Pathway specific markers for diagnosing irritable bowel syndrome
View Patent ↗The present invention provides methods for aiding in the diagnosis of irritable bowel syndrome (IBS) in an individual. In particular, the present invention is useful for determining whether the individual does not have either celiac disease or inflammatory bowel disease (IBD), and has IBS and/or a subtype thereof. Thus, the present invention provides an accurate diagnostic prediction of IBS and is useful for guiding treatment decisions.
1. A method for aiding in the diagnosis of irritable bowel syndrome (IBS) and a clinical subtype thereof in a subject by generating a series of at least three biomarker scores (a) through (f) from a sample, said method comprising
(a) detecting in a sample obtained from said subject the level of at least one bacterial antigen antibody marker to obtain a microbiome score;
(b) detecting in said sample the level of at least one mast cell marker to obtain a mast cell score;
(c) detecting in said sample the level of at least one inflammatory cell marker to obtain an inflammatory score;
(d) detecting in said sample the level of at least one bile acid malabsorption (BAM) marker to obtain a BAM score;
(e) detecting in said sample the level of at least one kynurenine marker to obtain an oxidative stress score;
(f) detecting in said sample the level of at least one serotonin marker to obtain a serotonin score; and
(g) applying a statistical algorithm to said at least three scores, wherein the at least three scores include the bile acid malabsorption score, the serotonin score, and the oxidative stress score, wherein the sample is from a subject with IBS or is suspected of having IBS.
2. The method of claim 1 , wherein the at least one bacterial antigen antibody marker is selected from the group consisting of an anti-Fla1 antibody, anti-Fla2 antibody, anti-FlaA antibody, anti-FliC antibody, anti-FliC2 antibody, anti-FliC3 antibody, anti-YBaN1 antibody, anti-ECFliC antibody, anti-Ec0FliC antibody, anti-SeFljB antibody, anti-CjFlaA antibody, anti-CjFlaB antibody, anti-SfFliC antibody, anti-CjCgtA antibody, anti-Cjdmh antibody, anti-CjGT-A antibody, anti-EcYidX antibody, anti-EcEra antibody, anti-EcFrvX antibody, anti-EcGabT antibody, anti-EcYedK antibody, anti-EcYbaN antibody, anti-EcYhgN antibody, anti-RtMaga antibody, anti-RbCpaF antibody, anti-RgPilD antibody, anti-LaFrc antibody, anti-LaEno antibody, anti-LjEFTu antibody, anti-BfOmpa antibody, anti-PrOmpA antibody, anti-Cp10bA antibody, anti-CpSpA antibody, anti-EfSant antibody, anti-LmOsp antibody, anti-SfET-2 antibody, anti-Cpatox antibody, anti-Cpbtox antibody, anti-EcSta2 antibody, anti-Ec0Stx2A antibody, anti-CjcdtB/C antibody, anti-CdtcdA/B antibody, and a combination thereof.
3. The method of claim 1 , wherein the at least one mast cell marker is selected from the group consisting of β-tryptase, histamine, prostaglandin E2 (PGE2), and combinations thereof.
4. The method of claim 1 , wherein the at least one inflammatory marker is selected from the group consisting of CRP, ICAM, VCAM, SAA, GROα, and combinations thereof.
5. The method of claim 1 , wherein the at least one bile acid malabsorption marker is selected from the group consisting of 7α-hydroxy-4-cholesten-3-one, FGF19, and a combination thereof.
6. The method of claim 1 , wherein the at least one kynurenine marker is selected from the group consisting of kynurenine (K), kynurenic acid (KyA), anthranilic acid (AA), 3-hydroxykynurenine (3-HK), 3-hydroxyanthranilic acid (3-HAA), xanthurenic acid (XA), quinolinic acid, tryptophan, 5-hydroxytryptophan (5-HTP), and combinations thereof.
7. The method of claim 1 , wherein the at least one serotonin marker is selected from the group consisting of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA), serotonin-O-sulfate, serotonin-O-phosphate, and combinations thereof.
8. The method of claim 1 , wherein the level of said bacterial antigen antibody marker, said mast cell marker, said inflammatory cell marker, said BAM marker, said kynurenine marker or said serotonin marker is independently detected with a hybridization assay, amplification-based assay, immunoassay, immunohistochemical assay, or a mobility assay.
9. The method of claim 8 , wherein the hybridization assay comprises an ELISA or a collaborative enzyme enhanced reactive (CEER) immunoassay.
10. The method of claim 1 , wherein at least four members selected from the following group are measured: microbiome score, a mast cell score, an inflammatory score, a bile acid malabsorption score, an oxidative stress score, and a serotonin score.
11. The method of claim 1 , wherein at least five members selected from the following group are measured: microbiome score, a mast cell score, an inflammatory score, a bile acid malabsorption score, an oxidative stress score, and a serotonin score.
12. The method of claim 1 , wherein all members of the following group are measured: microbiome score, a mast cell score, an inflammatory score, a bile acid malabsorption score, an oxidative stress score, and a serotonin score.