💡 This study delves into the association between gut dysbiosis and all-cause, as well as cause-specific mortality, within the context of solid organ transplant recipients (SOTR).
📌 The study employed multivariable Cox regression and machine learning to identify gut dysbiosis indicators and species abundances associated with mortality.
📍 Methods:
Cohort Selection: The study included 766 kidney, 334 liver, 170 lung, and 67 heart transplant recipients from the Transplant Lines Biobank and Cohort. These recipients were followed up for 6.5 years.
Metagenomic Analysis: Gut microbiome data was obtained from fecal samples. In addition, data from 8,208 metagenomic samples from a general population residing in the same geographical location was used for comparison.
Statistical Analysis: Multivariable Cox regression and machine learning algorithms were employed to explore the association between gut dysbiosis indicators, species abundances, and all-cause and cause-specific mortality.
📍 Key Findings:
Species Predictive of Mortality: Multivariable Cox regression identified 23 species that were associated with all-cause mortality. A machine learning algorithm further identified a log-ratio of 19 species predictive of all-cause mortality, and these species were consistent with those identified in the Cox regression analysis.
Diversity and Mortality: Lower Shannon diversity index was associated with a 29% higher risk of malignancy-related mortality. However, the Shannon diversity index was not significantly related to all-cause mortality in the overall SOTR population or when stratified by organ type.
Principal Component Analysis (PCA): PCA signatures were associated with mortality risk. SOTR with higher scores on the first principal component (PC1) had a 32% higher mortality risk, while those with lower scores on PC3 had a 20% lower mortality risk.
Butyrate-Producing Bacteria: Reduced abundance of four butyrate-producing bacteria (𝘎𝘦𝘮𝘮𝘪𝘨𝘦𝘳 𝘧𝘰𝘳𝘮𝘪𝘤𝘪𝘭𝘪𝘴, 𝘍𝘪𝘳𝘮𝘪𝘤𝘶𝘵𝘦𝘴 𝘣𝘢𝘤𝘵𝘦𝘳𝘪𝘶𝘮 𝘊𝘈𝘎 83, 𝘌𝘶𝘣𝘢𝘤𝘵𝘦𝘳𝘪𝘶𝘮 𝘩𝘢𝘭𝘭𝘪𝘪, 𝘢𝘯𝘥 𝘍𝘢𝘦𝘤𝘢𝘭𝘪𝘣𝘢𝘤𝘵𝘦𝘳𝘪𝘶𝘮 𝘱𝘳𝘢𝘶𝘴𝘯𝘪𝘵𝘻𝘪𝘪) was linked to increased mortality. This suggests that lower butyrate levels could have a direct role in mortality among SOTR.
🔴 This comprehensive analysis reveals a strong connection between gut dysbiosis and mortality in solid organ transplant recipients. The results support the emerging notion that gut dysbiosis is predictive of long-term survival, making it a promising target for interventions to enhance patient outcomes.