Gut Permeability, Transplant Recipient Immunity, and Acute Rejection

Fernando Yuen Chang, MB ChB, BSc, and others examined the relationship between gut microbiota and recipient immunity in kidney transplantation. Their findings were presented at the American Transplant Congress 2024.

The researchers hypothesized that increased gut permeability and reduced availability of bacterial-derived metabolites associated with immunoregulation promotes a less tolerogenic environment and increases the risk of acute rejection (AR) of the kidney. Their longitudinal study included 92 transplant recipients and 23 live donors. Blood, urine, and stool samples were collected at baseline and up to 12 months post-transplant.

They assessed regulatory B cells by using flow cytometry and gut permeability by measuring plasma intestinal fatty acid binding protein (i-FABP). They used 16S rRNA sequencing of fecal metagenome isolated from stool samples to assess the diversity, composition, and abundance of gut bacteria. Finally, they used mass spectroscopy to identify fecal short-chain fatty acids and indole derivatives.

Transplant recipients with biopsy-proven AR showed increased i-FABP before transplantation and decreased indole derivatives despite an increase in tryptophan availability post-transplantation. In AR, there was a decrease in IL-10:tumor necrosis factor ratio in CD19+ B cells, especially within the transitional B-cell compartment (CD45+CD19+CD24hiCD38hiIL10+), at 3 months (0.140 ± 0.107 vs 0.080 ± 0.040; P<.05) and 6 months (0.11 ± 0.05 vs 0.07 ± 0.05; P<.05) versus those who did not experience AR. There was an increased frequency of regulatory B cells in nonrejectors after transplantation compared with baseline (2.66% ± 1.86% vs 4.62% ± 1.99%; P=.01) and at 6 months compared with rejectors (2.96% ± 1.69% vs 1.75% ± 1.25%; P<.05).

In conclusion, the researchers found that increased gut permeability and reduced immunoregulatory metabolites are associated with a reduction in IL-10+ regulatory B cells, making AR more likely to occur.

Source: Yuen Chang F, Vaitkute A, Attrill M, et al. Altered intestinal barrier and immunoregulatory gut-derived metabolites contribute to acute rejection in renal transplantation. Abstract #547. Presented at the American Transplant Congress 2024; June 1-5, 2024; Philadelphia, Pennsylvania.