Gut microbiota dysbiosis and Long COVID susceptibility in chronic kidney disease

Patients with chronic kidney disease (CKD) may be more susceptible to long coronavirus disease (Long COVID), yet the underlying mechanisms remain unclear. In this case‒control study, 224 patients receiving maintenance hemodialysis who experienced severe acute respiratory syndrome coronavirus 2 infection were enrolled, among whom 35.3% developed Long COVID. Long COVID predominantly manifested as neurological symptoms, including fatigue (43.0%), sleep disturbances (29.1%), and memory impairment (24.1%), and was accompanied by elevated inflammatory markers such as interleukin‐6, high‐sensitivity C‐reactive protein, C‐reactive protein, and parathyroid hormone compared with CKD patients without Long COVID. Metagenomic sequencing and untargeted metabolomics were performed on fecal and serum samples from patients with Long COVID (LC‐CKD), matched CKD controls without Long COVID (NLC‐CKD), and healthy controls (NLC‐Control). LC‐CKD patients exhibited significant gut microbiota dysbiosis, characterized by an increased Firmicutes/Bacteroidetes ratio, depletion of beneficial genera including Phocaeicola and Prevotella, and enrichment of proinflammatory taxa such as Blautia and urease‐producing Lachnospiraceae. Metabolomic analysis revealed systemic metabolic alterations in LC‐CKD patients, including elevated uremic toxins, reduced prostaglandins, and disrupted tryptophan and tyrosine metabolism associated with Phocaeicola abundance. Distinct microbial virulence profiles were also observed, with upregulation of urease‐related genes (ureG and ureB) and stress‒response factors (groEL and sugC). Fecal microbiota transplantation from LC‐CKD patients into 5/6 nephrectomized mice induced anxiety‐like behaviors and increased neuroinflammatory markers, mirroring microbial alterations in donors. These findings indicate that gut microbiota dysbiosis is associated with increased susceptibility to These findings suggest an association between gut microbiota dysbiosis and increased susceptibility to Long COVID in CKD patients, potentially mediated through microbe–metabolite interactions, highlighting the need for further mechanistic studies to validate potential microbiota‐targeted interventions.