Probiotics and Diet Modifications: A Holistic Approach to Tackling Helicobacter pylori with the Help of the Gut Microbiota

doi:10.21203/rs.3.rs-3139132/v1

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Probiotics and Diet Modifications: A Holistic Approach to Tackling Helicobacter pylori with the Help of the Gut Microbiota

https://doi.org/10.21203/rs.3.rs-3139132/v1

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Background

Helicobacter pylori is a common gastrointestinal bacterium that can cause a range of diseases, including gastritis, peptic ulcer disease, and gastric cancer. The gut microbiota plays an important role in H. pylori colonization and associated diseases.

Main body:

Lifestyle factors, such as diet, stress, smoking, and alcohol consumption, can impact the gut microbiota composition and function, and may influence the risk of H. pylori colonization and H. pylori-associated diseases. Strategies to promote gut health, such as a healthy diet, stress reduction, smoking cessation, alcohol moderation, regular exercise, adequate sleep, antibiotic stewardship, and probiotic supplementation, may help to reduce the risk of H. pylori colonization and enhance the effectiveness of H. pylori eradication therapy. Furthermore, the gut microbiota may also be a potential target for H. pylori eradication, and personalized treatment approaches based on individual patient characteristics may be necessary to optimize H. pylori eradication rates and reduce the risk of adverse effects.

Conclusion

Further research is needed to better understand the role of the gut microbiota in H. pylori eradication and to develop more effective treatment strategies. By promoting gut health and developing personalized treatment approaches, we may be able to reduce the burden of H. pylori-associated diseases and improve patient outcomes.

Helicobacter pylori (H. pylori) is a common bacterial pathogen that infects the stomach and is known to cause a range of gastrointestinal disorders. The bacterium is highly adapted to its niche in the stomach, where it can survive and persist for decades, even in the presence of the host immune system. H. pylori infection is prevalent worldwide, with an estimated 50% of the world's population being infected (1). H. pylori is a gram-negative, spiral-shaped bacterium that colonizes the gastric mucosa. The bacterium produces various virulence factors, including urease, vacuolating cytotoxin A (VacA), and the cag pathogenicity island (cagPAI), which are responsible for its pathogenesis. These virulence factors enable the bacterium to evade the host immune system and cause damage to the gastric epithelium, leading to chronic gastritis, peptic ulcer disease, and gastric cancer (2).

Conventional treatments for H. pylori infection involve a combination of antibiotics and acid suppression therapy. However, these treatments have limitations, including the development of antibiotic resistance, adverse side effects, and a high rate of treatment failure. As such, there is a growing interest in alternative approaches to H. pylori eradication (3). One promising approach is the use of probiotics, which are live microorganisms that confer health benefits when consumed in adequate amounts. Research suggests that probiotics may help to eradicate H. pylori by altering the gut microbiota and inhibiting the growth of the bacterium. Probiotics such as Lactobacillus and Bifidobacterium have been shown to have H. pylori-inhibiting properties and may be useful as an adjunct therapy to conventional treatments (4).

Diet is another factor that may impact H. pylori infection and eradication. The gut microbiota plays an important role in mediating the effects of diet on H. pylori colonization. For example, a diet rich in fiber and prebiotics may promote the growth of beneficial gut bacteria, which in turn may inhibit the growth of H. pylori and other harmful bacteria. Similarly, dietary factors such as polyphenols and omega-3 fatty acids have been shown to have H. pylori-inhibiting properties. The Mediterranean diet, in particular, has been shown to be effective in promoting H. pylori eradication (5). Lifestyle modifications, such as reducing stress, quitting smoking, and avoiding excessive alcohol consumption, may also play a role in promoting a healthy gut microbiota and H. pylori eradication. These lifestyle factors have been shown to impact the gut microbiota and may contribute to the development and persistence of H. pylori infection (6).

