Gut as viral reservoir: lessons from gut viromes, HIV and COVID-19
Markus F. Neurath, Klaus Überla, Siew C. Ng
Abstract
The gut microbiota is composed of bacteria, fungi and viruses.1–3 While the presence and composition of the bacteriome have been extensively studied in recent years, the ‘dark matter’ of microbiomes including viruses (viral microbiome or virome) remains incompletely understood.4 Analysis of microbiotic communities in the gut showed that bacteria rapidly colonise the gut after birth, followed by the appearance of prophages by 1 month which are harboured by these bacteria. Subsequently, a gut virome dominated by bacteriophages develops and human viruses can be detected 4 months after birth.5 6 In adults, recent studies have analysed the gut virome in healthy individuals by using metagenomic approaches.7 8 For instance, a metagenome analysis in 1986 individuals identified 33 242 unique viral populations, demonstrating that the human gut contains a vast array of bacteriophages and eukaryotic RNA and DNA viruses with a predominance of bacteriophages. Specifically, several groups of prokaryotic crAss-like, Caudovirales and Microviridae bacteriophages and eukaryotic adenoviruses and herpesviruses were characterised as stable colonisers of the human gut. Further studies described the existence of individual-specific persistent personal viromes. These viromes displayed marked interindividual heterogeneity with age-dependent changes and were critically dependent on host factors such as geography and ethnicity-distinct diets.9 10 Moreover, the duration of urban residence was associated with the presence of multiple bacteriophages, including Lactobacillus and Lactococcus phages.9 Although the functions of most viruses in the gut viromes have not been fully characterised, it has been suggested that viromes play a crucial role in shaping the gut microbiome and intestinal health under homeostatic conditions. This concept was underlined by experimental studies in murine dextran sulfate sodium (DSS) colitis.11 12 Treatment of DSS colitis with a cocktail of antiviral nucleoside analogues led to augmented mucosal inflammation, while administration of agonists for Toll-like receptor 3 (TLR3: sensor …