There is currently little understanding of the role of the bacterial second messenger cyclic di-GMP (c-di-GMP) in the human gut microbiome. C-di-GMP is synthesized by highly conserved diguanylate cyclase (DGC) enzymes and degraded by highly conserved phosphodiesterase (PDE) enzymes. To begin to assess the prevalence of c-di-GMP signaling in the gut microbiome, we found on average 1.0 DGC and 0.8 PDE enzymes per million base pairs of metagenomic DNA derived from stool samples. Specific species encoding substantial numbers of GGDEF and EAL domains were the commensal species Faecalibacterium prausnitzii, Eubacterium rectale, and Mitsuokella multacida. The species Bilophila wadsworthia and Klebsiella oxytoca were identified as gut microbiome members that encode higher numbers of GGDEFs and EALs and are associated with gut dysbiosis and infection. Consistent with this result, genome analysis of several enteric pathogens revealed significantly higher numbers of GGDEFs and EALs per million base pairs compared to the gut microbiome. Our analysis indicates that c-di-GMP signaling is present but minimal in the gut microbiome, and we speculate that the numbers of GGDEFs and EALs in a given genome from a member of the gut microbiome positively correlates with pathogenic potential.
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