Bioenergetic mapping of ‘healthy microbiomes’ via compound processing potential imprinted in gut and soil metagenomes

Craig Liddicoat, Robert A. Edwards, Michael Roach, Jake M. Robinson, Kiri Joy Wallace, Andrew D. Barnes, Joel Brame, Anna Heintz-Buschart, Timothy R. Cavagnaro, Elizabeth A. Dinsdale, Michael P. Doane, Nico Eisenhauer, Grace Mitchell, Bibishan Rai, Sunita Ramesh, Martin F. Breed

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Despite mounting evidence of their importance in human health and ecosystem functioning, the definition and measurement of ‘healthy microbiomes’ remain unclear. More advanced knowledge exists on health associations for compounds used or produced by microbes. Environmental microbiome exposures (especially via soils) also help shape, and may supplement, the functional capacity of human microbiomes. Given the synchronous interaction between microbes, their feedstocks, and micro-environments, with functional genes facilitating chemical transformations, there exists an intriguing opportunity to examine microbiomes in terms of their capacity to process compounds relevant to human health. Here we integrate functional genomics and biochemistry frameworks to derive new quantitative measures of the potential for human gut and environmental soil metagenomes to process major compound classes (e.g., lipids, carbohydrates) and selected biomolecules (e.g., vitamins, short-chain fatty acids) linked to human health. Metagenome functional potential profile data were translated into a universal compound mapping ‘landscape’ based on bioenergetic van Krevelen mapping of function-level meta-compounds and corresponding functional relative abundances, reflecting imprinted genetic capacity of microbiomes to metabolize an array of different compounds. We show that measures of ‘compound processing potential’ associated with human health and disease (examining atherosclerotic cardiovascular disease, colorectal cancer, type 2 diabetes and anxious-depressive behavior case studies), and displayed seemingly predictable shifts along gradients of ecological disturbance in plant-soil ecosystems (three case studies). Ecosystem quality explained 60–92% of variation in soil metagenome compound processing potential measures in a post-mining restoration case study dataset. With growing knowledge of the varying proficiency of environmental microbiota to process human health associated compounds, we might design environmental interventions or nature prescriptions to modulate our exposures, thereby advancing microbiota-oriented approaches to human health. Compound processing potential offers a simplified, integrative approach for applying metagenomics in ongoing efforts to understand and quantify the role and linkages of microbiota in environmental- and human-health.
Original languageEnglish
Article number173543
Number of pages18
JournalScience of The Total Environment
Early online date29 May 2024
Publication statusPublished - 3 Jun 2024


  • Bioenergetic mapping
  • Compound processing potential
  • Healthy microbiome
  • Human health
  • Metagenomics
  • van Krevelen diagram


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