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The Bidirectional Relationship Between Gut Microbiome and GERD: Cause or Consequence?

GERD is a chronic condition that causes stomach acid flows back into the esophagus, causing symptoms like heartburn. Emerging research suggests a complex relationship between GERD and the gut microbiome, where imbalances in gut bacteria may contribute to the development and severity of GERD. Understanding this bidirectional relationship opens new possibilities for treatment, including microbiome-targeted therapies that go beyond traditional acid suppression methods.

AUTHOR: Ira Renko, MSc, Master in Molecular biotechnology

Background information

Gastroesophageal reflux disease (GERD) is one of the most common chronic conditions affecting the digestive system, affecting around 8% to 33% of people globally and 10% to 20% of the population in Europe1,2.

It is primarily driven by the dysfunction of the lower esophageal sphincter (LES), which acts as a barrier preventing the backflow of stomach contents into the esophagus. When the LES fails to function properly, it allows acidic gastric contents to reflux into the esophagus, causing irritation and inflammation3,4. This can lead to symptoms such as heartburn, regurgitation, and in severe cases, esophagitis. Several factors contribute to LES dysfunction, including obesity, diet, smoking, and certain medications. The chronic exposure of the esophagus to stomach acid can lead to complications like esophageal strictures, Barrett’s esophagus, and an increased risk of esophageal cancer5. While GERD has traditionally been attributed to mechanical and chemical factors, recent research suggests that the composition and functionality of the gut microbiome may also contribute to the pathogenesis of this condition6-8.

Bidirectional relationship: interplay between gut microbiome and GERD

The gut microbiome, comprising trillions of microorganisms residing in the gastrointestinal tract, plays a crucial role in maintaining overall health. Recent studies have begun to explore the connection between the gut microbiome and GERD. Although the exact nature of this relationship remains unclear9. Some research suggests that dysbiosis in the gut microbiome may contribute to the development of GERD10,11. For example, changes in the composition of the gut microbiota could affect gut motility, influence bile acid metabolism, or alter the production of short-chain fatty acids, all of which could impact the function of the LES and promote acid reflux12. Additionally, certain bacterial species have been found to influence the production of gases like hydrogen and methane, which can affect intra-abdominal pressure and potentially exacerbate GERD symptoms13,14.

Gut microbiome as a potential cause of GERD

The gut microbiome plays a significant role in regulating gastrointestinal motility. Specific bacterial species produce metabolites such as short-chain fatty acids (SCFAs), which influence gut motility by interacting with the enteric nervous system15. Dysbiosis, or an imbalance in the gut microbiota, can disrupt these processes, potentially leading to delayed gastric emptying or altered esophageal motility, both of which are risk factors for GERD10,11. Impaired gut motility can increase intra-abdominal pressure, leading to the relaxation of the lower esophageal sphincter (LES) and promoting acid reflux.

Furthermore, gut microbiota is involved in the metabolism of bile acids, which are critical for digestion and the absorption of dietary fats. Bile acids also play a role in regulating gut motility and maintaining the integrity of the gut barrier16. What is more, dysbiosis can alter the composition of bile acids, leading to an increase in deconjugated bile acids that are more likely to reflux into the esophagus and cause mucosal damage. This bile acid reflux, in conjunction with gastric acid, can exacerbate the symptoms of GERD and contribute to esophageal inflammation.

Since 70% of our immune system is in the gut, that has impact on overall health by modulation of inflammatory responses. Namely, dysbiosis can lead to an overproduction of pro-inflammatory cytokines and other mediators that can disrupt the esophageal mucosal barrier17,18. This disruption makes the esophageal lining more susceptible to acid damage and inflammation, both of which are characteristic of GERD. Additionally, certain microbial metabolites may directly affect the permeability of the esophageal epithelium, facilitating the penetration of acid and bile, thus worsening GERD symptoms19.

Some gut bacteria even produce gases such as hydrogen and methane during fermentation processes which can increase intra-abdominal pressure, which may contribute to the relaxation of the LES and the subsequent development of acid reflux. Methanogenic bacteria have been associated with slower gastrointestinal transit times and increased gas retention, factors that could potentially promote GERD. Researchers have showed that there is a specific gut microbiome profile in individuals with GERD. Compared to healthy individuals, there is a reduced number of beneficial bacteria Lactobacillus and Bifidobacterium and a higher abundance ofpathogenicsuch as Escherichia coli and Clostridium difficile, which are known to induce inflammation and disrupt gut barrier integrity20,21.

