Methods: We studied alterations in the host macroorganism and increased intestinal permeability as a result of a direct effect of bacteriophage cocktail. Healthy adult, albino Wistar rats, weighing 180-220g were given daily (for 10 days) phage cocktail (1.5 ml of 1×10⁶ plaque forming units/ml) active against Enterobacteriaceae, Staphylococcaceae, Streptococcaceae, and Pseudomonadaceae families (1). The lactulose-mannitol ratio was used as a marker of intestinal permeability (2). Circulating immune complexes (CIC) were evaluated as markers of endogenous intoxication (3). Metagenomic analysis was used to characterize the composition of microbiota before and after phage challenge.

Results: After 10 days of challenge, the rats showed weight loss, decreased activity. They displayed a significantly elevated lactulose:mannitol ratio with the mean increase 2.4 fold (2). The level of CIC was more than 2.5 times higher as compared to before treatment, indicating endogenous intoxication, caused by leaky gut (3). Metagenomic analysis revealed phage-induced altered microbiota composition that led to the increased intestinal permeability and transcriptome alterations were relevant to leaky gut syndrome.

Conclusions: To our knowledge, this study for the first time indicates the link between bacteriophages and mammalian pathologies associated with increased intestinal permeability such as systemic inflammatory and psychological or autoimmune disorders. This study demonstrates that increased intestinal permeability may be induced by bacteriophages that affect microbiota. We propose that infection of microbiota by bacteriophages can be considered a new group of viral diseases of mammals including humans (4).