Summary of Study ST004138

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 PR002603. The data can be accessed directly via it's Project DOI: 10.21228/M85Z50 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.

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Study IDST004138
Study TitleVariation in microbiome and metabolites are associated with advantageous effects of cholestyramine on primary biliary cholangitis with pruritus
Study SummaryThis study aimed to elucidate the gut microbiota-metabolite interplay in cholestatic pruritus associated with primary biliary cholangitis (PBC) and the therapeutic mechanisms of cholestyramine. A prospective cohort of 54 pruritic PBC patients and 25 asymptomatic controls underwent longitudinal multi-omics profiling. Participants received 4 g cholestyramine twice daily for 4 weeks, with paired fecal 16S rRNA sequencing, untargeted LC/MS metabolomics, and serum analyses (autotaxin [ATX], liver function) pre-/post-intervention. Key findings revealed: 1.Pruritic patients exhibited elevated cholestasis markers (bilirubin, ALP, GGT; P<0.01), ATX levels, and Gp210 antibody positivity. Cholestyramine significantly reduced 5-D itch scores, ATX, and cholestasis indices (P<0.01). 2.Gut microbial diversity (Shannon/Simpson) was depleted in pruritus, with enrichment of Romboutsia, Stenotrophomonas, and Achromobacter versus Lachnospiraceae/Bacteroidaceae in controls. 3.LC/MS metabolomics identified critical perturbations: ↓ Medium-chain fatty acids (MCFAs: C8-C14) ↓ Indole derivatives (e.g., norharman) 4.Microbial-metabolite-clinical correlations implicated the Romboutsia–norharman–ATX/ALP axis in pruritogenesis. Cholestyramine restored microbial diversity, normalized metabolites, and attenuated pruritus. Enterobacteriaceae/long-chain fatty acids predicted treatment response.
Institute
Hangzhou Xixi Hospital
Last NameZhou
First NameYijun
AddressNo.2, Hengbu Street, Xihu District, Hangzhou, Zhejiang Province, China, Hangzhou, Zhejiang, 310023, China
Email348611334@qq.com
Phone+8613588296223
Submit Date2025-07-27
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailLC-MS
Release Date2025-11-24
Release Version1
Yijun Zhou Yijun Zhou
https://dx.doi.org/10.21228/M85Z50
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR002603
Project DOI:doi: 10.21228/M85Z50
Project Title:Variation in microbiome and metabolites are associated with advantageous effects of cholestyramine on primary biliary cholangitis with pruritus
Project Summary:Pruritus in PBC arises from synergistic cholestasis and gut microbiome-metabolite dysregulation. Cholestyramine mitigates symptoms by modulating the microbiome - metabolite - host axis, highlighting its therapeutic potential through microbiota remodeling and metabolic homeostasis restoration.
Institute:Hangzhou Xixi Hospital
Last Name:Zhou
First Name:Yijun
Address:No.2, Hengbu Street, Xihu District, Hangzhou, Zhejiang Province, China, Hangzhou, Zhejiang, 310023, China
Email:348611334@qq.com
Phone:+8613588296223

Subject:

Subject ID:SU004288
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606

Factors:

Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id Sample source Treatment
SA476979C6human_stool post-4-week cholestyramine
SA476980C27human_stool post-4-week cholestyramine
SA476981C28human_stool post-4-week cholestyramine
SA476982C3human_stool post-4-week cholestyramine
SA476983C32human_stool post-4-week cholestyramine
SA476984C33human_stool post-4-week cholestyramine
SA476985C34human_stool post-4-week cholestyramine
SA476986C35human_stool post-4-week cholestyramine
SA476987C36human_stool post-4-week cholestyramine
SA476988C37human_stool post-4-week cholestyramine
SA476989C38human_stool post-4-week cholestyramine
SA476990C39human_stool post-4-week cholestyramine
SA476991C4human_stool post-4-week cholestyramine
SA476992C40human_stool post-4-week cholestyramine
SA476993C5human_stool post-4-week cholestyramine
SA476994C9human_stool post-4-week cholestyramine
SA476995C24human_stool post-4-week cholestyramine
SA476996P54human_stool post-4-week cholestyramine
SA476997P55human_stool post-4-week cholestyramine
SA476998P56human_stool post-4-week cholestyramine
SA476999P59human_stool post-4-week cholestyramine
SA477000P60human_stool post-4-week cholestyramine
SA477001P61human_stool post-4-week cholestyramine
SA477002P63human_stool post-4-week cholestyramine
SA477003P64human_stool post-4-week cholestyramine
SA477004P65human_stool post-4-week cholestyramine
SA477005P66human_stool post-4-week cholestyramine
SA477006P67human_stool post-4-week cholestyramine
SA477007P69human_stool post-4-week cholestyramine
SA477008P70human_stool post-4-week cholestyramine
SA477009P71human_stool post-4-week cholestyramine
SA477010C25human_stool post-4-week cholestyramine
SA477011P62human_stool post-4-week cholestyramine
SA477012C23human_stool post-4-week cholestyramine
SA477013C17human_stool post-4-week cholestyramine
SA477014C22human_stool post-4-week cholestyramine
SA477015C10human_stool post-4-week cholestyramine
SA477016C13human_stool post-4-week cholestyramine
SA477017C15human_stool post-4-week cholestyramine
SA477018C14human_stool post-4-week cholestyramine
SA477019C18human_stool post-4-week cholestyramine
SA477020C19human_stool post-4-week cholestyramine
SA477021C2human_stool post-4-week cholestyramine
SA477022C20human_stool post-4-week cholestyramine
SA477023C21human_stool post-4-week cholestyramine
SA477024P26human_stool pre-4-week cholestyramine
SA477025P33human_stool pre-4-week cholestyramine
SA477026P31human_stool pre-4-week cholestyramine
SA477027P30human_stool pre-4-week cholestyramine
SA477028P29human_stool pre-4-week cholestyramine
SA477029P28human_stool pre-4-week cholestyramine
SA477030P27human_stool pre-4-week cholestyramine
SA477031P21human_stool pre-4-week cholestyramine
SA477032P25human_stool pre-4-week cholestyramine
SA477033P24human_stool pre-4-week cholestyramine
SA477034P23human_stool pre-4-week cholestyramine
SA477035P22human_stool pre-4-week cholestyramine
SA477036P35human_stool pre-4-week cholestyramine
SA477037P20human_stool pre-4-week cholestyramine
SA477038P19human_stool pre-4-week cholestyramine
SA477039P34human_stool pre-4-week cholestyramine
SA477040P43human_stool pre-4-week cholestyramine
SA477041P37human_stool pre-4-week cholestyramine
SA477042P48human_stool pre-4-week cholestyramine
SA477043P73human_stool pre-4-week cholestyramine
SA477044P53human_stool pre-4-week cholestyramine
SA477045P52human_stool pre-4-week cholestyramine
SA477046P51human_stool pre-4-week cholestyramine
SA477047P50human_stool pre-4-week cholestyramine
SA477048P49human_stool pre-4-week cholestyramine
SA477049P47human_stool pre-4-week cholestyramine
SA477050P38human_stool pre-4-week cholestyramine
SA477051P46human_stool pre-4-week cholestyramine
SA477052P45human_stool pre-4-week cholestyramine
SA477053P44human_stool pre-4-week cholestyramine
SA477054P17human_stool pre-4-week cholestyramine
SA477055P42human_stool pre-4-week cholestyramine
SA477056P41human_stool pre-4-week cholestyramine
SA477057P40human_stool pre-4-week cholestyramine
SA477058P18human_stool pre-4-week cholestyramine
SA477059P10human_stool pre-4-week cholestyramine
SA477060P16human_stool pre-4-week cholestyramine
SA477061P5human_stool pre-4-week cholestyramine
SA477062P15human_stool pre-4-week cholestyramine
SA477063P1human_stool pre-4-week cholestyramine
SA477064P3human_stool pre-4-week cholestyramine
SA477065P4human_stool pre-4-week cholestyramine
SA477066P2human_stool pre-4-week cholestyramine
SA477067P6human_stool pre-4-week cholestyramine
SA477068P8human_stool pre-4-week cholestyramine
SA477069P9human_stool pre-4-week cholestyramine
SA477070P11human_stool pre-4-week cholestyramine
SA477071P13human_stool pre-4-week cholestyramine
SA477072P14human_stool pre-4-week cholestyramine
SA477073A15human_stool ursodeoxycholic acid
SA477074A24human_stool ursodeoxycholic acid
SA477075A23human_stool ursodeoxycholic acid
SA477076A22human_stool ursodeoxycholic acid
SA477077A21human_stool ursodeoxycholic acid
SA477078A20human_stool ursodeoxycholic acid
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Collection:

Collection ID:CO004281
Collection Summary:Patients were required to fast overnight before collection of stool samples on the morning of each visit. Stool samples were centrifuged at 2800 rpm for 15 minutes at 4℃ and serum were aliquoted and stored at -80℃ until analysis. Fecal samples were freshly collected and immediately frozen at -80℃.
Sample Type:stool

Treatment:

Treatment ID:TR004297
Treatment Summary:A total of 54 pruritic PBC patients with 25 matched non-pruritic PBC patients were enrolled in this study. Cholestyramine was administered twice daily (4 g/dose) before meals, with a mandatory 4-hour separation from other medications to prevent UDCA absorption interference. Biochemical parameters, serum, and stool samples were collected at baseline and 4-week follow-up.

Sample Preparation:

Sampleprep ID:SP004294
Sampleprep Summary:Faecal metabolome profiling and data preprocessing Metabolites were extracted using a methanol-water (80:20, v/v) solution.

Chromatography:

Chromatography ID:CH005215
Chromatography Summary:Metabolite profiling was performed using liquid chromatography-mass spectrometry (LC-MS). The extracted metabolites were separated on a C18 reversed-phase column using a gradient elution with mobile phases consisting of water (0.1% formic acid) and acetonitrile (0.1% formic acid).
Instrument Name:Agilent 1260
Column Name:Thermo Hypersil GOLD aQ (100 x 2.1mm,1.9um)
Column Temperature:40°C
Flow Gradient:0.2 mL/min
Flow Rate:0.2 mL/min
Solvent A:100% water; 0.1% formic acid
Solvent B:100% Methanol
Chromatography Type:Reversed phase

Analysis:

Analysis ID:AN006860
Analysis Type:MS
Chromatography ID:CH005215
Num Factors:3
Num Metabolites:1037
Units:Peak area
  
Analysis ID:AN006861
Analysis Type:MS
Chromatography ID:CH005215
Num Factors:3
Num Metabolites:691
Units:Peak area
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