Methods for identifying and treating inflammatory bowel disease

Abstract

This disclosure concerns metabolites that can be used to identify and characterize inflammatory bowel disease (IBD) as well as assess treatment for IBD.

Description

[0001]Attorney Docket No.: 56387-0005WO1 METHODS FOR IDENTIFYING AND TREATING INFLAMMATORY BOWEL DISEASE CROSS REFERENCE TO RELATED APPLICATIONS 5 This application claims the benefit of United States Provisional Application No. 63 / 688,332, filed on August 29, 2024, which is incorporated herein by reference in its entirety. TECHNICAL FIELD This disclosure concerns metabolites that can be used to identify and characterize 10 inflammatory bowel disease (IBD) as well as assess treatment for IBD. BACKGROUND Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract that includes two common subtypes: ulcerative colitis (UC) and Crohn’s 15 disease (CD). In both cases the gut environment is perturbed and the symptoms are similar. However, Crohn's disease can occur anywhere in the digestive tract, often spreading deep into the layers of affected tissues, while ulcerative colitis usually impacts the mucosa of the large intestine and rectum. The disease-causing mechanisms are very poorly understood. 20 SUMMARY OF THE DISCLOSURE This disclosure is based, at least in part, on the identification and characterization of several metabolites present in fecal samples that are significantly associated with a diagnosis of IBD. Described herein is a method for treating a human subject that is suffering from or at 25 risk of developing an inflammatory bowel disease (IBD), the method includes: (a) measuring a level of a plurality of biomarkers in a biological sample obtained from the subject; (b) comparing each of the biomarker levels determined at step (a) with a corresponding predetermined reference value; (c) determining that the subject is suffering from or is at risk of developing an IBD when one or more of the biomarker levels determined at step (b) are higher 30 than the one or more of the corresponding predetermined reference values; and (d) administering a treatment for IBD to the subject determined to be suffering from or at risk of developing an IBD in step (c), wherein the biomarkers are each independently selected from the group consisting of compounds 1-143 in Table 5. 1 4891-0404-1476.1 Attorney Docket No.56387-0005WO1 In certain embodiments, the plurality of biomarkers comprises 2, 3, 4, 5, 6, 7, 8, 9, 10 11 or 12 of the biomarkers, e.g., 12 of the biomarkers. In other embodiments, the plurality of biomarkers comprises 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, or 70 of the biomarkers, optionally wherein the plurality of biomarkers comprises 66 biomarkers, optionally wherein the 66 biomarkers are compounds 1-66 in Table 5. In still other embodiments, the plurality of biomarkers comprises 140, 141, 142, or 143 of the biomarkers, e.g., 143 biomarkers. In embodiments, the biomarkers are selected from: Taurine, Putrescine, Cadaverine, Methionine, N-propionyltaurine, N-propionylputrescine, N-propionylcadaverine, N-propionylmethionine, N-acetyltaurine, N-acetylputrescine, N-acetylcadaverine and N-acetylmethionine. Also described herein is a method for determining whether a subject is suffering from or at risk of developing an inflammatory bowel disease (IBD), the method comprising: (a) measuring an the level of a plurality of biomarkers in a biological sample obtained from the subject; (b) comparing each of the biomarker levels determined at step (a) with a corresponding predetermined reference value; (c) determining that the subject is suffering from or is at risk of developing an IBD when one or more of the biomarker levels determined at step (b) are higher than the one or more of the corresponding predetermined reference values, wherein the biomarkers are selected from: wherein the biomarkers are selected from: Taurine, Putrescine, Cadaverine, Methionine, N-propionyltaurine, N-propionylputrescine, N-propionylcadaverine, N-propionylmethionine, N-acetyltaurine, N-acetylputrescine, N-acetylcadaverine and N- acetylmethionine. In various embodiments: the plurality of biomarkers comprises 2, 3, 4, 5, 6, 7, 8, 9, 10 11 or 12 of the biomarkers; wherein the plurality of biomarkers is a preselected biomarker set; the preselected biomarker signature set; the biomarker signature set comprises at least one of Taurine, Putrescine, Cadaverine, and Methionine and one or both of the corresponding N- propionyl derivative and the N-acetyl derivative; the biomarker signature set comprises at least 2, 3 or 4 of Taurine, Putrescine, Cadaverine, and Methionine and one or both of the corresponding N-propionyl derivative and the N-acetyl derivative; the biomarker signature set