Fecal calprotectin and lactoferrin are proteins measured in stool that can accurately differentiate between inflammatory bowel disease and irritable bowel syndrome because they are elevated in the...
Mechanism
Synthesis from 1 study
When the gut lining gets damaged and lets bacteria through, it wakes up the immune system, which sends in white blood cells called neutrophils. These cells release proteins called calprotectin and lactoferrin, which show up in stool. In people without true inflammation, the gut lining stays sealed,...
Most probable mechanism
When the gut lining becomes leaky due to damage or weak connections between cells, bacteria and their parts can slip through and trigger immune cells to send out signals that attract neutrophils. These neutrophils rush into the gut wall, release calprotectin and lactoferrin as they fight, and leave behind high levels of these proteins in stool. In people without true inflammation, the gut lining stays intact, no neutrophils enter, and these proteins stay at low levels.
Reduced production of short-chain fatty acids from gut bacteria weakens the intestinal epithelial barrier by lowering expression of tight junction proteins such as occludin, claudin-1, and ZO-1.
Microbial components such as lipopolysaccharide and flagellin translocate across the compromised barrier and activate Toll-like receptors on immune cells in the lamina propria.
Toll-like receptor activation triggers NF-kB signaling, leading to production of chemokines that recruit neutrophils from the bloodstream into the intestinal tissue.
Infiltrating neutrophils release calprotectin and lactoferrin as part of their antimicrobial response, which accumulate in the gut lumen and are excreted in feces.
In the absence of barrier disruption and neutrophil infiltration, calprotectin and lactoferrin remain at baseline levels due to lack of sustained immune cell activation.
Less supported by current evidence, but not ruled out
Some bacteria can invade the gut lining and hide inside immune cells, where they multiply and keep triggering a long-term immune response that brings in neutrophils, which then release calprotectin and lactoferrin.
Adherent-invasive bacteria bind to overexpressed receptors on intestinal epithelial cells and invade the tissue.
These bacteria survive inside macrophages by avoiding cellular cleanup mechanisms, forming persistent bacterial communities.
Persistent intracellular infection continuously activates immune signaling pathways that recruit neutrophils to the site.
Neutrophils release calprotectin and lactoferrin in response to ongoing bacterial presence.
After a gut infection, the immune system may mistakenly attack proteins in the gut's nerve network, slowing down movement and letting bacteria build up, which then triggers low-level inflammation and neutrophil activity.
Antibodies made against a bacterial toxin cross-react with a protein in the gut's nerve network.
This cross-reaction damages cells that control gut movement, causing slow transit and bacterial overgrowth.
Bacterial overgrowth increases microbial load and barrier stress, leading to low-grade immune activation and neutrophil recruitment.
Neutrophils release calprotectin and lactoferrin in response to the increased bacterial burden.
Evidence from Studies
Supporting (1)
Community contributions welcome
Gut Microbiota in Irritable Bowel Syndrome and Inflammatory Bowel Disease: Differences in Pathophysiology, Biomarkers, and Treatment Implications
Contradicting (0)
Community contributions welcome
Gold Standard Evidence Needed
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