A spoonful of medicine helps the microbiota adapt

Maier L, Pruteanu M, Kuhn M et al. Extensive impact of non-antibiotic drugs on human gut bacteria. Nature 2018; 555 (7698):623–628.

Non-antibiotic drugs can affect the gut microbiome. This study aimed to systematically profile the effects of marketed drugs on individual gut bacteria. Nearly 1200 drugs were tested, three-quarters of which were human targeted and one-quarter of which were antimicrobials. Drugs were screened at 20 µM in vitro against 40 representative human gut bacterial species, all found in the healthy human microbiome. Of the antimicrobials, 78% of antibiotics were active against at least one bacterial species and more than half of antivirals were active. Interestingly 24% of the human-targeted drugs, from all therapeutic classes, exhibited anticommensal activity. Those bacteria with higher abundance across healthy individuals were most susceptible to human-targeted drugs, such as Eubacterium rectale and Bacteriodes vulgatus. Concordance was found with metagenomics data in vivo, in particular with proton pump inhibitors (PPIs) and antipsychotics. The classes of drugs with greater anticommensal activity were antimetabolites, antipsychotics and calcium channel blockers. Non-antibiotic drugs may promote antibiotic resistance, as the general resistance mechanisms of microbes to human-targeted drugs and to antibiotics overlapped. An example was the Escherichia coli tolC mutant which effluxes several antibiotics; the mutant was more resistant to both antibiotics and human-targeted drugs than wild-type E. coli. Many drug–microbe interactions are likely to be individual and this study paves the way for personalised drug therapies aimed at the individual gut microbiome. It could also lead to drug repurposing. Drugs with broad-spectrum bactericidal activity such as the ovulation stimulant clomiphene could act as a new broad-spectrum antibiotic, and drugs with narrow-spectrum activity could be used to modulate the microbiome.

Hepatocyte transdifferentiation can regenerate the biliary tree

Schaub JR, Huppert KA, Kurial SNT et al. De novo formation of the biliary system by TGFβ- mediated hepatocyte …