Summary of Study ST001718
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001102. The data can be accessed directly via it's Project DOI: 10.21228/M8840R This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST001718 |
| Study Title | Commensal intestinal microbiota regulates host luminal proteolytic activity and intestinal barrier integrity through β-glucuronidase activity |
| Study Type | Complex |
| Study Summary | Proteases constitute the largest enzyme gene family in vertebrates with intracellular and secreted proteases having critical roles in cellular and organ physiology. Intestinal tract contains diverse set of proteases mediating digestion, microbial responses, epithelial and immune signaling. Transit of chyme through the intestinal tract results in significant suppression of proteases. Although endogenous protease inhibitors have been identified, the broader mechanisms underlying protease regulation in the intestinal tract remains unclear. The objective of this study was to determine microbial regulation of proteolytic activity in intestinal tract using phenotype of post-infection irritable bowel syndrome, a condition characterized by high fecal proteolytic activity. Proteases of host pancreatic origin (chymotrypsin like pancreatic elastase 2A, 3B and trypsin 2) drove proteolytic activity. Of the 14 differentially abundant taxa, high proteolytic activity state was characterized by complete absence of the commensal Alistipes putredinis. Germ free mice had very high proteolytic activity (10-fold of specific-pathogen free mice) which dropped significantly upon humanization with microbiota from healthy volunteers. In contrast, high proteolytic activity microbiota failed to inhibit it, a defect that corrected with fecal microbiota transplant as well as addition of A. putredinis. These mice also had increased intestinal permeability similar to that seen in patients. Microbiota β-glucuronidases mediate bilirubin deconjugation and unconjugated bilirubin is an inhibitor of serine proteases. We found that high proteolytic activity patients had lower urobilinogen levels, a product of bilirubin deconjugation. Mice colonized with β-glucuronidase overexpressing E. coli demonstrated significant inhibition of proteolytic activity and treatment with β-glucuronidase inhibitors increased it. The findings establish that specific commensal microbiota mediates effective inhibition of host pancreatic proteases and maintains intestinal barrier function through the production of β-glucuronidases. This suggests an important homeostatic role for commensal intestinal microbiota. |
| Institute | Mayo Clinic |
| Department | Gastroenterology |
| Last Name | Grover |
| First Name | Madhu |
| Address | 200 First Street SW, Rochester, MN |
| dasari.surendra@mayo.edu | |
| Phone | 5072840513 |
| Submit Date | 2021-03-11 |
| Num Groups | 2 |
| Total Subjects | 16 |
| Num Males | 8 |
| Num Females | 8 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | d |
| Analysis Type Detail | LC-MS |
| Release Date | 2022-03-09 |
| Release Version | 1 |
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Factors:
Subject type: Mammal; Subject species: Homo sapiens (Factor headings shown in green)
| mb_sample_id | local_sample_id | Factor |
|---|---|---|
| SA161897 | ms5520-11 | case |
| SA161898 | ms5520-13 | case |
| SA161899 | ms5520-7 | case |
| SA161900 | ms5520-9 | case |
| SA161901 | ms5520-3 | case |
| SA161902 | ms5520-4 | case |
| SA161903 | ms5520-5 | case |
| SA161904 | ms5520-14 | control |
| SA161905 | ms5520-15 | control |
| SA161906 | ms5520-16 | control |
| SA161907 | ms5520-2 | control |
| SA161908 | ms5520-12 | control |
| SA161909 | ms5520-1 | control |
| SA161910 | ms5520-10 | control |
| SA161911 | ms5520-6 | control |
| SA161912 | ms5520-8 | control |
| Showing results 1 to 16 of 16 |
