Helicobacter pylori: what does it cause, how is it treated, is resistance a problem, and do probiotics help eradication?

What it is

Helicobacter pylori is a bacterium that infects the stomach of more than half of the world's population. The Maastricht VI consensus states that it always causes chronic gastritis, which can progress to peptic ulcer, gastric adenocarcinoma and gastric MALT lymphoma.

What the research says

The evidence that H. pylori causes gastritis and raises the risk of ulcer and stomach cancer is well established. In randomised trials in mostly Asian populations, eradicating it reduced gastric cancer incidence (moderate-quality evidence), but the reduction in gastric cancer deaths was not statistically significant. Resistance to clarithromycin now exceeds the 15% threshold in most regions, so guidelines favour bismuth quadruple therapy. Adding probiotics raised eradication rates modestly in pooled trials of low-to-medium quality, but the benefit was confirmed for only four strains, vanished when antibiotics already worked well, and fewer side effects were seen only in unblinded trials.

Evidence grade: Well established.

What goes wrong

Worldwide, roughly 28% of H. pylori isolates were resistant to clarithromycin, with very high heterogeneity between studies. (Source 1)

• Meta-analysis, Low certainty.
• Size: Not stated in the excerpt.
• Who: H. pylori isolates worldwide, studies to April 2021.
• How long: Not applicable.
• Result: Resistance 27.53%; I2 = 97.80%.
• Funding: Not stated.

Overall CLA resistance rate was 27.53%, worldwide.

Adverse events were reported by about three in four patients on real-world eradication therapy, most often metallic taste, nausea and abdominal pain. (Source 2)

• Cohort study, Low certainty.
• Size: 160 analysed (185 diagnoses)
• Who: Primary care patients in Braga, Portugal.
• How long: About 3 weeks after treatment.
• Result: Adverse events 73.8%; metallic taste 39.4%, nausea 36.9%, abdominal pain 31.2%; eradication 96.7% with bismuth therapy.
• Funding: Independent (no external funding)

Adverse events were reported in 73.8% of inquiries

Saccharomyces boulardii, a probiotic yeast used alongside antibiotics, was linked to bloodstream fungal infection: at least 43% of Saccharomyces fungemia patients in Finnish hospitals were taking it. (Source 3)

• Case-control study, Low certainty.
• Size: 46 fungemia patients.
• Who: Patients in 5 Finnish university hospitals, 2009 to 2018.
• How long: 10 years.
• Result: OR for S. boulardii use 14 (95% CI 4 to 44) vs bacteremia/candidemia controls; 72% had recent antimicrobials.
• Funding: Not stated.

We found 46 patients who had Saccharomyces fungemia; at least 20 (43%) were using S. boulardii probiotic.

What the evidence supports

An international consensus states H. pylori always causes chronic gastritis, which may progress to peptic ulcer, gastric cancer and MALT lymphoma. (Source 4)

• Official position, High certainty.
• Size: Not applicable.
• Who: Consensus statement (Maastricht VI/Florence)
• How long: Not applicable.
• Result: Not applicable.
• Funding: Not stated.

always causes chronic gastritis, that may progress to severe complications such as peptic ulcer disease, gastric adenocarcinoma and gastric MALT lymphoma

Eradication therapy reduced gastric cancer incidence in healthy infected people, mainly in Asian trials. (Source 5)

• Meta-analysis, Moderate certainty.
• Size: 6 RCTs; 6,497 participants.
• Who: Healthy asymptomatic H. pylori-infected adults, mostly Asian.
• How long: Trial follow-up (varied)
• Result: Gastric cancer 1.6% vs 2.4%; RR 0.66 (95% CI 0.46 to 0.95)
• Funding: Independent (funding: none)

Fifty one (1.6%) gastric cancers occurred among 3294 individuals who received eradication therapy versus 76 (2.4%) in 3203 control subjects (relative risk 0.66, 95% confidence interval 0.46 to 0.95).

Maastricht VI states the 15% clarithromycin-resistance threshold is now exceeded in most WHO regions and recommends bismuth quadruple therapy where resistance is high or unknown. (Source 4)

• Official position, Moderate certainty.
• Size: Not applicable.
• Who: Consensus statement.
• How long: Not applicable.
• Result: Not applicable.
• Funding: Not stated.

