The Reactobiome Unravels a New Paradigm in Human Gut Microbiome Metabolism

Abstract

Changes in microbial metabolism have been used as the main approach to assess function and elucidate environmental and host-microbiome interactions. This can be hampered by uncharacterised metagenome species and lack of metabolic annotation. To address this, we present a comprehensive computational platform for population stratification based on microbiome composition, the underlying metabolic potential and generation of metagenome species and community level metabolic models. We revisit the concepts of enterotype and microbiome richness introducing the reactobiome as a stratification method to unravel the metabolic features of the human gut microbiome. The reactobiome encapsulates resilience and microbiome dysbiosis at a functional level. We describe five reactotypes in healthy populations from 16 countries, with specific amino acid, carbohydrate and xenobiotic metabolic features. The validity of the approach was tested to unravel host-microbiome and environmental interactions by applying the reactobiome analysis on a one-year Swedish longitudinal cohort, integrating gut metagenomics, plasma metabolomics and clinical data.

Global and temporal state of the human gut microbiome in health and disease

“…We have performed a comprehensive integrative analysis of global and temporal gut microbiomes, and we provide an open access HMGA portal (http://microbiomeatlas.org). Con rming previous observations 29 , we have described the gut microbiome regional speci city, which needs to be taken into account before using the gut microbiome for the strati cation of patients or for designing intervention studies. Beyond previous observations, our function-based analysis indicates that the western-enriched bacteria might dominate the gut microbial community with the production of antimicrobial peptides and homoserine lactone, which may inhibit their competitors.…”

“…We used the GEMs of 30 IFS species and 34 OFS species with high prevalence (≥ 10%) and taxonomy annotated at species-level (i.e. excluding unclassi ed MSPs) using our recently reconstructed GEMs 29 and KEGG orthology (KO) annotation of the gut catalogue. The KO pro le of each MSP were mapped into KBase metabolic model 30 as reference model to provide reaction pro les.…”

Systematic analysis of gut microbiome reveals the role of bacterial folate and homocysteine metabolism in Parkinson’s disease

“…The Microbial and personalized GEM, REactobiome and community NEtwork modeling (MIGRENE) toolbox (https://github.com/ sysbiomelab/MIGRENE) (Bidkhori et al, 2021) was used for reaction abundance and enrichment analysis. KEGG metabolic pathways prevalence and maximal coverage was determined based on pathway presence and respective coverage in the generated microbial GEMs.…”

“…Personalised gut-microbial-community metabolic models Personalised community models were reconstructed for each sample in the PD cohort, using MIGRENE toolbox (Bidkhori et al, 2021). Due to computational power requirements and in order to assure model functionality, a maximum of 50 MSPs per community was stablished.…”

Metabolic modelling of the human gut microbiome in type 2 diabetes patients in response to metformin treatment

“…The MIcrobial and personalized GEM, REactobiome and community NEtwork modeling (MIGRENE) toolbox (https://github.com/sysbiomelab/MIGRENE) 29 was used for reaction abundance and pathway enrichment analysis. Microbial reaction abundance per sample of the metformin metagenomics was determined based on each MSP identified per sample that we could originate a functional metabolic model.…”