Characteristics of gut microbiota and metabolites in patients with ulcerative colitis with fatigue

Ulcerative colitis (UC) is a chronic, non-specific inflammatory bowel disease. The gut microbiome undergoes significant changes in UC. Fatigue is a highly prevalent and debilitating extraintestinal symptom of UC, which negatively affects quality of life. However, its relationship with gut microbes and metabolites remains unclear.

To assess the gut microbiota and metabolomic characteristics of patients with UC with fatigue (HUCF).

A total of 120 participants were recruited and divided into four groups (n = 30 per group) based on the diagnosis of UC and Fatigue Scale-14 scores: HUCF, UC without fatigue (HUCN), healthy with fatigue (HHF), and healthy without fatigue (HHN). Fresh stool samples were collected for 16S rRNA sequencing and untargeted metabolomic analysis.

Metabolomic analysis revealed significant differences among the four groups (principal component analysis/partial least squares discriminant analysis, P = 0.001), with differential expression of metabolites such as linoleoyl ethanolamide, arachidonoyl ethanolamide, glycocholic acid, and thromboxane (TX). Notably, TX was detected only in the HUCF group. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed alterations in eicosanoid, tryptophan, and tyrosine metabolism in the HUCF group. Microbial richness and diversity were significantly lower in the HUCF group than in the other three groups. The HUCF group showed enrichment of Hyphomicrobiales, Brucella, Eisenbergiella, Pediococcus, and Sellimonas. The HUCN group showed enrichment of Campylobacter-related taxa. The HHF group showed enrichment of Fusobacterium, Desulfovibrionaceae, and Bilophila. The HHN group showed enrichment of beneficial genera such as Adlercreutzia. Notably, Anaerococcus, a beneficial genus, was enriched in the HUCF group. Correlation analysis indicated that specific microbes (e.g., Faecalibacterium and Escherichia-Shigella) were associated with the severity of UC and fatigue.

Patients with HUCF exhibit a distinct gut microbial structure and metabolomic profile. The pro-inflammatory metabolite TX and the genus Anaerococcus are uniquely enriched in patients with HUCF, suggesting their potential roles in the development of HUCF. These findings provide novel insights and a theoretical basis for improving the clinical management of HUCF.