comprises at least 2, 3 or 4 of N-propionyltaurine, N-propionylputrescine, N- propionylcadaverine, N-propionylmethionine and the corresponding N-acetyl derivative; the inflammatory bowel disease is Crohn’s disease; the inflammatory bowel disease is ulcerative colitis; the biological sample is a fecal sample; the biological sample is a serum sample; and Attorney Docket No.56387-0005WO1 the subject has previously been treated with a therapeutic agent for treatment of IBD (e.g., a corticosteroid, an anti-TNF therapeutic and an anti-integrin therapeutic) Also described herein is a method for treating a human subject is suffering from or at risk of developing an inflammatory bowel disease (IBD), the method comprising: (a) measuring an the level of a plurality of biomarkers in a biological sample obtained from the subject; (b) comparing each of the biomarker levels determined at step (a) with a corresponding predetermined reference value; (c) determining that the subject is suffering from or is at risk of developing an IBD when one or more of the biomarker levels determined at step (b) are higher than the one or more of the corresponding predetermined reference values; and(d) administering a treatment for IBD to the subject determined to be suffering from or at risk of developing an IBD in step (c), wherein the biomarkers are selected from: Taurine, Putrescine, Cadaverine, Methionine, N-propionyltaurine, N-propionylputrescine, N-propionylcadaverine, N-propionylmethionine, N-acetyltaurine, N-acetylputrescine, N-acetylcadaverine and N- acetylmethionine. In various embodiments: the plurality of biomarkers comprises 2, 3, 4, 5, 6, 7, 8, 9, 10 11 or 12 of the biomarkers; wherein the plurality of biomarkers is a preselected biomarker set; the preselected biomarker signature set; the biomarker signature set comprises at least one of Taurine, Putrescine, Cadaverine, and Methionine and one or both of the corresponding N- propionyl derivative and the N-acetyl derivative; the biomarker signature set comprises at least 2, 3 or 4 of Taurine, Putrescine, Cadaverine, and Methionine and one or both of the corresponding N-propionyl derivative and the N-acetyl derivative; the biomarker signature set comprises at least 2, 3 or 4 of N-propionyltaurine, N-propionylputrescine, N- propionylcadaverine, N-propionylmethionine and the corresponding N-acetyl derivative; the inflammatory bowel disease is Crohn’s disease; the inflammatory bowel disease is ulcerative colitis; the biological sample is a fecal sample; the biological sample is a serum sample; and the subject has previously been treated with a therapeutic agent for treatment of IBD (e.g., a corticosteroid, an anti-TNF therapeutic and an anti-integrin therapeutic). In certain embodiments, the biomarker signature set comprises, or consists of, or consists essentially of cadaverine, putrescine, N-propionylcadaverine, N-propionylputrescine, N-acetylcadaverine, and N-acetylputrescine. In certain embodiments, the biomarker signature set comprises of, consists of, or consists essentially of cadaverine, putrescine, N-propionylcadaverine, N-propionylputrescine, N-acetylcadaverine, and N-acetylputrescine.; and the inflammatory bowel disease is Crohn’s disease. Attorney Docket No.56387-0005WO1 In certain embodiments, the biomarker signature set comprises, or consists of, or consists essentially of cadaverine, putrescine, N-propionylcadaverine, N-propionylputrescine, N-acetylcadaverine, and N-acetylputrescine; the inflammatory bowel disease is Crohn’s disease; and the subject has previously been treated with a therapeutic agent for treatment of IBD (e.g., a corticosteroid, an anti-TNF therapeutic and an anti-integrin therapeutic). In certain of the foregoing embodiments, the biological sample is a fecal sample. In other embodiments, the biological sample is a serum sample. In certain embodiments, the biomarker signature set comprises cadaverine, putrescine, N-propionylcadaverine, and N-propionylputrescine. In certain embodiments, the biomarker signature set comprises cadaverine, putrescine, N-propionylcadaverine, and N-propionylputrescine; and the inflammatory bowel disease is Crohn’s disease. In certain embodiments, the biomarker signature set comprises cadaverine, putrescine, N-propionylcadaverine, and N-propionylputrescine; the inflammatory bowel disease is Crohn’s disease; and the subject has previously been treated with a therapeutic agent for treatment of IBD (e.g., a corticosteroid, an anti-TNF therapeutic and an anti-integrin therapeutic). In certain of the foregoing embodiments, the biological sample is a fecal sample. In other embodiments, the biological sample is a serum sample. Also describe is a method for determining whether a treatment for inflammatory bowel disease (IBD) in subject that has been administered a first therapeutic agent for treatment of IBD is effective, the method comprising: (a) measuring an the level of a plurality of biomarkers in a biological sample obtained from the subject; (b) comparing each of the biomarker levels determined at step (a) with a corresponding predetermined reference value; (c) determining that the first therapeutic agent is not effective if one or more of the biomarker levels determined at step (b) are higher than the one or more of the corresponding predetermined reference values; and (d) administering an alternative therapeutic agent for IBD to the subject determined to have been administered a therapeutic agent determined to not be effective in (c), wherein the biomarkers are selected from: Taurine, Putrescine, Cadaverine, Methionine, N- propionyltaurine, N-propionylputrescine, N-propionylcadaverine, N-propionylmethionine, N- acetyltaurine, N-acetylputrescine, N-acetylcadaverine and N-acetylmethionine. In various embodiments: wherein the plurality of biomarkers comprises 2, 3, 4, 5, 6, 7, 8, 9, 10 11 or 12 of the biomarkers; wherein the plurality of biomarkers is a preselected biomarker set; the preselected biomarker signature set; the biomarker signature set comprises Attorney Docket No.56387-0005WO1 at least one of Taurine, Putrescine, Cadaverine, and Methionine and one or both of the corresponding N-propionyl derivative and the N-acetyl derivative; the biomarker signature set comprises at least 2, 3 or 4 of Taurine, Putrescine, Cadaverine, and Methionine and one or both of the corresponding N-propionyl derivative and the N-acetyl derivative; the biomarker signature set comprises at least 2, 3 or 4 of N-propionyltaurine, N-propionylputrescine, N- propionylcadaverine, N-propionylmethionine and the corresponding N-acetyl derivative; the inflammatory bowel disease is Crohn’s disease; the inflammatory bowel disease is ulcerative colitis; the biological sample is a fecal sample; the biological sample is a serum sample; the first therapeutic agent is selected from the group consisting of a corticosteroid, an anti-TNF therapeutic and an anti-integrin therapeutic; the alternative therapeutic agent is selected from the group consisting of: a corticosteroid, budesonide, prednisolone, beclomethasone, and immunosuppressive agent, an anti-TNF agent, immuazathioprine, methotrexate, 6- mercaptopurine, infliximab and adalimumab. The predetermined reference value is based on value determined in a population of subjects that is not suffering from IBD. The reference value of a biomarker may be an absolute or relative amount or concentration of the biomarker, a presence or absence of the biomarker, a range of amount or concentration of the biomarker, a minimum and / or maximum amount or concentration of the biomarker, a mean amount or concentration of the biomarker, and / or a median amount or concentration of the biomarker. The reference value of combinations of biomarkers may also be ratios of absolute or relative amounts or concentrations of two or more biomarkers with respect to each other. A reference value may be tailored to specific populations of subjects (e.g., it may be age-matched so that comparisons may be made between biomarker values in samples from subjects of a certain age and reference levels for a particular disease state, phenotype, or lack thereof in a certain age group). Reference values may also be tailored to specific techniques that are used to measure levels of biomarkers in biological samples (e.g., LC-MS, GC-MS, etc.), where the value of a given biomarker may differ based on the specific technique that is used. The biomarkers for inflammatory bowel disease also allow for monitoring progression / regression of inflammatory bowel disease in a subject. A method of monitoring the progression / regression of inflammatory bowel disease in a subject comprises: (1) analyzing a first biological sample from a subject to determine the level of one or more biomarkers for inflammatory bowel disease at a first time point, (2) analyzing a second biological sample from the subject to determine the level of the one or more biomarkers, at a second time point, and (3) comparing the level of one or more biomarkers in the first sample to the level of the one or Attorney Docket No.56387-0005WO1 more biomarkers in the second sample in order to monitor the progression / regression of inflammatory bowel disease in the subject. The results of the method are indicative of the course of inflammatory bowel disease (i.e., progression or regression, if any change) in the subject. Other features and advantages of the invention will be apparent from the following detailed description and figures, and from the claims. DESCRIPTION OF DRAWINGS