Reply to ‘Can we predict microbial keystones?’

In response to our recent Opinion article (Keystone taxa as drivers of microbiome structure and functioning. Nat. Rev. Microbiol. 16, 567–576 (2018))1, Röttjers and Faust (Can we predict keystones? Nat. Rev. Microbiol. https://doi.org/10.1038/s41579-018-0132-y (2018))2 highlight an important discussion in microbial ecology: how accurately can keystones be predicted from co-occurrence networks? We agree with their claim that the identification of highly connected OTUs (hubs) in microbial networks does not necessarily reveal their role as keystones. In our Review article1, we have extensively discussed the idea that the identification of keystones by network-based scores must be complemented with empirical data to uncover their true importance. Therefore, we summarized keystones into two categories: those identified through computational inference (‘keystone OTUs’) and those with explicit experimental evidence for their role in the microbiome (‘keystone taxa’). While Röttjers and Faust only consider empirically established keystone taxa, our aim was to generate a candidate list for further validation but also to identify keystone OTUs, for which it might be a daunting task to collect enough empirical evidence to classify them as keystone taxa. Some microorganisms are uncultivable, or current methods are not sensitive enough to culture them. Moreover, without an initial statistical screening for potential keystones, it may be nearly impossible to identify them in view of the enormous diversity and complexity in microbial communities (for example, almost any substrate on Earth is typically colonized by thousands of microbial taxa).