๐ก 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).
๐ The study employed multivariable Cox regression and machine learning to identify gut dysbiosis indicators and species abundances associated with mortality.
๐ 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.
๐ 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 (๐๐ฆ๐ฎ๐ฎ๐ช๐จ๐ฆ๐ณ ๐ง๐ฐ๐ณ๐ฎ๐ช๐ค๐ช๐ญ๐ช๐ด, ๐๐ช๐ณ๐ฎ๐ช๐ค๐ถ๐ต๐ฆ๐ด ๐ฃ๐ข๐ค๐ต๐ฆ๐ณ๐ช๐ถ๐ฎ ๐๐๐ 83, ๐๐ถ๐ฃ๐ข๐ค๐ต๐ฆ๐ณ๐ช๐ถ๐ฎ ๐ฉ๐ข๐ญ๐ญ๐ช๐ช, ๐ข๐ฏ๐ฅ ๐๐ข๐ฆ๐ค๐ข๐ญ๐ช๐ฃ๐ข๐ค๐ต๐ฆ๐ณ๐ช๐ถ๐ฎ ๐ฑ๐ณ๐ข๐ถ๐ด๐ฏ๐ช๐ต๐ป๐ช๐ช) was linked to increased mortality. This suggests that lower butyrate levels could have a direct role in mortality among SOTR.
๐ด 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.