Current status of the microbiome in renal transplantation

Abstract

Researchers have begun to identify dysbioses associated with clinical conditions, including chronic kidney disease, posttransplant infection, and rejection. This information will allow clinicians not only to select at-risk patients for early intervention, but also to develop therapies that restore the microbiota to a state of homeostasis or tolerance.

Urinary microbiome associated with chronic allograft dysfunction in kidney transplant recipients

“…Based on our study, in addition to other cited works, there is evidence that alterations in the microbiota of transplant recipients are correlated with allograft dysfunction, IFTA, and acute rejection. It is thought that alterations in microbiota are both reflections of and drivers for changes conferred by allotransplantation and immunosuppression, and there is increasing understanding of the alterations in adaptive immune responses conferred by changes in the microbiota following immunosuppression . How individual microbial communities interplay with the immune system to modulate the risk of various diseases is only starting to be investigated, but it is becoming increasingly clear that dysbiosis may be associated with chronic inflammatory conditions.…”

“…For example, there are multiple animal models in which immune tolerance to transplanted organs is prevented by inflammatory stimuli from bacteria . Such infections appear to stimulate the innate immune system that enhances alloreactivity in a bystander manner and switches the balance from regulatory to effector immune responses . Moreover, certain intestinal commensal communities, but not others, can enhance alloreactivity and accelerate skin graft rejection when transferred orally into germ‐free mice, demonstrating a different impact on allograft outcome of different commensal community structures.…”

“…It is thought that alterations in microbiota are both reflections of and drivers for changes conferred by allotransplantation and immunosuppression, and there is increasing understanding of the alterations in adaptive immune responses conferred by changes in the microbiota following immunosuppression. 7,9,[42][43][44] How individual microbial communities interplay with the immune system to modulate the risk of various diseases is only starting to be investigated, but it is becoming increasingly clear that dysbiosis may be associated with chronic inflammatory conditions. For example, there are multiple animal models in which immune tolerance to transplanted organs is prevented by inflammatory stimuli from bacteria.…”

“…The gut microbiome in allograft recipients has been studied, both to quantify alterations in normal gut flora following immunosuppressive therapies and the effects of microbiome alterations on immune function, although these studies have looked at mouse models or non‐transplant human cohorts . Alterations in the normal gut microbiome have been shown to stimulate intestinal innate and adaptive immune mechanisms, pro‐inflammatory cytokines, and inflammation . Conversely, absence of regulatory T cells in mice was associated with increased Th2‐type inflammation as well as alterations in microbiota, suggesting that chronic inflammation can result in dysbiosis .…”

“…6 Alterations in the normal gut microbiome have been shown to stimulate intestinal innate and adaptive immune mechanisms, pro-inflammatory cytokines, and inflammation. 7 Conversely, absence of regulatory T cells in mice was associated with increased Th2-type inflammation as well as alterations in microbiota, suggesting that chronic inflammation can result in dysbiosis. 8 Thus, the relationship between the microbiome and the transplanted host appears to be bidirectional.…”