Everyone has the responsibility to prevent and control Helicobacter pylori infection, the culprit of gastric cancer.

Gastric cancer culprit

--Everyone is responsible for the prevention and control of Helicobacter pylori infection.

Author: Xiao Yongliang

An expert in popularizing science in China, a member of the popular science expert team of the Chinese Nutrition Society, a health lecture expert in Gansu Province, a former part-time professor at the School of Public Health of Lanzhou University, and a graduate student supervisor.

[The Institute of Infectious Disease Prevention and Control of the Chinese Center for Disease Control and Prevention officially released the "White Paper on the Prevention and Control of Helicobacter pylori Infection in China" (hereinafter referred to as the "White Paper") in Beijing on June 3, 2023. It is a manual for the diagnosis, treatment and prevention of Helicobacter pylori (HP) infection with Chinese characteristics. To this end, the author read the 2022 Chinese Helicobacter pylori Infection Treatment Guidelines, the Fifth National Consensus Report on the Treatment of Helicobacter pylori Infection, and the Consensus on the Diagnosis and Treatment of Chronic Atrophic Gastritis with Integrated Traditional Chinese and Western Medicine, and combined with many years of popular science and HP prevention and treatment experience to write this article and share it with you]

Helicobacter pylori (Hp) infection is one of the main pathogens of chronic gastritis, peptic ulcer, gastric mucosa-associated lymphoid tissue lymphoma, gastric cancer and other systemic diseases in humans. It is also the main pathogen of gastric cancer. About 90% of gastric cancers in the world are associated with HP infection. In 1994, WHO classified it as a Class I carcinogen. HP infection is one of the common chronic infections in humans. One-third to two-thirds of the world's population is infected, with a median of 50%. The infection rate in my country is also in the range of 35.4%-66.4%, making it one of the major public health issues in the world.

1. Discovery and harm of Helicobacter pylori

1.1 Discovery and naming of HP

HP is an ancient microbial species, a spiral-shaped, slightly anaerobic, Gram-negative bacterium. Studies have shown that HP originated in Africa and has survived in the world for about 60,000 years. European and Middle Eastern HP strains are divided into four populations based on their genome composition and separation geographical location information: Northern Europe, Southern Europe, Southwestern Europe, and the Middle East. HP has accompanied humans in about three migrations to Eurasia and spread across the world.

HP was first recognized by humans in 1983, when it was successfully isolated from gastric mucosal biopsy tissue of patients with chronic active gastritis. It was also the first time that HP was recognized as the pathogen of gastritis. In 1984, gastroenterologist Barry Marshall did not hesitate to "drink" a glass of beef extract culture mixture containing a curved bacteria prepared by Australian scientist Neil Noakes. Three days later, he developed gastritis and was cured after taking antibiotics. He then verified the relationship between gastritis and ulcers and Helicobacter pylori infection. This famous self-proven experiment earned them the 2005 Nobel Prize in Physiology or Medicine.

When HP was first discovered, it was called gastric Campylobacter-like bacteria. In 1983, it was renamed Campylobacter Helicobacter, in 1987 it was renamed Campylobacter Helicobacter, and in 1989 it was renamed Helicobacter pylori (H.pylori, HP) and has been used ever since.

1.2 HP infection routes and colonization

As far as we know, HP is one of the microorganisms that can survive in the human stomach by tenaciously resisting gastric acid. It is infected through fecal-oral, oral-oral, oral-gastric and other routes. Studies have shown that oral HP infection is positively correlated with gastric HP infection. After entering the oral cavity, HP gradually multiplies and colonizes in the gingival sulcus and periodontal pocket, causing the oral microecological balance to be disturbed and becoming another storage reservoir for HP. It then slowly invades the stomach and eventually colonizes in the gastric mucosa and intercellular spaces, causing the gastric microecological balance to be unbalanced. The microecological structure of the human gastrointestinal tract also changes, and the diversity of intestinal flora decreases, which leads to a series of related diseases in humans.

1.3 Global Status and Hazards of HP

With the development of human microecology and tumor microecology, the relationship between HP and human health and disease is becoming clearer and clearer. It is not only directly related to the causes of chronic gastritis, peptic ulcer and gastric cancer, but also closely related to various extra-gastrointestinal diseases throughout the body as the infection of Helicobacter pylori progresses, and can develop into various types of inflammation, chronic diseases and tumors, such as oral diseases such as periodontitis and tumors, skin inflammation-immune thrombocytopenic purpura, vitamin B12 deficiency, unexplained iron deficiency anemia, etc. Although many countries have taken measures, the number of infected people remains high, and there is no vaccine for prevention and treatment, which seriously endangers human health.

