Summary of Study ST002094

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.

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Study IDST002094
Study TitleCommensal intestinal microbiota regulates host luminal proteolytic activity and intestinal barrier integrity through β-glucuronidase activity (Part 1)
Study TypeMS
Study SummaryProteases 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
DepartmentBiomedical Statistics and Informatics
Last NameDasari
First NameSurendra
Address200 First Street SW, Rochester, MN, 55905, USA
EmailDasari.Surendra@mayo.edu
Phone507-284-0513
Submit Date2022-02-17
Num Groups2
Total Subjects7
Raw Data AvailableYes
Raw Data File Type(s)d
Analysis Type DetailLC-MS
Release Date2022-03-09
Release Version1
Surendra Dasari Surendra Dasari
https://dx.doi.org/10.21228/M8840R
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Combined analysis:

Analysis ID AN003420 AN003421 AN003422
Analysis type MS MS MS
Chromatography type Reversed phase HILIC HILIC
Chromatography system Agilent 1290 Infinity Agilent 1290 Infinity Agilent 1290 Infinity
Column Waters Acquity BEH HSS T3 (100 x 2.1mm,1.8um) Waters Acquity BEH HILIC (150 x 2.1mm,1.7um) Waters Acquity BEH HILIC (150 x 2.1mm,1.7um)
MS Type ESI ESI ESI
MS instrument type QTOF QTOF QTOF
MS instrument name Agilent 6550 QTOF Agilent 6550 QTOF Agilent 6550 QTOF
Ion Mode POSITIVE POSITIVE NEGATIVE
Units raw intensity raw intensity raw intensity

Chromatography:

Chromatography ID:CH002530
Chromatography Summary:Reversed phase
Instrument Name:Agilent 1290 Infinity
Column Name:Waters Acquity BEH HSS T3 (100 x 2.1mm,1.8um)
Chromatography Type:Reversed phase
  
Chromatography ID:CH002531
Chromatography Summary:HILIC
Instrument Name:Agilent 1290 Infinity
Column Name:Waters Acquity BEH HILIC (150 x 2.1mm,1.7um)
Chromatography Type:HILIC
  
Chromatography ID:CH002532
Chromatography Summary:HILIC
Instrument Name:Agilent 1290 Infinity
Column Name:Waters Acquity BEH HILIC (150 x 2.1mm,1.7um)
Chromatography Type:HILIC
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