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Not only antibiotics 

affect the microbiota

The composition of the intestinal microbiota is strongly influenced by two factors: diet and medicine use. The effect of antibiotics on the microbiota has been extensively researched in recent years, but antibiotics are not the only type of drugs that affect the intestinal microbiota. Recent research has revealed that other, commonly prescribed drugs – including proton pump inhibitors (PPIs), statins and metformin – can also cause changes in the composition of the microbiota.

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The use of medicines, both prescription and over-the-counter, has been increasing for many years. (1) Medicines can have a major impact on the composition of the intestinal microbiota and thereby on health. Antibiotics are known to cause long-term disturbances in the intestinal microbiota, which can sometimes have severe consequences, including an increased risk of obesity and metabolic conditions and developing irritable bowel syndrome (IBS). In recent years, more has become known about how other, commonly used drugs can cause significant changes in the microbiota.



Impact of commonly prescribed drugs

In a recent systematic review, 20 studies involving the six most commonly prescribed groups of drugs were reviewed. (2) This research revealed that PPIs (e.g. omeprazole) were not only associated with a significant drop in α-diversity (the number of different bacterial species a person is host to) but also lead to a shift in the composition of the microbiota. For metformin and NSAIDs (non-steroidal anti-inflammatory drugs), no significant change in α-diversity was seen but the composition of the microbiota in metformin users was found to be markedly different.



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Systematic review: human gut dysbiosis induced by non-antibiotic prescription medications 





Research by the University of Groningen in the Netherlands showed that of all drugs (including antibiotics) PPIs have the strongest effect on the microbiota, followed by statins, and antibiotics ranking third. (5) Long-term use of PPIs, in particular, can lead to shifts in the composition of the microbiota. That is the result of the reduced amount of gastric acid, which would normally have a protective effect by killing any bacteria that enter the gastrointestinal tract via the mouth. (4)


Susceptibility to pathogens

Other studies also report that PPIs, metformin, NSAIDs, opioids and antipsychotics are associated with an increase in the so-called gammaproteobacteria. This group includes such genera as Enterobacter, Escherichia, Klebsiella and Salmonella, among which are some of the most common pathogenic bacterial species. PPIs and metformin may also lead to increased susceptibility to Clostridium difficile infections. 


The degree to which non-antibiotic drugs affect gut bacteria was also researched at the European Molecular Biology Laboratory (EMBL) in Germany.(3) EMBL researchers looked at the degree of influence of over 1,000 different drugs on 40 common gut bacteria. Of these drugs, 24% was shown to inhibit the growth of at least one bacterial strain in vitro. The researchers surmise that the actual effect of the drugs on human gut bacteria is greater, because they focused on a comparatively small number of bacteria. They also expect that the effect in vivo will be comparable, as the drug doses used in the study were equal to the amount that enters the human gut.





Research into the possibilities of probiotics in dysbiosis due to PPI use is only just beginning to gather steam. One study demonstrated that a two-week course of probiotics containing four different lactobacilli can help to reduce bacterial overgrowth in the stomach, restoring its barrier function. (6) In a second study with 128 children with gastro-oesophageal reflux, 64 children were given a PPI with probiotics for 12 weeks. The remaining 64 children were given a PPI with a placebo, also for 12 weeks. In the placebo group, 56.2% was found to have dysbiosis after the treatment, while in the probiotics group, only 6.2% had dysbiosis (p<0.001) – a significant difference. (7) This appears to indicate that probiotics can help to reduce the degree of dysbiosis caused by PPIs.  




Not only antibiotics but also several other commonly used drugs can affect the composition of the microbiota. These changes in the microbiota can increase susceptibility to intestinal infections. Of all drugs, PPIs cause the most severe disruption in the microbiota. Probiotics may help to minimise this disruption.




1.            CBS. Gezondheid, leefstijl, zorggebruik en -aanbod, doodsoorzaken; vanaf 1900 2018 [updated 29 december 2017. Available from:

2.            Le Bastard Q, Al‐Ghalith G, Grégoire M, Chapelet G, Javaudin F, Dailly E, et al. Systematic review: human gut dysbiosis induced by non‐antibiotic prescription medications. Alimentary pharmacology & therapeutics. 2018;47(3):332-45.

3.            Imhann F, Bonder MJ, Vila AV, Fu J, Mujagic Z, Vork L, et al. Proton pump inhibitors affect the gut microbiome. Gut. 2016;65(5):740-8.

4.            Clooney A, Bernstein C, Leslie W, Vagianos K, Sargent M, Laserna‐Mendieta E, et al. A comparison of the gut microbiome between long‐term users and non‐users of proton pump inhibitors. Alimentary pharmacology & therapeutics. 2016;43(9):974-84.

5.            Maier L, Pruteanu M, Kuhn M, Zeller G, Telzerow A, Anderson EE, et al. Extensive impact of non-antibiotic drugs on human gut bacteria. Nature. 2018.

6.            Del Piano M, Pagliarulo M, Tari R, Carmagnola S, Balzarini M, Lorenzini P, et al. Correlation between chronic treatment with proton pump inhibitors and bacterial overgrowth in the stomach: any possible beneficial role for selected lactobacilli? Journal of clinical gastroenterology. 2014;48:S40-S6.

7.            SFK. Data en feiten 2017. Den Haag: Stichting Farmaceutische Kengetallen; 2017.

Effect of medicine use on the microbiota

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