Disease-specific loss of microbial cross-feeding interactions in the human gut

Abstract

Many gut microorganisms critical to human health rely on nutrients produced by each other for survival; however, these cross-feeding interactions are still challenging to quantify and remain poorly characterized. Here, we introduce a Metabolite Exchange Score (MES) to quantify those interactions. Using metabolic models of prokaryotic metagenome-assembled genomes from over 1600 individuals, MES allows us to identify and rank metabolic interactions that are significantly affected by a loss of cross-feeding partners in 10 out of 11 diseases. When applied to a Crohn’s disease case-control study, our approach identifies a lack of species with the ability to consume hydrogen sulfide as the main distinguishing microbiome feature of disease. We propose that our conceptual framework will help prioritize in-depth analyses, experiments and clinical targets, and that targeting the restoration of microbial cross-feeding interactions is a promising mechanism-informed strategy to reconstruct a healthy gut ecosystem.

Demonstrating the Beneficial Effect of Low Protein Diet in Primary Sclerosing Cholangitis through a Randomized Clinical Trial and Multi-omics Data Analysis

“…We focused on genes involved with sulfur metabolism to decipher the relationship between sulfur-related metabolite changes and microbial functional changes. We referred to a comprehensive list of 74 genes involved in microbial sulfur metabolism in humans [39, 40]. Of these, 27 were detected in at least one sample in this study, with 6 (or 5) of these genes significantly decreasing (or increasing) during intervention in LPD responders (Wilcoxon rank-sum test, p-value < 0.05), and 4 genes increasing with marginal significance (0.05 < p-value < 0.06) ( Fig.…”

“…Interestingly, LPD led to a reduced amount of cysJ, a critical enzyme for producing hydrogen sulfide (H 2 S) from sulfite, and a reduced amount of dycD , key for H 2 S production from cysteine (Fig. 4k) [39, 40]. Conversely, the cysK gene, involved in metabolizing H 2 S in the biosynthesis of cysteine, increased throughout LPD (Fig.…”

“…Conversely, the cysK gene, involved in metabolizing H 2 S in the biosynthesis of cysteine, increased throughout LPD (Fig. 4k) [39, 40]. Similarly, there was an increase in the bsh gene that metabolizes taurine and aids in the deconjugation of tauro-conjugated bile acids excreted to the gut from the biliary tree (Fig.…”

Excess fermentation and lactic acidosis as detrimental functions of the gut microbes in treatment-naive TB patients

“…Rather, observed shifts reflect the number of carrying bacteria as a long-term response to altered environments in the intestine. Except for sophisticated assembly-based approaches ( Marcelino et al., 2023 ), current bioinformatic tools infer bacterial taxa and metabolic pathways separately, limiting our interpretation ( Douglas and Langille, 2021 ). Nevertheless, we attempted to link metabolic pathways with specific taxa using marker genes ( Figure 4 ).…”

A meta-analysis of the gut microbiome in inflammatory bowel disease patients identifies disease-associated small molecules

“…As our ability to de novo assemble metagenomic datasets gets better, and as new biosynthetic classes are characterized, the comprehensiveness of our approach will increase. Second, an enriched small molecule BGC does not necessitate a causative role in disease, but could also indicate a selection process as a consequence of the disease, where the produced molecule provides a survival or competitive advantage to the producer (Marcelino et al, 2023;Watson et al, 2023).…”