Conventional treatments for H. pylori eradication and their limitations

Conventional treatments for Helicobacter pylori (H. pylori) eradication typically involve a combination of antibiotics and acid suppression therapy. While effective in many cases, these treatments have several limitations. One of the main limitations is the development of antibiotic resistance. Overuse and misuse of antibiotics have led to the emergence of antibiotic-resistant strains of H. pylori, making it more difficult to treat infections. This is particularly problematic in regions with high rates of antibiotic use, such as Asia and Europe (7).

Another limitation of conventional treatments is their adverse side effects. Antibiotics can cause gastrointestinal symptoms, such as diarrhea and nausea, and may also lead to the development of secondary infections, such as Clostridioides difficile colitis. Acid suppression therapy can also have side effects, including headaches, dizziness, and the development of rebound hypersecretion of acid after treatment discontinuation (8). A high rate of treatment failure is another limitation of conventional treatments for H. pylori eradication. Treatment failure can occur due to antibiotic resistance, poor patient compliance, or underlying factors that contribute to the persistence of the infection, such as the presence of a biofilm (9).

Furthermore, conventional treatments may not be suitable for all patients, particularly those with comorbidities or who are taking other medications that may interact with the treatment regimen. This highlights the need for alternative approaches to H. pylori eradication (10). In light of these limitations, there is growing interest in alternative approaches to H. pylori eradication, such as the use of probiotics, diet, and lifestyle modifications. These approaches may have fewer side effects, be more effective in some patients, and have the potential to target the underlying factors that contribute to the persistence of H. pylori infection.

Probiotics

Probiotics are live microorganisms that, when consumed in adequate amounts, confer health benefits to the host. They are typically consumed as dietary supplements or added to foods such as yogurt, kefir, and sauerkraut. Probiotics are generally considered safe and have been shown to have a range of health benefits, including improving gut health, enhancing the immune system, and reducing the risk of certain gastrointestinal disorders (11). There are several types of probiotics, including:

Lactobacillus: This is a group of bacteria that is commonly found in the human gut and is also used in the production of fermented foods such as yogurt and kefir. Lactobacillus strains have been shown to have a range of health benefits, including improving gut health, reducing the risk of diarrhea, and enhancing the immune system (12).

Bifidobacterium: This is another group of bacteria that is commonly found in the human gut and is also used in the production of fermented foods. Bifidobacterium strains have been shown to have a range of health benefits, including improving gut health, reducing the risk of diarrhea, and enhancing the immune system (13).

Streptococcus: This is a group of bacteria that is commonly found in the human mouth and upper respiratory tract. Some strains of Streptococcus have been shown to have probiotic properties, including the ability to inhibit the growth of harmful bacteria and enhance the immune system (14).

Saccharomyces boulardii: This is a type of yeast that is commonly used as a probiotic. It has been shown to have a range of health benefits, including reducing the risk of antibiotic-associated diarrhea and improving gut health (15).

Escherichia coli Nissle 1917: This is a strain of the common gut bacterium Escherichia coli that has been shown to have probiotic properties. It has been used to treat a range of gastrointestinal disorders, including inflammatory bowel disease (16).

Overall, there are many different types of probiotics, and the specific strains and dosages that are most effective may vary depending on the individual and the condition being treated.

The potential role of the gut microbiota in H. pylori eradication

Emerging evidence suggests that the gut microbiota may play an important role in Helicobacter pylori (H. pylori) eradication. The gut microbiota is a complex ecosystem of microorganisms that resides in the gastrointestinal tract and plays a crucial role in maintaining gut homeostasis and host health. Alterations in the gut microbiota composition and function have been associated with a range of gastrointestinal disorders, including H. pylori infection (17). Several mechanisms have been proposed to explain the potential role of the gut microbiota in H. pylori eradication. One mechanism involves the production of antimicrobial compounds by the gut microbiota (18). It has been shown that certain gut bacteria, such as Lactobacillus and Bifidobacterium, produce antimicrobial compounds that can inhibit the growth of H. pylori. By modulating the gut microbiota composition and function, it may be possible to enhance the production of these antimicrobial compounds and promote H. pylori eradication (19).

