Human Herpesvirus-6B Infection and Alterations of Gut Microbiome in Patients with Fibromyalgia: A Pilot Study

Abstract

Fibromyalgia (FM) is a chronic disorder characterized by widespread musculoskeletal pain often accompanied by fatigue, sleep disturbances, memory issues, and mood disorders. The exact cause of FM remains unknown, and diagnosis is typically based on a history of persistent widespread pain, as there are no objective biomarkers usable in diagnosis of this disorder available. The aim of this study was to identify measurable indicators specific to FM with potential as biomarkers. This study included 17 individuals diagnosed with FM and 24 apparently healthy persons. Using real-time polymerase chain reaction (qPCR), we detected the presence of human herpesvirus (HHV)-6A and B genomic sequences in DNA isolated from peripheral blood mononuclear cells (PBMCs) and buccal swabs. HHV-6-specific IgG and IgM class antibodies, along with proinflammatory cytokine levels, were measured using enzyme-linked immunosorbent assay (ELISA) and bead-based multiplex assays. Additionally, the gut microbiome was analyzed through next-generation sequencing. HHV-6B was more frequently detected in the PBMCs of FM patients. FM patients with a body mass index (BMI) of 30 or higher exhibited elevated cytokine levels compared to the control group with the same BMI range. Gut microbiome analysis revealed significant differences in both α-diversity and β-diversity between the FM and control groups, indicating a shift in species abundance in the FM group.

Keywords: HHV-6; biomarkers; cytokines; fibromyalgia; gut microbiome.

Figure 1

Frequency of HHV-6B detection in PBMC DNA among FM patients and control group. FM—patients with fibromyalgia; CG—control group.

Figure 2

Comparison of anti-HHV-6 IgG detection frequency between FM patients and controls.

Figure 3

Comparison of cytokine plasma levels between FM and control groups (pg/mL).

Figure 4

Correlation heatmap between cytokine levels and Anti HHV-6 IgG, Age, BMI, and FSS—Fatigue Severity score, WPI—widespread pain index, SS—symptom severity score.

Figure 5

Community α- and ꞵ-diversity differences in gut microbiome at species level between CG and FM groups. Panel (A) represents the Shannon index measure; panel (B)—the inverse Simpson index, panel (C)—principal component analysis (PCA) with robust Aitchison distances.

Figure 6

Volcano plot with differentially abundant taxa at species level between control group (CG) and fibromyalgia group (FM). The X-axis shows the effect size (negative: abundant in CG; positive: abundant in FM), and the y-axis shows the log₁₀ false discovery rate (FDR)–adjusted p-values.