Lipocalin-2

Overview

Lipocalin-2 (LCN2), also called neutrophil gelatinase-associated lipocalin (NGAL), is a small secreted protein that rises rapidly during mucosal inflammation and infection and can be measured in blood, urine, and stool.^[1][2][3] In microbiome medicine, LCN2 is clinically useful because it reflects active epithelial and neutrophil-driven intestinal inflammation and simultaneously participates in nutrient control of microbes, making it both a biomarker and an effector of host defense.^[4][5]

How LCN2 shapes microbial ecology by starving bacteria of iron

Many gut bacteria require iron to replicate. During inflammation, bacteria often release siderophores, which are small iron-binding molecules that “steal” iron from the host. LCN2 binds the catecholate siderophore enterobactin, preventing bacterial re-uptake of iron and slowing growth of enterobactin-dependent organisms.^[6] This mechanism is a core component of mammalian innate immunity and is strongly induced by microbial sensing pathways.^[7]

Microbiome consequences are clinically relevant: in inflamed intestines, some pathogens gain a selective advantage by using “LCN2-resistant” iron acquisition systems. In experimental gut infection, Salmonella enterica benefits from inflammation because it can evade LCN2-mediated iron restriction, improving colonization of the inflamed gut compared with LCN2-susceptible competitors.^[8]

Fecal LCN2 as a noninvasive biomarker of intestinal inflammation

LCN2 is robust in stool and shows a wide dynamic range during colitis, supporting its use as a noninvasive marker of intestinal inflammation in preclinical models.^[9] In humans, fecal NGAL/LCN2 is detectable in active inflammatory bowel disease (IBD) and has been evaluated as a diagnostic and monitoring biomarker because it reflects mucosal inflammatory activity and epithelial involvement.^[10] Serum LCN2 also increases with IBD activity and is inducible in colonic epithelial cells by inflammatory cytokines, reinforcing its link to epithelial immune activation.^[11]

Translational relevance in microbiome medicine

Because LCN2 integrates host inflammatory tone with microbial iron competition, it is increasingly used to bridge clinical assessment (symptom and endoscopy-aligned inflammation) with microbiome-focused outcomes such as dysbiosis risk and pathogen expansion.^[12][13][14] In practice, LCN2 is best interpreted alongside clinical context and other inflammatory markers, but its biology uniquely connects intestinal barrier stress to microbiome selection pressures through iron restriction.^[15][16]

Research Feed

Update History

References

1. Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron. Flo TH, Smith KD, Sato S, et al.. (Nature. 2004)
2. An iron delivery pathway mediated by a lipocalin. Yang J, Goetz D, Li JY, et al.. (Mol Cell. 2002)
3. Lipocalin-2 resistance confers an advantage to Salmonella enterica serotype Typhimurium for growth and survival in the inflamed intestine.. Raffatellu M, George MD, Akiyama Y, et al.. (Cell Host Microbe. 2009)
4. Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron. Flo TH, Smith KD, Sato S, et al.. (Nature. 2004)
5. An iron delivery pathway mediated by a lipocalin. Yang J, Goetz D, Li JY, et al.. (Mol Cell. 2002)
6. Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron. Flo TH, Smith KD, Sato S, et al.. (Nature. 2004)
7. Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron. Flo TH, Smith KD, Sato S, et al.. (Nature. 2004)
8. Lipocalin-2 resistance confers an advantage to Salmonella enterica serotype Typhimurium for growth and survival in the inflamed intestine.. Raffatellu M, George MD, Akiyama Y, et al.. (Cell Host Microbe. 2009)
9. Fecal Lipocalin 2, a Sensitive and Broadly Dynamic Non-Invasive Biomarker for Intestinal Inflammation. Chassaing B, Srinivasan G, Delgado MA, Young AN, Gewirtz AT, Vijay-Kumar M.. (PLoS ONE. 2012)
10. Fecal Neutrophil Gelatinase Associated Lipocalin (NGAL) as a biomarker for Inflammatory Bowel Disease. Thorsvik S, Damås JK, Granlund AVB, Flo TH, Bergh K, Østvik AE, Sandvik AK.. (J Gastroenterol Hepatol. 2017)
11. Lipocalin-2 Is a Disease Activity Marker in Inflammatory Bowel Disease Regulated by IL-17A, IL-22, and TNF-α and Modulated by IL23R Genotype Status.. Stallhofer J, Friedrich M, Konrad-Zerna A, et al.. (Inflamm Bowel Dis. 2015)
12. Lipocalin-2 resistance confers an advantage to Salmonella enterica serotype Typhimurium for growth and survival in the inflamed intestine.. Raffatellu M, George MD, Akiyama Y, et al.. (Cell Host Microbe. 2009)
13. Fecal Neutrophil Gelatinase Associated Lipocalin (NGAL) as a biomarker for Inflammatory Bowel Disease. Thorsvik S, Damås JK, Granlund AVB, Flo TH, Bergh K, Østvik AE, Sandvik AK.. (J Gastroenterol Hepatol. 2017)
14. Lipocalin-2 Is a Disease Activity Marker in Inflammatory Bowel Disease Regulated by IL-17A, IL-22, and TNF-α and Modulated by IL23R Genotype Status.. Stallhofer J, Friedrich M, Konrad-Zerna A, et al.. (Inflamm Bowel Dis. 2015)
15. Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron. Flo TH, Smith KD, Sato S, et al.. (Nature. 2004)
16. Lipocalin-2 resistance confers an advantage to Salmonella enterica serotype Typhimurium for growth and survival in the inflamed intestine.. Raffatellu M, George MD, Akiyama Y, et al.. (Cell Host Microbe. 2009)