Longitudinal Trends in Gut Microbial Community Diversity among HF Patients Undergoing LVAD

Abstract

Purpose Left ventricular assist device (LVAD) is an established treatment for advanced heart failure (aHF) with notable improvement in patient survival, yet complications remain. AHF is associated with gut microbial community dysbiosis (i.e. reduced diversity of microbial communities). Changes in gut diversity following LVAD might offer a precision medicine oriented approach to predicting the clinical trajectory of patients. In this analysis we explored longitudinal trends in gut microbial diversity before/after LVAD. Methods We prospectively enrolled 66 AHF patients (59.4±13.4 yrs old; 88% M; 56% White). A total of n=99 stool samples (n=34 pre-LVAD, n=36 LVAD 1 mo, n=29 LVAD 3-6 mo) were collected. 16S rRNA sequencing was performed on all samples. Alpha diversity metrics (number and evenness of bacterial taxa within samples) were estimated using Shannon index and the # of observed taxa. Repeated measures models were used to regress alpha diversity on time post-LVAD, adjusted for age, gender and race/ethnicity. Beta diversity (microbial difference between samples) was estimated by Bray-Curtis dissimilarity. DESeq regression analyses explored differences in individual taxa over time and the false discovery rate (FDR) adjusted for multiple comparisons Results Alpha diversity (# observed) increased by 3-6 mo following LVAD implantation (p=0.004, Figure 1). Trends were consistent for Shannon index (Figure 1). No differences in beta diversity were observed following LVAD (p=0.23). There were 32 taxa that differed between pre- vs. post-LVAD 3-6 mo with FDR Conclusion After an initial trend for decrease in gut microbial diversity at 1 mo, these metrics increased by 3-6 mo post-LVAD, which could be reflective of improved clinical status. Future studies are necessary to determine the relevance of these findings to clinical outcomes among LVAD patients and to explore the biological relevance of the taxa underlying these changes.