FIG 1: Metabolic differences between patients with IBD and donors without IBD. Values reflect averages for metabolites across cohorts. FIG. 2 shows the chemical structures for the twelve metabolites shown in Table 1. FIG. 3A is a volcano plot showing statistically significant metabolite elevation in IBD patients versus non-IBD patients in a 12-metabolite panel (see metabolites delineated in Table 1 and FIG. 2). In each instance, the parent amine metabolites demonstrated statistically significant elevation as did the corresponding N-acetylated and N-propionylated conjugates. Key: ● = parent amine; ♦ = acetyl conjugate; and ■ = propionyl conjugate. FIG. 3B is a volcano plot showing statistically significant metabolite elevation in CD patients versus non-IBD patients in a 12-metabolite panel (see metabolites delineated in Table 1 and FIG. 2). In each instance, the parent amine metabolites demonstrated statistically significant elevation as did the corresponding N-acetylated and N-propionylated conjugates. Key: ● = parent amine; ♦ = acetyl conjugate; and ■ = propionyl conjugate. FIG. 3C is a volcano plot showing statistically significant metabolite elevation in UC patients versus non-IBD patients in a 12-metabolite panel (see metabolites delineated in Table 1 and FIG. 2). In each instance, the parent amine metabolites demonstrated statistically significant elevation as did the corresponding N-acetylated and N-propionylated conjugates. Key: ● = parent amine; ♦ = acetyl conjugate; and ■ = propionyl conjugate. FIG. 4A is a volcano plot showing statistically significant metabolite elevation in IBD patients versus non-IBD patients in a 143-metabolite panel (see metabolites delineated in Table 6). Key: ● = parent amine; ♦ = acetyl conjugate; and ■ = propionyl conjugate. FIG. 4B is a volcano plot showing statistically significant metabolite elevation in CD patients versus non-IBD patients in a 143-metabolite panel (see metabolites delineated in Table 7). Key: ● = parent amine; ♦ = acetyl conjugate; and ■ = propionyl conjugate. FIG. 4C is a volcano plot showing statistically significant metabolite elevation in UC patients versus non-IBD patients in a 143-metabolite panel (see metabolites delineated in Table 8). Key: ● = parent amine; ♦ = acetyl conjugate; and ■ = propionyl conjugate. Attorney Docket No.56387-0005WO1 DETAILED DESCRIPTION The invention is further described in the following examples, which do not limit the scope of the invention described in the claims. Example 1: Identification of biomarker metabolites Metabolomics data generated from fecal samples obtained from more than 1000 subjects with IBD (either Chron’s Disease (CD) or Ulcerative Colitis (UC)) and more than 500 without IBD across three studies was analyzed to identify unknown compounds associated with IBD. This analysis identified compounds whose identity was unknown and that were significantly differentially abundant between IBD and healthy subjects. Of these, approximately 100 unknowns presented significant associations in the same direction across the three studies, with the majority (60 compounds) being positively associated with IBD. Of these compounds, N-propionyltaurine was the most significantly up-regulated unknown compound in IBD, CD, and UC relative to healthy controls in both cohorts. In other metrics, N-propionyltaurine was also positively associated with dysbiosis, CD severity (as determined by Simple Endoscopic Score for Crohn’s Disease), UC extent, and IBD disease duration. Given that both the N-acetyl and N-propionyl conjugates of taurine were found to be up-regulated in IBD, the presence of other N-acetylated compounds that were elevated in both cohorts that might also have corresponding unknown N-propionyl conjugates was investigated. Trends in significantly elevated acetylated metabolites were uniform across studies: N- acetyltaurine was the most upregulated acetylated compound, followed by N-acetylputrescine, N-acetylcadaverine, and N-acetylmethionine. While all N-acetylated compounds detected by our global platform were not significantly upregulated in IBD, all of the most significant N- acetyl associations are with amino-linked carbon chains. Importantly, all parent compounds for each of these up-regulated metabolites were similarly elevated in IBD, although these associations are often not as significant or consistent as observed for the N-acetyl or N- propionyl conjugates. A heatmap reflecting average regression coefficients and P values for relevant metabolites across both studies is shown in FIG. 1. N-propionylmethione, which had previously been annotated by our global platform, was significantly up-regulated in IBD and CD across cohorts (FIG 1). The propionyl conjugates of putrescine or cadaverine were