Is Your Proton Pump Inhibitor Worsening Your Mental Health?

By Dr. Nicole Cain ND, MA

How a commonly prescribed medicine for heartburn reflux may threaten the health of the gut-brain axis.


You’ve been struggling with heartburn- you know, those feelings of constriction, burning, pressure and pain in your chest, throat and stomach, and your doctor gave you a prescription for a medication called a proton pump inhibitor (PPI). PPIs are one of the most common types of prescriptions for treating heartburn, however, its benefits come with a significant trade-off: Your mental health, which will be the focus of this article.

If you’re suffering from gastrointestinal (GI) distress such as gas, bloating, indigestion, heartburn, gastroesophageal reflux disease (GERD), nausea, or vomiting,  and using PPIs to relieve your symptoms, it is likely that at one point or another your doctor has suggested a type of acid-reducing medication called a proton pump inhibitor (PPI).

Proton pump inhibitors (PPIs) are among the most prescribed medications for GI disorders in the US. In fact, according to a 2022 report in BMC Public Health approximately, one in ten people takes a PPI daily, with prescriptions increasing to over 54.6% of individuals over 65 years taking PPIs, despite the fact that, according to Drug Watch “studies suggest as many as 70 percent of people taking PPIs get no benefit from them.”

Wondering how PPIs can be harmful to your gut-brain axis? ? Let’s explore what PPIs are and how their use can affect your gut microbiome.

What are PPIs?

Proton Pump Inhibitors, or PPIs, can be defined as a group of medications that inhibit stomach acid-producing cells in your gut. People typically are prescribed these medications for the relief of symptoms related to acid reflux or gastroesophageal reflux disease (GERD). Additionally, PPIs may be used to reduce pain and burning associated with a duodenal or stomach (gastric) ulcer.

Some of the most common groups of PPIs include omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole, dexlansoprazole, and zegerid. Usually, they are taken orally, and dispensed as tablets or capsules, and can be bought over the counter without a prescription.

Concerns about possible adverse effects specifically related to the use of PPIs have springboarded research into the long-term risks and benefits of PPI use.  A 2021 study published in the journal BMJ Open Gastroenterology suggested that the long-term use of PPIs (between 2-6 months) could impair the absorption of calcium and magnesium (Haastrup et al., 2021), which can lead to bone fractures, damage your kidney, or even promote the development of Alzheimer’s disease or gastric cancer. A 2016 study explored the relationship between long-term PPI use and the gut microbiome and researchers reported that PPI use was associated with an increased risk of Clostridium difficile infection (CDI) in the gut and that PPI use was associated with negative changes in the microbiome.  (Clooney, A.G., et al, 2016)

How Do PPIs Impact the Gut Microbiome?

Before we discuss how PPIs impact the gut microbiome, it’s important to understand how they work in general. Usually, proton pump inhibitors reduce the activity of the gastric hydrogen potassium ATPase or “pumps” in the gastric lining. As a result, your stomach produces a lower amount of acid.

Whenever the stomach is functioning normally, it can easily destroy the organisms that function to inhibit the oral cavity and can’t tolerate the low pH of stomach acids. However, PPIs reduce acid production, and therefore, they also decrease the barrier of intestinal entry. Consequently, microorganisms simply find their way into your gut microbiome, residing there and inhibiting your intestines. This, in turn, often leads to upsetting the gut microbiome and causing dysbiosis — the imbalance of the organisms in the gut microflora.

To be more precise, the latest studies about the connection between proton pump inhibitors and dysbiosis (e.g., Bruno et al., 2019) show that PPIs lead to specific changes in the gut microbiome– a condition called dysbiosis. Dysbiosis threatens the health of the gut-brain axis and leads to symptoms impacting your immune, endocrine, and nervous systems.

