Both diet and medications are among the strongest variables affecting the gut microbiome. When it comes to medications, although antibiotics have been repeatedly shown to affect the human gut microbiome, little is known regarding the impact of non-antibiotic prescription drugs on the gut microbiome.
A review, led by Dr. Emmanuel Montassier from the MiHAR Lab at Institut de Recherche en Santé 2, Université de Nantes (Nantes, France), has concluded that some non-antibiotic prescription drugs have a notable impact on the gut microbiome to the same extent as antibiotics.
The researchers conducted a systematic review for assessing the impact of the most frequently non-antibiotic prescribed therapeutic drug categories -proton pump inhibitors (PPIs), metformin, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, statins and antipsychotics- on the gut microbiome. Studies that included preclinical models and those that studied the gastric microbiota or were based on culture-dependent techniques were ruled out.
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used for the selection of studies, and finally, 20 studies were included in the systematic review.
PPIs and antipsychotic medications were associated with a decrease in a diversity -the average species diversity within an individual site- in the gut microbiome, whereas opioids were associated with an increase in a diversity. On the other hand, metformin and NSAIDs were not associated with significant changes in a diversity. Besides this, all prescribed therapeutic drugs except NSAIDs led to a significant alteration of b diversity -that is, the intervariability or diversity between different samples. Further studies are needed in order to better characterize gut dysbiosis related to these drugs, as well as their functional impact. In this context, a previous study found the relative abundance of specific bacterial taxa was associated with exposure to PPIs, antidepressants and antipsychotics in hospitalized elderly individuals, a population often polymedicated and with high multimorbidity. In those elderly hospitalized patients with the lowest microbiome diversity, the researchers detected an increased mortality after a 2-year follow-up.
Specifically, the review reported taxonomic changes induced by medications. PPI use was related to a decrease in Clostridiales and an increase in Actinomycetales, Micrococcaceae and Streptococcaceae, which are changes that have previously been involved in gut dysbiosis and increased susceptibility to Clostridium difficile infection. Noticeably, microbial families that were abundant in the guts of PPI users were more often found in the mouth/throat, skin/nose or vaginal sites of healthy individuals rather than in their guts.
PPIs, metformin, NSAIDs, opioids and antipsychotics were associated with increases in either members of class Gammaproteobacteria (including Enterobacter, Escherichia, Klebsiella, Citrobacter, Salmonella and Proteus) or members of family Enterococcaceae. All of them are frequently isolated pathogens from blood culture samples of patients with sepsis, especially critically ill and cancer patients.
Finally, the authors noted that weight gain and increased visceral fat as a common side effect related to second-generation antipsychotics may be partially mediated through their effects on the gut microbiome.
Mechanisms by which drugs influence the gut microbiome are diverse and include:
- PPIs: pH elevation throughout the digestive tract, especially in the stomach and small bowel due to Helicobacter pylori elimination.
- Metformin: alteration of the enterohepatic recirculation of bile acids involving modulation of gut microbiome.
- NSAIDs: alteration of function in the small intestine.
- Opioids: through delaying transit time, opioids may lead to an increase diversity.
- Statins: interaction with bile acids and impact upon expression of inflammatory markers.
- Antipsychotics: direct interaction with the growth of commensal gut microorganisms.
In conclusion, many non-antibiotic prescription drugs have a notable effect on the structure of the gut microbiome. Further research is needed in order to better clarify the impact of non-antibiotic prescription drugs, not only on gut microbiota composition, but also on its functional diversity and metabolomics. The authors also propose that other frequently prescribed drugs should be investigated in terms of their effects on the gut microbiota.
Le Bastard Q, Al-Ghalith GA, Grégoire M, et al. Systematic review: human gut dysbiosis induced by non-antibiotic prescription medications. Aliment Pharmacol Ther. 2018; 47(3):332-45. doi: 10.1111/apt.14451.