identified by structural elucidation of candidate unknown metabolites matching their target mass. Both N-propionylputrescine and N- propionylcadaverine were significantly upregulated in individuals with IBD across all cohorts analyzed (FIG 1). These metabolites also comprised several of the most significant Attorney Docket No.56387-0005WO1 associations with diagnoses for specific classes of IBD, with N-propionylcadaverine being the strongest indicator of CD overall in more than one study. Four parent compounds elevated in IBD (Taurine, Putrescine, Cadaverine and Methionine) were also observed to be N-acetylated and N-propionylated, collectively comprising a group of twelve related compounds (Table 1) that are consistently up-regulated in IBD. Three of these compounds were unknown metabolites, all of which are propionyl conjugates that are a consistent indicator of IBD diagnosis and disease severity using multiple independent metrics (Simple Endoscopic Score for Crohn’s Disease, UC extent ranking, and IBD disease duration). In particular, the abundance of N-propionyltaurine, N- propionylputrescine, and N-propionylcadaverine represent several of the most substantial associations, in terms of both significance and fold-change, with diagnosis of IBD and Crohn’s Disease (CD). Table 1: Biomarker Metabolites The chemical structures of the twelve metabolites in Table 1 are provided in FIG. 2. The twelve metabolites in Table 1 can be used in both diagnosis for IBD and prognosis for therapeutics targeting IBD. Of the three formerly unknown metabolites described here, only N-propionyltaurine presents significant associations with IBD diagnosis in serum, where N- propionyltaurine is negatively associated with IBD. Each of the biomarker metabolites can be detected and measured in a biological sample, e.g., feces or serum by any of a variety of method, including, but not limited to: enzyme-linked immunosorbent assay (ELISA), nuclear magnetic resonance (NMR), liquid chromatography with tandem mass spectrometry (LC-MS / MS), or single-molecule array (Simoa). An elevated level of two or more of the metabolites in a biological sample from a subject compared to a reference value obtained from a healthy human cohort can be used to Attorney Docket No.56387-0005WO1 diagnose IBD. In addition, such elevated level case be used to assess the success of a IBD therapy for the subject. with the term “elevated” defined as significantly greater than levels observed in a healthy human reference cohort. In an independent cohort that included 129 individuals diagnosed with inflammatory bowel disease (IBD), including both CD and UC, together with 40 non-IBD control subjects, was evaluated for validation purposes. In each instance in which the parent amine metabolite demonstrated statistically significant elevation, the corresponding N-acetylated and N- propionylated conjugates were likewise observed to be elevated in IBD. For IBD versus non- IBD individuals, see volcano plot in FIG.3A and Table 2. For CD versus non-IBD individuals, see volcano plot in FIG.3B and Table 3. For UC versus non-IBD individuals, see volcano plot in FIG. 3C and Table 4. Table 2 Table 3 Attorney Docket No.56387-0005WO1 Table 4 An expanded set of N-acetyl and N-propionyl conjugates were determined to be more broadly detectable in human fecal samples (see listing of metabolites in Table 5). In total, this expanded panel includes 143 metabolites and provides a framework for surveying the metabolic alterations characteristic of IBD. Within the cohort of 129 IBD subjects and 40 non- IBD controls, 66 of these metabolites were detected. Association with IBD status was Attorney Docket No.56387-0005WO1 compared between cohorts, and metabolites detected in both were observed to be consistently elevated or unchanged. For IBD versus non-IBD individuals, see volcano plot in FIG.4A and Table 6. For CD versus non-IBD individuals, see volcano plot in FIG. 4B and Table 7. For UC versus non-IBD individuals, see volcano plot in FIG. 4C and Table 8. Table 5 Attorney Docket No.56387-0005WO1 Attorney Docket No.56387-0005WO1 Attorney Docket No.56387-0005WO1 Table 6 Attorney Docket No.56387-0005WO1 Attorney Docket No.56387-0005WO1 Table 7 Attorney Docket No.56387-0005WO1 Attorney Docket No.56387-0005WO1 Table 8 Attorney Docket No.56387-0005WO1 Attorney Docket No.56387-0005WO1 Attorney Docket No.56387-0005WO1 OTHER EMBODIMENTS It is to be understood that while the invention has been described in conjunction with the detailed description thereof, the foregoing description is intended to illustrate and not limit the scope of the invention, which is defined by the scope of the appended claims. Other aspects, advantages, and modifications are within the scope of the following claims.

