Helicobacter pylori: What we know so far?

24 May

“The Kitchen is your lab and food is your best medicine!”

~ Dr Nina

Helicobacter pylori (H. pylori) is a Gram-negative, spiral-shaped bacteria that infects the stomach lining. It was discovered in 1983 by Australian scientists Barry Marshall and Robin Warren. It is one of the most frequent pathogens worldwide and colonizes around 50% of the population in developed countries and up to 80% in developing countries (approximately 4.4 billion people).

H. pylori has been implicated in various gastrointestinal conditions, including duodenal and gastric ulcers, gastric adenocarcinoma, chronic gastritis, gastric mucosa-associated lymphoid tissue (MALT) lymphoma. It has also been linked to non-ulcer dyspepsia, vitamin B12 deficiency, iron-deficient anaemia and immune thrombocytopenic purpura.

In 1994, the International Agency for Research on Cancer classified H. pylori in Group I carcinogen in humans. Gastric cancer is the fifth most common cancer and the third most common cause of cancer death globally. Infection with H. pylori is considered to be the most significant risk factor for gastric cancer and about 89% of gastric cancers are related to H. pylori infection. At the same time only 1-3% of H. pylori infected individuals will develop gastric cancer.

Recent research suggests that relationship between humans and H. pylori is more complex than previously thought. Despite a clear indication for its eradication some cases for H. pylori being a “friend” were recently made.

- H. pylori may help modulate the immune system, potentially protecting against certain autoimmune and allergic diseases. Its presence has been linked to a lower incidence of conditions like asthma, allergies, and inflammatory bowel disease. The bacteria might promote a more balanced immune response, preventing the immune system from overreacting to harmless substances.

- In certain situations, H. pylori can decrease stomach acid production, which may lower the risk of gastroesophageal reflux disease (GERD) and oesophageal cancer. However, very low stomach acid can lead to maldigestion, malnutrition, bacterial and fungal overgrowth (SIBO, SIFO).

- H. pylori has coexisted with humans for millennia, suggesting a complex coevolutionary relationship. This long-term association indicates that the bacteria may have roles beyond causing disease, possibly beneficially influencing various physiological processes. It can also have been a part of a diverse and balanced gut microbiome.

- H. pylori can influence levels of ghrelin and leptin, which are involved in appetite regulation, and therefore body weigh management and energy balance.

So, is the only good H. pylori - dead H. pylori? Not necessarily. While it is necessary to eradicate it in individuals at high risk for gastric cancer (family history, genetic mutations, previous stomach surgery, pernicious anaemia, chronic gastritis, obesity, high alcohol consumption, low fruit and vegetable intake, smoking, high salt intake), a blanket approach may not be beneficial to everyone and could lead to unintended health consequences.

Symptoms and Diagnosis:

In many cases, H. pylori infection is asymptomatic, meaning it doesn’t cause any noticeable symptoms. However, when symptoms do occur, they may include:

dull or burning abdominal pain or discomfort (especially on an empty stomach)
bloating
nausea
acid reflux
loss of appetite
frequent burping
unintended weight loss
vomiting
unexplained iron and vitamin B12 deficiency
fatigue

In countries with high gastric cancer rates such as Japan, Korea and China, population-based H. pylori screening has begun or is under consideration. This is not the case in countries where the prevalence is lower. However, if you experience any of the above symptoms, this could be considered as an indication for a testing. Diagnosis of H. pylori infection typically involves one or more of the following methods:

- Urea Breath Test: This test measures the presence of urease, an enzyme produced by H. pylori, in the breath after swallowing a urea solution.

- Stool Antigen Test: This test detects H. pylori antigens in a stool sample.

- Blood Test: This can identify antibodies against H. pylori, although it is less commonly used due to its inability to distinguish between current and past infections.

- Endoscopy: A biopsy taken during an endoscopy can directly identify the presence of H. pylori.

How H. pylori survives:

H. pylori possess some unique features which help it to survive and thrive in the harsh acidic environment of the human stomach.

1. Urease production:

H. pylori produces large amounts of the enzyme urease, which catalyses the breakdown of urea (present in the stomach) into ammonia and carbon dioxide. The ammonia helps neutralize the stomach acid around the bacterium, creating a more hospitable microenvironment.

2. Flagella and motility:

H. pylori is equipped with multiple flagella, whip-like structures that allow it to move. The bacteria use its flagella to burrow through the mucus layer of the stomach lining to reach the less acidic environment close to the epithelial cells.

3. Adhesion to gastric epithelium:

H. pylori can adhere to the epithelial cells lining the stomach using specific adhesins (surface proteins). This adhesion helps the bacteria to achieve high colonisation despite epithelial cell shedding, mucus layer turnover and the physical force involved in gastric emptying, all of which act to reduce colonisation.

4. Altering the host’s immune response:

H. pylori can express proteins that mimic host cell surface molecules, reducing the chances for it to be recognised as a foreign pathogen by the immune system. It can frequently change the expression of its surface proteins, affect the function of dendritic cells, which are crucial for initiating immune response and promote production of regulatory T cells, which suppress immune response. H. pylori can induce the production of certain cytokines: pro-inflammatory leading to chronic inflammation that creates a perfect environment for it to persist; anti-inflammatory modulating the immune response preventing an excessive inflammatory response that could clear the infection.

5. Biofilm Formation:

H. pylori can form biofilms, which are protective layers that shield the bacteria from the immune system and antibiotics. Biofilms protect the bacteria from the hostile environment and from the host’s immune defences.

