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If you have Helicobacter pylori in your stomach, the strain matters more than the infection itself. Not all H. pylori strains carry the same risk. Some quietly colonize the stomach for decades without causing problems, while others produce a powerful toxin that drives chronic inflammation, ulcers, and gastric cancer.
This test looks at one of those defining differences: the vacA (vacuolating cytotoxin A) gene. Knowing which version of vacA your strain carries helps clarify whether you are infected with a more aggressive bacterium or a milder one, which can change how seriously you and your clinician treat the infection.
VacA is a protein toxin made and released by H. pylori bacteria. Once secreted, it inserts itself into the membranes of cells lining your stomach and forms tiny channels that let ions flow through. This drives the formation of large bubble-like structures (vacuoles) inside the cell, damages the energy-producing compartments inside cells (mitochondria), and weakens the seals between neighboring stomach cells.
VacA also targets your immune system. It blocks the activation and multiplication of T cells, the white blood cells that would normally help clear the infection, and it interferes with how B cells present bacterial fragments. The net effect is that H. pylori can persist in your stomach for years or decades, even though your body keeps trying to fight it off.
The vacA gene varies from strain to strain in three regions: the signal region (s), the intermediate region (i), and the middle region (m). The combinations of these regions determine how toxic a strain is and are reported as patterns like s1/m1, s2/m2, or i1.
As a rule, s1, i1, and m1 versions produce more active toxin and are linked to more severe disease. The s2 and m2 versions produce much less active toxin. The result on this test is categorical, meaning it tells you which version your strain carries rather than a number on a continuous scale.
| vacA Pattern | What It Suggests | Typical Disease Link |
|---|---|---|
| s1/m1 (often with i1) | More active toxin, stronger gastric damage | Stronger inflammation, peptic ulcers, higher gastric cancer risk |
| s1a subtype | High inflammation potential | Marked immune cell infiltration, very high duodenal ulcer rate |
| s2/m2 | Much less active toxin | Less inflammation, lower ulcer prevalence, common in many children |
| i1 with high vacA expression | Higher toxin output | More inflammation, immune cell infiltration, atrophy of stomach lining |
Source: Atherton et al. 1997; El Khadir et al. 2017 (sample size 1,079); Sinnett et al. 2016; Hussein et al. 2023 (sample size 115); Memon et al. 2014 matched case-control study.
VacA genotype is one of the strongest bacterial predictors of who develops peptic ulcers. In an Iranian meta-analysis of pooled cohorts, the m1, s1m1, and s2m1 genotypes were significantly tied to peptic ulcer disease. In a study of 1,079 Moroccan patients, the combination of vacA s1 and a positive cagA gene marked out duodenal ulcer cases.
In a Belgian matched case-control study, the s1 and i1 vacA genotypes were strong markers of duodenal ulcer-associated H. pylori strains. The s1a subtype specifically was associated with high rates of duodenal ulceration in earlier work that established this framework.
What this means for you: if your test shows an s1, i1, or m1 vacA pattern, your H. pylori is more likely to be the kind that causes ulcers, and treating it promptly is more important than waiting to see if symptoms develop.
H. pylori is one of the most established human carcinogens, but vacA helps explain why some infected people develop gastric cancer while most do not. A meta-analysis of multiple cohorts found that vacA s1 and m1 polymorphisms strongly increased the risk of intestinal metaplasia and gastric cancer. A separate meta-analysis confirmed that infection with vacA s1, m1 strains carries higher gastric cancer risk.
In the 1,079-patient Moroccan study, the vacA i1 genotype emerged as the strongest single marker of gastric cancer risk. A 1,303-patient follow-up study from the same group reinforced that vacA i1 was the most predictive virulence factor for precancerous gastric lesions, identifying patients at high risk for gastric cancer.
Across diverse U.S. populations totaling 8,126 participants, antibodies against the VacA protein in blood were associated with increased colorectal cancer risk, particularly in African Americans. A separate meta-analysis found that serum VacA antibody status was significantly tied to peptic ulcer, gastric ulcer, and duodenal ulcer risk.
