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. 2014 Nov 4;20(5):719-730.
doi: 10.1016/j.cmet.2014.10.016. Epub 2014 Nov 4.

Specialized metabolites from the microbiome in health and disease

Gil Sharon  1 , Neha Garg  2 , Justine Debelius  3 , Rob Knight  4 , Pieter C Dorrestein  5 , Sarkis K Mazmanian  6
Affiliations

Specialized metabolites from the microbiome in health and disease

Gil Sharon et al. Cell Metab. .

Abstract

The microbiota, and the genes that comprise its microbiome, play key roles in human health. Host-microbe interactions affect immunity, metabolism, development, and behavior, and dysbiosis of gut bacteria contributes to disease. Despite advances in correlating changes in the microbiota with various conditions, specific mechanisms of host-microbiota signaling remain largely elusive. We discuss the synthesis of microbial metabolites, their absorption, and potential physiological effects on the host. We propose that the effects of specialized metabolites may explain present knowledge gaps in linking the gut microbiota to biological host mechanisms during initial colonization, and in health and disease.

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Figures

Figure 1
Figure 1. The production-absorption-target site pathway of metabolites
A product of microbial metabolism from dietary or metabolic precursors (left panel), specialized metabolites are absorbed through epithelial barriers. A major site for absorption of specialized metabolites is the intestine where metabolites cross the intestinal epithelium and enter the circulation through the portal vein, via the liver (middle panel). Once in the circulation, metabolites travel to various target sites (organs, tissue, cells, etc) in the mammalian host (right panel).
Figure 2
Figure 2. Modes of absorption for specialized metabolites
Metabolites can cross epithelial barriers via various passive and active processes, through cells (transcellular), diffusing through the membrane or using various transporter enzymes. Alternatively, metabolites can cross the barrier between cells (paracellular), a process mediated by tight-junction proteins, namely Claudins. During inflammation, often mediated by cytokines such as IL-6 and IL-1β, the intestinal barrier is disrupted, allowing uncontrolled paracellular passage to metabolites that are excluded by the intact epithelium.
Figure 3
Figure 3. Specialized metabolites, synthesized by the gut microbial community from various precursors, reach target sites and mediate health and disease
SCFA: Short-Chain Fatty-Acids; TMAO:trimethylamine N-oxide; DCA:deoxycholic acid; 4EPS:4-ethylphenyl sulfate.
See this image and copyright information in PMC

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