Profiling the human intestinal environment under physiological conditions

Nature, Journal Year: 2023, Volume and Issue: 617(7961), P. 581 - 591

Published: May 10, 2023

The spatiotemporal structure of the human microbiome

Language: Английский

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The Bile Acid Receptor GPBAR1 Regulates the M1/M2 Phenotype of Intestinal Macrophages and Activation of GPBAR1 Rescues Mice from Murine Colitis

The Journal of Immunology, Journal Year: 2017, Volume and Issue: 199(2), P. 718 - 733

Published: June 13, 2017

Abstract GPBAR1 (TGR5 or M-BAR) is a G protein–coupled receptor for secondary bile acids that highly expressed in monocytes/macrophages. In this study, we aimed to determine the role of mediating leukocyte trafficking chemically induced models colitis and investigate therapeutic potential BAR501, small molecule agonist GPBAR1. These studies demonstrated gene ablation enhanced recruitment classically activated macrophages colonic lamina propria worsened severity inflammation. contrast, activation by BAR501 reversed intestinal inflammation trinitrobenzenesulfonic acid oxazolone reducing Ly6C+ monocytes from blood mucosa. Exposure shifted (CD11b+, CCR7+, F4/80−) an alternatively CCR7−, F4/80+) phenotype, reduced expression inflammatory genes (TNF-α, IFN-γ, IL-1β, IL-6, CCL2 mRNAs), attenuated wasting syndrome (≈70% reduction Colitis Disease Activity Index). The protective effect was lost Gpbar1−/− mice. increased IL-10 TGF-β mRNAs percentage CD4+/Foxp3+ cells. beneficial effects were Il-10−/− macrophage cell line, regulation dependent mediated CREB its responsive element promoter. conclusion, circulating macrophages, promotes IL-10–dependent shift toward phenotype. targeting may offer options bowel diseases.

Language: Английский

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Role of bile acids and their receptors in gastrointestinal and hepatic pathophysiology

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2022, Volume and Issue: 19(7), P. 432 - 450

Published: Feb. 14, 2022

Language: Английский

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Gut microbial β-glucuronidases reactivate estrogens as components of the estrobolome that reactivate estrogens

Journal of Biological Chemistry, Journal Year: 2019, Volume and Issue: 294(49), P. 18586 - 18599

Published: Oct. 22, 2019

Gut microbial β-glucuronidase (GUS) enzymes have been suggested to be involved in the estrobolome, collection of reactions involving estrogens. Furthermore, bacterial GUS within gastrointestinal tract postulated a contributing factor hormone-driven cancers. However, date, there has no experimental evidence support these hypotheses. Here we provide first vitro analysis ability 35 human gut reactivate two distinct estrogen glucuronides, estrone-3-glucuronide and estradiol-17-glucuronide, estrone estradiol, respectively. We show that certain members Loop 1, mini-Loop FMN-binding classes can estrogens from their inactive glucuronides. molecular details key interactions facilitate catalytic processes present structures novel related estrobolome. Further, demonstrate reactivation by 1 inhibited both purified fecal preparations mixed murine microbiota. Finally, however, despite ex vivo data, GUS-specific inhibitor is not capable reducing development tumors PyMT mouse model breast cancer. These findings validate participate estrobolome but also suggest multidimensional set on-going mammalian likely involves many enzymes, including several types proteins.

Language: Английский

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Bile acid metabolism and signaling, the microbiota, and metabolic disease

Pharmacology & Therapeutics, Journal Year: 2022, Volume and Issue: 237, P. 108238 - 108238

Published: July 2, 2022

Language: Английский

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