Identification of Akkermansia Muciniphila and Bacteroides Thetaiotaomicron Associated with the Alleviation of Peritransplant Liver Damage in Mouse Recipients

K. Dery¹, H. Kojima², H. Hirao², K. Kadono³, T. Dong², J. Kupiec-Weglinski⁴

¹Surgery, UCLA, Los Angeles, CA, ²UCLA, Los Angeles, CA, ³Liver Transplant Surgery, UCLA, Los Angeles, CA, ⁴UCLA Medical Center, Los Angeles, CA

Meeting: 2022 American Transplant Congress

Abstract number: 1243

Keywords: Genomics, Ischemia, Warm ischemia

Topic: Basic Science » Basic Science » 08 - Innate Immunity; Chemokines, Cytokines, Complement

Session Information

Session Name: Innate Immunity; Chemokines, Cytokines, Complement

Session Type: Poster Abstract

Date: Monday, June 6, 2022

Session Time: 7:00pm-8:00pm

Presentation Time: 7:00pm-8:00pm

Location: Hynes Halls C & D

*Purpose: Although recent evidence shows that modifications of gut microbiota by antibiotics (Abx) influences liver allograft function, its compositional role in orthotopic liver transplantation (OLT) remains unknown. Here, we aimed to determine whether Akkermansia muciniphila and/or Bacteroides thetaiotaomicron affect hepatic ischemia-reperfusion injury (IRI) and OLT outcomes.

*Methods: To identify beneficial bacteria associated with hepatic IRI resistance, groups of C57BL/6 recipient mice were pretreated with amoxicillin (Amx) prior to transplantation of Balb/c livers subjected to ex-vivo hepatic cold storage (18 h/4C). Fecal microbiota transfer (FMT) of feces from naïve C57BL/6 mice (200 mg/ml; day -1 and 0) prior to OLT served as controls. Genomic DNA of fecal samples were isolated and subjected to microbiome 16S rRNA gene sequencing.

*Results: Taxonomic classification revealed significant differences between the Amx-treated and untreated groups in the family-, genus, and species-level analyses. Faith’s Phylogenetic Diversity index, Shannon Index, and Chao1 Index all revealed declines in taxon richness, species diversity, and overall abundance after Amx-treatment alone (p<0.0001 in each index). By contrast, FMT re-established the microbiota to Sham and OLT-levels, suggesting that commensal flora is antagonistic to liver IRI-resistance. The bacterial phyla Verrucomicrobia and Firmicutes showed the largest decline of representation in the Amx-treated microbiota compared to Sham-treated mice. Taxonomic composition at the genus level by DESEq2 showed an increased abundance of Gram-negative A. muciniphila and B. thetaiotaomicron with a concomitantly decreased abundance of Gram-positive Turicibacter. sp. LA61 and Clostridium perfringens after Amx, (q-value<0.05). By comparison, FMT isolates revealed the loss of both A. muciniphila and B. thetaiotaomicron and restoration of T. sp. LA61, and C. perfringens.

*Conclusions: This study identifies taxa associated with attenuated microbial dysbiosis in hepatic IR-stressed mouse OLT; and identifies specific microbiota profiles that could serve as targets for innovative therapeutic strategies in IRI-OLT.

To cite this abstract in AMA style:

Dery K, Kojima H, Hirao H, Kadono K, Dong T, Kupiec-Weglinski J. Identification of Akkermansia Muciniphila and Bacteroides Thetaiotaomicron Associated with the Alleviation of Peritransplant Liver Damage in Mouse Recipients [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/identification-of-akkermansia-muciniphila-and-bacteroides-thetaiotaomicron-associated-with-the-alleviation-of-peritransplant-liver-damage-in-mouse-recipients/. Accessed November 21, 2024.

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