Fibromyalgia-associated hyperalgesia is related to psychopathological alterations but not to gut microbiome changes

Abstract

Fibromyalgia-syndrome (FMS) is a complex disease characterized by chronic widespread pain and additional symptoms including depression, cognitive dysfunction (“fibro-fog”) and maldigestion. Our research team examined whether FMS-related pain parameters assessed by quantitative sensory testing (QST) and psychological disturbances are accompanied by alterations of the fecal microbiome. We recruited 25 patients with FMS and 26 age- and sex-matched healthy controls. Medical background, food habits, psychopathology and quality of life were assessed through questionnaires. Stool samples were analyzed by 16S rRNA gene amplification and sequencing. QST was performed according to the protocol of the German Network for Neuropathic Pain. QST showed that both lemniscal and spinothalamic afferent pathways are altered in FMS patients relative to healthy controls and that peripheral as well as central pain sensitization processes are manifest. Psychometric assessment revealed enhanced scores of depression, anxiety and stress. In contrast, neither the composition nor the alpha- and beta-diversity of the fecal microbiome was changed in FMS patients. FMS patients segregate from healthy controls in various parameters of QST and psychopathology, but not in terms of composition and diversity of the fecal microbiome. Despite consideration of several confounding factors, we conclude that the contribution of the gut microbiome to the pathophysiology of FMS is limited.

Microbial Composition and Stool Short Chain Fatty Acid Levels in Fibromyalgia

“…In addition, a Spanish study measured serum metabolite levels, reporting that glutamate and serine are involved in neurotransmitter metabolism [ 10 ]. However, another study from Austria that included 25 patients with FMS and 26 age- and sex-matched controls failed to show any significant differences in gut bacterial diversity between the two groups [ 11 ].…”

Gut dysbiosis in patients with chronic pain: a systematic review and meta-analysis

“…Non-significant results were revealed for the abundance coverage estimator ( 33 , 47 ), as confirmed with a meta-analysis (SMD of -0.17 (95% CI from -0.44 to 0.10), p=0.22). For evenness, the Pielou metric resulted in significantly lower values in patients with ME/CFS compared to controls ( 36 ), while other reports did not reveal significant differences ( 29 , 47 ). For richness/evenness, 15 studies explored the Shannon index with significant differences in favor of chronic pain patients ( 37 ), in favor of controls ( 29 , 32 , 35 , 36 , 44 ), and no significant difference between controls and chronic pain patients ( 30 , 33 , 34 , 38 , 41 , 42 , 47 , 48 ).…”

“…Egger’s test did not reveal indications for funnel plot asymmetry (t=0.9, df=9, p=0.39). For Chao1, significantly reduced values were obtained in patients with CRPS ( 44 ) and in one study with ME/CFS patients ( 35 ), while the other studies did not reveal significant differences between chronic pain patients and controls ( 30 , 33 , 40 , 41 , 47 , 48 ). Non-significant results were revealed for the abundance coverage estimator ( 33 , 47 ), as confirmed with a meta-analysis (SMD of -0.17 (95% CI from -0.44 to 0.10), p=0.22).…”

“…For Chao1, significantly reduced values were obtained in patients with CRPS ( 44 ) and in one study with ME/CFS patients ( 35 ), while the other studies did not reveal significant differences between chronic pain patients and controls ( 30 , 33 , 40 , 41 , 47 , 48 ). Non-significant results were revealed for the abundance coverage estimator ( 33 , 47 ), as confirmed with a meta-analysis (SMD of -0.17 (95% CI from -0.44 to 0.10), p=0.22). For evenness, the Pielou metric resulted in significantly lower values in patients with ME/CFS compared to controls ( 36 ), while other reports did not reveal significant differences ( 29 , 47 ).…”

“…Sixteen studies provided data for alpha-diversity, evaluated through 8 different metrics. When evaluating richness through observed species, non-significant differences were revealed for patients with axial spondyloarthritis ( 30 ), ME/CFS ( 36 , 40 , 41 ), migraine ( 32 ), and fibromyalgia ( 33 , 47 ) compared to controls. For patients with ME/CFS, only one study found significant differences with higher richness in controls compared to patients ( 35 ).…”