Unraveling the fatigue puzzle: insights into the pathogenesis and management of IBD-related fatigue including the role of the gut-brain axis

Abstract

A significant percentage of patients with an inflammatory bowel disease (IBD) encounter fatigue which can profoundly diminish patients' quality of life, particularly during periods of disease remission when gastrointestinal symptoms have receded. Various contributing risk factors have been identified including active inflammation, anemia, psychological, lifestyle and drug-related factors. While addressing these risk factors has been suggested as the initial approach to managing fatigue, a considerable number of patients still experience persisting symptoms, the primary causes of which remain incompletely understood. Recent insights suggest that dysfunction of the gut-brain axis may play a pathogenic role. This review provides an overview of established risk factors for fatigue, alongside emerging perspectives on the role of the gut-brain axis, and potential treatment strategies.

Keywords: Crohn’s disease; fatigue; gut-brain axis; tiredness; ulcerative colitis.

Figure 1

Risk factors associated with IBD-related fatigue. Figure created with BioRender.com.

Figure 2

Schematic overview of different gut-brain communication pathways that could contribute to the pathogenesis of IBD-related fatigue. Figure created with BioRender.com; the HPA axis and potential impacts of IBD on the axis was created based on the Biorender.com template from Camilla Maria Fontana, University of Padova. 5-HTP, 5-hydroxytrypthophan; ACh, acetylcholine; ACTH, adrenocorticotropic hormone; BBB, blood–brain barrier; CNS, central nervous system; CRH, corticotropin releasing hormone; IBD, inflammatory bowel disease; HAAO, 3-hydroxyanthranillic acid 3,4-dioxygenase; KATs, kynurenine aminotransferases; KMO, kynurenine 3-monooxygenase; KYNU, kynureninase; IDO1, indoleamine 2,3-dioxygenase 1; SCFAs, short chain fatty-acids; TDO, tryptophan 2,3-dioxygenase.

Figure 3

Proposed flowchart for the management of fatigue in IBD, adapted from Hindryckx et al. (21), Nocerino et al. (22), and Borren et al. (192). Figure created with BioRender.com.