Novel Fecal Biomarkers That Precede Clinical Diagnosis of Ulcerative Colitis
| Autor: | Charles Bernstein, David R. Mack, Dan Turner, Karen Madsen, Anne M. Griffiths, Heather J. Galipeau, Bruce A. Vallance, Guy Aumais, M Bermudez-Brito, D.O. Krause, Michael G. Surette, Josie Libertucci, Maria Cino, Andy Stadnyk, Wael El-Matary, Brian G. Feagan, Jeff Critch, Williams Turpin, Michael Surette, Juan Antonio Raygoza Garay, Jerry McGrath, Paul Beck, Gilaad G. Kaplan, Marco Constante, Michelle I. Smith, Hien Q. Huynh, Jeff Hyams, Colette Deslandres, John Marshall, Hans H Herfarth, Mark S. Silverberg, Premysl Bercik, Leo Dieleman, Alex Clarizio, Alberto Caminero, Alain Bitton, Mark J. Ropeleski, Remo Panancionne, Hillary Steinhart, Ernest G. Seidman, Kevan Jacobson, Elena F. Verdu, Lee A. Denson, Alba Santiago, Scott B. Snapper, Paul Moayyedi, Kenneth Croitoru, Anthony R. Otley, David S. Guttman, Sarah Armstrong, Peter D.R. Higgins, Thomas D. Walters, Gaston Rueda |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Crohn's disease Hepatology biology Gastroenterology Gut flora medicine.disease biology.organism_classification Inflammatory bowel disease Ulcerative colitis Microbiology 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Immune system medicine 030211 gastroenterology & hepatology Microbiome Bacteroides Feces |
| Zdroj: | Gastroenterology. 160:1532-1545 |
| ISSN: | 0016-5085 |
| DOI: | 10.1053/j.gastro.2020.12.004 |
| Popis: | Background & Aims Altered gut microbiota composition and function have been associated with inflammatory bowel diseases, including ulcerative colitis (UC), but the causality and mechanisms remain unknown. Methods We applied 16S ribosomal RNA gene sequencing, shotgun metagenomic sequencing, in vitro functional assays, and gnotobiotic colonizations to define the microbial composition and function in fecal samples obtained from a cohort of healthy individuals at risk for inflammatory bowel diseases (pre-UC) who later developed UC (post-UC) and matched healthy control individuals (HCs). Results Microbiota composition of post-UC samples was different from HC and pre-UC samples; however, functional analysis showed increased fecal proteolytic and elastase activity before UC onset. Metagenomics identified more than 22,000 gene families that were significantly different between HC, pre-UC, and post-UC samples. Of these, 237 related to proteases and peptidases, suggesting a bacterial component to the pre-UC proteolytic signature. Elastase activity inversely correlated with the relative abundance of Adlercreutzia and other potentially beneficial taxa and directly correlated with known proteolytic taxa, such as Bacteroides vulgatus. High elastase activity was confirmed in Bacteroides isolates from fecal samples. The bacterial contribution and functional significance of the proteolytic signature were investigated in germ-free adult mice and in dams colonized with HC, pre-UC, or post-UC microbiota. Mice colonized with or born from pre-UC–colonized dams developed higher fecal proteolytic activity and an inflammatory immune tone compared with HC-colonized mice. Conclusions We have identified increased fecal proteolytic activity that precedes the clinical diagnosis of UC and associates with gut microbiota changes. This proteolytic signature may constitute a noninvasive biomarker of inflammation to monitor at-risk populations that can be targeted therapeutically with antiproteases. |
| Databáze: | OpenAIRE |
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