Skip to main content

Advertisement

SpringerLink
Log in

Significant gut microbiota related to patterns of drinking and alcohol relapse in patients with alcoholic hepatitis undergoing stool transplant or corticosteroid therapy

  • Short Report
  • Published:
Indian Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Alcohol-induced gut microbiota (GM) alterations are linked to alcohol use disorder (AUD) pathogenesis. Healthy donor stool transplant (fecal microbiota transplant [FMT]) reduced alcohol desire and improved clinical outcomes in small animal and human studies. Baseline and post-therapy-related GM changes in a real-world cohort with severe alcohol-related liver disease and AUD, patterns of drinking, and relapse have not been studied. We prospectively analyzed retrospective clinical data and stored samples to examine GM alterations in a cohort of severe alcohol-associated hepatitis (SAH) patients who underwent FMT or corticosteroid treatment followed for at least 12 months. The GM changes at baseline in the context of a pattern of drinking (binge vs. every day) and baseline and post-treatment alcohol relapse status (relapser vs. non-relapser). We identified 28 patients on FMT and 25 on corticosteroids who survived 1 year post-treatment. After necessary exclusions, the final cohort for various grouped GM analysis included 16 patients in the FMT arm and 14 on corticosteroids. Pedobacter and Streptophyta species at the commencement of treatment predicted alcohol relapse in steroid-ineligible patients receiving FMT and steroid-treated patients, respectively. At 6–12 months post-FMT, non-relapsers had elevated short-chain fatty acid-producing bacterial taxa linked with lower alcohol cravings. Alcohol relapse was significantly more in those on steroid therapy and was associated with the upregulation of the nucleotide metabolism pathway related to ethanol metabolism. We demonstrate pertinent baseline and post-treatment intestinal bacterial alterations that impact patterns of AUD patterns and relapse in SAH patients in the context of the therapy offered.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

References

  1. Dubinkina VB, Tyakht AV, Odintsova VY, et al. Links of gut microbiota composition with alcohol dependence syndrome and alcoholic liver disease. Microbiome. 2017;5:141. 

    Article  PubMed  PubMed Central  Google Scholar 

  2. Bajaj JS, Gavis EA, Fagan A,  et al. A randomized clinical trial of fecal microbiota transplant for alcohol use disorder. Hepatology. 2021;73:1688–700. 

    Article  CAS  PubMed  Google Scholar 

  3. Philips CA, Ahamed R, Rajesh S, Abduljaleel JKP, Augustine P. Long-term outcomes of stool transplant in alcohol-associated hepatitis-analysis of clinical outcomes, relapse, gut microbiota and comparisons with standard care. J Clin Exp Hepatol. 2022;12:1124–32. 

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Wolstenholme JT, Saunders JM, Smith M,  et al. Reduced alcohol preference and intake after fecal transplant in patients with alcohol use disorder is transmissible to germ-free mice. Nat Commun. 2022;13:6198.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Mathurin P, O’Grady J, Carithers RL, et al. Corticosteroids improve short-term survival in patients with severe alcoholic hepatitis: meta-analysis of individual patient data. Gut. 2011;60:255–60.

    Article  CAS  PubMed  Google Scholar 

  6. Philips CA, Ahamed R, Rajesh S, et al. Clinical outcomes and gut microbiota analysis of severe alcohol-associated hepatitis patients undergoing healthy donor fecal transplant or pentoxifylline therapy: single-center experience from Kerala. Gastroenterol Rep (Oxf). 2022;10:goac074.

  7. Quast C, Pruesse E, Yilmaz P,  et al. The SILVA ribosomal RNA gene database project: improved data processing and web-based tools. Nucleic Acids Res. 2013;41(Database issue):D590-6.. 

