Functional enrichment of immune targeted gut microbiota in post-infectious myalgic encephalomyelitis/chronic fatigue syndrome

Post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS) is a debilitating condition characterized primarily by profound fatigue and cognitive impairment, often accompanied by gastrointestinal disturbances. Increased intestinal permeability has been proposed as a contributing mechanism, yet the role of host–microbe interaction remains poorly defined. Here, we examined intestinal microbial interactions with systemic immunoglobulin G (IgG) to assess potential microbial translocation across the intestinal barrier. Paired stool and serum samples were collected from individuals with PI-ME/CFS ( n = 16) and healthy volunteers (HV, n = 19). Microbes were fractionated into IgG-positive and IgG-negative subsets and analyzed by 16 S rRNA gene sequencing. IgG scores were derived from log-transformed read counts in positive versus negative fractions. Predicted microbial functions were inferred using PICRUSt2. Diversity and composition of the pre-sort microbiota was most-similar to IgG-Positive samples in HV and PI-ME/CFS. Nine taxa in the HVs and 11 in PI-ME/CFS exhibited elevated IgG scores ( P < .05), primarily comprised from members of the Lachnospiraceae , Eggerthellaceae , and Ruminococcaceae families. Exploration of predicted functions found that IgG scores of several pathways and genes were enriched specifically in PI-ME/CFS, including several related to prokaryotic stress and defense mechanisms. Limited evidence of microbial translocation was observed in either HV or PI-ME/CFS; however, IgG-targeted microbes in PI-ME/CFS showed distinct predicted functional enrichment, particularly in stress and defense pathways. These findings suggest an altered host–microbe interaction that could contribute to intestinal barrier dysfunction in individuals with PI-ME/CFS.