Another mechanism involves the modulation of the host immune response. The gut microbiota plays a critical role in shaping the host immune response, and alterations in the gut microbiota composition and function have been shown to impact the host immune response to H. pylori infection. By modulating the gut microbiota, it may be possible to enhance the host immune response to H. pylori infection and promote H. pylori eradication (20). Additionally, the gut microbiota may impact the efficacy of H. pylori eradication therapies. It has been shown that the gut microbiota composition and function can impact the pharmacokinetics and pharmacodynamics of antibiotics, which are a key component of H. pylori eradication therapies. By modulating the gut microbiota, it may be possible to enhance the efficacy of H. pylori eradication therapies and reduce the risk of treatment failure (21).

Mechanisms of action of probiotics in H. pylori eradication

Probiotics have been shown to have several potential mechanisms of action in Helicobacter pylori (H. pylori) eradication as shown in Figure (1):

Inhibition of H. pylori growth: Some probiotic strains, such as Lactobacillus and Bifidobacterium, have been shown to produce antimicrobial compounds that can inhibit the growth of H. pylori. These compounds can include organic acids, bacteriocins, and hydrogen peroxide. By inhibiting the growth of H. pylori, probiotics may help to reduce the bacterial load and promote H. pylori eradication (22).

Modulation of the host immune response: Probiotics have been shown to modulate the host immune response to H. pylori infection. They can enhance the production of anti-inflammatory cytokines, such as interleukin-10 (IL-10), and reduce the production of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-8 (IL-8). By modulating the host immune response, probiotics may help to reduce inflammation and promote H. pylori eradication (23).

Modulation of the gut microbiota composition and function: Probiotics can alter the gut microbiota composition and function, which can impact H. pylori colonization and persistence. For example, probiotics can increase the abundance of beneficial gut bacteria, such as Lactobacillus and Bifidobacterium, which can inhibit the growth of H. pylori and other harmful bacteria. They can also reduce the abundance of harmful bacteria, such as Enterobacteriaceae, which have been associated with H. pylori infection (24).

Enhancement of the efficacy of H. pylori eradication therapies: Probiotics have been shown to enhance the efficacy of H. pylori eradication therapies. For example, they can improve the pharmacokinetics and pharmacodynamics of antibiotics, leading to increased antibiotic activity and reduced antibiotic resistance. They can also reduce the side effects of antibiotics, such as diarrhea and nausea, which can improve patient compliance and reduce treatment failure (25).

Evidence supporting the use of probiotics in H. pylori eradication

There is accumulating evidence supporting the use of probiotics in Helicobacter pylori (H. pylori) eradication. Several randomized controlled trials (RCTs) have investigated the efficacy of probiotics as adjunct therapy to conventional H. pylori eradication therapy. A meta-analysis of 23 RCTs involving a total of 2,391 participants found that probiotics significantly improved H. pylori eradication rates compared to placebo or no treatment. The meta-analysis also found that probiotics reduced the risk of antibiotic-associated diarrhea and improved the tolerability of H. pylori eradication therapy (26). Several probiotic strains have been shown to be effective in promoting H. pylori eradication. For example, a strain of Lactobacillus acidophilus called Lactobacillus acidophilus ATCC 4356 has been shown to enhance the efficacy of H. pylori eradication therapy in RCTs. Bifidobacterium animalis subsp. lactis Bi-07 has also been shown to improve H. pylori eradication rates in RCTs (27). Studies have also investigated the mechanisms of action of probiotics in H. pylori eradication. For example, a study published in the Journal of Gastroenterology and Hepatology found that a combination of Lactobacillus acidophilus and Bifidobacterium bifidum enhanced H. pylori eradication rates by reducing inflammation and increasing the production of anti-inflammatory cytokines (28).

