Oral T4-like phage cocktail application to healthy adult volunteers from Bangladesh

Abstract

The genomic diversity of 99 T4-like coliphages was investigated by sequencing an equimolar mixture with Illumina technology and screening them against different databases for horizontal gene transfer and undesired genes. A 9-phage cocktail was given to 15 healthy adults from Bangladesh at a dose of 3×10(9) and 3×10(7) plaque-forming units and placebo respectively. Phages were detected in 64% of the stool samples when subjects were treated with higher titer phage, compared to 30% and 28% with lower-titer phage and placebo, respectively. No Escherichia coli was present in initial stool samples, and no amplification of phage was observed. One percent of the administered oral phage was recovered from the feces. No adverse events were observed by self-report, clinical examination, or from laboratory tests for liver, kidney, and hematology function. No impact of oral phage was seen on the fecal microbiota composition with respect to bacterial 16S rRNA from stool.

A bacteriophage cocktail targetingEscherichia colireducesE. coliin simulated gut conditions, while preserving a non-targeted representative commensal normal microbiota

“…Of the few studies examining phage therapy, none have reported any adverse effects on human health, or major alterations of the microbiome. 17 , 18 , 35 , 36 The present study corroborated those findings. Noteworthy, the bacteriophage cocktail did also lyse a large number of other E. coli strains in vitro ; i.e., it was not solely lytic for one targeted E. coli strain.…”

Therapeutic potential of phages in autoimmune liver diseases

“…It should be emphasized that no clinical or laboratory signs of hepatic injury were noted in normal individuals and patients treated with phages [although some of them had some extent of liver dysfuntion (moderate elevation of aminotransferases)], so clinical phage therapy appears to be free of hepatotoxicity 58, 59, 60. This confirms earlier data from experiments in mice 61 and in broilers in which dietary supplementation with phages increased liver weight 62.…”

Bacteriophages and Their Derivatives as Biotherapeutic Agents in Disease Prevention and Treatment

“…No adverse events were observed by selfreport, clinical examination, or from laboratory tests for liver, kidney, and hematology function. In addition, no impact was seen on the fecal microbiota composition with respect to bacterial 16S rRNA from stool [77].…”