Can bile acid diarrhea cause elevated Matrix Metalloproteinase 9 (MMP 9), beta defensin 2, lactoferrin, and eosinophil protein x in a stool sample, or hyperferritinemia, elevated vitamin B12, elevated Lactate Dehydrogenase (LDH), mildly elevated Aspartate Aminotransferase (AST), or vitamin D deficiency in laboratory results?

Bile Acid Diarrhea Does Not Cause These Inflammatory Markers

Bile acid diarrhea (BAD) is a non-inflammatory condition that does not cause elevated fecal inflammatory markers (MMP-9, beta-defensin-2, lactoferrin, eosinophil protein X) or the systemic inflammatory laboratory abnormalities you describe. The presence of these markers strongly suggests an alternative diagnosis requiring investigation for inflammatory bowel disease, eosinophilic disorders, or other organic pathology 1.

Fecal Markers: Why BAD Doesn't Elevate Them

Lactoferrin and Eosinophil Protein X

• Fecal lactoferrin is a neutrophil-derived protein that reflects intestinal inflammation, not bile acid malabsorption 2, 3
• Lactoferrin at thresholds of 4.0–7.25 mg/g achieves 79% sensitivity and 93% specificity for identifying inflammatory bowel disease, not functional disorders like BAD 1, 2
• Eosinophil protein X (EPX) is released during active inflammatory bowel disease and correlates with disease activity markers like fecal hemoglobin and alpha-1-antitrypsin 4
• EPX is more stable in feces than eosinophil cationic protein and serves as a marker for eosinophilic inflammation, which does not occur in BAD 4

Beta-Defensin-2 and MMP-9

• Beta-defensin-2 is an antimicrobial peptide of the innate immune system that is elevated in inflammatory conditions, including ulcerative colitis and even IBS with immune activation 5
• One study found beta-defensin-2 levels of 106.9 ng/g in active ulcerative colitis and 76.0 ng/g in IBS patients (versus 29.9 ng/g in healthy controls), indicating mucosal immune activation 5
• Matrix metalloproteinase-9 (MMP-9) is released from inflammatory cells during active intestinal inflammation and has been investigated as a biomarker for IBD activity 6
• BAD is a malabsorptive disorder without mucosal inflammation, so these immune markers should remain normal 1, 7

Systemic Laboratory Findings: Not Consistent with BAD

Ferritin, B12, and LDH

• High ferritin, elevated B12, and elevated LDH suggest systemic inflammation, hemolysis, or tissue damage—none of which are features of bile acid diarrhea 1
• Interestingly, vitamin B12 malabsorption (not elevation) can occur in ulcerative colitis due to bile acid deconjugation, but this is the opposite of what you're describing 8
• Elevated B12 is typically seen in myeloproliferative disorders, liver disease, or as an acute phase reactant—not in BAD 8

Mildly Elevated AST

• Transaminase elevation suggests hepatocellular injury or systemic inflammation, which are not features of BAD 1
• While BAD involves altered bile acid metabolism, it does not cause liver enzyme elevation unless there is concurrent liver disease 1, 7

Low Vitamin D

• Vitamin D deficiency can occur in any chronic diarrheal condition due to malabsorption, including BAD, but is non-specific 1
• This is the only laboratory finding on your list that could plausibly be associated with BAD, though it provides no diagnostic specificity 1

What This Pattern Actually Suggests

Inflammatory Bowel Disease

• The combination of elevated fecal lactoferrin, beta-defensin-2, eosinophil protein X, and MMP-9 strongly suggests active intestinal inflammation consistent with IBD 2, 9, 6
• Fecal calprotectin should be measured (threshold 50-60 mg/g) as the primary screening test, with colonoscopy and biopsy if positive 1, 2, 9
• Systemic markers (high ferritin, elevated LDH, mildly elevated AST) support active inflammatory disease 9

Eosinophilic Gastrointestinal Disorder

• Elevated eosinophil protein X specifically suggests eosinophilic involvement, which warrants evaluation for eosinophilic gastroenteritis or colitis 4
• This would require colonoscopy with biopsies showing tissue eosinophilia (>20 eosinophils per high-power field) 4

Critical Diagnostic Algorithm

1. Order fecal calprotectin immediately (if not already done) to quantify inflammatory burden 1, 2, 9
2. Proceed to colonoscopy with biopsies from right and left colon (not rectum) to evaluate for IBD, microscopic colitis, or eosinophilic colitis 7, 9
3. Screen for celiac disease with IgA tissue transglutaminase plus total IgA level, as this can coexist with diarrhea 1, 7
4. Consider testing for Giardia using antigen test or PCR, as chronic infection can cause inflammation 1, 7
5. Only after excluding inflammatory conditions should BAD testing be pursued with serum C4 or SeHCAT (if available) 1, 7

Common Pitfall to Avoid

• Do not pursue empiric bile acid sequestrant trials when inflammatory markers are elevated 7
• The British Society of Gastroenterology strongly recommends against empiric treatment instead of making a positive diagnosis, and your patient's inflammatory markers demand investigation for organic disease first 7
• BAD can coexist with microscopic colitis or post-inflammatory states, but the active inflammation must be identified and treated 7