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. Transplant rejection or failure can reduce the lifespan of transplant patients. It is linked to the status of the person's immune system. The community of bacteria in the gut, known as the gut microbiome, can interact with the immune system. The gut microbiome could therefore influence transplant rejection by altering immune status. Currently, the link between the gut microbiome and transplant rejection is unclear. This study analyzed existing data and found that the amount of a type of bacteria called Bifidobacteriaceae might affect the risk of transplant rejection or failure. This needs to be investigated further. Supplementing with Bifidobacteriaceae might help to prevent transplant rejection or failure in transplant patients. Transplant rejection or even transplant failure severely jeopardizes the health and safety of transplant recipients. Immune-mediated transplant rejection is one of the leading causes of transplant failure. The gut microbiota may influence the success rate of transplantation by modulating the human immune system. Mendelian randomization is currently the most frequently employed method for causal inference analysis. Mendelian randomization studies have shown that a lower abundance of Bifidobacteriaceae in the gut could increase the risk of transplant failure.