Following that, interventions aimed at modulating the gut microbiome have shown promise in managing GERD symptoms. Probiotic supplementation, for instance, has been reported to improve GERD symptoms by restoring the balance of the gut microbiota, reducing inflammation, and enhancing gut motility. These findings suggest that targeting the gut microbiome could be a viable therapeutic strategy for GERD.

GERD as a leader of gut microbiome alterations

While the gut microbiome may play a role in the development of gastroesophageal reflux disease (GERD), it is equally important to consider how GERD itself might lead to changes in the gut microbiome. The chronic acid reflux characteristic of GERD, as well as the treatments commonly used to manage it, can significantly impact the composition and function of the gut microbiota. The chronic exposure of the esophagus and upper gastrointestinal tract to stomach acid can create an unfavourable environment for certain bacterial species, leading to dysbiosis22. Moreover, the use of proton pump inhibitors (PPIs), a common treatment for GERD, has been shown to alter the composition of the gut microbiome23. By reducing stomach acidity, PPIs create conditions that favour the survival and overgrowth of bacteria typically suppressed by normal gastric acid levels. This can lead to conditions like small intestinal bacterial overgrowth (SIBO), which not only complicates GERD but also introduces a new set of gastrointestinal challenges24,25.

The acidic pH, combined with the presence of bile and digestive enzymes, can inhibit the growth of acid-sensitive microorganisms while allowing acid-resistant species to proliferate. This selective pressure can lead to a shift in the microbial composition of the esophagus and, potentially, the upper gastrointestinal tract 26.

What is more, the chronic reflux of gastric acid into the esophagus and, at times, into the pharynx and oral cavity, can disrupt the normal microbiota of the stomach and small intestine. This disruption can decrease microbial diversity and the overgrowth of pathogenic bacteria. The altered microbial environment may further impair digestive processes and contribute to the progression of GERD symptoms27,28.

A study by Nobile et al. (2020) found that patients with GERD exhibited significant differences in gut microbiota composition compared to healthy controls, with a reduction in the abundance of Lactobacillus species, known for their protective effects on the gut lining29. Conversely, research by Imhann et al. (2016) demonstrated that long-term use of PPIs in GERD patients was associated with a shift in the gut microbiome, including an increase in potentially pathogenic bacteria such as Enterococcus and Clostridium difficile30.

Implications for treatment and management

The bidirectional relationship between the gut microbiome and GERD has significant implications for how the disease is treated. Traditional approaches that focus solely on acid suppression may not address the underlying microbiome imbalances that contribute to GERD. Integrative treatments that consider both the microbiome and GERD symptoms could offer more effective and long-lasting relief. For instance, combining PPI therapy with probiotics or dietary interventions aimed at restoring microbial diversity might help break the cycle of dysbiosis and reflux, leading to better outcomes for patients12.

Table 1. presents some of the most known probiotics that showed a positive impact on the progression of GERD

Specific strains of Lactobacillus and Bifidobacterium have been associated with improvements in gut motility, enhancement of the mucosal barrier, and reduction of inflammation31-41. These effects can help alleviate GERD symptoms and potentially reduce reliance on PPIs. Prebiotics, which are nondigestible fibers that promote the growth of beneficial bacteria, can also play a role in maintaining a healthy gut microbiome and supporting overall gastrointestinal health. Dietary interventions that emphasize the consumption of fiber-rich foods, fermented products, and foods low in refined sugars and fats can help support a diverse and balanced gut microbiome42. Additionally, dietary adjustments such as reducing the intake of trigger foods (e.g., fatty foods, caffeine, chocolate) can directly help manage GERD symptoms while also supporting microbiome health 43,44.

Conclusion

The relationship between the gut microbiome and GERD is a complex and dynamic interplay where each influences the other significantly.

It is unclear whether alterations in the gut microbiome contribute to the development of GERD or whether GERD itself leads to changes in the gut microbiome.

While the precise mechanisms by which the gut microbiome may cause GERD are still being elucidated, the evidence points to a significant role of microbial dysbiosis in the pathogenesis of this condition. Alterations in gut motility, bile acid metabolism, esophageal mucosal integrity, and intra-abdominal pressure are all potential pathways through which the gut microbiome could influence GERD development. Understanding these mechanisms not only enhances our knowledge of GERD but also opens up new possibilities for treatment strategies that target the gut microbiome to alleviate GERD symptoms and prevent its progression.

Likely, future GERD management will increasingly incorporate microbiome-focused therapies, especially probiotics,  leading to more comprehensive and personalized care. However, further research is needed to clarify the causal relationships and to explore how specific microbial interventions might be optimized for GERD management.

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