Update on clinical and research application of fecal biomarkers for gastrointestinal diseases

Table 1 Fecal biomarkers for gastrointestinal diseases in clinical use with established diagnostic accuracies

S#	Name	Indication	Limitations	Sensitivity	Specificity
Biomarkers of IBD
1	Calprotectin	Distinguishing functional from organic bowel disease and predicting relapse in IBD	Disease nonspecific Affected by age, comorbidities, NSAIDs use Day to day variations Miss low level inflammatory activity	70%-100%	70%-100%
2	S100 proteins	Inflammatory marker for IBD		60%-67%	70%-90%
3	Lactoferrin	Markers of inflammation, Distinguish between IBS and IBD	Nonspecific marker of inflammation Raised in breastfeeding infants Cannot predict low level inflammation	67%-87%	90%-100%
Biomarker of cell turnover
4	M2-PK	Screening of gastrointestinal tract cancers	Also raised in inflammation	67%-93%	88%-92%
Biomarkers of digestion and malabsorption
5	Elastase-1 (e1)	Pancreatic insufficiency	Low specificity, also affected by other intestinal disorders	100%	96%
6	Fecal fat	Liver damage, hypolipidemic drugs, impaired gallbladder function, Celiac disease, Small bowel bacterial overgrowth	Cannot predict severity of disease Cannot be performed in diarrhea Not accurate or specific test	70%-94%	80%-99%
7	Α1-antitrypsin	Protein-Losing Enteropathy, Whipple lipodystrophy, gastric carcinoma, intestinal lymphangiectasia	Nonspecific marker. Levels affected by inflammation	60%-78%	80%-85%

IBD: Inflammatory bowel disease; IBS: Irritable bowel syndrome; NSAID: Nonsteroidal anti-inflammatory drug.

Table 2 Fecal biomarkers under investigation for evaluating gastrointestinal diseases

S#	Name	Source	Function	Indication	Limitations
Biomarkers of inflammatory bowel disease
1	Cathelicidins	Secreted by Neutrophils, keratinocytes and epithelial cells of gastrointestinal tract, respiratory tract, urogenital tract	Antibacterial activity, modulate inflammation by altering cytokine response, chemoattraction of inflammatory cells in diseased tissues	Marker of inflammation (IBD) and Shigellosis	Antimicrobial peptides so also increased in GI infections
2	Osteoprotegerin	Member of the TNF receptor superfamily	Binds to RANKL and blocks its interaction with RANK	Marker of inflammation (IBD)	Plays a role in bone metabolism so levels are increased in bone diseases
3	Beta-glucuronidase	Produced by colonocytes Also produced by anaerobic gut bacteria (particularly E. coli)	Enzyme that breaks down complex carbohydrates Deconjugate glucuronide molecules from a variety of toxins, carcinogens, hormones, and drugs	Marker of inflammation (IBD)	False results in cases of GI bacterial infection
4	Neutrophil Gelatinase Associated lipocalin	Member of the lipocalin family, secreted by neutrophils	Immunomodulation. Attaches to and neutralizes bacterial formylpepetides	Marker of inflammation (IBD)	Also increased in GI infections like enterocolitis
Eosinophil related proteins
5	Eosinophil Protein X	When lamina propria is damaged, eosinophils migrate into the gut lumen Released by eosinophil; contribute to ongoing inflammation and tissue destruction	Marker of Eosinophil activity, Allergic and Parasitic influences	IgE-mediated food allergy Intestinal parasitic infection IBD	Also increased in GI inflammation
Biomarker of cell turnover
6	Defensins	Expressed by neutrophils, epithelial and mucosal lining cell in small and large intestine	Antimicrobial peptide	Markers of colorectal cancer	Also raised in inflammation
Biomarkers of gut health
7	Fecal secretory IgA	Secreted from mucosal surfaces	Gut epithelial barrier; Defense against the entry of enteric toxins and pathogenic organisms Development of immune tolerance of normal commensal gut organisms	Evaluate immunological response to intestinal pathogens Colorectal cancer	Cannot be used in subjects with immunoglobulin deficiency
8	SCFAs	Products of fermentation by colonic microbial flora; common ones are propionate, acetate, and butyrate	Provides 60%-70% of colonocytes energy requirements Lower colonic pH	Marker of inflammation (IBD)	< 5% of SCFA produced is excreted in stool Also levels altered by diet and rate of transit

SCFAs: Short-chain fatty acids; TNF: Tumor necrosis factor; IBD: Inflammatory bowel disease; GI: Gastrointestinal; RANK: Receptor activator of nuclear factor kappa B ligand.