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Clinical Trial
. 2005 Jul;49(7):2874-8.
doi: 10.1128/AAC.49.7.2874-2878.2005.

Human volunteers receiving Escherichia coli phage T4 orally: a safety test of phage therapy

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Clinical Trial

V体育平台登录 - Human volunteers receiving Escherichia coli phage T4 orally: a safety test of phage therapy

Anne Bruttin et al. Antimicrob Agents Chemother. 2005 Jul.

V体育ios版 - Abstract

Fifteen healthy adult volunteers received in their drinking water a lower Escherichia coli phage T4 dose (10(3) PFU/ml), a higher phage dose (10(5) PFU/ml), and placebo. Fecal coliphage was detected in a dose-dependent way in volunteers orally exposed to phage. All volunteers receiving the higher phage dose showed fecal phage 1 day after exposure; this prevalence was only 50% in subjects receiving the lower phage dose. No fecal phage was detectable a week after a 2-day course of oral phage application. Oral phage application did not cause a decrease in total fecal E. coli counts. In addition, no substantial phage T4 replication on the commensal E. coli population was observed VSports手机版. No adverse events related to phage application were reported. Serum transaminase levels remained in the normal range, and neither T4 phage nor T4-specific antibodies were observed in the serum of the subjects at the end of the study. This is, to our knowledge, the first safety test in the recent English literature which has measured the bioavailability of oral phage in humans and is thus a first step to the rational evaluation of phage therapy for diarrheal diseases. .

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Figures

FIG. 1.
FIG. 1.
Fecal phage and E. coli counts in the five individual volunteers receiving the products in the sequence placebo-higher phage dose-lower phage dose during the study period (time in hours after start of treatment) (panels a to e). (f) Excretion pattern of a possible “low phage responder” receiving the sequence lower phage dose-placebo-higher phage dose. The fecal phage titers (expressed as log10 PFU/g stool) are represented by squares, whereas the fecal E. coli counts (expressed as log10 CFU/g stool) are depicted with diamonds.
FIG. 2.
FIG. 2.
Gastrointestinal phage transit in human volunteers. Fifteen adult volunteers received the lower phage T4 dose (squares), the higher phage T4 dose (diamonds), and no phage (triangles) in their drinking water for 2 days (the treatment period is marked by a horizontal bar). The stool samples were tested for the presence of phages starting 1 day preceding the intervention. (a) The prevalence (in percent) of phage-positive stool samples; (b) the time development of the mean phage titer in the feces of the volunteers (expressed as PFU/g stool). Each datum point represents the results from all 15 volunteers. The mean titers for the recipients of the lower phage dose were 17 and 68 at days 2 and 3, respectively; they are too small to be visible at the chosen scale.

References

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