According to global cancer statistics in 2020, about half of the world's 8 billion people are infected, with gastric cancer incidence and mortality rates of 1,089,100 and 76,900, respectively, and 47,900 and 37,400, respectively, in China. According to national statistics in 2021, of the country's 1.41 billion people, about 768 million people and 494 million families are infected, with an average family size of 2.62 people; more than 50% of the population in my country is infected, making it one of the high-incidence areas of Helicobacter pylori and gastric cancer.

1.3.1 HP infection presents a “three highs and one low” trend and its factors

The diagnosis and treatment research of the current status of HP believes that HP presents a "three highs and one low" situation of high infection rate, high drug resistance rate, high pathogenicity and low eradication rate. The main factors for the low eradication rate are: bacterial factors, such as HP's drug resistance and bacterial spherical morphological variation, which should be the main reason for the decline in eradication rate; human factors, such as cytochrome gene (P4502C19) polymorphism affecting the therapeutic effect of proton pump inhibitors (PPI); physician factors, such as blindness in diagnosis and treatment, repetitive and irregular treatment plans, etc.; patient factors, such as poor compliance, inadequate protection and prevention, etc.

1.3.2 The rate of antibiotic resistance in HP is increasing and is showing an increasing trend

As the global trend of increasing resistance to HP antibiotics intensifies, my country is also among them or has a worsening trend. Since its establishment in 2018, the Chinese Center for Molecular Medicine (CCHpMM) has stored 20,000 HP strains, of which 13,000 are resistant strains. For example, CCHpMM resistance monitoring data showed that the primary resistance rates of HP in China to clarithromycin, levofloxacin, and metronidazole were 37.00%, 34.21%, and 87.87%, respectively, and the secondary resistance rates were as high as 76.93%, 61.58%, and 93.48%. The resistance of some antibiotics that were rarely resistant in the past, such as amoxicillin, furazolidone, and tetracycline, has also increased in some areas.

1.3.3 HP infection rate in households remains high

On January 23, 2023, a nationwide, large-scale, family-based epidemiological study of HP infection in 29 provinces was published in the journal Gut; the HP infection rate of families in the 29 provinces ranged from 50.27% to 85.06%, with an average of 71.21%, of which 19.70% of family members were all infected, and 71.13% of family members had 1-7 infected people; 28.87% of families were uninfected. The average individual HP infection rate was 40.66%, of which 43.45% were adults and 20.55% were children and adolescents; children's infection was significantly correlated with parental infection.

1.3.4 Independent risk factors for family infection

Contact with infected family members may be the main source of transmission. Independent risk factors for family infection are mainly related to infected family members and living in high-infection areas and large families with many infected people; lower infection rates are associated with higher education and income levels, and the use of spoons or chopsticks. Independent risk factors for family infection include: ① the number of infected family members, such as the OR of 5 infected members is 2.72, 95%CI: 1.86-4.00. ② Living in high-infection areas and living in large families, such as the OR of Northwest China is 1.83, 95%CI: 1.57-2.13; the OR of a family of three is 1.97, 95%CI: 1.76-2.21. ③ Education level and income level (OR 0.85, 95%CI: 0.79-0.91). ④ The infection rate was lower among family members who used serving spoons or chopsticks, had more generations (e.g., OR for three-generation families was 0.79, 95%CI: 0.69-0.92) and were younger (OR 0.57, 95%CI: 0.46-0.7) (P < 0.05).

2. HP prevention, control and recommendations

HP is one of the infectious bacteria with a long history in human history. It has the characteristics of high infection rate, heavy disease burden and high drug resistance rate. HP infection is difficult to heal on its own, and if not treated, it often leads to lifelong infection. Controlling HP infection is the most controllable and important means to prevent gastric cancer: everyone should be responsible, prevention should be the priority, combining Chinese and Western medicine, balanced diet, balanced microecology, focusing on the grassroots, moving the threshold of HP infection prevention and control forward, and integrating it into local policies and families or all residents.

