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Characterization of Gut Microbiome in Liver Transplant Recipients With Nonalcoholic Steatohepatitis.

ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) and its progressive form nonalcoholic steatohepatitis (NASH) are a growing problem globally and recur even after liver transplant (LT). We aim to characterize the gut dysbiosis in patients who developed recurrent NAFLD compared with patients without recurrence following LT. Methods:Twenty-one patients who received LT for NASH and had a protocol liver biopsy performed beyond 1-y post-LT were included prospectively (January 2018-December 2018). Genomic DNA extraction, next-generation sequencing, and quantitative PCR analysis were performed on stool samples collected within 1.1 ± 1.6 y from time of liver biopsy. Results:Recurrent NAFLD was noted in 15 of the 21 included patients. Stool microbiome analysis at the genus level showed significant loss of Akkermansia and increasing Fusobacterium associated with NAFLD recurrence. Quantitative PCR analysis revealed significantly decreased relative abundance of Firmicutes in patients with NAFLD activity scores (NASs) ?5 as compared with patients with lower NAS scores, whereas Bacteroidetes were significantly increased with higher NAS (P < 0.05). Firmicutes (P = 0.007) and Bifidobacterium group (P = 0.037) were inversely correlated, whereas Bacteroidetes (P = 0.001) showed a positive correlation with higher hepatic steatosis content. The Firmicutes/Bacteroidetes ratios were higher in patients without NAFLD or NASH as compared with patients diagnosed with NAFLD or NASH at the time of sample collection. Conclusions:Akkermansia, Firmicutes, and Bifidobacterium may play protective roles in the development of recurrent NAFLD in LT recipients, whereas Fusobacteria and Bacteroidetes may play pathogenic roles. These findings highlight the potential role of the "gut-liver" axis in the pathogenesis of NAFLD recurrence after LT.

SUBMITTER: Satapathy SK

PROVIDER: S-EPMC7665248 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Characterization of Gut Microbiome in Liver Transplant Recipients With Nonalcoholic Steatohepatitis.

Satapathy Sanjaya K SK Banerjee Pratik P Pierre Joseph F JF Higgins Daleniece D Dutta Soma S Heda Rajiv R Khan Sabrina D SD Mupparaju Vamsee K VK Mas Valeria V Nair Satheesh S Eason James D JD Kleiner David E DE Maluf Daniel G DG

Transplantation direct 20201110 12

Nonalcoholic fatty liver disease (NAFLD) and its progressive form nonalcoholic steatohepatitis (NASH) are a growing problem globally and recur even after liver transplant (LT). We aim to characterize the gut dysbiosis in patients who developed recurrent NAFLD compared with patients without recurrence following LT.<h4>Methods</h4>Twenty-one patients who received LT for NASH and had a protocol liver biopsy performed beyond 1-y post-LT were included prospectively (January 2018-December 2018). Genom ...[more]

PMID: 33204823

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Project description:Background & aimsThe aim of this study was to investigate gut microbiome (GM) dynamics in relation to carbapenem-resistant Enterobacterales (CRE) colonization, CRE infection, and non-CRE infection development within 2 months after liver transplant (LT).MethodsA single-center, prospective study was performed in patients undergoing LT from November 2018 to January 2020. The GM was profiled through 16S rRNA amplicon sequencing of a rectal swab taken on the day of transplantation, and fecal samples were collected weekly until 1 month after LT. A subset of samples was subjected to shotgun metagenomics, including resistome dynamics. The primary endpoint was to explore changes in the GM in the following groups: (1) CRE carriers developing CRE infection (CRE_I); (2) CRE carriers not developing infection (CRE_UI); (3) non-CRE carriers developing microbial infection (INF); and (4) non-CRE carriers not developing infection (NEG).ResultsOverall, 97 patients were enrolled, and 91 provided fecal samples. Of these, five, nine, 22, and 55 patients were classified as CRE_I, CRE_UI, INF, and NEG, respectively. CRE_I patients showed an immediate and sustained post-LT decrease in alpha diversity, with depletion of the GM structure and gradual over-representation of Klebsiella and Enterococcus. The proportions of Klebsiella were significantly higher in CRE_I patients than in NEG patients even before LT, serving as an early marker of subsequent CRE infection. CRE_UI patients had a more stable and diverse GM, whose compositional dynamics tended to overlap with those of NEG patients.ConclusionsGM profiling before LT could improve patient stratification and risk prediction and guide early GM-based intervention strategies to reduce infectious complications and improve overall prognosis.Impact and implicationsLittle is known about the temporal dynamics of gut microbiome (GM) in liver transplant recipients associated with carbapenem-resistant Enterobacterales (CRE) colonization and infection. The GM structure and functionality of patients colonized with CRE and developing infection appeared to be distinct compared with CRE carriers without infection or patients with other microbial infection or no infection and CRE colonization. Higher proportions of antimicrobial-resistant pathogens and poor representation of bacteria and metabolic pathways capable of promoting overall host health were observed in CRE carriers who developed infection, even before liver transplant. Therefore, pretransplant GM profiling could improve patient stratification and risk prediction and guide early GM-based intervention strategies to reduce infectious complications and improve overall prognosis.

Dataset Information

Characterization of Gut Microbiome in Liver Transplant Recipients With Nonalcoholic Steatohepatitis.

Publications

Characterization of Gut Microbiome in Liver Transplant Recipients With Nonalcoholic Steatohepatitis.

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