The impact of diet on the gut microbiota and H. pylori colonization

Diet has been shown to have a significant impact on the gut microbiota composition and function, which in turn can impact Helicobacter pylori (H. pylori) colonization. Several dietary factors have been shown to influence the gut microbiota composition and function, including:

Fiber: Dietary fiber is a type of carbohydrate that cannot be digested by the human body. It passes through the digestive tract largely intact and provides a food source for beneficial gut bacteria, such as Bifidobacterium and Lactobacillus. These bacteria ferment the fiber and produce short-chain fatty acids (SCFAs), which have anti-inflammatory and immunomodulatory effects. Good sources of dietary fiber include fruits, vegetables, legumes, whole grains, and nuts. A diet low in fiber has been associated with a less diverse gut microbiota and increased H. pylori colonization (29).

Fat: High-fat diets have been shown to alter the gut microbiota composition and function, promoting the growth of harmful bacteria and reducing the abundance of beneficial bacteria (30). A high-fat diet has also been associated with increased H. pylori colonization and increased risk of H. pylori-associated diseases (31).

Protein: There is evidence to suggest that protein-rich diets can have an impact on the gut microbiota and the development and progression of H. pylori infection. One way in which protein-rich diets may affect H. pylori is by increasing the production of harmful metabolites by the gut microbiota (32). When protein is broken down by the gut microbiota, it can produce metabolites such as ammonia, amines, and sulfides, which can be harmful to the gastrointestinal tract and promote the growth of H. pylori. Studies have shown that diets high in protein can lead to an increase in these harmful metabolites, thereby promoting the growth and survival of H. pylori (33). In addition to producing harmful metabolites, protein-rich diets may also affect the gut microbiota by altering its composition and diversity. Studies have shown that diets high in animal protein can lead to a decrease in the abundance of beneficial gut bacteria, such as Bifidobacterium and Lactobacillus, and an increase in potentially harmful bacteria, such as Clostridium difficile (34).

Prebiotics: Prebiotics are a type of non-digestible carbohydrate that selectively stimulate the growth and activity of beneficial gut bacteria (35). They are typically found in foods such as chicory root, Jerusalem artichoke, onions, garlic, leeks, asparagus, bananas, and whole grains. Prebiotics are fermented by gut bacteria, producing SCFAs and other beneficial compounds that can improve gut health and immune function (36).

Fermented foods: Fermented foods, such as yogurt, kefir, and sauerkraut, contain live bacteria that can have probiotic effects on the gut microbiota. These probiotic bacteria can inhibit the growth of H. pylori and promote gut health (37).

Polyphenols: Polyphenols are a group of compounds found in plant-based foods, such as fruits, vegetables, tea, coffee, and chocolate. They have been shown to have prebiotic effects on the gut microbiota, promoting the growth of beneficial bacteria and inhibiting the growth of harmful bacteria. Some polyphenols, such as green tea catechins and resveratrol, have also been shown to have anti-inflammatory and antioxidant effects (38).

Omega-3 fatty acids: Omega-3 fatty acids, found in fatty fish, flaxseeds, chia seeds, and walnuts, have been shown to have anti-inflammatory effects and can promote the growth of beneficial gut bacteria, such as Bifidobacterium and Lactobacillus (39).

Garlic: garlic has been found to contain a compound called allicin, which has been shown to have antimicrobial properties against a variety of pathogens, including H. pylori. Allicin is produced when garlic is crushed or chopped and is responsible for the characteristic pungent odor of garlic (40). Several studies have investigated the effects of garlic on H. pylori infection. One study found that garlic extract inhibited the growth of H. pylori in vitro. Another study found that garlic extract reduced H. pylori colonization in mice. A third study found that garlic powder reduced H. pylori infection in humans (41). While the evidence is promising, more research is needed to fully understand the potential benefits of garlic in the management and prevention of H. pylori infection. It is important to note that garlic should not be used as a sole treatment for H. pylori infection. Rather, it may be used as a complementary therapy in conjunction with standard antibiotic treatment (42).

