Diagnostic utility of faecal biomarkers in patients with irritable bowel syndrome

Table 1 Studies investigating faecal markers in the differentiation of inflammatory bowel disease or healthy controls vs irritable bowel syndrome

Study	Marker	Cutoff value	Se	Sp	PPV	NPV	Subjects (n)	CD (n)	UC (n)	IBS (n)	HC (n)	Other (n)	Other diagnosis (n)	Verification
Kaiser et al[35] 2007	S100A12CP	> 0.8 mg/kg> 50 mg/kg	86% 63%	96% 86%	98% 90%	76% 51%	195	32	27	24	24	88	Bacterial (65) and viral (23) enteritis	Endoscopy/histology; immunohistochemistry
Sidler et al[42] 2008	S100A12CP	> 10 mg/kg> 50 mg/kg	97%100%	97% 67%	97% 75%	97%100%	61	30	1	14	0	16	Reflux esophagitis (6), juvenile polyp (2); eosinophilic GI disorder (3), others (5)	Endoscopy/histology
Tibble et al[26] 2000	CP	> 30 mg/L	100%	97%	-	-	276	31	0	159	56	30	Microscopic colitis (6), polyps (3), CRC (2), diverticulosis (19)	Radiology and/or colonoscopy
Tibble et al[28] 2002	CP	> 10 mg/L	89%	79%	76%	89%	602	102	87	339	0	74	Coeliac disease (12), diarrhea (14), CRC (7), colitis (6), small bowel enteropathy (21), diverticulosis (14)	Radiology and/or colonoscopy
Carroccio et al[32] 2003	CP	> 50 μg/g> 100 μg/g	66% 46%	84% 93%	83% 90%	68% 59%	158	18	0	55	20	65	Cow’s milk/food intolerance (22), coeliac disease (23), CRC/ polyps (3), diverticulosis (4), colitis (2), CD (9), giardiasis (2)	Endoscopy/histology (in selected patients only)
Fagerberg et al[33] 2006	CP	> 50 μg/g	95%	93%	95%	93%	36	10	7	5	0	14	Indeterminate colitis/IBD (3), polyps (1), proctitis (1), food intolerance (4), others (5)	Endoscopy/histology
Sydora et al[47] 2012	CP	> 150 μg/g(desk top device)	56%-100%	100%	-	-	42	7	9	7	19	0	-	Mayo clinic or harvey bradshaw index
Dolwani et al[91] 2004	CP	> 60 μg/g	100%	79%	60%	100%	138	25	0	24	26	63	Symptoms of diarrhea and/or abdominal pain (63)	Barium follow through
Costa et al[29] 2003	CP	> 50 μg/g	83%	82%	90%	71%	239	49	82	48	34	26	Intestinal neoplasms (26)	Colonoscopy and/or radiology
Canani et al[31] 2006	CP	> 95 μg/g	93%	89%	93%	89%	45	17	10	8	0	10	Food allergy (5), infectious enterocolitis (4), familial Mediterranean fever (1)	Endoscopy, histology and radiology
Summerton et al[40] 2002	CP	> 50 mg/kg	82%	73%	-	-	134	4	10	7	28	85	CRC (8), upper-GI lesions (44), diverticulosis (15), polyps (12), colon adenoma (6)	Upper or lower endoscopy
Dai et al[92] 2007	LF	> 24 μg/g	100%	100%	-	-	177	18	59	25	34	41	Bacteria infectious bowel disease (41)	Colonoscopy
Walker et al[70] 2007	LF	> 7.25 μg/mL	84%	97%	99%	55%	170	79	62	7	22	0	-	Endoscopy and/or radiology (in selected patients only)
Kane et al[68] 2003	LF	> 4 μg/g	86%	100%	100%	87%	271	104	80	31	56	0	-	Clinical, radiographic, endoscopic, and histological criteria, as appropriate
Sidhu et al[71] 2010	LF	> 7.25 µg/g	67%	96%	87%	87%	465	104	126	137	98	0	-	Colonoscopy (in selected patients only), questionnaires
Schoepfer et al[25] 2008	CPLF	> 50 μg/mL> 7 μg/mL	83% 87%	100% 96%	100% 98%	74% 77%	136	36	28	30	42	0	-	Endoscopy/histology
D’Inca et al[30] 2007	CPLF	> 50 mg/kg> 0.04 OD	78% 80%	83% 85%	86% 87%	-	144	31	46	20	0	47	CRC (8), polyps (26), diverticulosis (11), CD (2)	Colonoscopy/histology
Otten et al[41] 2008	CPCP FRTCP FRTLFLF FRT	> 50 mg/kg> 15 mg/kg> 60 mg/kg> 7.25 mg/mL> 128 ng/mL	96%100% 61% 78% 78%	87% 95% 98% 90% 99%	65% 82% 88% 67% 95%	99%100% 91% 94% 95%	114	6	5	91	0	12	Unspecified colitis/IBD (12)	Colonoscopy/sigmoidoscopy
Schröder et al[38] 2007	CPLFPMNE	> 24 μg/g> 8.9 μg/g> 19 ng/g	93% 82% 84%	100%100% 87%	100%100% 91%	91% 80% 79%	76	25	20	31	0	0	-	Endoscopy/histology; clinical disease activity indices
Langhorst et al[36] 2008	CPLFPMNE	> 48 μg/mL> 7.05 μg/mL> 0.062 μg/mL	82% 87% 77%	84% 77% 77%	-	-	139	43	42	54	0	0	-	Clinical disease activity indices; endoscopy
Langhorst et al[37] 2009	HBD2	MedianUC: 107 μg/gIBS: 76 μg/gHC: 30 μg/g	-	-	-	-	100	0	30	46	24	0	-	Endoscopy/histology; immunohistochemistry; faecal CP and LF
Ohman et al[87] 2012	CgBSgII	< 0.48 nmol/g> 0.16 nmol/g	78%80%	69% 79%	-	-	111	0	0	82	29	0	-	Faecal CP; rectal sensitivity; colon transit time; questionnaires
Annaházi et al[86] 2013	MMP-9	> 0.245 ng/mL	85%	100%	-	-	94	0	47	23	24	0	-	Clinical and endoscopic Mayo score; faecal CP
Silberer et al[39] 2005	CPLFPMNE	> 18.6 μg/g> 6.64 μg/g> 124 ng/g	62%33%80%	95% 95% 95%	-	-	119	21	18	40	40	0	-	Endoscopy/histology
Jeffery et al[82] 2009	M2PKCP	> 4 U/mL> 50 μg/g	67%93%	88% 92%	47%62%	94%99%	199	9	1	91	94	4	Collagenous colitis (1), CRC (1), stricture (1), coeliac disease (1)	Colonoscopy (n = 87) or radiology (n = 4)
Chung-Faye et al[81] 2007	M2PKCP	> 3.7 U/mL> 25 μg/g	73%80%	74% 74%	89%87%	57%65%	131	31	50	43	0	7	CRC (7)	Endoscopy/histology

