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... Show moreEmerging 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. Show less
We present a comprehensive investigation of the cosmological evolution of the luminosity function of galaxies and active galactic nuclei (AGNs) in the infrared (IR). Based on the observed... Show moreWe present a comprehensive investigation of the cosmological evolution of the luminosity function of galaxies and active galactic nuclei (AGNs) in the infrared (IR). Based on the observed dichotomy in the ages of stellar populations of early-type galaxies on one side and late-type galaxies on the other, the model interprets the epoch-dependent luminosity functions at z {gt}= 1.5 using a physical approach for the evolution of proto-spheroidal galaxies and of the associated AGNs, while IR galaxies at z {lt} 1.5 are interpreted as being mostly late-type ''cold'' (normal) and ''warm'' (starburst) galaxies. As for proto-spheroids, in addition to the epoch-dependent luminosity functions of stellar and AGN components separately, we have worked out, for the first time, the evolving luminosity functions of these objects as a whole (stellar plus AGN component), taking into account in a self-consistent way the variation with galactic age of the global spectral energy distribution. The model provides a physical explanation for the observed positive evolution of both galaxies and AGNs up to z ~{}= 2.5 and for the negative evolution at higher redshifts, for the sharp transition from Euclidean to extremely steep counts at (sub-)millimeter wavelengths, as well as the (sub-)millimeter counts of strongly lensed galaxies that are hard to account for by alternative, physical or phenomenological, approaches. The evolution of late-type galaxies and z {lt} 1.5 AGNs is described using a parametric phenomenological approach. The modeled AGN contributions to the counts and to the cosmic infrared background (CIB) are always sub-dominant. They are maximal at mid-IR wavelengths: the contribution to the 15 and 24 {$μ$}m counts reaches 20% above 10 and 2 mJy, respectively, while the contributions to the CIB are of 8.6% and of 8.1% at 15 {$μ$}m and 24 {$μ$}m, respectively. The model provides a good fit to the multi-wavelength (from the mid-IR to millimeter waves) data on luminosity functions at different redshifts and on number counts (both global and per redshift slices). A prediction of the present model, useful to test it, is a systematic variation with wavelength of the populations dominating the counts and the contributions to the CIB intensity. This implies a specific trend for cross-wavelength CIB power spectra, which is found to be in good agreement with the data. Show less
