Extragastrointestinal Symptoms and Sensory Responses During Breath Tests Distinguish Patients With Functional Gastrointestinal Disorders

Clive H Wilder-Smith, Asbjørn M Drewes, Andrea Materna, Søren S Olesen, Clive H Wilder-Smith, Asbjørn M Drewes, Andrea Materna, Søren S Olesen

Abstract

Introduction: Patients with functional gastrointestinal disorders (FGIDs) are classified based on their gastrointestinal (GI) symptoms, without considering their frequent extra-GI symptoms. This study defined subgroups of patients using both GI and extra-GI symptoms and examined underlying mechanisms with fructose and lactose breath tests.

Methods: Latent class analysis defined distinct clusters of patients with FGID based on their long-term GI and extra-GI symptoms. Sensory and breath gas responses after fructose and lactose ingestion were compared across symptom clusters to investigate differences in sensory function and fermentation by intestinal microbiota.

Results: Six symptom clusters were identified in 2,083 patients with FGID. Clusters were characterized mainly by GI fermentation-type (cluster 1), allergy-like (cluster 2), intense pain-accentuated GI symptoms (cluster 3), central nervous system (cluster 4), musculoskeletal (cluster 5), and generalized extra-GI (cluster 6) symptoms. In the 68% of patients with complete breath tests, the areas under the curve of GI and central nervous system symptoms after fructose and lactose ingestion differed across the clusters (P < 0.001). The clusters with extensive long-term extra-GI symptoms had greater symptoms after the sugars and were predominantly women, with family or childhood allergy histories. Importantly, the areas under the curves of hydrogen and methane breath concentrations were similar (P > 0.05) across all symptom clusters. Rome III criteria did not distinguish between the symptom clusters.

Discussion: Patients with FGID fall into clusters defined extensively by extra-GI symptoms. Greater extra-GI symptoms are associated with evidence of generalized sensory hypersensitivity to sugar ingestion, unrelated to intestinal gas production. Possible underlying mechanisms include metabolites originating from the intestinal microbiota and somatization.

Trial registration: ClinicalTrials.gov NCT02085889.

Conflict of interest statement

Guarantor of the article: Clive H. Wilder-Smith, MD.

Specific author contributions: Study design: C.H.W.-S.. Study execution: C.H.W.-S. and A.M.. Study analysis and interpretation: C.H.W.-S., A.M.D., and S.S.O., . Paper writing: C.H.W.-S., A.M.D., A.M., and S.S.O. All authors approved the final version of the manuscript.

Financial support: None to report.

Potential competing interests: None to report.

ClinTrials.gov: NCT02085889.

Figures

Figure 1.
Figure 1.
Flowchart of patients recruited and analyzed in study. FGID, functional gastrointestinal disorder.
Figure 2.
Figure 2.
Radar plot of main symptom groups and self-diagnosed intolerances in the 6 long-term symptom clusters defined by latent class analysis. Data normalized to a 0–100 scale are shown. CNS, central nervous system.
Figure 3.
Figure 3.
Pediatric and family histories in the 6 long-term symptom clusters defined by latent class analysis.
Figure 4.
Figure 4.
Probabilities of being classified as having FD (upper panel) or IBS (lower panel) in the symptom clusters using Rome III criteria. Results of the age- and sex-adjusted analysis are shown. CI, confidence interval; FD, functional dyspepsia; IBS, irritable bowel syndrome; OR, odds ratio.
Figure 5.
Figure 5.
Prevalence of FD (upper panel) and IBS (lower panel) Rome III subtypes across the 6 long-term symptom clusters defined by latent class analysis. FD-EP, functional dyspepsia epigastric pain subtype; FD-PDS, functional dyspepsia postprandial distress subtype; IBS, irritable bowel syndrome; IBS-C, irritable bowel syndrome constipation subtype; IBS-D, irritable bowel syndrome diarrhea subtype; IBS-M, irritable bowel syndrome mixed subtype; IBS-U, irritable bowel syndrome unsubtyped.

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Source: PubMed

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