Alterations to the Intestinal Microbiome Are Associated with Post-Heart Transplant Outcomes in Children

Abstract

<h3>Purpose</h3> Alterations to the intestinal microbiome are associated with mortality after stem cell transplant in adults. We hypothesize that alterations to the intestinal microbiome occur in children after pediatric heart transplant (HTx) and are associated with post-HTx outcomes. <h3>Methods</h3> Pre-HTx and post-HTx stool specimens were prospectively collected from 9/2018 - 7/2020. Bacterial DNA was extracted and processed through an Illumina MiSeq 16S sequencing pipeline. Separate regions of the 16S rRNA gene, V1V3 and V4, were targeted for sequencing. Resulting raw sequences were analyzed utilizing the UPARSE algorithm for clustering of sequences into operational taxonomic units (OTUs) and the SILVA v123 database for taxonomic classification of each OTU. The outcome was a composite "event" (infection, graft rejection, or transplant coronary artery disease) at the time of stool collection. <h3>Results</h3> There were 316 stool specimens (138 pre-HTx, 178 post-HTx) collected from 105 patients, including from 28 patients with sequential samples who underwent HTx during the study period. There are compositional differences between pre-HTx vs post-HTx patients (Fig 1A), most notably in the abundance of <i>Bacteroides, Enterococcus</i>, and <i>Akkermansia</i> species, and compositional shifts depending on time elapsed from HTx (Fig 1B). There were also specific compositional differences among patients with post-HTx events (most notably in the abundance of <i>Clostridium and Ruminococcus</i> species<i>;</i> Fig 1C) and among patients with post-HTx rejection (most notably in <i>Enterococcus, Bifidobacterium, and Akkermansia</i> species; Fig 1D). <h3>Conclusion</h3> Compositional alterations to the intestinal microbiome occur in children undergoing HTx. Specific differences were observed in children experiencing post-HTx composite events, including specific compositional changes among children with post-HTx rejection. Whether these compositional alterations are a cause or effect, or if they can be reversed, remains to be elucidated.