The bacterial chemical repertoire mediates metabolic exchange within gut microbiomes

Abstract

Microbial communities in the gut have been hypothesized to play key roles in the health of the host organism. Exploring the relationship between these populations and disease states has been a focus of the human microbiome project. However, the biological roles of the compounds produced by the gut bacteria are largely unknown. We hypothesize that these compounds act as metabolic exchange factors-mediating inter-species and intra-species interactions in the microbiome. This view is supported through this review of known bacterial metabolic exchange factors and evidence for uncharacterized metabolic exchange factors in the gut. The impact of model systems and technological developments in exploring this hypothesis are also discussed. Together, these investigations are revolutionizing our understanding of the gut microbiome-presenting the possibility of identifying new strategies for treating disease in the host.

Figure 1. The bacterial chemical repertoire as metabolic exchange factors within the gut microbiome

A. The human digestive tract is populated by diverse bacteria, forming the microbiome, from esophagus to anus. B. A fluorescence confocal microscopy image of the small intestine. C. A schematic illustrating hypothetical metabolic exchange between host, Escherichia coli and Klebsiella pneumonia. Metabolic exchange can be intraspecies (e.g. quorum-sensing), interspecies, or host-symbiont communication.

Figure 2. Known gut microbiome metabolic exchange factors

Compounds are grouped by known biological role including iron acquisition, host-microbe metabolic exchange, intermicrobial metabolic exchange, and intramicrobial metabolic exchange. Compound name, producing bacteria, bacterial group, and biosynthetic origin are noted. -S- is a thioether linkage. Abu, Dha, and Dhb are the non-canonical amino acids aminobutyric acid, dehydroalanine, and dehydrobutyrine.

Figure 3. Exploring metabolic exchange factors in the gut microbiome

A. A hypothetical experiment is comparing germ-free versus gnotobiotic mouse (E. coli and K. pneumonia) gut to determine the role of these strains in host-microbe interactions. B. Imaging mass spectrometry of the mouse gut, comparing germ-free and gnotobiotic animals, allows putative bacterial metabolic exchange factors to be localized and identified chemically without labeling. Each false color image represents a given m/z value (CMR and PCD).