If individual susceptibility testing is not yet available, the first line recommended treatment for areas of high (>15%) or unknown clarithromycin resistance is BQT.

Adding probiotics to eradication therapy modestly increased eradication rates in pooled RCTs. (Source 6)

• Meta-analysis, Low certainty.
• Size: 33 RCTs; 4,459 patients.
• Who: Adults receiving H. pylori eradication therapy.
• How long: Treatment course (varied)
• Result: Eradication RR 1.122 (95% CI 1.086 to 1.159), ITT.
• Funding: Independent (National Natural Science Foundation of China)

Overall, the pooled eradication rate in probiotics supplementation groups was significantly higher than in controls

What the evidence does not support

The reduction in deaths from gastric cancer after eradication was not statistically significant. (Source 5)

• Meta-analysis, Moderate certainty.
• Size: 3 RCTs; 4,475 participants.
• Who: Healthy asymptomatic infected adults.
• How long: Trial follow-up (varied)
• Result: RR of death from gastric cancer 0.67 (95% CI 0.40 to 1.11)
• Funding: Independent (funding: none)

relative risk of death from gastric cancer with eradication therapy compared with placebo was 0.67 (95% confidence interval 0.40 to 1.11)

Probiotics reduced side effects only in unblinded trials; double-blinded trials showed no significant reduction, and trial quality was medium to low. (Source 6)

• Meta-analysis, Low certainty.
• Size: 20 RCTs assessing side effects.
• Who: Adults receiving eradication therapy.
• How long: Treatment course.
• Result: Side effects pooled RR 0.589 (non-blinded) vs 0.889 (double-blinded, not significant)
• Funding: Independent.

The quality of the trials was medium to low and no study had a low risk of bias across all Cochrane criteria.

Where the evidence is mixed

The authors cautioned that the gastric cancer benefit may not extend beyond Asian populations. (Source 5)

• Meta-analysis, Moderate certainty.
• Size: 6 RCTs.
• Who: Healthy asymptomatic infected adults.
• How long: Not applicable.
• Result: Not applicable.
• Funding: Independent (funding: none)

these data cannot necessarily be extrapolated to other populations

The eradication benefit was confirmed only for four individual strains (Lactobacillus acidophilus, Lactobacillus casei DN-114001, Lactobacillus gasseri and Bifidobacterium infantis 2036) and for relatively ineffective antibiotic therapies. (Source 6)

• Meta-analysis, Low certainty.
• Size: 33 RCTs.
• Who: Adults receiving eradication therapy.
• How long: Treatment course.
• Result: Strain-level subgroup analysis.
• Funding: Independent.

Sub group-analysis could, however, confirm this finding only for four individual strains (Lactobacillus acidophilus, Lactobacillus casei DN-114001, Lactobacillus gasseri, and Bifidobacterium infantis 2036) and for relatively ineffective antibiotic therapies.

Non-invasive tests for H. pylori are fairly accurate, but a Cochrane review judged nearly all diagnostic studies to be of poor quality. (Source 7)

• Systematic review, Low certainty.
• Size: 101 studies; 11,003 participants.
• Who: People tested for H. pylori.
• How long: Not applicable.
• Result: Per 1000 tested: false negatives 30 (13C urea breath test), 42 (14C), 86 (serology), 89 (stool antigen)
• Funding: Not stated.

Except for one study, all the studies were of poor methodological quality, which makes their results unreliable.

Where the research disagrees

Whether probiotic add-ons meaningfully help eradication

• Dang et al. (2014) conclusion, Meta-analysis of 33 RCTs: may be considered an option for increasing eradication rates, particularly when antibiotic therapies are relatively ineffective (Source 6)
• Same meta-analysis, blinded-trial subgroup, Subgroup analysis: only results from non-blinded trials provided evidence for the reduction of side-effects (Source 6)

How much

• Studied: Probiotic trials added strains such as Lactobacillus acidophilus, Lactobacillus casei DN-114001, Lactobacillus gasseri and Bifidobacterium infantis 2036 to standard antibiotic regimens. (Source 6)

A common belief, and what the research shows

The belief: Probiotics alone can get rid of H. pylori, or any probiotic helps the antibiotics.

