Editors' ChoiceGut Microbiome

Catching a Glimpse of Gut Bacteria–Drug Interactions

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Science Translational Medicine  30 Jan 2013:
Vol. 5, Issue 170, pp. 170ec21
DOI: 10.1126/scitranslmed.3005776

Our second genome, the microbiome, is well hidden in the depths of our colonized body cavities. Having established who’s who in these bacterial communities, researchers are now tooling up to tease out interdependencies between the microbiota and its host. The research trio of Maurice, Haiser, and Turnbaugh has paired cell-sorting with RNA sequencing and backed these approaches up with metagenomic studies to study the effects of xenobiotic drugs on the human microbiome. Prompted by findings that the members of microbial communities can show wildly different physiological states, the authors found by means of fluorescent staining that only slightly more than half of the bacteria in stool samples from healthy volunteers are metabolically active. Nearly a third of the gut microbial cells had impaired membrane integrity, and another quarter showed profound damage. Members of the phylum Firmicutes tended to be metabolically active, whereas Bacteroidetes were less so. Damaged bacteria showed a similar communal structure to the active group, suggesting that the increase in metabolism leads to a higher-paced cellular turnover. Gene expression was higher in the active Firmicutes than in the less active Bacteroidetes.

This analysis sets the stage to explore the responses of these human gut microbes to small molecules. The authors chose a battery of 14 xenobiotics, which included antibiotics and other, host-targeted drugs, for incubation with fecal samples under ex vivo conditions. As expected, antibiotics induced a more pronounced effect on microbial physiology than did the drugs designed to target host physiology. Antibiotics altered gene expression in about 1700 gene clusters, inducing antibiotic-resistance genes and stress-response pathways. Even the less-effective host-targeting drugs induced gene expression changes in ~300 microbial gene clusters, which included candidate genes for the biotransformation of drugs. As the authors discuss, these findings point the way to mechanistic studies on the modulation of drug efficacy or toxicity by individual or groups of gut microbes.

C. F. Maurice et al., Xenobiotics shape the physiology and gene expression of the active human gut microbiome. Cell 152, 39–50 (2013). [Abstract]

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