*Purpose: Kidney transplantation (KT) is the best treatment for end-stage renal disease. Although rejection is a normal immune response of the body to a foreign body, acute rejection (AR) reduces allograft survival. Recently, accumulated evidence has shown that gut microbiota interacts with immune cells and modulates both innate and adaptive immune pathways. Here, we evaluated the association between the gut microbiota change and AR after KT.

*Methods: We prospectively enrolled 46 patients undergoing KT at two tertiary centers. We collected serial fecal specimens before and at 3 and 12 months after transplantation. Metagenomic DNA was isolated from stool and sequenced using by Illumina MiSeq system. We investigated the relationship between the composition of gut microbiota and the biopsy-proven AR.

*Results: A total of 138 fecal samples were collected for the final analysis. The mean age was 49.5 ± 12.0 years and 23 (50.0%) were women. Among them, 10 (21.7%) experienced AR. At each time point, the Shannon diversity index as makers of microbial diversity had no significant difference between the AR groups and the no AR groups. Microbial diversity between 0 and 3 months showed significant decreases in both AR and no AR groups (p=0.052; p=0.000). In contrast, the diversity between 0 and 12 months after KT showed a significant decrease in only no AR group (p=0.000). At the phylum level, microbial compositions between the two groups had no significant differences. At the genus level, we identified significant decreases in the abundances of Phascolarctobacterium, Parabacteroides, and Subdoligranulum in the AR group before KT. At 3 months post-transplantation, Prevotella, Phascolarctobacterium, and Lachnospira were decreased in the AR group. At 12 months post-transplantation, microbiota compositions showed no significant differences between the two groups. Fecal Bacteroides abundance was positively correlated with eGFR at 3 months (R=0.30, P=0.042) and eGFR at 12 months (R=0.37, P=0.012). In contrast, fecal Eisenbergiella abundance was negatively correlated with eGFR at 3 months (R=-0.29, P=0.052) and eGFR at 12 months (R=-0.29, P=0.050).

*Conclusions: Our findings showed that AR is associated with compositional changes of the gut microbiota and decreases in butyrate-producing bacteria and anti-inflammatory symbionts. Further study is needed to evaluate the mechanisms explaining the effects of gut microbiota in AR.

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