New Insights into the Gut Microbiota
The gut microbiota plays a crucial role in human health. Over the past decade, the viral fraction of the gut microbiota, which essentially consists of phages that infect bacteria, has gained increasing importance. In parallel with the development of viral metagenomics, numerous new phage families have been discovered. However, since the discovery of intestinal phages by d’Hérelle in 1917, our understanding of the influence of phages on the structure of the gut microbiota remains limited. Changes in the composition of the viral community have been observed in various diseases. However, whether these changes reflect a direct involvement of phages in disease development or are simply due to alterations in bacterial composition is currently unknown. Here, we provide an overview of the current state of knowledge regarding intestinal phages, their identity, their lifestyle, and their potential impact on the gut microbiota. We also compile the most important data on phage interactions with the immune system, with a particular focus on the latest findings.
Conclusions
Over the last decade, viral metagenomics has elucidated the taxonomic composition and dynamics of the viral component of the gut microbiota. Deep sequencing and novel assembly methods have enabled the description of entirely new phage families. These approaches have primarily shown that the composition of the virome is highly variable, with only a small fraction of phages being shared between individuals. Unsurprisingly, the most abundant viruses infect Bacteroides and Clostridiales species, which are dominant in the microbiota. In parallel, experiments on animals with a simplified microbiota allowed the exploration of phage-bacteria antagonistic interactions in the gut and revealed variable results. In some phage-bacteria pairs, the gut environment somehow protects the bacteria, and only a small proportion of genetically susceptible bacteria are killed by their specific phages. In other cases, the majority of the phage-susceptible bacterial population is replaced by resistant mutants within a few days, indicating a very efficient phage infection. Therefore, it remains difficult to predict which outcome will prevail in the complex natural microbiota. Traces of phage predation can be found in the genomes of gut bacteria, but these traces could be due to low phage-induced mortality. Low phage predation could nevertheless be crucial for shaping the composition and functionality of the microbiota by influencing bacterial evolution through horizontal gene transfer, but also by promoting bacterial diversity. For shorter ecological timescales, the influence of phages is less well established. In particular, the role of phages in the dysbioses that accompany various pathological conditions is not yet sufficiently defined. Thanks to recent advances in determining phage-bacteria pairs, longitudinal studies can now be conducted to identify possible relationships between temporal shifts in bacteria and their associated phages, and to delineate whether phages contribute to dysbiosis and disease or, on the contrary, can contribute to maintaining the stability of the microbiota by preserving bacterial diversity.
Further studies are also required to demonstrate possible direct interactions of phages with immune cells and to define if and how such direct effects can alter the composition of the bacterial microbiota and influence host health or disease. Defining the mechanisms that determine the outcome of phage-bacteria interactions in the gut is particularly important for the perspective of phage therapy, which, to quote Brüssow,125 “is undoubtedly an interesting approach to the problem of antibiotic resistance and deserves increased research to move beyond the fruitless confrontation between Eastern enthusiasm and persistent Western skepticism.”
Translation of the source: https://www.nature.com/articles/s41385-019-0250-5