What this means for you: a high-virulence vacA result on a known H. pylori infection moves the conversation from "watch and treat if symptoms appear" to "eradicate now and consider closer surveillance for precancerous changes," especially if you have a family history of gastric cancer.
In a study of patients undergoing endoscopy, gastric vacA expression was directly tied to the level of inflammation and the extent of premalignant changes in the stomach lining. A genetic difference at a specific position in the vacA gene determined how much toxin the strain produced, which then stratified disease risk. Higher transcription of i1 strains was linked to more inflammation, neutrophil infiltration, and atrophy.
This explains why two people with H. pylori can have very different outcomes. The strain producing more VacA causes more damage to the stomach lining, more thinning of the protective tissue (atrophy), and more changes that can eventually progress toward cancer.
vacA genotype also tracks with how easily H. pylori can be killed by antibiotics, though the relationships are complex. A systematic review and meta-analysis found that cagA-positive strains had higher resistance to metronidazole, while vacA s1m1 strains had lower resistance to metronidazole. The s2m2 "less virulent" strains generally showed lower antibiotic resistance overall.
In a meta-analysis examining eradication outcomes, infection with vacA s1, cagA-positive strains was actually more conducive to successful H. pylori eradication than s2, cagA-negative strains. This means that virulent strains are sometimes easier to clear with standard therapy, even though they cause more disease while present.
This test uses a stool sample. The lab uses a technique called PCR (polymerase chain reaction), which copies and reads bacterial DNA from your stool. Rather than measuring a level of VacA protein in your blood, it identifies which vacA gene variants the H. pylori in your gut carries.
Because vacA is reported as genotype categories rather than as a number, there are no traditional reference ranges (like "normal" or "high") for this test. Results indicate which version of the gene is present, and the interpretation comes from comparing your strain's pattern to the disease risk patterns established in research.
This is a research-validated genotyping marker rather than a routine clinical lab value with universally agreed thresholds. There are no standardized clinical cutpoints, no "optimal" range, and no published guideline thresholds that vary by age, sex, or ethnicity.
Lab-to-lab variation in PCR methodology can produce slightly different reporting formats, so compare results within the same lab if you retest after treatment.
vacA genotype itself does not change in a given strain over time, but the more important question is whether your H. pylori infection is still present after treatment. Standard practice is to confirm eradication after antibiotic therapy, typically four to eight weeks after finishing treatment, using a follow-up test.
If you tested vacA-positive with a high-virulence pattern, eradication confirmation matters more, not less. The combination of a virulent strain and incomplete eradication is the worst-case scenario for long-term gastric cancer risk. Repeat testing also matters because reinfection is possible, especially within close family members.
A reasonable cadence: test before treatment to confirm both H. pylori presence and strain virulence, retest 4 to 8 weeks after completing the full antibiotic course to confirm eradication, and consider periodic follow-up if you have additional gastric cancer risk factors like family history or significant atrophy already documented on endoscopy.
A vacA-positive result on a stool DNA test means H. pylori is present in your gut and you can identify which strain you have. The standard next step is eradication therapy, typically a combination of two antibiotics plus a stomach acid blocker for 10 to 14 days.
For patients with a high-risk vacA strain who have a first-degree relative with gastric cancer, a referral to a gastroenterologist for a personalized surveillance plan is reasonable, even after successful eradication.
Recent antibiotic use can suppress H. pylori below detection levels without truly eradicating it, producing a falsely negative test or making vacA genotyping unreliable. Wait at least 4 weeks after completing any antibiotic course before testing.
Proton pump inhibitors (acid-blocking medications like omeprazole, esomeprazole, and pantoprazole) can lower bacterial load enough to reduce test sensitivity. If possible, hold these for 1 to 2 weeks before testing, in consultation with your clinician. Bismuth-containing products have a similar effect.
Some people carry more than one H. pylori strain at the same time. Mixed infections can produce results showing both s1 and s2 or both m1 and m2 alleles, which can make interpretation less clean. The lab generally reports the dominant pattern, but a mixed result is not an error.
Evidence-backed interventions that affect your Virulence Factor, vacA level
Virulence Factor, vacA is best interpreted alongside these tests.