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Fatigue in IBD: epidemiology, pathophysiology and management

Abstract

Fatigue is an important clinical problem in patients with IBD, affecting nearly 50% of patients in clinical remission and > 80% of those with active disease. The resulting decrease in quality of life and impaired work productivity and functioning contribute markedly to the societal costs of fatigue. However, despite the burden and effects of fatigue, little is known about its aetiology and pathophysiology, which impairs our ability to effectively treat this symptom. Here, we review the theories behind the development of fatigue in IBD and the role of contributing factors, including nutritional deficiency, inflammation and altered metabolism. We also explore the potential role of the gut microbiome in mediating fatigue and other psychological symptoms through the gut–brain axis. We discuss the efficacy of nutrient repletion and various psychological and pharmacological interventions on relieving fatigue in patients with IBD and expand the discussion to non-IBD-related fatigue when evidence exists. Finally, we present a therapeutic strategy for the management of fatigue in IBD and call for further mechanistic and clinical research into this poorly studied symptom.

Key points

  • Fatigue is one of the most frequently reported concerns of patients with IBD and can result in a decrease in quality of life and impaired work productivity.

  • Fatigue in IBD is multifactorial, with contributions from active inflammation, nutritional deficiency, altered metabolism and psychological comorbidity.

  • Emerging evidence also suggests a possible role for bidirectional communication between the gut and central nervous system (the gut–brain axis) in mediating fatigue.

  • The multidimensionality of contributing factors could imply that the mechanism of fatigue is not uniform in all patients and that there might be different subtypes of fatigue.

  • The multidimensionality of fatigue suggests the existence of different subtypes that respond to different interventions.

  • Studies conducted in the past few years suggest a potential role for psychological interventions, physical activity and microbiome-directed therapies for relief of fatigue.

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Fig. 1: Proposed multidimensional pathophysiology of fatigue in IBD.
Fig. 2: MRI changes associated with fatigue in IBD.
Fig. 3: Bidirectional communication between the gut microbiota and the brain.
Fig. 4: Proposed algorithm for multidisciplinary management of fatigue in IBD.

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All authors contributed equally to all aspects of the manuscript.

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Correspondence to Ashwin N. Ananthakrishnan.

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C.J.v.d.W. has served on advisory boards for Celltrion and Pfizer. She is supported by research funding from Pfizer, Takeda and Tramedico and has received a speaker fee from Takeda and Jansen. A.N.A. has served on advisory boards for Abbvie, Merck and Takeda. He is supported by research funding from the Crohn’s and Colitis Foundation, NIH and Pfizer. N.Z.B. declares no competing interests.

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Borren, N.Z., van der Woude, C.J. & Ananthakrishnan, A.N. Fatigue in IBD: epidemiology, pathophysiology and management. Nat Rev Gastroenterol Hepatol 16, 247–259 (2019). https://doi.org/10.1038/s41575-018-0091-9

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