6. Modification of the Stomach’s Mucus Layer:

H. pylori secretes enzyme mucinase, which alter the consistency of the mucus layer. This makes it easier for the bacterium to penetrate and colonise the stomach lining.

7. Genetic Adaptability:

H. pylori exhibits high genetic variability and adaptability. This genetic flexibility allows it to quickly adapt to the changing conditions within the stomach and evade the host’s immune system.

These strategies collectively enable H. pylori to persist in the stomach, where it can cause chronic infections that may lead to various gastrointestinal diseases. Understanding these mechanisms is crucial for developing effective treatments against H. pylori infections.

Treatments:

The traditional treatment regime is known as triple therapy. It includes two antibiotics and a proton pump inhibitor (PPI). The commonly used antibiotics are amoxicillin or clarithromycin (in case of penicillin allergy) and metronidazole. PPI (typically omeprazole) is used to raise intragastric pH to 6 or higher to optimise stability, bioavailability and efficacy of antibiotics. PPI can also inhibit urease production by H. pylori and it has an antibiotic effect on their own. It also promotes healing of the stomach lining due to increased pH.

Sometimes, a bismuth compound may be added to the regimen, creating a quadruple therapy, especially in cases where initial treatment fails or resistance is suspected.

Despite the effectiveness of triple and quadruple therapies, several challenges persist in eradicating H. pylori and it fails in about 25-30% of cases:

- Antibiotic resistance: the increasing resistance of H. pylori to commonly used antibiotics is a significant concern, necessitating alternative treatment strategies and the development of new antibiotics.

- Compliance: completing the full course of treatment can be difficult for some patients due to the side effects of multiple medications and the length of the treatment regimen.

- Insufficient acid suppression.

Therefore, alternative or supplemental methods for its eradication have been studied. Use of natural clinoptilolte has shown to reduce the growth of H. pylori by binding to the ammonia (see urease) and breaking down its protective shield exposing bacteria to the stomach acid.

Lactoferrin has shown a broad-spectrum antibacterial activity, which could inhibit Gram-negative and Gram-positive bacteria. Moreover, it has shown a direct antimicrobial activity against antibiotic resistant H. pylori strains and synergistic antibacterial effect in combination with triple therapy regime. In addition, it may improve the symptoms of gastric ulcer, gastric mucosal injury and inflammation.

Use of N-acetyl cysteine (NAC) as a biofilm disruptor is well documented. This is especially beneficial in cases of failed triple therapy. NAC should be taken a week prior to the antibiotics, to start to liquefy the biofilms and continued for the whole duration of treatment.

The use of probiotics as monotherapy or in combination with standard triple therapy has been researched. However, due to adverse physiological conditions of the stomach (highly acidic environment, gastric enzymes, peristalsis) the survival and activity of probiotics is limited. Interestingly, researchers have identified a specific Lactobacillus reuteri strain (DSM17648) that can work under harsh stomach conditions by binding and co-aggregating H. pylori. The aggregated H. pylori no longer can adhere to the gastric mucosa and the Lactobacillus/Helicobacter complexes are flushed out with natural bowel movement.

Saccharomyces boulardii is a non-pathogenic yeast, which is resistant to gastric acid, bile and proteolysis. And the most importantly it is naturally resistant to antibiotics, so it can be used as a part of the triple therapy. The studies have shown that use of S. boulardii in combination with the triple therapy significantly increased H. pylori eradication rates and reduced some adverse effects of the medications.

Both mastic gum and berberine have shown to be effective against H. pylori either on its own or in combination with the standard triple therapy.

Nutrition:

Diet plays a significant role in managing H. pylori infection and its associated symptoms. Anti-inflammatory foods can help healing while probiotic-rich foods (yogurt, kefir, sauerkraut, kimchi, miso) can restore a healthy gut microbiome. Particularly, incorporation of cruciferous vegetables (broccoli, broccoli sprouts, kale, cauliflower, cabbage, bok choy etc.), containing sulforaphane, has been shown to have a beneficial effect due to its antibacterial action against H. pylori. Omega-3 fatty acids (salmon, mackerel, sardines, flaxseeds, chia seeds, walnuts) have anti-inflammatory properties that can reduce inflammation of the stomach lining.

Processed, fried, spicy foods are better to be avoided as they can irritate the already damaged stomach lining and worsen the symptoms. Caffeine and alcohol should be avoided or at least limited during the treatment.

Interestingly, the high salt intake with H. pylori infection can lead to more severe gastroenteritis and increased risk of gastric cancer.

Conclusion:

H. pylori is pervasive bacteria with significant implications for gastrointestinal health. While effective treatments are available, challenges such as antibiotic resistance and reinfection remain. H. pylori is neither purely a friend nor a foe; it embodies elements of both. While its role in causing gastrointestinal diseases cannot be ignored, its potential benefits in modulating the immune system and regulating stomach acidity offer a more nuanced perspective. By adopting targeted and personalized approaches to its management, we can harness the beneficial aspects of H. pylori while mitigating its risks, ultimately promoting better overall health.

References:

https://doi.org/10.1016/S0140-6736(20)31288-5

https://doi.org/10.3748/wjg.v20.i27.8979

https://doi.org/10.3390/diseases9040066

https://doi.org/10.2174/1566524020666201203165649

https://doi.org/10.3390/microorganisms11051312

https://doi.org/10.4178/epih.e2020004

https://doi.org/10.1038/s41572-023-00431-8

https://doi.org/10.3748/wjg.v21.i31.9430

https://bnf.nice.org.uk/treatment-summaries/helicobacter-pylori-infection/

https://doi.org/10.1007/s11938-020-00300-3

https://doi.org/10.1016/j.micromeso.2019.109592