Altered Fecal Microbial and Metabolic Profiles Reveal Potential Mechanisms Underlying Anemia in Patients with Chronic Renal Failure

Background: The gut microbiomes communicate with kidney and may play a crucial role in the development of anemia in patients with chronic renal failure (CRF). However, the alterations in microbiota and their association with functional metabolites remain unclear. Methods: We performed metagenomics and untargeted metabolomics in a cohort of 30 patients with anemia of CRF and 20 healthy controls to identify the characteristics of the gut microbiome and explore its potential interactions with the host. Results: Patients with anemia of CRF exhibited reduced gut microbiota diversity and compositional alterations, notably Faecalibacterium prausnitzii, Prevotella copri, and Escherichia coli, which correlated closely with hemoglobin (Hb) levels and estimated glomerular filtration rate. Metabolomic analyses revealed significant fecal metabolic changes, including 12-KETE-LTB4 (arachidonic acid metabolism), uracil, L-aspartic acid (β-alanine metabolism), and gulonic acid (ascorbate metabolism), alongside 15 serum metabolites linked to Hb. Furthermore, we observed a complex co-occurrence between anemia of CRF-related gut microbiota species and the characterized metabolites. Moreover, a non-invasive diagnostic model combining Faecalibacterium prausnitzii, Prevotella copri, and the four fecal metabolites effectively distinguished patients with anemia of CRF (area under the curve: 0.879). Conclusion: Our results suggest a disordered gut microbiome associated with functional metabolites may be a non-invasive diagnostic and therapeutic target for anemia of CRF. Funding: Government Support – Non-U.S.Altered Gut Microbiota in CRF Anemia and Metabolic Correlations. (A) A linear discriminant analysis effect size (LEfSe) analysis revealed distinct gut bacterial taxa between CRF-anemia patients and HCs (LDA>4.0, P<0.05). (B) Sankey diagram linked gut dysbiosis to characterized functional fecal and serum metabolites. (C) The potential for non-invasive diagnosis of CRF anemia based on fecal microbiota and metabolites. CRF, chronic renal failure; HC, healthy control; eGFR, estimated glomerular filtration rate; Hb, hemoglobin; Alb, albumin; AUC, area under the curve.