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

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 3×109 and 3×107 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.

► We applied a T4 phage cocktail at two concentrations to healthy adults.
► We counted the phage in the feces and its impact on the fecal microbiota.
► We did not observe adverse effects on liver, kidney and blood functions.
► Only one percent of the oral phage survives unprotected gastric passage.
► We sequenced a T4 phage collection and analyzed it for safety and homology.