Observational study links metabolites, microbiota, and brain connectivity in functional dyspepsia.
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Key Takeaway
Consider the observed metabolite and brain connectivity alterations in functional dyspepsia as associative, not causal.
This is an observational cross-sectional original research article investigating functional dyspepsia (FD). The study included 46 patients with Rome IV-diagnosed FD and 30 healthy controls for metabolomics, with a subset undergoing functional MRI. The authors used targeted metabolomics, fecal microbiota profiling, and resting-state fMRI to explore associations.
Key findings include higher urinary indole-3-acetate (IAA) levels (P=0.018), lower serum kynurenine (P=0.030), and lower plasma propionate (P=0.0055) in FD patients versus controls. Resting-state brain connectivity showed significant alterations in 44 predefined regions (P<0.0001 for a classifier). A connectivity-based classifier discriminated FD from controls with 82.3% sensitivity and 66.7% specificity (P<0.0001). Differences in connectivity measures mediated the higher urinary IAA levels in FD.
The authors note limitations, including a small sample size and a cross-sectional design that limits causal inference. It was not reported if metabolites were measured at multiple time points. The study reports associations; no causal claims are made, and certainty is not quantified.
Practice relevance is not reported. The findings suggest potential biomarkers and brain-gut interactions in FD but are preliminary. Further research is needed to validate these associations and explore their clinical utility.
View Original Abstract ↓
Background and aims Disturbances in the microbiota-gut-brain axis are thought to contribute to the pathophysiology of disorders of gut-brain interaction, including functional dyspepsia (FD), although comprehensive human data remain scarce. We aimed to study the relationships among microbiota-produced metabolites including tryptophan metabolites and short-chain fatty acids (SCFA), and functional brain connectivity in FD, in relation to symptomatology. Methods In 46 patients with Rome IV-diagnosed FD and 30 healthy controls (HC), targeted metabolomics using chromatography and mass spectrometry was conducted to quantify metabolites in blood, urine, and stool. Associations with gut microbiota and symptomatology were tested using fecal quantitative microbiota profiling and validated symptom questionnaires. Resting-state functional magnetic resonance imaging in 27 patients and 36 HC enabled analysis of functional connectivity in selected brain networks. Results Patients with FD exhibited distinct profiles of tryptophan metabolites and SCFA with higher urinary indole-3-acetate (IAA, P=0.018), lower serum kynurenine (P=0.030) and lower plasma propionate (P=0.0055) concentrations. FD-specific metabolite alterations were associated with more severe GI and psychological symptoms. The fecal microbiota profile was similar between FD and HC. Complementary analyses demonstrated significant alterations in resting-state brain connectivity of 44 predefined regions between FD and HC, while a connectivity-based classifier discriminated FD from HC (82.3% sensitivity, 66.7% specificity, P<0.0001). Differences in connectivity measures mediated the higher urinary IAA levels in FD. Conclusion Dysregulated functional brain connectivity supports an objective pathophysiology in FD. Alterations in specific tryptophan metabolite and SCFA levels were linked to symptomatology, highlighting their potential as biomarkers, and warranting further investigation on microbiota modulating therapies for FD.
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