Causal associations between gut Bifidobacteriaceae and transplant failure: a Mendelian randomization study

Aim: Transplant rejection and failure are the primary causes of shortened lifespan in transplant patients and are closely associated with the status of the human immune system. Gut microbiota have the capacity to modulate the human immune system. However, it remains unclear whether any gut microbiota can influence the risk of transplant failure.Materials & methods: A Mendelian randomization study was conducted to explore the causal relationship between gut microbiota and transplant failure. This study utilized three Genome-Wide Association Study results focusing on the gut microbiome, transplant failure and transplantation status. Single nucleotide polymorphisms that were strongly associated with gut microbiota abundance were selected as instrumental variables.Results: The abundance of Bifidobacteriaceae demonstrated a significant causal relationship with transplant failure (inverse variance weighted [IVW] p = 0.049, OR = 0.658, 95% CI: 0.433-0.998), but was not related to the risk of transplantation status (IVW p > 0.200). Notably, a higher intestinal abundance of Bifidobacteriaceae corresponded to a decreased risk of transplant failure. Bifidobacteriaceae instrumental variables were enriched in pathways related to synapses and membranes.Conclusion: The Bifidobacteriaceae may play a crucial role in the mechanism of transplant failure. These study results contribute to elucidating the mechanisms underlying transplant failure.