2.1 Community screening, community eradication prevention and control, and recommendations

Given the serious disease burden of HP infection-related gastritis, peptic ulcer, gastric cancer and other major diseases, the overall benefit of eradicating HP infection is significantly higher than that of not eradicating it. Therefore, early screening and early eradication can effectively reduce the incidence of gastric cancer. As shown in the figure (picture source: Understanding Helicobacter pylori - the past and present of Helicobacter pylori https://mp.weixin.qq.com/s/XmxVS737gw2IGf50143JOg):

2.1.1 Community Health Checkup-Early Screening

Community health check-up is an important platform for HP infection diagnosis, and it is simple, easy to implement, and has low economic cost. It mainly uses 13C- or 14C-urea breath test, serological test, etc., combined with the specific situation of the patient to determine whether HP is infected.

On the basis of focusing on infection diagnosis, the drug resistance detection of HP-infected strains will be gradually included, such as feces-based Helicobacter pylori resistance gene detection, which will help guide the subsequent formulation of eradication treatment plans.

2.1.2 Early eradication in the community - implementation of eradication treatment plan

2.1.2.1 Blocking transmission routes

It is recommended to manage HP prevention and control in the community with each family as the unit. An important feature of HP transmission is family cluster infection. The main transmission is through fecal-oral, oral-oral, oral-gastric and other routes. Water, food and various items contaminated by Helicobacter pylori and family gatherings are the most common transmission. In the family, infected parents, especially infected mothers, are an important link. Spouses and siblings can also be infected.

2.1.2.2 Treatment options in the guidelines

At present, the preferred treatment for Hp infection is still the bismuth quadruple regimen, which is the most commonly used regimen in the clinical HP eradication treatment guidelines ("2022 China Hp Infection Treatment Guidelines"), such as the bismuth-containing quadruple regimen, which includes 2 antibiotics, an acid suppressant and a bismuth agent, with a course of 14 days.

Among them, commonly used antibiotics include amoxicillin, clarithromycin, levofloxacin, metronidazole, etc.; non-antibiotic drugs are also involved, including acid inhibitors, gastric mucosal protectants, traditional Chinese medicine, and proecological preparations.

The guidelines recommend the use of traditional Chinese medicine for sequential treatment of HP infection: the addition of the following traditional Chinese medicine to the bismuth quadruple regimen may improve the eradication rate; after treatment, Jinghua Weikang Capsules (160 mg, 3 times/d or 240 mg, 2 times/d, for a course of 3-4 weeks) or Banxia Xiexin Decoction, or traditional Chinese medicine prescriptions with rhubarb, coptis chinensis, and scutellaria baicalensis as the main ingredients may be used sequentially.

The Chinese herbal medicine information compiled by the author is shown in the figure and is for reference only.

2.1.2.3 Experience-based prevention and treatment + probiotics solutions and precautions

The author now shares the author's prevention and treatment methods for eradicating HP infection over the past 20 years (the HP eradication rate can reach more than 98%) as follows:

① Omeprazole, 20 mg, once in the morning and evening on an empty stomach. The course of treatment is 14-20 days.

② Livzon-Vitamin Triple, use according to the instructions. The course of treatment is 14 days. Note that the two colored tablets should be taken with meals to reduce gastrointestinal irritation.

③ Take 10 mg of Litrin, once in the morning and once in the evening, together with two tablets of Livzon-Vitamin Tri-link. A course of treatment is 14 days.

④ Oral probiotics to prevent oral and intestinal flora imbalance. Take 1-2 strips of the 4-linked or 18-linked probiotics independently developed by the author at around 2:30 p.m. every day, drink with boiled water or pour into the mouth and hold. Take orally for more than half a year since the start of treatment.

⑤ Notes: After the first course of treatment, wait one month before the second course of treatment. After the second course of treatment, wait three months before the third course of treatment. At the beginning of treatment, towels, toothbrushes, bowls, chopsticks and your own trousers must be disinfected, and used toilet paper in the bathroom must be strictly managed.

For patients with low levels of folic acid in the body, appropriate folic acid supplementation can improve the pathological tissue state of chronic atrophic gastritis and reduce the occurrence of gastric cancer.

For patients with chronic atrophic gastritis, appropriate Chinese medicine is selected to consolidate treatment based on syndrome differentiation and treatment.

