Gut microbiota and acute rejection in solid organ transplantation

The microbiota can modulate immune responses. Associations between dysbiosis and acute allograft rejection have been observed in clinical transplantation and investigated mechanistically in animal models. Recent advances will be reviewed.

Reductions in gut microbial diversity, as well as loss of short-chain fatty acid (SCFA)-producing taxa have been reported to precede diagnosis of acute rejection in solid organ transplant patients, and these signatures can sometimes be found even before transplantation. Experimental models have identified the ability of certain bacterial strains or of oral supplementation with SCFA to prolong graft survival. Conversely, serum accumulation of the bacterial-derived metabolite lysophosphatidic acid (LPA) has been associated with rejection. Microbial and metabolic changes may alter either the priming phase or the effector phase of the alloimmune response.

Dysbiosis can precede acute rejection and some strains and metabolites appear protective while others may be detrimental to the graft. The ability for microbial taxa or communities, or their derived metabolites, to affect different immune phases of the alloresponse suggests that combining therapeutic targeting of these microbial axes may have additive or synergistic effects.