Claims

Attorney Docket No.56387-0005WO1 WHAT IS CLAIMED IS:

1. A method for treating a human subject that is suffering from or at risk of developing an inflammatory bowel disease (IBD), the method comprising: (a) measuring a level of a plurality of biomarkers in a biological sample obtained from the subject; (b) comparing each of the biomarker levels determined at step (a) with a corresponding predetermined reference value; (c) determining that the subject is suffering from or is at risk of developing an IBD when one or more of the biomarker levels determined at step (b) are higher than the one or more of the corresponding predetermined reference values; and (d) administering a treatment for IBD to the subject determined to be suffering from or at risk of developing an IBD in step (c), wherein the biomarkers are each independently selected from the group consisting of compounds 1-143 in Table 2.

2. The method of claim 1, wherein the plurality of biomarkers comprises 2, 3, 4, 5, 6, 7, 8, 9, 1011, or 12 of the biomarkers.

3. The method of claim 1, wherein the plurality of biomarkers comprises 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, or 70 of the biomarkers.

4. The method of claim 1, wherein the plurality of biomarkers comprises 140, 141, 142, or 143 of the biomarkers.

5. The method of any one of claims 1-4, wherein the plurality of biomarkers is a preselected biomarker set.

6. The method of claim 5, wherein the preselected biomarker set is a biomarker signature set.

7. The method of claim 6, wherein the biomarker signature set comprises at least one of Taurine, Putrescine, Cadaverine, and Methionine and one or both of the corresponding N-propionyl derivative and the N-acetyl derivative.Attorney Docket No.56387-0005WO1 8. The method of claim 6, wherein the biomarker signature set comprises at least 2, 3 or 4 of Taurine, Putrescine, Cadaverine, and Methionine and one or both of the corresponding N-propionyl derivative and the N-acetyl derivative.