2.1.3 Maintaining and maintaining the balance of the human microecology is the key to consolidating eradication treatment

After eradication treatment of HP infection, the antibiotics used will cause imbalance of human microecology, such as oral microecology imbalance will cause fungal stomatitis, intestinal flora imbalance will cause fungal enteritis, immune dysfunction, etc. Therefore, the key after treatment is to restore the balance of human microecology to prevent recurrence and reinfection.

The treatment guidelines and the Maastricht VI Consensus (in 2022, the European Hp and Microbiology Group released the "Management of Hp Infection: Maastricht VI Consensus Report", referred to as the "Maastricht VI Consensus") clearly stated that some probiotics (such as Lactobacillus reuteri, Bifidobacterium, Lactobacillus, Saccharomyces boulardii, etc.) combined with quadruple therapy can improve the eradication rate of Hp infection and reduce the occurrence of adverse events such as diarrhea. The quadruple regimen combined with probiotics can be used for patients with unstable intestinal microecology, and a mixed strain of Lactobacillus should be taken for at least 2 weeks before and during eradication treatment.

Many studies have shown that probiotics can antagonize HP through a variety of regulatory mechanisms. Their mechanisms of action can be summarized as regulating oral and intestinal microecology, forming mechanical and chemical biological barriers, secreting anti-inflammatory factors, regulating immune mechanisms, etc. Recently, the Oxford University scientific team published an article in the journal Science, stating that microbial diversity resists pathogens through nutritional blocking. The more bacterial species there are and the higher the diversity of the bacterial community, the stronger the resistance to pathogen colonization; the higher the metabolic overlap with pathogens, the more likely the bacterial species are to become the core of colonization resistance. This further confirms the relationship between the diversity of the human microecological balance and health, and that food diversity brings benefits of microbial diversity to the healthy microecological balance of humans.

2.2 Healthy people should try their best to avoid HP infection

HP is mainly transmitted through oral-oral and fecal-oral routes, as well as water and food contaminated by HP. Therefore, people who are not infected should do their best to prevent and develop good protective habits. For example:

① Wash your hands before and after meals, and brush your teeth after meals to clean up food residues in your mouth in time to prevent bacteria from entering your mouth and causing oral flora imbalance;

② Do not eat raw food or drink raw water - raw meat, vegetables, well water, etc. may be contaminated by HP;

③ The tableware must be disinfected - it is recommended to eat separately. If you have a meal outside, insist on using serving chopsticks and spoons to reduce cross infection.

④ Reasonable diet and balanced nutrition - for example, cabbage, broccoli, cloves, turmeric, fish oil, etc. have the effect of antagonizing HP, so be careful to consume them for a long time.

⑤ Quit smoking and limit alcohol consumption-both of these can cause oral flora imbalance.

⑥ Ensure effective sleep and reasonable exercise to strengthen physical fitness and improve the body's immunity.

3. Summary

The "White Paper on Prevention and Control of Helicobacter pylori (HP) Infection in China" has been officially released. Everyone has the responsibility to prevent and control HP infection, the culprit of gastric cancer.

Hp is the main pathogen of gastric cancer. The WHO classified it as a Class I carcinogen in 1994. The global infection rate of HP is about 1/3-2/3, and the infection rate in my country is about 1/2 (35.4%-66.4%). It is one of the major public health problems in the world. HP has the characteristics of high infection rate, heavy disease burden, and high drug resistance rate. HP infection is difficult to heal on its own, and if not treated, it often remains a lifelong infection.

Oral HP infection is positively correlated with gastric HP infection. HP infects humans through fecal-oral, oral-oral and other routes. After entering the oral cavity, it gradually multiplies and colonizes in the gingival sulcus and periodontal pockets, disrupting the balance of the oral microecology. The oral cavity becomes another storage bacteria reservoir for HP, disrupting the balance of the oral microecology. It then slowly invades the stomach, disrupting the balance of the gastric microecology, and finally colonizes in the gastric mucosa and cell gaps, causing a series of related diseases in humans.

HP infection prevention and control is the most important means of preventing gastric cancer. Everyone should be responsible, prevention should be the priority, Chinese and Western medicine should be combined, diet should be balanced, microecology should be balanced, the grassroots should be the focus, and blocking the transmission route is the key. The threshold for prevention and control of HP infection should be moved forward and integrated into local policies and families or all residents.

The key after treatment is to restore the balance of the human microecology to prevent recurrence and reinfection. Healthy people should do their best to "avoid" HP infection.

References

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