Managing an H. pylori Infection with High-Risk Virulence Factors

Using GI-MAP to Find the Root Cause of Nausea and Abdominal Pain

Cristina is a 58-year-old female who presented to my clinic with persistent nausea. For the year before seeing me, she felt so nauseous upon awakening that she felt the urge to vomit. Cristina also reported acute abdominal pain with onset ~ 30 minutes after eating, regardless of what foods she ate.

Cristina was previously diagnosed with small intestinal bacterial overgrowth (SIBO). She underwent both herbal and pharmaceutical treatments but never experienced significant improvement. To find the root cause of Cristina's chronic symptoms, I ordered a GI-MAP^™ for her.

GI-MAP Revealed H. pylori with Two High-Risk Virulence Factors

The GI-MAP results showed that Cristina was positive for H. pylori. Her quantitative result was 2.0e3, which is equivalent to 2000 organisms per gram of stool. What's more, she was also positive for four virulence factors — cagA, iceA , virB and virD. Vir B and D are part of the CagA pathogenicity island. When they are positive, they tend to make cagA more virulent.

H. pylori infections are highly prevalent and affect about half of the world's population. Disease presentation can range from a mild asymptomatic gastritis to peptic ulcer disease and even gastric cancer.¹ The diverse clinical presentations of H. pylori are based on its virulence factors.

Positive H. pylori virulence factors on the GI-MAP represent the genetic potential for an H. pylori strain to cause pathology. H. pylori virulence factors can be broken down into three major pathogenic processes:

1. Colonization
2. Immune escape
3. Disease induction²

H. pylori is notorious for evading both the innate and acquired immune system. It is often acquired in childhood and then it thrives in the stomach for decades with a potential to cause many issues with the normal human physiology.³ This process is known as "immune escape." Different H. pylori virulence factors can contribute to one or all of the pathogenic processes, and the more each infection contains, the more significant the infection.

Virulence Factor	Pathogenic Process	Associated Disease
babA	Colonization/Adhesion	Neutralized gastric acid and causes hypochlorhydria
cagA	Immune escape and disease induction	Gastric adenocarcinoma and peptic ulcer disease
dupA	Disease induction	Peptic ulcer disease
iceA	Disease induction	Peptic ulcer disease
oipA	Colonization and disease induction	Peptic ulcer disease
vacA	Immune escape and disease induction	Gastric adenocarcinoma and peptic ulcer disease4
virB & virD	Part of the CagA "pathogenicity island"	Potentiate CagA virulence

Managing H. pylori with Virulence Factors that Pose a Potential Cancer Risk

When managing patients who are H. pylori positive, practitioners must always be on the lookout for positive virulence factors — a unique feature of the GI-MAP stool test. When H. pylori with virulence factor cagA enters the stomach, it alters intracellular signal transduction pathways that facilitate malignant transformation of gastric epithelial cells. H. pylori with virulence factor vacA behaves in a similar way to cagA. Both vacA and cagA carry a higher risk of gastric adenocarcinoma and peptic ulcer disease.

When virulence factors for vacA and or cagA are positive on a GI-MAP, complete eradication of the H. pylori infection is the goal. Due to the risks posed by these virulence factors, it's beneficial to run a follow-up GI-MAP after treatment to gauge treatment success.

Insights from GI-MAP Help Guide Treatment and Improve Outcomes

Due to Cristina's symptoms, the level of H. pylori in her stool, and the significant positive virulence factors, I started her on a four-pronged conventional treatment protocol. I prescribed a combination of bismuth, metronidazole, and tetracycline and had Cristina take it three times a day for ten days. I also had her take a protein pump inhibitor (PPI) for thirty days to help alleviate the uncomfortable symptoms she was experiencing.

When dealing with H. pylori, it is always difficult to decide when to use herbal interventions and when to treat pharmaceutically. This choice always comes down to three key factors:

1. Patient preference
2. Significance of symptoms and patient's discomfort
3. Previous treatments sought and the success with those treatments

Pharmaceutical protocols are more established in literature. However, the treatment is very strong and patients who don't tolerate antibiotics or have many drug allergies will not tolerate that treatment as well. Patients who prefer natural routes of treatment must be educated that herbs, while effective, can take longer to treat and might not be a fit for some people. Certain patients, who are more chronic, might need both the pharmaceutical and natural approaches.

After the ten-day course of bismuth, metronidazole, and tetracycline, Cristina's symptoms decreased significantly. She was still suffering from nausea but not to the extent as before treatment. After weaning off the PPI at the thirty-day mark, most of her symptoms had resolved.

H. pylori can appear in stool for over six weeks following treatment. As a result, I don’t run a follow-up GI-MAP until eight weeks post treatment. I use the follow-up GI-MAP to see if the H. pylori infection has been eradicated. Also, if the patient remains symptomatic, the follow-up test will help me see if treatment has impacted the patient’s microbiome and if additional supportive gut health treatments are necessary.

The GI-MAP's quantitative results allowed me to see how prolific Cristina's H. pylori infection was. Further, because GI-MAP included critical information about the virulence factors she had, I was able to recognize the seriousness of her infection. As a result, I was able to personalize a protocol for her that not only helped her feel better, but also reduces the potential health risks that are associated with the cagA virulence factor.

---

---

REFERENCES

1. Amieva MR, El-Omar EM. Host-bacterial interactions in Helicobacter pylori infection. Gastroenterology. 2008 Jan;134(1):306-23. doi: 10.1053/j.gastro.2007.11.009. PMID: 18166359.
2. Chang WL, Yeh YC, Sheu BS. The impacts of H. pylori virulence factors on the development of gastroduodenal diseases. J Biomed Sci. 2018 Sep 11;25(1):68. doi: 10.1186/s12929-018-0466-9. PMID: 30205817; PMCID: PMC6131906.
3. Lina TT, Alzahrani S, Gonzalez J, Pinchuk IV, Beswick EJ, Reyes VE. Immune evasion strategies used by Helicobacter pylori. World J Gastroenterol. 2014 Sep 28;20(36):12753-66. doi: 10.3748/wjg.v20.i36.12753. PMID: 25278676; PMCID: PMC4177461.
4. Chang WL, Yeh YC, Sheu BS. The impacts of H. pylori virulence factors on the development of gastroduodenal diseases. J Biomed Sci. 2018 Sep 11;25(1):68. doi: 10.1186/s12929-018-0466-9. PMID: 30205817; PMCID: PMC6131906.
5. Backert S, Blaser MJ. The Role of CagA in the Gastric Biology of Helicobacter pylori. Cancer Res. 2016 Jul 15;76(14):4028-31. doi: 10.1158/0008-5472.CAN-16-1680. PMID: 27655809; PMCID: PMC5798256.