Antibiotics are not the only culprits
Antibiotics have been much maligned for promoting resistant strains of pathogenic bacteria and wiping out good bacteria in the gut. While caution is definitely warranted, it turns out that a number of other drugs have deleterious effects on the gut microbial ecosystem, especially in reducing colonization resistance to pathogenic bacteria.
Two articles in this week’s Nature deal with interactions between drugs and the gut microbiota. The influence goes both ways, as drugs influence the gut microbial ecosystem, which in turns may alter certain drugs. The study of the latter is called “pharmaco-microbiomics” and addresses how drugs are metabolized by microbial organisms. Both papers deal with the latter, more familiar landscape of how drugs impact the gut. Both point to the worrisome consequences of our pill-popping culture:
The first one, led by @andrew goodman at @yale university (Identification of medication–microbiome interactions that affect gut infection), identifies “medications that are associated with an increased risk of gastrointestinal infections across a population cohort of more than one million individuals monitored over 15 years”, including the heart drug digoxin, which is “sufficient to alter the composition of the microbiome and the risk of infection with Salmonella enterica subsp. enterica serovar Typhimurium (S. Tm) in mice. The effect of digoxin treatment on S. Tm infection is transmissible through the microbiome, and characterization of this interaction highlights a digoxin-responsive β-defensin that alters the microbiome composition and consequent immune surveillance of the invading pathogen.” Wow!
On a side note, digoxin is one of the canonical examples in pharmaco-microbiomics: it can be deactivated by certain gut bacteria such as Eggerthella lenta, which convert digoxin into a much less active form, dihydrodigoxin, with the cardiac glycoside reductase (cgr) enzyme system.
The second article, led by @lisa maier of the University of Tübingen in Germany (Non-antibiotics disrupt colonization resistance against enteropathogens), addresses pretty much the same issue but with in vitro assays “to assess enteropathogen growth in drug-perturbed microbial communities”. Pathogenic microbial organisms were more resistant to non-antibiotics than the friendly gut bacteria: in other words, the good guys were diminished, leaving the terrain available for colonization by pathogens. “For 28% of the 53 drugs tested, the growth of Salmonella enterica subsp. enterica serovar Typhimurium. (S. Tm) in synthetic and human stool-derived communities was increased, and similar effects were observed for other enteropathogens. Non-antibiotics promoted pathogen proliferation by inhibiting the growth of commensals, altering microbial interactions and enhancing the ability of S. Tm to exploit metabolic niches. Drugs that promoted pathogen expansion in vitro increased the intestinal S. Tm load in mice.”