The Gut Microbiome and the Influence of Non-Antibiotic Medication

The Gut Microbiome and the Influence of Non-Antibiotic Medication

October 9, 2023

Joy Stepinski, MSN, RN-BC

In a previous article, I discussed the profound effects that antibiotics have on the gut microbiome. Other medications greatly influence the microbiota, as well. One of the most widely-used medications is the proton pump inhibitor (PPI). In fact, in 2013 esomeprazole (Nexium, also known as “the purple pill”) was the second largest revenue-making drug in the United States [1]. Other examples include Prilosec (omeprazole), Prevacid (lansoprazole), and Protonix (pantoprazole).

PPI drugs block a protein responsible for releasing hydrochloric acid into the stomach lumen [2]. Gastroenterologists often prescribe PPI medications for esophagitis, reflux, heartburn, peptic ulcer disease, and prevention of ulcers caused by nonsteroidal anti-inflammatory drugs (NSAIDs) [3]. PPIs are thought to be among the most profitable medications, but are susceptible to overuse and believed to be inappropriately prescribed about 70% of the time [2].

In a Dutch study, the effect of PPIs on the gut microbiome was investigated. Three independent cohorts (n = 1815 adults) included PPI-users versus non-users (n = 211). The outcomes demonstrated that PPIs greatly change the gut microbiome, with an impact more than antibiotics [1].

Stomach acidity is one of the main defenses for the body. When the stomach environment is less acidic, other bacteria can thrive. The study discovered that oral microbiota was more abundant in the gut among PPI users. These bacteria survive the stomach acidity and travel to the intestines, which is not their home. Normally the stomach environment is too acidic for bacteria found in the mouth. Furthermore, the reduction of microbial diversity within the gut microbiome caused susceptibility to intestinal diseases, such as Clostridium difficile, a debilitating diarrheal infection.

In a separate large population-based cohort, British researchers investigated the fecal samples of healthy twins (n = 1,827) [4]. Participants self-reported their PPI and antibiotic use, along with their diet through a food-frequency questionnaire. The average age was 62 years old among a predominantly female population (90%). Within this group, 49% reported being prescribed PPIs due to a gastrointestinal-related problem, 12% had been prescribed for vague reasons, and 39% were never prescribed. Similar to the previous study, these results showed a lower gut microbiome diversity among PPI users, with an increased prevalence of pharyngeal bacteria in the gut.

Specifically, these studies demonstrate that PPIs influence the gut diversity, causing certain microbial families to increase (i.e., Enterobacteriaceae, Enterococcaceae, and Lactobacillaceae), while other families decrease (i.e., Ruminococcaceae and Bifidobacteriaceae). Oral microbes, such as Rothia dentocariosa and Actinomyces survive the less acidic stomach environment. Research discusses that these changes occur regardless of the type of PPI medication used. The larger the dose, the greater the alterations within the gut microbiome [5]. As discussed last month, effects on microbial diversity may play a role in gut health.

PPIs and antibiotics are not the only drug class that affects the gut microbiome. Other medications that influence the microbiome include statins, metformin, cardiac medications (i.e., ACE-inhibitors and ARBs), aspirin, opioids, laxatives, antidepressants, and vitamin D [5]. Laxatives, for example, directly affect stool characteristics, such as stool transit time, consistency, overall bacterial composition, and cause an increase of Bacteroides bacteria in the gut microbiome. Some of the long-term effects of other drugs are not known.

The consequence of taking medications may result in other considerations. Research indicates that the microbiome diversity is influenced by medication, but the reverse can happen, as well. The microbes within the gut microbiome may alter the way a patient responds to a drug. This may impact the absorption of the drug by the body, the role that the drug plays, and its toxicity [5].

As a patient, learning about the full scope of benefits and drawbacks to medical treatment is vital to health decisions. Consider the patient diagnosed with gastroesophageal reflux disease (GERD). On one hand, the PPI may relieve symptoms of reflux. On the other hand, the gut diversity may be changed to create new health conditions. These decisions are important factors to weigh.

Furthermore, another choice less discussed is intentional lifestyle modifications. Gastroesophageal Reflux Disease (GERD), for instance, is related to salivary pH changes, increased gastric acid secretion by the stomach, and delayed intestinal motility. The disease is characterized by belching, cough, and nausea. Complications include Barrett’s esophagus, among others. Studies show that adopting lifestyle modifications can greatly improve GERD, including a healthy weight, diet high in fiber and low in fat, fruit and vegetable consumption, physical activity, smoking cessation, and limiting alcohol intake [6].

When faced with a medical decision, consider the long-term effect of the treatment, as well as the side effects. Explore other avenues, such as lifestyle modifications. Consuming healthier food and exercising can greatly enhance quality of life!

 References

1.    Imhann, F., Bonder, M. J., Vila, A. V., Fu, J., Mujagic, Z., Vork, L., … & Zhernakova, A. (2016). Proton pump inhibitors affect the microbiome. Gut, 65(5), 740 748.

2.    Jackson, M. A., Goodrich, J. K., Maxan, M. E., Freedberg, D. E., Abrams, J. A., Poole, A. C., Sutter, J. L., … & Steves, C. J. (2016). Proton Pump Inhibitors alter the composition of the gut microbiota. Gut, 65, 749 – 756. https://doi.org/10.1136/gutjnl-2015-310861

3.    Ahmed, A., Clarke, J. O. (2023). Proton pump inhibitors (PPI). StatePearls [Internet]. StatPearls Publishing.

4.    Jackson, M. A., Goodrich, J. K., Maxan, M. E., Freedberg, D. E., Abrams, J. A., Poole, A. C., ... & Steves, C. J. (2016). Proton pump inhibitors alter the composition of the gut microbiota. Gut, 65(5), 749-756.

5.    Weersma, R. K. Zhernakova, A., & Fu, J. (2020). Interaction between drugs and the gut microbiome. Gut, 69(8), 1510 – 1519.

6.    Commisso, A., & Lim, F. (2019). Lifestyle modifications in adults and older adults with chronic gastroesophageal reflux disease (GERD). Critical Care Nursing Quarterly, 42(1), 64-74.