Common Oral Medications Lead to Prophage Induction in Bacterial Isolates from the Human Gut.

Steven G Sutcliffe,Michael Shamash,Alexander P Hynes,Corinne F Maurice

doi:10.3390/v13030455

Abstract

Many bacteria carry bacteriophages (bacterial viruses) integrated in their genomes in the form of prophages, which replicate passively alongside their bacterial host. Environmental conditions can lead to prophage induction; the switching from prophage replication to lytic replication, that results in new bacteriophage progeny and the lysis of the bacterial host. Despite their abundance in the gut, little is known about what could be inducing these prophages. We show that several medications, at concentrations predicted in the gut, lead to prophage induction of bacterial isolates from the human gut. We tested five medication classes (non-steroidal anti-inflammatory, chemotherapy, mild analgesic, cardiac, and antibiotic) for antimicrobial activity against eight prophage-carrying human gut bacterial representative isolates in vitro. Seven out of eight bacteria showed signs of growth inhibition in response to at least one medication. All medications led to growth inhibition of at least one bacterial isolate. Prophage induction was confirmed in half of the treatments showing antimicrobial activity. Unlike antibiotics, host-targeted medications led to a species-specific induction of Clostridium beijerinckii, Bacteroides caccae, and to a lesser extent Bacteroides eggerthii. These results show how common medication consumption can lead to phage-mediated effects, which in turn would alter the human gut microbiome through increased prophage induction.

Highlights

The human gut is at the intersection of host cells, trillions of microorganisms, and all the different compounds we ingest, termed xenobiotics
Twelve medications from multiple classes were screened to explore their role in prophage induction on eight bacterial lysogens from the human gut
We show that bacterial growth inhibition by these medications leads to prophage induction in at least 55% of cases

Summary

Introduction

The human gut is at the intersection of host cells, trillions of microorganisms (bacteria, archaea, eukaryotes, and viruses), and all the different compounds we ingest, termed xenobiotics. Medication of a variety of classes can have major effects on the gut bacteriome [4,5,6,7,8,9,10,11,12] leading to species-specific bacterial growth inhibition [13] or community-level shifts in bacterial diversity [4,5,6,7,8,9,10,11,12]. Medication can alter the gut virome [14], which is highly correlated with the bacterial community [15]. This is because the gut virome is dominated by bacteriophages [16]

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