Inflammatory Bowel Disease-Associated Gut Commensals Degrade Components of the Extracellular Matrix
ABSTRACT Extracellular matrix (ECM) remodeling has emerged as a key feature of inflammatory bowel disease (IBD), and ECM fragments have been proposed as markers of clinical disease severity. Recent studies report increased protease activity in the gut microbiota of IBD patients. Nonetheless, the rel...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2022-12-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mbio.02201-22 |
| _version_ | 1828089674376151040 |
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| author | Ana Maria Porras Hao Zhou Qiaojuan Shi Xieyue Xiao Randy Longman Ilana Lauren Brito |
| author_facet | Ana Maria Porras Hao Zhou Qiaojuan Shi Xieyue Xiao Randy Longman Ilana Lauren Brito |
| author_sort | Ana Maria Porras |
| collection | DOAJ |
| description | ABSTRACT Extracellular matrix (ECM) remodeling has emerged as a key feature of inflammatory bowel disease (IBD), and ECM fragments have been proposed as markers of clinical disease severity. Recent studies report increased protease activity in the gut microbiota of IBD patients. Nonetheless, the relationship between gut microbiota and ECM remodeling has remained unexplored. We hypothesized that members of the human gut microbiome could degrade the host ECM and that bacteria-driven remodeling, in turn, could enhance colonic inflammation. Through a variety of in vitro assays, we first confirmed that multiple bacterial species found in the human gut are capable of degrading specific ECM components. Clinical stool samples obtained from ulcerative colitis patients also exhibited higher levels of proteolytic activity in vitro, compared to those of their healthy counterparts. Furthermore, culture supernatants from bacteria species that are capable of degrading human ECM accelerated inflammation in dextran sodium sulfate (DSS)-induced colitis. Finally, we identified several of the bacterial proteases and carbohydrate degrading enzymes (CAZymes) that are potentially responsible for ECM degradation in vitro. Some of these protease families and CAZymes were also found in increased abundance in a metagenomic cohort of IBD. These results demonstrate that some commensal bacteria in the gut are indeed capable of degrading components of human ECM in vitro and suggest that this proteolytic activity may be involved in the progression of IBD. A better understanding of the relationship between nonpathogenic gut microbes, host ECM, and inflammation could be crucial to elucidating some of the mechanisms underlying host-bacteria interactions in IBD and beyond. IMPORTANCE Healthy gut epithelial cells form a barrier that keeps bacteria and other substances from entering the blood or tissues of the body. Those cells sit on scaffolding that maintains the structure of the gut and informs our immune system about the integrity of this barrier. In patients with inflammatory bowel disease (IBD), breaks are formed in this cellular barrier, and bacteria gain access to the underlying tissue and scaffolding. In our study, we discovered that bacteria that normally reside in the gut can modify and disassemble the underlying scaffolding. Additionally, we discovered that changes to this scaffolding affect the onset of IBD in mouse models of colitis as well as the abilities of these mice to recover. We propose that this new information will reveal how breaks in the gut wall lead to IBD and will open up new avenues by which to treat patients with IBD. |
| first_indexed | 2024-04-11T05:45:39Z |
| format | Article |
| id | doaj.art-63f251a66b9c4c39b54e1a5209bfd9c1 |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-04-11T05:45:39Z |
