Emerging research supports that triclosan (TCS), an antimicrobial agent found in thousands of consumer products, exacerbates colitis and colitis-associated colorectal tumorigenesis in animal models. While the intestinal toxicities of TCS require the presence of gut microbiota, the molecular mechanisms involved have not been defined. Here we show that intestinal commensal microbes mediate metabolic activation of TCS in the colon and drive its gut toxicology. Using a range of in vitro, ex vivo, and in vivo approaches, we identify specific microbial β-glucuronidase (GUS) enzymes involved and pinpoint molecular motifs required to metabolically activate TCS in the gut. Finally, we show that targeted inhibition of bacterial GUS enzymes abolishes the colitis-promoting effects of TCS, supporting an essential role of specific microbial proteins in TCS toxicity. Together, our results define a mechanism by which intestinal microbes contribute to the metabolic activation and gut toxicity of TCS, and highlight the importance of considering the contributions of the gut microbiota in evaluating the toxic potential of environmental chemicals.
Technologies capable of noninvasively sampling different locations in the gut upstream of the colon enable new insights into the role of organ‐specific microbiota in human health. Herein, an ingestible, biocompatible, battery‐less, 3D‐printed microengineered pill with an integrated osmotic sampler and microfluidic channels for in vivo sampling of the gut lumen and its microbiome upstream of the colon is discussed. The pill's sampling performance is characterized using realistic in vitro models and validated in vivo in pigs and primates. Herein, the results show that the bacterial populations recovered from the pill's microfluidic channels closely resemble the bacterial population demographics of the microenvironment to which the pill is exposed. Herein, it is believed that such lab‐on‐a‐pill devices revolutionize the understanding of the spatial diversity of the gut microbiome and its response to medical conditions and treatments.
- NSF-PAR ID:
- 10114100
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Advanced Intelligent Systems
- Volume:
- 1
- Issue:
- 5
- ISSN:
- 2640-4567
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Odontotaenius disjunctus . We developed a Percoll-based centrifugation method to isolate and enrich the wood particles from the anterior hindgut, allowing us to access the wood fibers and their associated microbiome. We then performed assays of enzyme activity and used short-read and long-read amplicon sequencing of the 16S rRNA gene to identify the composition of the fiber-associated microbiome.Results Our assays demonstrated that the anterior hindgut, which houses a majority of the bacterial load, is an important site for lignocellulose digestion. Wood particles enriched from the anterior hindgut contribute to a large proportion of the total enzyme activity. The sequencing revealed that
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