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

Abstract

Microbiomes 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.

Urban sports fields support higher levels of soil butyrate and butyrate‐producing bacteria than urban nature parks

“…This aligns with findings in Liddicoat et al. ( 2023 ), who reported increased potential metabolism of acetate in more highly disturbed (compared to more mature and natural) plant–soil systems. Though we did not evaluate acetate in this study, future research could further examine the role of acetate in shaping urban greenspace soil microbial communities.…”

Light–dark cycles may influence in situ soil bacterial networks and diurnally‐sensitive taxa

“…Soil bacterial communities are highly diverse and are involved in many ecosystem processes (e.g. nutrient cycling, soil formation, plant health) (Liddicoat et al, 2023;van der Heijden et al, 2008).…”

“…While studies have reported higher soil bacterial heterogeneity across samples from remnant vegetation compared to cleared or urban lawns (Delgado-Baquerizo et al, 2021) and the occurrence of notable bacterial functional groups in soils (e.g. butyrate-producers) (Liddicoat et al, 2020(Liddicoat et al, , 2023Roslund et al, 2020), further research is needed to improve knowledge on how land cover type and factors such as light-dark cycles interact to influence soil bacterial communities.…”

“…Soil bacterial communities are highly diverse and are involved in many ecosystem processes (e.g. nutrient cycling, soil formation, plant health) (Liddicoat et al., 2023 ; van der Heijden et al., 2008 ). Our understanding of soil bacterial communities is increasing due in part to their links with human and ecosystem health (Liddicoat et al., 2019 ; Roslund et al., 2022 ; Singh et al., 2023 ) and advances in genomics (Berg et al., 2020 ; Liu et al., 2021 ; Mohr et al., 2022 ).…”