Journal of Gastroenterology and Hepatology

Volume 39, Issue 4 pp. 762-771

Original Article - Hepatology (Clinical)

Rifaximin treatment shapes a unique metagenome-metabolism network in patients with decompensated cirrhosis

Mei-Tong Nie,

Mei-Tong Nie

Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China

Mei-Tong Nie and Pei-Qin Wang, contributed equally to this work.Search for more papers by this author

Pei-Qin Wang,

Pei-Qin Wang

Department of Gastroenterology, Changzheng Hospital, Naval Medical University, Shanghai, China

Mei-Tong Nie and Pei-Qin Wang, contributed equally to this work.Search for more papers by this author

Pei-Mei Shi,

Pei-Mei Shi

Department of Gastroenterology, Changzheng Hospital, Naval Medical University, Shanghai, China

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Xia-Lu Hong,

Xia-Lu Hong

Department of Gastroenterology, Changzheng Hospital, Naval Medical University, Shanghai, China

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Xin Zhang,

Xin Zhang

Department of Gastroenterology, Changzheng Hospital, Naval Medical University, Shanghai, China

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Baoyu Xiang,

Baoyu Xiang

State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China

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Menghui Zhang,

Menghui Zhang

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Wei-Fen Xie,

Corresponding Author

Wei-Fen Xie

[email protected]

orcid.org/0000-0002-7137-112X

Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China

Department of Gastroenterology, Changzheng Hospital, Naval Medical University, Shanghai, China

Correspondence

Wei-Fen Xie, Department of Gastroenterology, Changzheng Hospital, Naval Medical University, Shanghai, China.

Email: [email protected]

Search for more papers by this author

Mei-Tong Nie,

Mei-Tong Nie

Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China

Mei-Tong Nie and Pei-Qin Wang, contributed equally to this work.Search for more papers by this author

Pei-Qin Wang,

Pei-Qin Wang

Department of Gastroenterology, Changzheng Hospital, Naval Medical University, Shanghai, China

Mei-Tong Nie and Pei-Qin Wang, contributed equally to this work.Search for more papers by this author

Pei-Mei Shi,

Pei-Mei Shi

Department of Gastroenterology, Changzheng Hospital, Naval Medical University, Shanghai, China

Search for more papers by this author

Xia-Lu Hong,

Xia-Lu Hong

Department of Gastroenterology, Changzheng Hospital, Naval Medical University, Shanghai, China

Search for more papers by this author

Xin Zhang,

Xin Zhang

Department of Gastroenterology, Changzheng Hospital, Naval Medical University, Shanghai, China

Search for more papers by this author

Baoyu Xiang,

Baoyu Xiang

Search for more papers by this author

Menghui Zhang,

Menghui Zhang

Search for more papers by this author

Wei-Fen Xie,

Corresponding Author

Wei-Fen Xie

[email protected]

orcid.org/0000-0002-7137-112X

Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China

Department of Gastroenterology, Changzheng Hospital, Naval Medical University, Shanghai, China

Correspondence

Wei-Fen Xie, Department of Gastroenterology, Changzheng Hospital, Naval Medical University, Shanghai, China.

Email: [email protected]

Search for more papers by this author

First published: 17 January 2024

https://doi.org/10.1111/jgh.16484

Declaration of conflict of interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Author contribution: WFX conceived and designed the experiments; MTN performed bioinformatic analysis, visualized results, and wrote the original draft; PQW collected and managed clinical data; PMS collected samples and data; XLH, BYX, and MHZ assisted with the bioinformatic analysis; XZ reviewed and provided suggestions for the article; all authors corrected and approved the final manuscript.

Financial support: This work was supported by the National Natural Science Foundation of China (NSFC) (grant number: 82030021), New Cutting-edge Technology Joint Research Project of Shanghai Shenkang Center (grant number: SHDC12016103), and The Scientific Research Project of Shanghai Municipal Health Commission (grant number: 202140335).

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Abstract

Background

Patients with decompensated cirrhosis face poor prognosis and increased mortality risk. Rifaximin, a non-absorbable antibiotic, has been shown to have beneficial effects in preventing complications and improving survival in these patients. However, the underlying mechanisms of rifaximin's effects remain unclear.

Methods

We obtained fecal samples from decompensated cirrhotic patients undergoing rifaximin treatment and controls, both at baseline and after 6 months of treatment. Shotgun metagenome sequencing profiled the gut microbiome, and untargeted metabolomics analyzed fecal metabolites. Linear discriminant and partial least squares discrimination analyses were used to identify differing species and metabolites between rifaximin-treated patients and controls.

Results

Forty-two patients were enrolled and divided into two groups (26 patients in the rifaximin group and 16 patients in the control group). The gut microbiome's beta diversity changed in the rifaximin group but remained unaffected in the control group. We observed 44 species with reduced abundance in the rifaximin group, including Streptococcus_salivarius, Streptococcus_vestibularis, Haemophilus_parainfluenzae, etc. compared to only four in the control group. Additionally, six species were enriched in the rifaximin group, including Eubacterium_sp._CAG:248, Prevotella_sp._CAG:604, etc., and 14 in the control group. Furthermore, rifaximin modulated different microbial functions compared to the control. Seventeen microbiome-related metabolites were altered due to rifaximin, while six were altered in the control group.

Conclusion

Our study revealed distinct microbiome-metabolite networks regulated by rifaximin intervention in patients with decompensated cirrhosis. These findings suggest that targeting these specific metabolites or related bacteria might be a potential therapeutic strategy for decompensated cirrhosis.

Graphical Abstract

Open Research

Data availability statement

The original sequencing data can be accessed at Genome Sequence Archive (GSA) HRA004464 (https://ngdc.cncb.ac.cn/search/?dbId=hra&q=HRA004464).

Supporting Information

Filename	Description
jgh16484-sup-0001-Fig sup1.tifTIFF image, 1.3 MB	Figure S1. Differential species regulated by rifaximin showed significant change between decompensated cirrhotic cohort and healthy control. A) Increased species in the decompensated cirrhotic patients compared with healthy control, which were decreased by the six-month rifaximin treatment. B) Decreased species in the decompensated cirrhotic patients compared with healthy control, which were increased by the six-month rifaximin treatment (Eubacterium_sp__CAG_248 and Prevotella_sp__CAG_604) and the six-month conventional treatment (the rest species).
jgh16484-sup-0002-Supplementary materials.docxWord 2007 document , 33.8 KB	Table S1. The statistics of differential intestine metabolites by rifaximin. Table S2. The statistics of differential intestine metabolites by conventional treatment.
jgh16484-sup-0003-Supplementary table3.csvplain text document, 53.3 KB	Table S3. Supporting Information.
jgh16484-sup-0004-Supplementary table4.csvplain text document, 7.3 KB	Table S4. Supporting Information.

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

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Volume39, Issue4

April 2024

Pages 762-771