Gut microbial dysbiosis is associated with fatigue in Behçet’s Disease.

Abstract

Purpose : The gut microbiota is important in the regulation of energy haemostasis and modulation of the immune system. This study tested the hypothesis that alterations in the gut microbiota is associated with fatigue in patients with Behçet’s Disease (BD).

Methods : Patients with BD fulfilling the Behçet’s Syndrome International Study Group criteria were recruited to the study, along with disease and healthy controls. Mucous Membrane Pemphigoid (MMP) was used as disease control as it is a multisystem disease with mucocutaneous involvement, similar to BD.

Participants completed the Modified Fatigue Impact Scale(MFIS) questionnaire which assessed the effects of fatigue on physical, cognitive and psychosocial functioning. Based on the total MFIS scores, participants were divided into a Low Fatigue Group (LFG) and High Fatigue Group (HFG).

The V4 region of the 16S rRNA gene of bacterial DNA from fresh faecal samples was amplified and sequenced on Illumina MiSeq. Microbial 16S sequence data was analysed using Quantitative Insights Into Microbial Ecology (QIIME) and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) software.

To reduce potential dietary bias, a weekly food-frequency questionnaire was administered. C-reactive protein levels were used as marker for systemic inflammatory status.

Results : A total of 65 participants were recruited to the study [BD (n=32); MMP (n= 13); HC (n=10)]. Patients with BD reported higher scores in all components of the MFIS [MFIS Physical (BD: median:25, interquartile range (IQR) 18-32; MMP: 19, 16-28; HC: 6, 0-11) (p=<0.0001); MFIS Cognitive (BD: 23, 16-29; MMP: 13, 6-17; HC: 11, 6-17) (p<0.0001); MFIS Psychosocial (BD: 5, 4-7; MMP: 4, 3-7; HC: 1, 0-3) (p<0.0001)].

The dominant phyla were Firmicutes (LFG : 47.1±6.3%; HFG: 58.5±2.0%) and Bacteroides (LFG: 24.6±8.8%; HFG: 8.1±3.0%) followed by Verrucomicrobia (LFG: 10.5±0.0%; HFG: 3.9±0.0%) and Actinobacteria (LFG: 4.9±2.0%; HFG: 7.0±2.2%).

Predictive functional profile of the gut microbiome of patients in the HFG group had a lower relative abundance of bacterial genes related to protein processing in endoplasmic reticulum (p<0.0001) and PPAR signalling pathway (p<0.0001), known to be important in the regulation of lipid metabolism and gluconeogenesis.

Conclusions : Dysbiosis in the predicted functional profile of gut microbiome is associated with higher levels of fatigue in BD.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.