Our findings also imply that CRISPR spacers are actively acquired
in response to phages in the human gut. First, the large
number of unique phage-matching spacers we detected is suggestive
of the numerous events in which such interactions have occurred.
Second, we have identified cases in which the most recently
acquired spacers in the rapidly evolving CRISPR array
perfectly match a phage co-occurring in the same gut, at apparently
depressed levels (e.g., Fig. 3), as well as absolutely no conservation
of the most recently acquired spacer in a particular array
across individuals (Supplemental Table S3). Finally, our data suggest
that CRISPR spacers usually successfully exclude targeted
phages, while showing positive correlation of highly matching
spacers (thus also likely to be recently acquired) with targeted
phages about to be completely excluded. Combined, this evidence
suggests that there is an ongoing ‘‘immune’’ interaction between
phages and their bacterial hosts within the gut microbial community,
whose potential effect remains to be fully characterized. It
is possible that the rapid nature of this dynamic is what has made it
so difficult to capture in previous studies. Notably, although the
typical ecological manifestations of predatory interactions were
observed in numerous niches, past studies did not report on such
dynamics in the gut, and this study was not suited to examine it
directly due to the lack of time-series data.
It is also not entirely clear how to reconcile phage–bacteria
infection–resistance interactions through the CRISPR system with
the apparent abundance of lysogenic phages in the gut, which this
study also supports. This suggests there may be some form of
protection of the bacterial genome (harboring the prophage) from
the CRISPR system (Stern et al. 2010). A recent study (Edgar and
Qimron 2010) has shown that acquisition of spacers against a lysogenized
phage can lead to bacterial cell death but may also prevent
prophage induction and subsequent cell lysis to the benefit of
bacteria under certain circumstances. Spacers against a phage not
yet integrated were shown to prevent lysogenization (Edgar and
Qimron 2010). This study and our findings suggest the CRISPR
system may have important roles in regulating phage–bacteria
interactions even when they are not primarily lytic.
It is clear, therefore, that further study is warranted to unravel
the seemingly unique ecology of the human gut microbiome in
this respect. Our identification of the gut bacterial targets for more
than 130 phages, based on evidence for integration into the bacterial
host genome (Fig. 4) or on CRISPR-derived phage–host assignment
(Fig. 3), now opens the window for future, detailed timecourse
studies on the dynamic effect of phages on individual
bacterial species and on the gut microbial consortium as a whole.
Our findings also imply that CRISPR spacers are actively acquired
in response to phages in the human gut. First, the large
number of unique phage-matching spacers we detected is suggestive
of the numerous events in which such interactions have occurred.
Second, we have identified cases in which the most recently
acquired spacers in the rapidly evolving CRISPR array
perfectly match a phage co-occurring in the same gut, at apparently
depressed levels (e.g., Fig. 3), as well as absolutely no conservation
of the most recently acquired spacer in a particular array
across individuals (Supplemental Table S3). Finally, our data suggest
that CRISPR spacers usually successfully exclude targeted
phages, while showing positive correlation of highly matching
spacers (thus also likely to be recently acquired) with targeted
phages about to be completely excluded. Combined, this evidence
suggests that there is an ongoing ‘‘immune’’ interaction between
phages and their bacterial hosts within the gut microbial community,
whose potential effect remains to be fully characterized. It
is possible that the rapid nature of this dynamic is what has made it
so difficult to capture in previous studies. Notably, although the
typical ecological manifestations of predatory interactions were
observed in numerous niches, past studies did not report on such
dynamics in the gut, and this study was not suited to examine it
directly due to the lack of time-series data.
It is also not entirely clear how to reconcile phage–bacteria
infection–resistance interactions through the CRISPR system with
the apparent abundance of lysogenic phages in the gut, which this
study also supports. This suggests there may be some form of
protection of the bacterial genome (harboring the prophage) from
the CRISPR system (Stern et al. 2010). A recent study (Edgar and
Qimron 2010) has shown that acquisition of spacers against a lysogenized
phage can lead to bacterial cell death but may also prevent
prophage induction and subsequent cell lysis to the benefit of
bacteria under certain circumstances. Spacers against a phage not
yet integrated were shown to prevent lysogenization (Edgar and
Qimron 2010). This study and our findings suggest the CRISPR
system may have important roles in regulating phage–bacteria
interactions even when they are not primarily lytic.
It is clear, therefore, that further study is warranted to unravel
the seemingly unique ecology of the human gut microbiome in
this respect. Our identification of the gut bacterial targets for more
than 130 phages, based on evidence for integration into the bacterial
host genome (Fig. 4) or on CRISPR-derived phage–host assignment
(Fig. 3), now opens the window for future, detailed timecourse
studies on the dynamic effect of phages on individual
bacterial species and on the gut microbial consortium as a whole.
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