Understanding Microbial Cross-Feeding Loss in Disease
The human gut microbiome consists of a vast network of interdependent microorganisms that rely on each other’s metabolic by-products for survival. These cross-feeding interactions help maintain gut health, but when disrupted, they can contribute to disease. Identifying and quantifying these disruptions is critical for understanding gut microbiome-related conditions.
In their study, Disease-Specific Loss of Microbial Cross-Feeding Interactions in the Human Gut, Vanessa R. Marcelino and colleagues introduce a Metabolite Exchange Score (MES) to measure the extent of microbial interactions lost in disease states. Supported by the Australian Research Council and Australian National Health and Medical Research Council, this large-scale analysis examines stool samples from 1,661 individuals across 15 countries to compare gut microbiomes in both health and disease.
Microbial Cross-Feeding: A Key to Gut Resilience
In a healthy gut, microbes exchange metabolites, creating a stable ecosystem. If a species that produces an essential nutrient is lost, functionally redundant species may compensate. However, in disease, this redundancy often breaks down, leading to nutrient deficiencies and microbial imbalances. The study reveals that 10 out of 11 diseases analyzed—including Crohn’s disease, type 2 diabetes, and colorectal cancer—show a significant loss of microbial cross-feeding interactions.
Hydrogen Sulfide and Crohn’s Disease
Using MES, the researchers identified a major microbial imbalance in Crohn’s disease (CD):
Hydrogen sulfide (H₂S), a microbial metabolite, is overproduced due to a lack of species capable of consuming it.
In healthy individuals, H₂S is regulated through microbial consumption and conversion into sulfur-containing amino acids like cysteine.
In CD, the number of H₂S-consuming species is 56% lower, disrupting this balance.
Excess hydrogen sulfide weakens the intestinal barrier, leading to chronic inflammation, a hallmark of CD.
Other Disease-Specific Metabolite Imbalances
Beyond Crohn’s disease, MES analysis highlighted key metabolic disruptions:
Colorectal cancer: Ethanol metabolism is altered, potentially increasing levels of acetaldehyde, a known carcinogen.
Rheumatoid arthritis: Microbial metabolism of ribosyl nicotinamide, a precursor of NAD⁺, is significantly reduced, potentially worsening inflammation and joint damage.
Toward Microbiome-Based Therapeutics
By quantifying how microbial cross-feeding is disrupted in disease, this study provides a roadmap for microbiome-targeted therapies. Restoring lost microbial interactions—whether through probiotics, prebiotics, or microbial transplantation—could help rebalance gut ecosystems and mitigate disease progression. Future work using genome-scale metabolic models (GEMs) will refine these findings, helping prioritize species and metabolites for therapeutic interventions.
References:
Marcelino, V.R., Welsh, C., Diener, C. et al. (2023). Disease-specific loss of microbial cross-feeding interactions in the human gut. Nat Commun 14, 6546.