Bacteriophages as modulator for the human gut microbiota: Release from dairy food systems and survival in a dynamic human gastrointestinal model

Abstract

Understanding the functions of the human gut microbiota and its associated phageome is of major interest. The human gut contains about 1015 phage particles, suggesting that phages may modulate the gut microbiota. Nevertheless, the targeted application of phages in the human gastrointestinal tract (GIT) faces numerous challenges, i.e., availability of appropriate phage delivery systems and sensitivity of phages to gastrointestinal conditions. In the present study, a dynamic gastrointestinal model (TIM-1 system) was used to investigate i) the survival kinetics of the lactococcal phage P008 added to three different “test meals” and ii) the delivery of this phage to the large intestine. In the stomach compartment, a protective effect of the food matrix was documented on phage stability. The highest survival rate in the stomach was observed for encapsulated phages and a residual phage titer (in total) of 8 log pfu was detected after 240 min digestion at a pH < 2.0. However, release from the gastric compartment appeared to be significantly delayed in this case. Regardless of the used "test meal", high phage delivery from the ileal compartment was observed after 4 h of digestion, with a maximum value of 27% for phages suspended in milk concentrate. Hence, this study indicates that phages survive in significant numbers (i.e., >90%) during passage through the upper human GIT and may hence be able – when added e.g. to a dairy food matrix – to affect the activity of the human gut microbiota.