Fecal Short Chain Fatty Acids Profiling to Predict Complications in Kidney Transplant Recipients

• Applicant: Friederike Selbach
• Subject Area: Nephrology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 539291308

Kidney transplantation (KTx) is the treatment of choice for patients with end-stage kidney disease. Urinary tract infections (UTIs) and allograft rejection remain major causes of post-transplant morbidity, mortality, and graft loss. Emerging evidence highlights the gut microbiome’s pivotal role in transplant outcomes through its immunomodulatory and metabolic functions. Commensal gut bacteria that produce short-chain fatty acids (SCFA), such as acetate, butyrate, and propionate, are associated with a reduced risk of both UTI and rejection. UTIs are the most common infectious complication after KTx, yet traditional risk factors do not fully explain their occurrence. Enrichment of uropathogens such as Escherichia and Enterococcus in the gut predicts subsequent bacteriuria, whereas SCFA-producing commensal bacteria exert protective effects. SCFA have direct antimicrobial activity by inhibiting Enterobacteriaceae growth and help maintain microbial balance, thereby reducing susceptibility to Enterobacteriaceae-associated UTIs. Our preliminary data indicate that low fecal SCFA levels are associated with an increased risk of developing Enterobacteriaceae bacteriuria. Beyond infection control, SCFA influence allograft immunity by signaling through G-protein–coupled receptors to promote the differentiation and suppressive function of regulatory T cells, enhancing immune tolerance. Clinical data further show that reduced microbial diversity and depletion of SCFA-producing bacteria precede acute rejection episodes and are associated with impaired graft tolerance. This study leverages two KTx recipient cohorts to investigate fecal SCFA as functional biomarkers linking gut microbial metabolism to post-transplant complications. By integrating SCFA quantification with microbial sequencing, we aim to elucidate their predictive and mechanistic roles in UTI and allograft rejection. SCFA profiling provides a direct, rapid, and cost-effective measure of gut microbial activity and may enable early detection, risk stratification, and personalized prevention strategies to improve long-term graft and patient outcomes after kidney transplantation.

• DFG Programme: WBP Fellowship
• International Connection: USA
• Hosts: Professor Dr. John R. Lee; Dr. Manikkam Suthanthiran