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

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.