Cranberry: cranberry has been found to contain a compound called proanthocyanidin, which has been shown to have antimicrobial properties against a variety of pathogens, including H. pylori. Proanthocyanidins are a type of polyphenol that are found in high concentrations in cranberries (43). Several studies have investigated the effects of cranberry on H. pylori infection. One study found that cranberry juice inhibited the growth of H. pylori in vitro. Another study found that cranberry extract reduced H. pylori colonization in mice. A third study found that cranberry extract reduced H. pylori infection in humans (44). A varied and balanced diet rich in polyphenols, omega-3 fatty acids, garlic, cranberry, and fermented foods can help to inhibit the growth of H. pylori and other harmful bacteria in the gut and promote gut health. However, it is important to note that these dietary factors should not be used as a replacement for conventional H. pylori eradication therapy and should only be used as adjunct therapy under the guidance of a healthcare professional.

Lifestyle modifications

Reducing stress, quitting smoking, and avoiding excessive alcohol consumption are important strategies for promoting a healthy gut microbiota. These lifestyle factors can have a significant impact on the gut microbiota composition and function, and may influence the risk of various gastrointestinal disorders, including Helicobacter pylori (H. pylori) infection and associated diseases (45).

Reducing stress: Chronic stress has been shown to alter the gut microbiota composition and function, promoting the growth of harmful bacteria and reducing the abundance of beneficial bacteria (46). Stress can also weaken the immune system, making it more difficult to fight off H. pylori infections. Strategies for reducing stress may include mindfulness meditation, yoga, deep breathing exercises, and regular physical activity (47).

Quitting smoking: Smoking has been shown to alter the gut microbiota composition and function, promoting the growth of harmful bacteria and reducing the abundance of beneficial bacteria (48). Smoking has also been associated with an increased risk of H. pylori colonization and associated diseases (49). Quitting smoking may help to promote a more diverse and beneficial gut microbiota composition, and reduce the risk of H. pylori-associated diseases (50).

Avoiding excessive alcohol consumption: Heavy alcohol consumption has been shown to alter the gut microbiota composition and function, promoting the growth of harmful bacteria and reducing the abundance of beneficial bacteria (51). Alcohol has also been associated with an increased risk of H. pylori colonization and associated diseases. Avoiding excessive alcohol consumption may help to promote a more diverse and beneficial gut microbiota composition, and reduce the risk of H. pylori-associated diseases (52).

Dietary changes: A balanced diet rich in fiber, prebiotics, and probiotics can help promote a more diverse and beneficial gut microbiota composition. Prebiotics are non-digestible fibers that serve as food for beneficial gut bacteria, while probiotics are live microorganisms that provide health benefits when consumed in adequate amounts (53).

Antibiotic stewardship: Antibiotic stewardship is an important approach to promoting responsible and appropriate use of antibiotics in order to prevent the development and spread of antibiotic-resistant bacteria, as well as to minimize the potential harm caused by antibiotic use. Overuse or inappropriate use of antibiotics can promote the growth of H. pylori, leading to increased colonization and the potential development of antibiotic resistance (54). When antibiotics are prescribed for non-bacterial infections or for conditions that do not require antibiotic treatment, the beneficial bacteria in the gut may be disrupted, leading to an increase in the growth of harmful bacteria such as H. pylori. Additionally, the overuse or misuse of antibiotics can lead to the development of antibiotic-resistant strains of bacteria, including H. pylori, which can be difficult to treat and can lead to more severe and potentially life-threatening infections (55). In addition to appropriate use of antibiotics, other strategies for managing and preventing H. pylori infection include lifestyle modifications, such as maintaining a healthy diet and avoiding tobacco use, as well as the use of complementary therapies such as probiotics and certain dietary supplements, as discussed in previous answers. Overall, a multi-faceted approach is necessary for effectively managing and preventing H. pylori infection (56).

