Key Takeaways
- Long-term use of benzodiazepines, antidepressants, and PPIs may disrupt gut microbiota more than antibiotics.
- These effects can persist for years and may influence mental and metabolic health.
- The study suggests that common non-antibiotic medications deserve closer scrutiny for their microbiome impact.
In recent years, the role microorganisms found in the gastrointestinal tract play in regulating overall health has become more acknowledged, being the subject of a significant number of papers. In the early days of this awareness, it became known that long-term antibiotic therapy could severely deplete beneficial gut microflora, in some cases leading to pseudomembranous colitis. The role of these microflora in producing essential vitamins and maintaining neurohormonal balance has also been well studied. With this knowledge in mind, the way we use antibiotics has changed. Antibiotics are now prescribed for as short a duration as possible and are often followed up by a course of prebiotics or probiotics to replenish the gut’s microflora. Recent research, however, is showing that our understanding of drug-microflora interaction, while not wrong, is incomplete.
Intestinal Microbiota
Drug effects may last longer than we thought
The Estonian microbiome cohort was established in 2017, and in addition to oral and blood samples, it has been collecting stool samples from 2509 participants. Using data from this cohort, Oliver Aasmets and other researchers from the University of Tartu, Estonia, found out that changes in gut microflora constitution could be detected in people who had taken antibiotics anytime in the past five years. The changes noted in taking these drugs were more significant than the changes caused by whatever diseases were being managed.
Psychiatric and Digestive Medications May Disrupt Gut Microbiota
While the classic case of drug-microflora interactions involves antibiotics, Aasmets et al found similar interactions involving non-antibiotic drugs, including benzodiazepines, antidepressants, and proton pump inhibitors. In the case of benzodiazepines, the impact on gut microflora was more widespread and lasted longer when compared to the impact from several classes of antibiotics. This counter-intuitive finding is explained by drugs that are targeted at human cells also having the ability to eliminate certain strains of bacteria, and inducing antimicrobial resistance genes in others.
Mental Health and the Gut
The gut is known to influence brain function through chemical signaling, often referred to as the gut-brain axis. Changes in gut microflora have been linked to mood, cognition, and behavior. Given that benzodiazepines and antidepressants act on the brain, their added disruption of gut bacteria could, in theory, feed back into the very symptoms they aim to manage. This raises important questions about long-term use and treatment strategy.
Drug effects are temporarily summative
The observed effects of these drugs were noticed to increase if the drugs were used for longer periods of time or if multiple drug classes were employed during patient management. This implies that older patients, who are often on multiple drugs for long periods of time, will face a greater disruption to their gut microflora constitution, a hypothesis which is backed up by the study.
Why This Matters for Prescribers and Long-Term Health
It is the greatest fear of any microbiologist to face a superbug that has mutated to be able to survive any agent used against it. To prevent this from happening, strict care is employed in the prescription of antibiotics. The study, currently available as a preprint and not yet peer-reviewed, suggests that antibiotics may not be the only significant disruptors of gut microflora. While the findings are compelling, further validation from clinical research is necessary before they influence prescribing practices. Benzodiazepines like Valium also contribute significantly in this regard. Not only that, these effects can remain for a significant amount of time into the future. With that in mind, prescribers should show as much care while prescribing benzodiazepines, antidepressants, and proton pump inhibitors as they do while prescribing antibiotics.
Related Reading:
Imbalanced Gut Microbiota: Tips on How to Restore and Maintain a Healthy Intestinal Flora
Effects of Antibiotics on the Intestinal Microbiome and How to Restore Internal Microbial Balance
Withdrawing Antibiotics Temporarily Could Restore Their Effectiveness Against Resistant Bacteria
FAQs: Gut Microflora, Medications, and Mental Health
What’s the gut microbiome and why does it matter?
It’s the community of bacteria and other microbes in your digestive system. These microbes help with digestion, immunity, and even affect brain function.
How do medications affect gut bacteria?
Some drugs—especially when used long-term—can disrupt this balance by killing beneficial strains or encouraging harmful ones.
Isn’t this mostly a concern with antibiotics?
No. The study found that certain non-antibiotic drugs may have even greater effects on gut microflora than antibiotics.
Which medications are we talking about?
The study highlights benzodiazepines like Xanax (alprazolam), Ativan (lorazepam), Valium (diazepam), and Klonopin (clonazepam); antidepressants such as Zoloft (sertraline), Prozac (fluoxetine), Lexapro (escitalopram), Effexor XR (venlafaxine), and Wellbutrin (bupropion); and proton pump inhibitors (PPIs) like Prilosec (omeprazole), Nexium (esomeprazole), Prevacid (lansoprazole), and Protonix (pantoprazole).
Why would psychiatric drugs affect gut bacteria?
Even though they target the brain, they can also affect gut cells and microbes—sometimes in ways not fully understood.
How does this relate to mental health?
The gut and brain are connected. Disrupting gut bacteria may affect mood, stress response, and cognition, possibly reinforcing the symptoms these drugs aim to treat.
How long do these effects last?
The study found changes in gut microflora years after drug use, even without recent antibiotic exposure.
Are some people more at risk?
Yes. Older adults and those on multiple prescriptions are more likely to experience lasting disruption to their microbiome.
Should I stop taking these medications?
No. These drugs are important and often necessary. The takeaway is that gut health should be monitored alongside long-term treatment.
Can probiotics or diet help restore balance?
They might help, but results vary. More personalized approaches to gut support are still under study.
What does this mean for doctors and patients?
It suggests the need for a more holistic view—where both gut and brain health are considered when managing long-term psychiatric and digestive conditions.
Final Thoughts
The findings raise a larger concern: if drugs like benzodiazepines and antidepressants disrupt gut microflora more than antibiotics, they may be contributing to a cycle where the microbiome changes worsen the very symptoms these drugs aim to treat. The gut-brain connection is well established, and altering gut bacteria may impact mood, cognition, and mental health over time. As we learn more, it may become necessary to approach psychiatric and gastrointestinal prescribing with equal caution, especially for long-term or multi-drug treatments.
References
Aasmets, O., Taba, N., Krigul, K. L., Andreson, R., Estonian Biobank Research Team, & Org, E. (2024). Long-term consequences of drug usage on the gut microbiome. bioRxiv. https://doi.org/10.1101/2024.07.17.24310548
