CRISPR spacer acquisition is a rare event in human gut microbiome

Host-parasite (host-virus) interactions are important for all cellular life, for example, human immunity and SARS-COV2. In bacteria and archaea, CRISPR systems actively acquire spacers to ensure continued defense against phages, which have been reported to acquire a new spacer within a few hours or days in an experimental setting. However, spacer acquisition in natural environments has often been too slow to observe, and limited literature reports suggest a much slower rate (new spacers only acquired over months or years). This high variance highlights the need to improve our understanding of host-parasite interactions in nature.
By investigating temporal WGS datasets and metagenomes of human gut microbiome in healthy individuals, we found that spacer acquisition is a rare event in human gut microbiome, with an average rate of 1 spacer per 2,142-5,000 cell divisions, i.e. over 7-8 years. This low rate reflects only a small proportion of phage challenged the CRISPR systems in the human gut microbiome.
Bifidobacterium longum shows a significantly higher rate of spacer acquisition than the other gut microbiome species. We found six recently acquired spacers were highly prevalent, consecutive in the same order, in B.longum lineages from 14 different human subjects in both the United States and Europe. Those six spacers locate on different parts of the B.longum genomes, while their neighborhood (50k-135k bp) remains highly similar across B.longum lineages, including a transposase and the whole CRISPR system. This indicates that the high spacer acquisition rate in B.longum is mainly contributed by horizontal gene transfer.
The rare spacer acquisition in CRISPR suggests that CRISPR might not be the primary risk of effective phage therapy for the majority of human microbiome. The results of this study may inform future efforts involving phage therapy and pandemic defense.