What the research shows: The trials tested probiotics added to antibiotics, and the benefit held for only a few strains: "Sub group-analysis could, however, confirm this finding only for four individual strains (Lactobacillus acidophilus, Lactobacillus casei DN-114001, Lactobacillus gasseri, and Bifidobacterium infantis 2036)."

Questions and answers

What does H. pylori cause?

It always causes chronic stomach inflammation (gastritis), which may progress to peptic ulcer, stomach cancer or MALT lymphoma. Eradication reduced gastric cancer incidence in trials in Asian adults. (Source 4)

What eradication regimens are used, and is antibiotic resistance a problem?

Clarithromycin resistance averages about 28% worldwide and is rising, above the 15% threshold in most regions. The Maastricht VI consensus therefore recommends bismuth quadruple therapy first where susceptibility testing is not available. (Source 4)

Do probiotics help eradication?

Pooled trials show a small increase in eradication (RR 1.12), confirmed for only four strains and absent when antibiotics already worked well. Reductions in side effects appeared only in unblinded trials, and trial quality was medium to low. (Source 6)

What is it?

A stomach bacterium carried by more than half of people worldwide. (Source 4)

What does it do in the body?

It inflames the stomach lining and can lead to ulcers and stomach cancer. (Source 4)

Is it good or bad for you?

The consensus view is harmful: it always causes gastritis. Eradication lowered gastric cancer incidence in Asian trials, though the fall in gastric cancer deaths was not statistically significant. (Source 5)

How do you get more of it?

Does not apply: H. pylori is treated as a pathogen. How it is transmitted was not covered by the sources reached this session. (Source 4)

We searched: Maastricht VI abstract; transmission papers were not reached.

If it is harmful, what reduces it?

Antibiotic combinations with acid suppression; bismuth quadruple therapy is first line where clarithromycin resistance is high or unknown. Side effects are common, and probiotic add-ons help only modestly. (Source 4)

Why might someone be low in it or missing it?

Not applicable in the usual sense; being uninfected is the normal target. Whether its absence has any downside was not addressed in the sources reached this session. (Source 4)

We searched: Searched eradication and consensus sources only.

Which whole foods contain it or feed it?

No food evidence was reached this session. (Source 4)

We searched: Food and dietary-component studies (e.g. broccoli sprouts, cranberry) were not searched within budget.

What happens if you do not have it?

Without infection, the chronic gastritis it causes does not occur; in trials, eradication reduced gastric cancer incidence in Asian adults. (Source 5)

How can you test for it, and how reliable is that test?

Urea breath tests, stool antigen tests and blood serology. Out of 1,000 people tested in the review's hypothetical example (about 54% infected), breath tests would miss about 30 to 42 infections versus about 86 to 89 for serology or stool antigen, but nearly all diagnostic studies were of poor quality. (Source 7)

References

1. PeerJ. The prevalence of clarithromycin-resistant Helicobacter pylori isolates: a systematic review and meta-analysis. 2023. DOI 10.7717/peerj.15121. Read the source
2. International Journal of Environmental Research and Public Health. Multicentric Study to Assess Helicobacter pylori Incidence, Patient Reported Adverse Events, Compliance and Effectiveness, in Real-World Setting. 2022. DOI 10.3390/ijerph191912847. Read the source
3. Emerging Infectious Diseases. Fungemia and Other Fungal Infections Associated with Use of Saccharomyces boulardii Probiotic Supplements. 2021. DOI 10.3201/eid2708.210018. Read the source
4. Gut. Management of Helicobacter pylori infection: the Maastricht VI/Florence consensus report. 2022. DOI 10.1136/gutjnl-2022-327745. Read the source
5. BMJ. Helicobacter pylori eradication therapy to prevent gastric cancer in healthy asymptomatic infected individuals: systematic review and meta-analysis of randomised controlled trials. 2014. PMID 24846275, DOI 10.1136/bmj.g3174. Read the source
6. PLOS ONE. The Effect of Probiotics Supplementation on Helicobacter pylori Eradication Rates and Side Effects during Eradication Therapy: A Meta-Analysis. 2014. DOI 10.1371/journal.pone.0111030. Read the source
7. Cochrane Database of Systematic Reviews. Accuracy of different non-invasive methods for identifying Helicobacter pylori (Cochrane review CD012080). 2018. Read the source