Immune Response of an Oral Enterococcus faecalis Phage Cocktail in a Mouse Model of Ethanol-Induced Liver Disease

Abstract

Cytolysin-positive Enterococcus faecalis (E. faecalis) cause more severe alcohol-associated hepatitis, and phages might be used to specifically target these bacteria in a clinical trial. Using a humanized mouse model of ethanol-induced liver disease, the effect of cytolytic E. faecalis phage treatment on the intestinal and liver immune response was evaluated. The observed immune response was predominantly anti-inflammatory and tissue-restoring. Besides, live phages could be readily recovered from the serum, spleen, and liver following oral gavage in ethanol-fed mice. We also isolated 20 new phages from the sewage water; six of them exhibited a relatively broad host range. Taken together, the oral administration of cytolytic E. faecalis phages leads to the translocation of phages to the systemic circulation and appears to be safe, following chronic-binge ethanol administration. A cocktail of three phages covers the majority of tested cytolysin-positive E. faecalis strains and could be tested in a clinical trial.

Isolation and identification of specific Enterococcus faecalis phage C-3 and G21-7 against Avian pathogenic Escherichia coli and its application to one-day-old geese

“…It has been reported that the oral T4 phage treatment of 75 children with acute bacterial diarrhea safety analysis, liver, kidney and hematological function is normal (Sarker et al, 2016). Oral of E. faecalis phage did not cause damage to mice with ethanol-induced liver disease and inhibited E. faecalis (Mendes et al, 2022. In the safety evaluation of this study, oral phage did not cause the death of geese, and it was unexpectedly found that the feed efficiency of oral phage on geese was significantly higher than that of the injection group and the control group. In the treatment effect evaluation test, it was found that the survival rate of the phage group was higher than that of some antibiotic groups, and the same phenomenon was also found in the phage treatment of mice infected with pseudomonas aeruginosa, and the survival rate of the phage treatment was 25% higher than that of the antibiotic treatment (Koderi Valappil et al, 2021).…”

Using a human colonoid-derived monolayer to study bacteriophage translocation

“… 52 , 53 Detection of gastrointestinal phages in “sterile” sites of the body, such as the blood or cerebrospinal fluid, suggests that they can be translocated from their primary gut niche. Indeed, oral administration of high-titer phages in mouse studies has shown translocation into blood and tissue, 54 even in the absence of disease. 55 As phages have the potential to elicit context-dependent inflammatory, and anti-inflammatory responses in systemic circulation, 29–31 , 56 physiologically relevant models to understand gastrointestinal phage translocation are sorely needed.…”

Phage therapy: Targeting intestinal bacterial microbiota for the treatment of liver diseases

“…We previously reported that phages even spread systemically when administered orally in mice subjected to chronic ethanol feeding. 110 From this perspective, besides editing the gut microbiota, systemic or intraperitoneal administration of phages may also be effective for the treatment of spontaneous bacterial peritonitis and liver abscesses. These would be similar applications to the case report of a patient with necrotising pancreatitis and an infected pancreatic pseudocyst.…”