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.
Commensal bacteria and their genes associated with host are known as microbiome. In recent years, microbial influence on host endocrine system has been under detailed investigation. The role of microbiome in the pathogenesis of insulin resistance and obesity, the function of hypothalamic-pituitary-adrenal axis and secretion of hormones regulating appetite is well described in world literature. In this article we discuss poorly reviewed issues: the microbiome role in modulation of non-peptide (sex and thyroid) and peptide (growth hormone and parathyroid hormone) functions. Understanding complex bidirectional relations between host endocrine system and bacteria is of fundamental importance to understanding microbial impact on host reproduction, risk of endocrine-related cancers, pathogenesis of non-thyroidal illness syndrome, growth failure in children and hormonal changes during chronic kidney disease. This article also highlights effects of dietary compounds on microbiome composition and bacterial enzymes activity, and thus host hormonal status.