Overview.
Gut health extends far beyond digestion. The GI tract is a primary interface between your body and the environment, housing 70% of your immune system and profoundly influencing metabolism, mood, and systemic inflammation. Yet most routine blood panels miss gut-specific pathology entirely. A targeted combination of blood tests and stool markers can identify celiac disease, inflammatory bowel disease, liver dysfunction, H. pylori infection, and metabolic disruption — conditions that affect 30%+ of the population and are frequently missed for years.
Ranked biomarkers.
#1 Fecal Calprotectin
The gold standard non-invasive marker for intestinal inflammation. Distinguishes IBD from IBS with >90% sensitivity. A normal result (<50 μg/g) effectively rules out significant mucosal inflammation without colonoscopy. In known IBD, serial monitoring predicts relapse 2-3 months before symptoms worsen.
Optimal range: <50 μg/g (normal); 50-250 = indeterminate; >250 = inflammation likely
Key insight: This is a stool test, not a blood test — but it's more specific to the gut than any blood marker. If you have chronic diarrhoea and your calprotectin is normal, you almost certainly don't have IBD.
#2 tTG-IgA (Tissue Transglutaminase)
The primary screening test for celiac disease — an autoimmune condition affecting 1% of the population with 70% undiagnosed. Sensitivity >93%, specificity >95%. Catches cases presenting as 'just' iron deficiency, unexplained osteoporosis, or chronic bloating without classic diarrhoea.
Optimal range: <10 U/mL (negative); must check total IgA simultaneously to avoid false negatives
Key insight: You must be eating gluten at the time of testing. Going gluten-free before testing causes false negatives. Always request total IgA alongside tTG-IgA — 2-3% of celiac patients have IgA deficiency that makes the test unreliable.
#3 H. pylori Stool Antigen
Detects active H. pylori infection — the cause of most peptic ulcers and the strongest risk factor for gastric cancer. Unlike serology, stool antigen distinguishes current from past infection and confirms eradication after treatment. Sensitivity and specificity both >95%.
Optimal range: Negative (no active infection)
Key insight: Blood antibody tests (H. pylori IgG) remain positive for years after successful treatment — they tell you if you were ever infected, not if you currently are. Stool antigen or urea breath test is the correct test for both diagnosis and confirming eradication.
#4 ALT (Alanine Aminotransferase)
The most specific marker for hepatocyte (liver cell) damage. Elevated in fatty liver disease (MASLD, affecting 25-30% of adults), hepatitis, alcohol injury, and — importantly — as a hidden presentation of celiac disease. Standard lab upper limits (40-55 U/L) are too high; optimal is <30 U/L for men and <19 U/L for women.
Optimal range: Men: <30 U/L; Women: <19 U/L (not the standard lab range of <55 U/L)
Key insight: Up to 30% of patients with MASLD (fatty liver) have ALT within the standard 'normal' range. The most common cause of persistently mildly elevated ALT in non-drinkers is MASLD. Calculate FIB-4 score from routine blood work (age, AST, ALT, platelets) to assess fibrosis without imaging.
#5 GGT (Gamma-Glutamyl Transferase)
The most sensitive liver enzyme for biliary obstruction and cholestasis. Confirms hepatic origin of elevated alkaline phosphatase (vs bone). Sensitive to alcohol use, MASLD, and metabolic syndrome. Emerging evidence links elevated GGT to cardiovascular risk independent of liver disease.
Optimal range: <30 U/L (optimal); standard range up to 55 U/L
Key insight: Isolated elevated GGT (with normal ALT/AST) is commonly from enzyme induction by medications or alcohol, not active liver damage. But GGT + elevated ALT together suggests real hepatocellular injury worth investigating.
#6 CRP / hs-CRP
Systemic inflammation marker used alongside fecal calprotectin in IBD monitoring. Elevated CRP in GI symptoms pushes toward organic rather than functional causes. However, CRP can be normal in active mucosal IBD (especially UC), so it complements but does not replace calprotectin.
Optimal range: <1.0 mg/L (optimal); <3.0 mg/L (low cardiovascular risk)
Key insight: A normal CRP does NOT rule out active IBD. Calprotectin is more sensitive for gut-specific inflammation. But CRP >10 mg/L with GI symptoms strongly suggests an organic inflammatory or infectious cause.
#7 Fasting Insulin / HOMA-IR
Insulin resistance is the metabolic engine behind MASLD (fatty liver), and it alters gut motility and microbiome composition. HOMA-IR >2.5 identifies patients whose 'gut' symptoms have a metabolic root. In MASLD, addressing insulin resistance improves liver enzymes more than any liver-targeted therapy.
Optimal range: HOMA-IR <2.0; fasting insulin <5 μIU/mL (optimal)
Key insight: The gut-liver-metabolic axis is bidirectional. Gut dysbiosis worsens insulin resistance; insulin resistance worsens fatty liver; fatty liver worsens gut barrier function. Breaking this cycle at any point (diet, exercise, weight loss) improves all three.
#8 Vitamin D (25-OH)
Vitamin D receptors are expressed throughout the GI tract, and deficiency is associated with increased IBD risk and disease activity. Low vitamin D is also a marker of malabsorption from celiac disease. Repletion is associated with reduced IBD flares in observational studies.
Optimal range: >30 ng/mL (sufficient); target 40-60 ng/mL for immune health
Key insight: Unexplained vitamin D deficiency despite supplementation should trigger celiac disease screening. Malabsorption from villous atrophy is a common cause of treatment-resistant vitamin D deficiency.
How to test.
Start with: tTG-IgA + total IgA (celiac screen), CBC, CMP (liver panel including ALT), CRP, ferritin. Add fecal calprotectin (stool test) if chronic diarrhoea or suspected IBD. Add H. pylori stool antigen if dyspepsia. Add GGT and fasting insulin if metabolic risk factors or elevated ALT. Vitamin D for malabsorption screening. Most can be ordered by your GP without specialist referral.
FAQs.
Which test should I do first if I have chronic bloating?
tTG-IgA + total IgA (celiac screen) and TSH (thyroid) are the highest-yield first-line tests. If negative, add fecal calprotectin to rule out IBD. This combination catches the most common treatable causes of chronic bloating with minimal cost.
Do I need a colonoscopy if these tests are normal?
If all blood and stool markers are normal — particularly calprotectin <50 μg/g — a functional diagnosis (IBS, functional dyspepsia) is likely and colonoscopy may not be needed. However, colonoscopy is still recommended for age-appropriate cancer screening (45+), alarm symptoms, or family history of colorectal cancer.
Can I test gut health with a microbiome test?
Commercial microbiome tests (stool DNA sequencing) are marketed for gut health but have limited clinical validation. They tell you what bacteria are present but not whether they're causing symptoms. The biomarkers above have decades of validation and directly actionable results. Microbiome testing is currently a research tool, not a clinical one.
Why isn't a standard metabolic panel enough?
Standard panels (CMP) include ALT but not GGT, calprotectin, tTG-IgA, or H. pylori testing. They miss celiac disease, IBD, and H. pylori — three of the most common treatable GI conditions. You need to specifically request gut-focused tests.
Verdict.
These 8 biomarkers cover the major actionable dimensions of gut health: intestinal inflammation (calprotectin, CRP), autoimmune enteropathy (tTG-IgA), gastric infection (H. pylori), hepatobiliary function (ALT, GGT), metabolic-gut interaction (fasting insulin), and micronutrient absorption (vitamin D). Most are inexpensive, non-invasive, and available through any GP. The key is knowing to ask for them — standard panels miss most gut-specific pathology.