Benzodiazepines, Antidepressants, and Proton Pump Inhibitors May Impact Gut Microflora More Severely Than Antibiotics

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.

Drug effects may last longer than we thought

The Estonian microbiome cohort was established in 2017, and in addition to oral and blood samples, had 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.

Drug effects noted beyond antibiotics

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.

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.

Clinical significance

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. With this study, it has become clear that antibiotics are not the sole driver of antimicrobial resistance mutations and gut microflora disturbance. 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.

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