUSi also inhibits the processing of TCS-G by FMN-binding GUS enzymes. The researchers also used GUSi to determine the effect of the gut microbiome GUS enzyme in the process in which TCS causes colitis, and they found that exposure to TCS increased the severity of colitis in mice, and this result was eliminated by GUSi. Thus, the inhibition of the gut microbial GUS enzyme eliminates the colitis-promoting effect of TCS.
Taken together, this study shows that after exposure to TCS, the enterotoxicity of TCS is stimulated under the action of the human gut microbiome GUS enzyme, which in turn leads to the appearance of enteritis. By targeting the inhibition of gut microbial GUS enzymes, the harm caused by TCS to the human intestine may be eliminated. This study also confirms that TCS, a common ingredient in daily necessities, will cause certain harm to the human body, so you must pay more attention when choosing daily necessities!
bibliography:
[1] Zhang J, Walker ME, Sanidad KZ, et al. Microbial enzymes induce colitisby reactivating triclosan in the mouse gastrointestinal tract. Nat Commun. 2022 Jan 10;13(1):136. doi: 10.1038/s41467-021-27762-y. PMID: 35013263; PMCID:PMC8748916.
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