Abstract:

Background and aims: Chronic fatigue is common in patients with inflammatory bowel disease (IBD). The gut microbiota, specifically, microbial diversity and butyrate-producing bacteria have been linked to the fatigue pathogenesis. High-dose oral thiamine reduces fatigue, potentially through gut microbiota modification. In this study, we investigated how the gut microbiota influences the efficacy of high-dose thiamine in alleviating chronic fatigue in quiescent IBD.

Methods: We analyzed the microbiota and short-chain fatty acids (SCFAs) concentrations in fecal samples from patients with quiescent IBD, with (n=40) or without (n=20) chronic fatigue. The 40 patients with quiescent IBD and fatigue were included in a randomized, placebocontrolled, crossover trial to assess a 4-week high-oral dose thiamine regimen.

Results: Butyrate and butyrate-producing bacteria were similar in patients with and without fatigue and did not change with high-dose thiamine treatment. Notably, Faecalibacterium prausnitzii was more abundant in thiamine responders compared with non-responders both pre-treatment (p=0.019) and post-treatment (p=0.038). The relative abundances of Faecalibacterium prausnitzii and Roseburia hominis, both pre- and post-treatment, inversely correlated with IBD fatigue score changes for patients with chronic fatigue (PRE; R=-0.48, p=0.004, and R=-0.40, p=0.018; POST; R=-0.42, p=0.012, and R=-0.40, p=0.017) respectively.

Conclusion: Faecalibacterium prausnitzii and Roseburia hominis may serve as markers for response to high-dose thiamine in alleviating chronic fatigue in patients with quiescent IBD. The mechanistic role of gut bacteria and butyrate in patients with chronic fatigue and quiescent IBD should be further explored.

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