9. The method of claim 6, wherein the biomarker signature set comprises at least 2, 3 or 4 of N-propionyltaurine, N-propionylputrescine, N-propionylcadaverine, N- propionylmethionine and the corresponding N-acetyl derivative.

10. The method of claim 6, wherein the biomarker signature set comprises or consists of: o Taurine, o Putrescine, o Cadaverine, o Methionine, o N-propionyltaurine, o N-propionylputrescine, o N-propionylcadaverine, o N-propionylmethionine, o N-acetyltaurine, o N-acetylputrescine, o N-acetylcadaverine and o N-acetylmethionine.

11. The method of any one of claims 1-10, wherein the inflammatory bowel disease is Crohn’s disease.

12. The method of any one of claims 1-10, wherein the inflammatory bowel disease is ulcerative colitis.

13. The method of any one of claims 1-12, wherein the biological sample is a fecal sample.

14. The method of any one of claims 1-12, wherein the biological sample is a serum sample.

15. The method of any one of claims 1-14, wherein the subject has previously been treated with a therapeutic agent for treatment of IBD.Attorney Docket No.56387-0005WO1 16. The method of claim 15, wherein the therapeutic agent is selected from the group consisting of a corticosteroid, an anti-TNF therapeutic and an anti-integrin therapeutic.

17. A method for treating inflammatory bowel disease (IBD) in a subject that has been administered a first therapeutic agent for treatment of IBD determined not to be effective for treatment of IBD, the method comprising: (a) measuringa level of a plurality of biomarkers in a biological sample obtained from the subject; (b) comparing each of the biomarker levels determined at step (a) with a corresponding predetermined reference value; (c) determining that the first therapeutic agent is not effective if one or more of the biomarker levels determined at step (b) are higher than the one or more of the corresponding predetermined reference values; and (d) administering an alternative therapeutic agent for IBD to the subject determined to have been administered a therapeutic agent determined to not be effective in (c), wherein the biomarkers are each independently selected from the group consisting of compounds 1-143 in Table 1, optionally wherein the biomarkers are selected from the group consisting of: o Taurine, o Putrescine, o Cadaverine, o Methionine, o N-propionyltaurine, o N-propionylputrescine, o N-propionylcadaverine, o N-propionylmethionine, o N-acetyltaurine, o N-acetylputrescine, o N-acetylcadaverine and o N-acetylmethionine.

18. The method of claim 17, wherein the plurality of biomarkers comprises 2, 3, 4, 5, 6, 7, 8, 9, 1011 or 12 of the biomarkers.

19. The method of claim 17, wherein the plurality of biomarkers comprises 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, or 70 of the biomarkers.

20. The method of claim 17, wherein the plurality of biomarkers comprises 140, 141, 142, or 143 of the biomarkers.Attorney Docket No.56387-0005WO1 21. The method of claim 17, wherein the plurality of biomarkers is a preselected biomarker set.

22. The method of claim 21, wherein the preselected biomarker set is a biomarker signature set.

23. The method of claim 22, wherein the biomarker signature set comprises at least one of Taurine, Putrescine, Cadaverine, and Methionine and one or both of the corresponding N-propionyl derivative and the N-acetyl derivative.

24. The method of claim 22, wherein the biomarker signature set comprises at least 2, 3 or 4 of Taurine, Putrescine, Cadaverine, and Methionine and one or both of the corresponding N-propionyl derivative and the N-acetyl derivative.

25. The method of claim 22, wherein the biomarker signature set comprises at least 2, 3 or 4 of N-propionyltaurine, N-propionylputrescine, N-propionylcadaverine, N- propionylmethionine and the corresponding N-acetyl derivative.

