Pathogenic functions of host microbiota

Silke Rath, Tatjana Rud, André Karch, Dietmar Helmut Pieper, Marius Vital

It is becoming evident that certain features of human microbiota, encoded by distinct autochthonous taxa, promote disease. As a result, borders between the so-called opportunistic pathogens, pathobionts, and commensals are increasingly blurred, and specific targets for manipulating microbiota to improve host health are becoming elusive. In this study, we focus on the functions of host bacterial communities that have the potential to cause disease, proposing the term "pathogenic function (pathofunction)". The concept is presented via three distinct examples, namely, the formation of (i) trimethylamine, (ii) secondary bile acids, and (iii) hydrogen sulfide, which represent metabolites of the gut microbiota linked to the development of non-communicable diseases. Using publicly available metagenomic and metatranscriptomic data (n = 2975), we quantified those pathofunctions in health and disease and exposed the key players. Pathofunctions were ubiquitously present with increased abundances in patient groups. Overall, the three pathofunctions were detected at low mean concentrations (< 1% of total bacteria carried respective genes) and encompassed various taxa, including uncultured members. We outline how this function-centric approach, where all members of a community exhibiting a particular pathofunction are redundant, can contribute to risk assessment and the development of precision treatment directing gut microbiota to increase host health.