A Desulfovibrio desulfuricans-H2S-Roseburia intestinalis-butyrate antagonistic axis mechanistically explains inulin response heterogeneity, providing a rationale for personalized nutrition and supporting a clinically translatable predictive index and targeted intervention strategy.
Key Findings
Results
Interindividual variability in metabolic response to prebiotic inulin is driven by antagonism between Desulfovibrio desulfuricans and Roseburia intestinalis in the gut microbiome.
Humanized obese mice were generated by high-fat diet preconditioning followed by one-to-one fecal microbiota transplantation to recapitulate donor-specific response differences.
The antagonistic relationship between D. desulfuricans and R. intestinalis was identified as the key microbial interaction governing differential responsiveness to inulin.
Causal links were validated via multi-omics integration, in vitro co-culture, in vivo bacterial recolonization/clearance, and independent cohort verification.
Results
Hydrogen sulfide (H2S) produced by Desulfovibrio desulfuricans directly suppresses Roseburia intestinalis growth and butyrate production.
The mechanistic pathway was established as D. desulfuricans → H2S production → suppression of R. intestinalis growth → reduced butyrate production.
This interaction was confirmed through in vitro co-culture experiments.
The H2S-mediated suppression of R. intestinalis was functionally relevant to the heterogeneous metabolic responses observed with inulin supplementation.
Results
An inulin response index (IRI) based on the Roseburia-to-Desulfovibrio abundance ratio prospectively predicted responder phenotypes.
The IRI was defined as the ratio of Roseburia to Desulfovibrio abundance in the gut microbiome.
The index was validated in an independent cohort.
The IRI provides a clinically translatable predictive biomarker system for identifying likely responders versus non-responders to inulin supplementation.
Results
D. desulfuricans gavage markedly attenuated inulin metabolic benefits in high-responder microbiota-colonized mice.
Direct inoculation of D. desulfuricans into mice colonized with high-responder microbiota was sufficient to diminish the metabolic improvements conferred by inulin.
This experiment provided in vivo causal evidence that D. desulfuricans abundance is a determinant of inulin responsiveness.
The finding supports D. desulfuricans as a functionally relevant driver of low-response phenotypes.
Results
Sodium molybdate-mediated H2S inhibition, R. intestinalis supplementation, or sodium butyrate supplementation each restored metabolic benefits in low-responder microbiota-colonized mice.
Three distinct intervention strategies were tested in low-responder mice: pharmacological H2S inhibition with sodium molybdate, probiotic supplementation with R. intestinalis, and direct butyrate supplementation with sodium butyrate.
All three approaches rescued the metabolic response to inulin in low-responder microbiota-colonized mice.
These findings provide mechanistic rationale for targeted intervention strategies in individuals predicted to be non-responders to inulin.
Results
Butyrate conferred metabolic protection through strengthening gut barrier function, activating GLP-1/PYY secretion, and suppressing adipose inflammation.
The downstream effector pathways of butyrate were identified as three distinct mechanisms: gut barrier reinforcement, incretin hormone (GLP-1 and PYY) secretion, and anti-inflammatory effects in adipose tissue.
These butyrate-mediated pathways represent the downstream effectors translating microbiome composition into differential metabolic outcomes.
GLP-1 (glucagon-like peptide-1) and PYY (peptide YY) are satiety hormones relevant to obesity-related metabolic disturbances.
What This Means
This research suggests that the reason some people benefit from taking inulin (a dietary fiber used as a prebiotic supplement) while others do not comes down to a specific battle happening in the gut between two types of bacteria. One bacterium, Desulfovibrio desulfuricans, produces hydrogen sulfide gas that kills off or suppresses another bacterium, Roseburia intestinalis. Roseburia is beneficial because it makes butyrate, a short-chain fatty acid that helps improve metabolism in obese individuals. When Desulfovibrio is dominant, it essentially blocks the beneficial chain of events that inulin is supposed to trigger.
The researchers demonstrated this mechanism using mouse experiments where they transplanted gut bacteria from human donors into mice, confirming that the human donors' response patterns were reproduced in the mice. They were able to both create non-responders (by adding Desulfovibrio to responder mice) and rescue non-responders using three different strategies: blocking hydrogen sulfide production with a drug called sodium molybdate, adding Roseburia bacteria directly, or supplementing with butyrate itself. The butyrate produced by Roseburia works by strengthening the intestinal lining, stimulating the release of hormones that promote fullness (GLP-1 and PYY), and reducing inflammation in fat tissue.
This research suggests it may be possible to predict ahead of time who will benefit from inulin by measuring the ratio of Roseburia to Desulfovibrio bacteria in a person's gut — a metric the researchers call the Inulin Response Index (IRI). People with a low ratio (more Desulfovibrio relative to Roseburia) might not benefit from inulin alone but could be helped by additional targeted interventions. This work provides a scientific basis for personalized nutrition approaches where dietary supplements are matched to individuals based on their gut microbiome composition.
Check Your Own Numbers
Upload your bloodwork. We'll cross-reference your results against this study and 4,700 others.
Zhang Y, Liu Z, Wang X, Qin Z, Ren X, Zhang T, et al.. (2026). A Desulfovibrio-Roseburia antagonism axis dictates interindividual variability in the metabolic response to inulin.. Food & function. https://doi.org/10.1039/d6fo03036j