26. The method of claim 22, wherein the biomarker signature set comprises: o Taurine, o Putrescine, o Cadaverine, o Methionine, o N-propionyltaurine, o N-propionylputrescine, o N-propionylcadaverine, o N-propionylmethionine, o N-acetyltaurine, o N-acetylputrescine, o N-acetylcadaverine and o N-acetylmethionine.

27. The method of any one of claims 17-26, wherein the inflammatory bowel disease is Crohn’s disease.

28. The method of any one of claims 17-26, wherein the inflammatory bowel disease is ulcerative colitis.Attorney Docket No.56387-0005WO1 29. The method of any one of claims 17-26, wherein the biological sample is a fecal sample.

30. The method of any one of claims 17-26, wherein the biological sample is a serum sample.

31. The method of any one of claims 17-26, wherein the first therapeutic agent is selected from the group consisting of a corticosteroid, an anti-TNF therapeutic and an anti- integrin therapeutic.

32. The method of claim 1, wherein the therapeutic agent is selected from the group consisting of: a corticosteroid, budesonide, prednisolone, beclomethasone, and immunosuppressive agent, an anti-TNF agent, immuazathioprine, methotrexate, 6- mercaptopurine, infliximab and adalimumab.

33. A method for determining whether a subject is suffering from or at risk of developing an inflammatory bowel disease (IBD), the method comprising: (a) measuring a level of a plurality of biomarkers in a biological sample obtained from the subject; (b) comparing each of the biomarker levels determined at step (a) with a corresponding predetermined reference value; (c) determining that the subject is suffering from or is at risk of developing an IBD when one or more of the biomarker levels determined at step (b) are higher than the one or more of the corresponding predetermined reference values, wherein the biomarkers are selected from: o Taurine, o Putrescine, o Cadaverine, o Methionine, o N-propionyltaurine, o N-propionylputrescine, o N-propionylcadaverine, o N-propionylmethionine, o N-acetyltaurine, o N-acetylputrescine, o N-acetylcadaverine andAttorney Docket No.56387-0005WO1 o N-acetylmethionine.

34. The method of claim 33, wherein the plurality of biomarkers comprises 2, 3, 4, 5, 6, 7, 8, 9, 1011 or 12 of the biomarkers.

35. The method of claim 34, wherein the plurality of biomarkers is a preselected biomarker set.

36. The method of claim 35, wherein the preselected biomarker set is a biomarker signature set.

37. The method of claim 36, wherein the biomarker signature set comprises at least one of Taurine, Putrescine, Cadaverine, and Methionine and one or both of the corresponding N-propionyl derivative and the N-acetyl derivative.

38. The method of claim 36, wherein the biomarker signature set comprises at least 2, 3 or 4 of Taurine, Putrescine, Cadaverine, and Methionine and one or both of the corresponding N-propionyl derivative and the N-acetyl derivative.

39. The method of claim 36, wherein the biomarker signature set comprises at least 2, 3 or 4 of N-propionyltaurine, N-propionylputrescine, N-propionylcadaverine, N- propionylmethionine and the corresponding N-acetyl derivative.

40. The method of any one of claims 33-39, wherein the inflammatory bowel disease is Crohn’s disease.

41. The method of any one of claims 33-39, wherein the inflammatory bowel disease is ulcerative colitis.

42. The method of any one of claims 33-39, wherein the biological sample is a fecal sample.

43. The method of any one of claims 33-39, wherein the biological sample is a serum sample.Attorney Docket No.56387-0005WO1 44. The method of any one of claims 33-39, wherein the subject has previously been treated with a therapeutic agent for treatment of IBD.

45. The method of claim 44, wherein the therapeutic agent is selected from the group consisting of a corticosteroid, an anti-TNF therapeutic and an anti-integrin therapeutic.

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