Se: Sensitivity; Sp: Specificity; PPV: Positive predictive value; NPV: Negative predictive value; CD: Crohn’s disease; UC: Ulcerative colitis; IBS: Irritable bowel syndrome; HC: Healthy control; CP: Calprotectin; LF: Lactoferrin; PMNE: Polymorphonuclear elastase; MMP: Matrix-metalloprotease; HBD: Human β-defensin; Cg: Chromogranin; Sg: Secretogranin; MPO: Myeloperoxidase; M2PK: M2-pyruvate kinase; IBD: Inflammatory bowel disease; GI: Gastrointestinal; CRC: Colorectal cancer; FRT: Faecal rapid test.

Table 2 Overall diagnostic accuracy of faecal markers in the differentiation of inflammatory bowel disease vs irritable bowel syndrome in relation to the size of study cohorts

	Se	n	Sp	n	PPV	n	NPV	n	Ref.
Calprotectin	85%	2984	85%	2984	81%	2274	82%	2130	[25,26,28-33,35,36,38-42,47,81,82,91]
S100A12	89%	256	96%	256	98%	256	81%	256	[35,42]
Laktoferrin	78%	1811	94%	1811	91%	1376	82%	1232	[25,30,36,38,39,41,68,70,71,92]
M2-PK	69%	330	82%	330	64%	330	79%	330	[81,82]

Se: Sensitivity; Sp: Specificity; PPV: Positive predictive value; NPV: Negative predictive value; n: Number of study subjects; M2PK: M2-pyruvate kinase.