Metabolic Exchange In Microbial Communities
Authors: Osterman Andrei 
Published: November 2023

Cross‐feeding of intermediary metabolites is expected to strongly contribute to the resilience and dynamics of microbial communities. This conjecture is strongly supported by a comparative genomic reconstruction of major metabolic and associated regulatory subnetworks (transcriptional regulons) across numerous species comprising host‐associated as well as environmental microbial communities. Thus, a subsystems‐based reconstruction of biogenesis and homeostasis of 8 major universally indispensable metabolic cofactors (such as TPP, FAD, NAD, etc) revealed a substantial fraction of species auxotrophic for some of the respective B‐vitamins (thiamin or B1, riboflavin or B2, niacin or B3, etc) in both types of communities. This observation along with human gut microbiome metagenomic profiling and functional genomics analyses point to the extensive B‐vitamin exchange between prototrophic (PRO) and auxotrophic (AUX) constituents of microbial consortia. In addition to a mosaic distribution of predicted B‐vitamin AUX/PRO phenotypes across different phyla, we observe the presence of partially truncated biosynthetic pathways that have not been previously detected in singly cultivated microbes. This allowed us to tentatively expand the B‐vitamin “market” by several pathway intermediates including those in the biosynthesis of biotin and Coenzyme A. Accurate identification of respective transporters is crucial for a more accurate inference of phenotypes and potential engagement of individual species in the community‐wide vitamin exchange. Although the homology analysis alone often fails to reliably assign substrate specificity to transporters, in many cases this challenge can be effectively addressed by genomic context analysis including reconstruction of associated transcriptional regulons. A genomic reconstruction of subsystems covering metabolism of amino acids, major building blocks of cellular proteins, reveals a different pattern of predicted AUX/PRO phenotypes. In contrast to micronutrients, such as B‐vitamins, amino acid AUX phenotypes are quite rare among human gut microbiota, and hardly ever observed in autotrophic microbial mats. Even human gut Firmicutes that are commonly AUX for ≥ ½ of all B‐vitamins, have a predicted AUX phenotype for ≤ 2 amino acids, typically those with relatively low abundance in proteins and the most extended de novo biosynthetic pathways (such as Trp and His). Given a perceived scarcity of amino acids in distal guts (which is supported by recent experimental data), the actual source of these nutrients (e.g. host or/and bacterial proteins) remains to be elucidated. A subsystems‐based genomic reconstruction also allows us to tentatively predict a menu of sugars (mono‐ and di‐saccharides) that comprise a catabolic potential of diverse heterotrophic bacteria with respect to the prime source of carbon and energy. Combined with a far more challenging specificity analysis of extracellular carbohydrate‐degrading enzymes, it would help to elucidate yet another type of metabolic exchange, when some species in a community hydrolyze polysaccharides and share the products with their neighbors. Elucidation of the metabolic potential and exchange between individual species in the human gut microbiome provides important guidelines for the development of therapeutic probiotics and prebiotics.Support or Funding InformationNIH grant GM108527 (PI, S. Peterson)