Phase II Feasibility Study of the Efficacy, Tolerability, and Impact on the Gut Microbiome of a Low-Residue (Fiber) Diet in Adult Patients With Mitochondrial Disease

Background and Aims: Gastrointestinal (GI) dysmotility is a common and debilitating clinical manifestation in patients with mitochondrial DNA (mtDNA)–related disease with no curative and few effective symptomatic therapies. A low-residue diet (LRD) has been shown to be effective at reducing bowel urgency, pain, and distension in functional GI-related conditions. We assessed tolerability and effects of an LRD on bowel habits in patients with mtDNA-related disease. Methods: This was a 12-week single-arm pilot study in patients with genetically determined primary mtDNA-related disease, meeting the ROME III constipation criteria. The co-primary outcomes were tolerability of an LRD (<10 g fiber per day) assessed by food diaries and changes in stool frequency and consistency. The secondary outcomes included GI symptoms, disease burden, laxatives, physical activity levels, colonic transit time using radiopaque markers, gut microbiome (patients and controls), and metabolomics. The gut microbiome of the mtDNA-related disease patients was compared against controls for observational purpose only. Results: Twenty-eight patients were enrolled, and 24 completed the LRD intervention. The LRD was well tolerated with a mean fold change of −34% in dietary fiber (5.3 ± 10.4 grams) per day (P = .03, confidence interval = 0.7–9.9) with no adverse events. The proportion of stool samples with normal stool consistency increased from 36% to 49% (P = .01); GI symptoms and laxative use were reduced. However, the LRD did not change stool frequency, stool output, and colonic transit time. The gut microbiome was significantly different between patients and controls but was not modulated by the dietary intervention. Conclusion: The LRD in patients with mtDNA-related mitochondrial disease and significant constipation is well tolerated and a promising treatment for alleviating GI symptoms. These positive findings should be confirmed in a randomized controlled trial.ClinicalTrials.gov Identifier: NCT03388528.