The attached publication is central to the topic of gene-environment interactions. Beneficial bacteria (and perhaps a few viruses and fungi) — which normally inhabit our bodies — has been termed “the microbiome.” Although the microbiome has largely been overlooked (except for attempts to suppress or eradicate micro-organisms from our bodies), they comprise 90% of the total number of cells associated with our bodies; in other words human host cells make up only the remaining 10%..!! Small-molecular-weight chemicals, produced and enzymatically altered in the gut flora, are often chemically similar in structure to drugs, as well as to the ligands that activate the host’s endogenous receptors and lipid mediators that participate in second-messenger pathways mediated by the arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid cascades.
It is well known that drugs can have both beneficial and undesirable effects. The purpose of studies on the mechanisms of action and off-target spectra of various drugs is to improve their efficacy and reduce unwanted side effects. Although many drugs have gastrointestinal side-effects (most commonly, nausea, abdominal cramping and diarrhea) and although the gut microbiome itself is pivotal for human health, the role of the microbiome in these processes is rarely considered. Recently, administration of certain oral drugs designed to target human cells and not microbes –– such as anti-diabetics (metformin), proton-pump inhibitors (PPIs), nonsteroidal anti-inflammatory drugs (NSAIDs), and atypical anti-psychotics (AAPs) –– has been associated with changes in microbiome composition. One large-cohort study suggested that medication can alter gut microbiome composition in more general ways (I foresee many studies going further in this direction).
Authors [see attached report] screened >1,000 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; moreover, particular classes, such as the chemically diverse anti-psychotics, were overrepresented in this group. Effects of human-targeted drugs on the microbiome imitated their antibiotic-like side-effects in humans.
Susceptibility to antibiotics and human-targeted drugs was correlated across bacterial species, suggesting common resistance mechanisms, which authors verified for several drugs [see attached]. The potential risk of non-antibiotics that promote antibiotic resistance warrants further exploration.
These intriguing data provide a resource for future research on drug–microbiome interactions. This study opens new paths for side-effect control and drug repurposing –– and should broaden the overview of clinicians who are investigating antibiotic resistance.
Nature 29 Mar 2o18; 555: 623–628