There is a significant connection between the gut and mood. Specifically, gut bacteria are responsible for producing about 95% of the body’s serotonin, and this, in turn, affects mood. As a result of changes in the composition and function of gut microbes, they might lead to specific symptoms of mood disorders such as depression. The reason is that alterations in gut microbes might trigger inflammation and, consequently, lead to depression symptoms. This can be explained by the fact that inflammation takes part in glutamatergic neurotransmission, which is an important process for mood regulation.

However, research shows that psychobiotics provide effective solutions to regulate mood and manage anxiety (e.g., Kadosh et al., 2021). The mechanism is that certain psychobiotics produce serotonin, dopamine, noradrenaline, and GABA neurotransmitters that take part in mood regulation. Furthermore, studies suggest that psychobiotics are an effective alternative for individuals dealing with the side effects of psychotropic medications, such as dependence or withdrawal.

Effects of PPIs on SIBO (Small Intestinal Bacterial Overgrowth)

Small intestinal bacterial overgrowth (SIBO) is a condition when the overall bacterial population increases abnormally in the small intestine. As a result, people experience symptoms such as bloating, abdominal pain, and distention. Usually, SIBO is caused by types of bacteria that are foreign to the digestive tract. It happens when an excessive number of microbes enter the small intestinal tract. Considering this, the consumption of PPIs is also related to small intestinal bacterial overgrowth.

As we already mentioned, proton pump inhibitors reduce the ability of gastric acid to disrupt microorganisms from migrating into the small intestine. It’s especially common with rifaximin. In fact, 87-91% of people who consumed high doses of this medication reported an increased incidence of SIBO.

Therefore, if patients use PPIs regularly, the chances of developing small intestinal bacterial overgrowth are significantly increased (Su et al., 2018). Consequently, individuals with SIBO experience symptoms such as bloating, weight loss, or diarrhea.

Can Proton Pump Inhibitors Lead to “Leaky Gut”?

Have you heard anything about the theory of leaky gut syndrome? Well, it’s an idea that intestinal permeability is a cause of gastrointestinal disease instead of its symptom. People with a “leaky gut” have damaged the gastrointestinal lining, which can no longer work as a barrier to foreign organisms. As a result, harmful bacteria, gluten, and undigested food can easily migrate into your gut and lead to problems with your digestive health.

The chronic use of PPIs can damage the balance of friendly bugs in the large intestine, which, as discussed above, leads to dysbiosis. This means that proton pump inhibitors increase the risk of developing leaky gut syndrome and cause severe conditions such as inflammatory bowel disease, autoimmune disease, and even depression, which is significantly connected to gut microflora.

Final Thoughts

To sum up, despite the positive impact of PPIs on GI disorders found in the earlier studies, it turns out that regular use of proton pump inhibitors negatively affects the gut microbiome, posing a serious threat to your digestive health. Considering this, it’s essential to explore natural treatments for reflux and mood, using a more holistic approach.

One of the most effective methods of improving digestion, reducing heartburn, and stabilizing your mood is taking targeted probiotics that are designed to repair and balance your gut microbiome.

A 2020 study published by Nature reported that patients who took a daily multi-strain probiotic for 6 months reported a strengthened intestinal barrier in the gut microflora (Horovath et al., 2020). A 2016 study that explored the connection between the gut microbiome and PPIs also demonstrated that probiotics reduce bacteria in the gut microbiome by 20% (Imshann et al., 2016). However, some studies suggest possible implications of PPI-induced dysbiosis in chronic users of these medications (Macke et al., 2020)

This means that understanding the side effects of PPIs and taking specific probiotics can help you avoid the damaging effects and increase the effective function of your gut.

Check out our favorite probiotics for mental health by clicking HERE.

This article is for educational purposes only and is not intended as medical advice. Whenever considering changing your protocol whether it includes a change of medications, supplements, diet or lifestyle, always speak with your primary care physician first.

Dr. Nicole Cain is an advocate for empowering people around the world to help themselves via her educational free resources, online courses, and membership group. You can receive the tools you need to find the root cause of your symptoms and feel healthy again.