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

Abstract

AbstractMicrobiomes are critical to the health and functioning of humans and ecosystems. Defining ‘healthy microbiomes’, however, remains elusive. More advanced knowledge exists on health associations for the compounds used or produced by microbes. Because microbes, their feedstocks and micro-environments interact synchronously, using functional genes to facilitate chemical transformations, this presents an intriguing opportunity to examine microbiomes through their potential to process compounds associated with human health. There is also growing interest in environmental microbiota that might be efficient at processing health-associated compounds because these microbes may readily transfer to humans and environmental interventions could modulate our exposure to them. Here we propose a bioenergetic mapping approach to microbiome assessments that examines the compound processing potential imprinted in human gut and environmental soil metagenomes. From shotgun metagenomics functional profiling, we derive quantitative measures of compound processing potential for human health-associated compound classes (e.g., lipids, carbohydrates) and selected biomolecules of interest (e.g., vitamins, short-chain fatty acids). We mapped microbial functions to compounds using the complexity-reducing van Krevelen bioenergetic mapping framework, based on carbon-hydrogen-oxygen stoichiometry and principal axes that explain variation in microbial distribution and chemical speciation. We found differences in compound processing potential within gut metagenomes comparing health- and disease-associated samples, including atherosclerotic cardiovascular disease, colorectal cancer, type 2 diabetes and anxious-depressive behaviors. Patterns of compound processing potential in soil metagenomes were linked with ecosystem maturity. Assessment of compound processing potential offers a new lens to explore mechanisms of microbiome-mediated human health including connections to health-promoting environmental microbiomes.Significance StatementDespite mounting evidence of their importance, the definition and measurement of ‘healthy microbiomes’ remain unclear. Knowledge gaps hinder development of microbiota-oriented approaches in human health, including potential for environmental interventions. By integrating interdisciplinary knowledge frameworks including functional genomics and biochemistry, we derive summary measures of potential for human gut and environmental soil metagenomes to process major compound classes and biomolecules linked to human health. Measures of compound processing potential were linked with states of human health and disease; and displayed seemingly predictable shifts along gradients of ecological disturbance in plant-soil systems. Compound processing potential offers a simplifying approach for applying powerful and otherwise complex metagenomics in ongoing efforts to understand and quantify the role of microbiota in human- and environmental-health.