| publishDate | 2022-12-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-63f251a66b9c4c39b54e1a5209bfd9c12022-12-22T04:42:14ZengAmerican Society for MicrobiologymBio2150-75112022-12-0113610.1128/mbio.02201-22Inflammatory Bowel Disease-Associated Gut Commensals Degrade Components of the Extracellular MatrixAna Maria Porras0Hao Zhou1Qiaojuan Shi2Xieyue Xiao3Randy Longman4Ilana Lauren Brito5J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, Florida, USAMeinig School of Biomedical Engineering, Cornell University, Ithaca, New York, USAMeinig School of Biomedical Engineering, Cornell University, Ithaca, New York, USAMeinig School of Biomedical Engineering, Cornell University, Ithaca, New York, USAJill Roberts Institute for IBD Research, Weill Cornell Medicine, New York, New York, USAMeinig School of Biomedical Engineering, Cornell University, Ithaca, New York, USAABSTRACT Extracellular matrix (ECM) remodeling has emerged as a key feature of inflammatory bowel disease (IBD), and ECM fragments have been proposed as markers of clinical disease severity. Recent studies report increased protease activity in the gut microbiota of IBD patients. Nonetheless, the relationship between gut microbiota and ECM remodeling has remained unexplored. We hypothesized that members of the human gut microbiome could degrade the host ECM and that bacteria-driven remodeling, in turn, could enhance colonic inflammation. Through a variety of in vitro assays, we first confirmed that multiple bacterial species found in the human gut are capable of degrading specific ECM components. Clinical stool samples obtained from ulcerative colitis patients also exhibited higher levels of proteolytic activity in vitro, compared to those of their healthy counterparts. Furthermore, culture supernatants from bacteria species that are capable of degrading human ECM accelerated inflammation in dextran sodium sulfate (DSS)-induced colitis. Finally, we identified several of the bacterial proteases and carbohydrate degrading enzymes (CAZymes) that are potentially responsible for ECM degradation in vitro. Some of these protease families and CAZymes were also found in increased abundance in a metagenomic cohort of IBD. These results demonstrate that some commensal bacteria in the gut are indeed capable of degrading components of human ECM in vitro and suggest that this proteolytic activity may be involved in the progression of IBD. A better understanding of the relationship between nonpathogenic gut microbes, host ECM, and inflammation could be crucial to elucidating some of the mechanisms underlying host-bacteria interactions in IBD and beyond. IMPORTANCE Healthy gut epithelial cells form a barrier that keeps bacteria and other substances from entering the blood or tissues of the body. Those cells sit on scaffolding that maintains the structure of the gut and informs our immune system about the integrity of this barrier. In patients with inflammatory bowel disease (IBD), breaks are formed in this cellular barrier, and bacteria gain access to the underlying tissue and scaffolding. In our study, we discovered that bacteria that normally reside in the gut can modify and disassemble the underlying scaffolding. Additionally, we discovered that changes to this scaffolding affect the onset of IBD in mouse models of colitis as well as the abilities of these mice to recover. We propose that this new information will reveal how breaks in the gut wall lead to IBD and will open up new avenues by which to treat patients with IBD.https://journals.asm.org/doi/10.1128/mbio.02201-22gut microbiomeinflammatory bowel diseaseextracellular matrixhost-microbe interactionscolitisproteases |
| spellingShingle | Ana Maria Porras Hao Zhou Qiaojuan Shi Xieyue Xiao Randy Longman Ilana Lauren Brito Inflammatory Bowel Disease-Associated Gut Commensals Degrade Components of the Extracellular Matrix mBio gut microbiome inflammatory bowel disease extracellular matrix host-microbe interactions colitis proteases |
| title | Inflammatory Bowel Disease-Associated Gut Commensals Degrade Components of the Extracellular Matrix |
| title_full | Inflammatory Bowel Disease-Associated Gut Commensals Degrade Components of the Extracellular Matrix |
| title_fullStr | Inflammatory Bowel Disease-Associated Gut Commensals Degrade Components of the Extracellular Matrix |
| title_full_unstemmed | Inflammatory Bowel Disease-Associated Gut Commensals Degrade Components of the Extracellular Matrix |
| title_short | Inflammatory Bowel Disease-Associated Gut Commensals Degrade Components of the Extracellular Matrix |
| title_sort | inflammatory bowel disease associated gut commensals degrade components of the extracellular matrix |
| topic | gut microbiome inflammatory bowel disease extracellular matrix host-microbe interactions colitis proteases |
| url | https://journals.asm.org/doi/10.1128/mbio.02201-22 |
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