PXD071836-1

PXD071836 is an original dataset announced via ProteomeXchange.

Title	Faecal Proteases and Immune Signatures Drive Subtype-Specific Enteric Neuronal Activation in IBS
Description	Background: Luminal proteases have been implicated in epithelial barrier dysfunction and visceral hypersensitivity in irritable bowel syndrome (IBS), yet their impact on the enteric nervous system (ENS), the principal regulator of gastrointestinal function, remains unknown. We investigated whether faecal mediators differentially activate enteric neurons across IBS subtypes and whether proteolytic and proteomic profiles explain neuronal phenotypes. Methods: The effects of faecal supernatants from 21 IBS-D, 9 IBS-C patients, and 18 healthy controls on guinea pig distal colon submucous plexus neurons were assessed using a neuroimaging technique. Faecal proteolytic activities and proteomic profiles were also analyzed. Results: IBS-D and IBS-C supernatants evoked significantly stronger neuronal activation than healthy controls, demonstrating for the first time that faecal mediators directly modulate enteric neurons. In IBS-D, but not in IBS-C, effects were mediated by serine and cysteine proteases and PAR-1. Proteome analysis revealed a significant difference in 48 proteins between IBS-D and healthy controls, including several immunoglobulin components, underlying the role of microinflammation in IBS-D. Three proteins demonstrated high diagnostic performance to distinguish IBS-D from controls. Conclusion: These findings uncover a previously unrecognised luminal–neuronal communication axis in IBS and reveal fundamentally different pathological mechanisms between IBS-D and IBS-C. IBS-D is characterised by proteases and PAR-1 dependent neuronal activation and a distinct immune-enriched faecal proteome, whereas mediators in IBS-C act through protease-independent pathways. These findings establish a functional link between faecal protease activity, ENS signalling, and molecular biomarkers, highlighting new therapeutic and diagnostic avenues for subtype-specific management of IBS.
HostingRepository	PRIDE
AnnounceDate	2026-09-10
AnnouncementXML	Submission_2026-09-10_06:50:13.380.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christina Ludwig
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2025-12-10 14:56:13	ID requested
⏵ 1	2026-09-10 06:50:14	announced

Rid, ž, al L, Frieling T, R, ó, ka R, Inczefi O, Bacsur P, Bajcsi D, Neunlist MM, Cardaillac C, Theodorou V, Yoon H, Wang J, Ludwig C, Wudy SI, Pankotai T, P, á, hi ZG, Mansouri N, Luksch H, Michel K, Schemann M, Annah, á, zi A, Faecal proteases and immune signatures drive subtype-specific enteric neuronal activation in IBS. Gut, ():(2026) [pubmed]

10.1136/gutjnl-2025-337949;

submitter keyword: Protease-activated receptors (PARs),Irritable Bowel Syndrome, Serine and cysteine protease activity, Faecal Supernatant Proteomics, Luminal–neuronal signalling axis

Christina Ludwig
contact affiliation	Bavarian Center for Biomolecular Mass Spectrometry (BayBioMS) Technical University of Munich (TUM) Gregor-Mendel-Strasse 4 85354 Freising Germany
contact email	tina.ludwig@tum.de
lab head
Christina Ludwig
contact affiliation	TU Munich
contact email	tina.ludwig@tum.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD071836
     1. Label: PRIDE project
     2. Name: Faecal Proteases and Immune Signatures Drive Subtype-Specific Enteric Neuronal Activation in IBS