Extensive impact of non-antibiotic drugs on human gut bacteria

Abstract

A few commonly used non-antibiotic drugs have recently been associated with changes in gut microbiome composition, but the extent of this phenomenon is unknown. We screened >1000 marketed drugs against 40 representative gut bacterial strains, and found that 24% of the drugs with human targets, including members of all therapeutic classes, inhibited the growth of at least one strain. Particular classes such as the chemically diverse antipsychotics were overrepresented. The effects of human-targeted drugs on gut bacteria are reflected on their antibiotic-like side effects in humans and are concordant with existing human cohort studies, providing in vivo relevance for our screen. Susceptibility to antibiotics and human-targeted drugs correlates across bacterial species, suggesting that non-antibiotics may promote antibiotic resistance. Our results provide a comprehensive resource for future research on drug-microbiome interactions, opening new paths for side effect control and drug repurposing, and broaden our view on antibiotic resistance.

Role of Microbiota and Tryptophan Metabolites in the Remote Effect of Intestinal Inflammation on Brain and Depression

“…Enterococcus and some anaerobic bacteria such as Clostridium difficile and Clostridium perfringens [3,[120][121][122]. Similarly, Gram-negative bacteria such as Citrobacter spp, Pseudomonas aeruginosa, Klebsiella pneumoniae and Morganella morganii have been proven to be susceptible to SSRIs [120,123].…”

“…These gut bacteria has coevolved with the human body to perform numerous beneficial functions ranging from being simple fermenters of food to having profound effects on the host immune development, metabolism and food preferences, brain development, stress responses, pain and behavior [1][2][3][4][5]. Consequently, disruptions or alterations in this resilient relationship is a significant factor in many diseases such as inflammatory gastrointestinal diseases, and neuropsychiatric disorders, including depression [1,[6][7][8].…”

How to Determine the Role of the Microbiome in Drug Disposition

“…The final version may differ from this version. representative gut bacterial strains and demonstrated that many of them inhibited bacterial growth in vitro (Maier et al, 2018); however, it was not determined whether metabolism took place. Such systematic screening methodologies coupled with analytical techniques for drug quantification and speciation will help uncover additional interactions between drugs and the gut microbiome.…”

“…Furthermore, care needs to be taken to sync the growth phase of control and drug exposed cultures to avoid false positives due to changes in cellular physiology. Finally, many non-antibiotic drugs can have bacteriostatic or even bacteriocidal effects during in vitro growth (Maier et al, 2018) 11 the translation of these results. Recently, by screening a collection of 25 Coriobacteriia strains and using our ElenMatchR tool for comparative genomics , we were independently able to identify a single genomic loci conserved in all strains capable of digoxin metabolism (Koppel et al, 2018).…”

Microbiota and Neurodevelopmental Trajectories: Role of Maternal and Early-Life Nutrition

“…Recently, Maier et al [70] showed that a large amount of non-antibiotic human-targeted drugs have antimicrobial properties. Among them, drugs that can be prescribed during pregnancy, such as proton pump inhibitors, were found to disturb the growth of commensal bacteria (Table 2).…”