Illuminating microbial dark matter: Dietary alterations uncover microbial regulation of immunity and metabolism.

In his 1907 book The Prolongation of Life, Élie Metchnikoff wrote, "Our actual knowledge of the intestinal flora is still very imperfect," and "a rational solution of the problem must be sought." Over 100 years later, we can still say the same about our gut microbiome. We have learned a great deal about specific microbiota species and their regulation of fundamental physiological processes including immunity (1, 2) and metabolism (3, 4). However, how the microbiota mediate these effects on the host remains elusive (5, 6). We have just begun to appreciate that many of the microbiota's regulatory effects are mediated by microbiota-derived bioactive small-molecule metabolites that circulate throughout the body and enable the gut microbiome to act like an endocrine system (7, 8). Much work has focused on the correlation between specific bacterial species and the phenotypes they generate. Yet, many different bacterial species can produce the same phenotype if they harbor identical genes for metabolite synthesis. Therefore, specific microbiota species may be sufficient, but not necessary, for a specific host phenotype. [ABSTRACT FROM AUTHOR]