Probiotic supplementation: there is evidence to suggest that probiotic supplementation may help promote a more diverse and beneficial gut microbiota composition, which in turn may reduce the risk of H. pylori infection. Probiotics are live microorganisms that, when consumed in adequate amounts, can confer health benefits on the host by improving the balance of the gut microbiota (57). Several studies have investigated the effects of probiotics on H. pylori infection. One study found that probiotic supplementation reduced H. pylori infection in children. Another study found that probiotic supplementation improved the efficacy of standard antibiotic therapy for H. pylori infection in adults (58).

Medical treatment: Medical treatment, such as H. pylori eradication therapy, may be necessary to treat H. pylori infections and associated diseases (59). However, it is important to note that medical treatment should only be prescribed by a healthcare professional and should be used appropriately to avoid the development of antibiotic resistance (60). A variety of strategies can help promote a healthy gut microbiota and reduce the risk of H. pylori colonization and associated diseases. These strategies may include lifestyle changes, dietary modifications, antibiotic stewardship, probiotic supplementation, and medical treatment, depending on individual circumstances and risk factors.

In conclusion, the gut microbiota plays an important role in H. pylori colonization and associated diseases. Lifestyle factors, such as diet, stress, smoking, and alcohol consumption, can impact the gut microbiota composition and function, and may influence the risk of H. pylori colonization and H. pylori-associated diseases. Strategies to promote gut health, such as a healthy diet, stress reduction, smoking cessation, alcohol moderation, regular exercise, adequate sleep, antibiotic stewardship, and probiotic supplementation, may help to reduce the risk of H. pylori colonization and enhance the effectiveness of H. pylori eradication therapy.

Furthermore, the gut microbiota may also be a potential target for H. pylori eradication, as changes in the gut microbiota composition and function have been associated with H. pylori colonization and associated diseases. Personalized treatment approaches based on individual patient characteristics, such as gut microbiota composition and antibiotic resistance patterns, may be necessary to optimize H. pylori eradication rates and reduce the risk of adverse effects.

There is a need for further research to better understand the role of the gut microbiota in H. pylori eradication and to develop more effective treatment strategies. This may include studies investigating the mechanisms by which lifestyle factors impact H. pylori infection and exploring the potential of probiotic supplementation, fecal microbiota transplantation, and other gut microbiota-targeted therapies for H. pylori eradication. By advancing our understanding of the gut microbiota and H. pylori infection, we may be able to develop more personalized and effective treatment approaches for this common and potentially serious gastrointestinal condition.

H. pylori - Helicobacter pylori; GI – Gastrointestinal; PUD - Peptic Ulcer Disease; GMC - Gut Microbiota Composition, GMD - Gut Microbiota Diversity; AA - Antibiotic Associated; AR - Antibiotic Resistance; FMT - Fecal Microbiota Transplantation

Ethics approval and consent to participate: Not Applicable

Consent for publication: Not Applicable

Availability of data and materials: all data are available and sharing is available as well as publication.

COMPETING INTERESTS: The authors hereby that they have no competing interests.

Funding: All study materials were supplied by Corresponding author. There was no further funding for this study.

Author's contributions: Authors completed the study protocol and were the main organizer of data collection drafting and revising the manuscript perfectly. Tamer A. Addissouky has written the article and guarantees the paper carefully. All authors contributed to the discussion and reviewed the manuscript as well as they helped in designing the study and protocol and engaged in a critical discussion of the draft manuscript. All authors have affirmed on the final copy of the manuscript. Moreover, all authors have read and approved the manuscript.

Acknowledgements: Authors thank all the researchers who have done great efforts on their studies. Moreover, we are grateful to the editors, reviewers, and reader of this journal.

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Probiotics and Diet Modifications: A Holistic Approach to Tackling Helicobacter pylori with the Help of the Gut Microbiota

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