    Article  CAS  PubMed  Google Scholar 

  8. Bolyen E, Rideout JR, Dillon MR,  et al. Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2. Nat Biotechnol. 2019;37:852–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Segata N, Izard J, Waldron L,  et al. Metagenomic biomarker discovery and explanation. Genome Biol. 2011;12:R60.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Langille MG, Zaneveld J, Caporaso JG,  et al. Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences. Nat Biotechnol. 2013;31:814–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Xu Y, Xie Z, Wang H,  et al. Bacterial diversity of intestinal microbiota in patients with substance use disorders revealed by 16S rRNA gene deep sequencing. Sci Rep. 2017;7:3628.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Gilbertson R, Prather R, Nixon SJ. The role of selected factors in the development and consequences of alcohol dependence. Alcohol Res Health. 2008;31:389–99.

    PubMed  PubMed Central  Google Scholar 

  13. Braidy N, Villalva MD, van Eeden S. Sobriety and satiety: is NAD+ the answer? Antioxidants (Basel). 2020;9:425. 

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Leclercq S, Schwarz M, Delzenne NM, Stärkel P, de Timary P. Alterations of kynurenine pathway in alcohol use disorder and abstinence: a link with gut microbiota, peripheral inflammation and psychological symptoms. Transl Psychiatry. 2021;11:503. 

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Li Q, Chen S, Liu K,  et al. Differences in gut microbial diversity are driven by drug use and drug cessation by either compulsory detention or methadone maintenance treatment. Microorganisms. 2020;8:411.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Bajaj JS, Shamsaddini A, Sikaroodi M,  et al. Active alcohol misuse is linked with lower short-chain fatty acid producing microbiota in a matched study of 450 patients with cirrhosis. J Hepatol. 2022;77:S119–388.

    Article  Google Scholar 

  17. Cai X, Bao L, Wang N,  et al. Dietary nucleotides protect against alcoholic liver injury by attenuating inflammation and regulating gut microbiota in rats. Food Funct. 2016;7:2898–908. 

    Article  CAS  PubMed  Google Scholar 

  18. Li F, Zhao C, Shao T, et al. Cathelicidin-related antimicrobial peptide alleviates alcoholic liver disease through inhibiting inflammasome activation. J Pathol. 2020;252:371–83. 

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Clinical and Translational Hepatology and Monarch Liver Laboratory Center for Excellence in Gastrointestinal Sciences, Ground Floor, The Liver Institute, Rajagiri Hospital, Phase II, Tower -3, Aluva, 683 112, India

    Cyriac Abby Philips

  2. Gastroenterology and Advanced GI Endoscopy, Center of Excellence in GI Sciences, Rajagiri Hospital, Chunangamvely, Aluva, 683 112, India

    Rizwan Ahamed, Jinsha K Abduljaleel, Ajit Tharakan & Philip Augustine

  3. Interventional Hepatobiliary Radiology, Center of Excellence in GI Sciences, The Liver Institute, Rajagiri Hospital, Chunangamvely, Aluva, 683 112, India

    Sasidharan Rajesh

Authors
  1. Cyriac Abby Philips
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rizwan Ahamed
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jinsha K Abduljaleel
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sasidharan Rajesh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ajit Tharakan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Philip Augustine
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Cyriac Abby Philips: conceptualization, methodology, data curation, writing (first draft and editing); Rizwan Ahamed: writing (review and editing), data curation, validation, supervision; Jinsha K Abduljaleel: writing (review and editing), validation, supervision; Sasidharan Rajesh: writing (review and editing), validation; Ajit Tharakan: writing (review and editing), data curation, validation, supervision; Philip Augustine: writing (review and editing), validation, supervision.

Corresponding author

Correspondence to Cyriac Abby Philips.

Ethics declarations

Conflict of interest

CAP, RA, JKA, SR, AT and PA declare no competing interests.                                                                                                         

Ethics statement

The study was performed conforming to the Helsinki Declaration of 1975, as revised in 2000 and 2008 concerning human and animal rights and the authors followed the policy concerning informed consent as shown on Springer.com.

Disclaimer

The authors are solely responsible for the data and the contents of the paper. In no way, the Honorary Editor-in-Chief, Editorial Board Members, the Indian Society of Gastroenterology or the printer/publishers are responsible for the results/findings and content of this article.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Philips, C.A., Ahamed, R., Abduljaleel, J.K. et al. Significant gut microbiota related to patterns of drinking and alcohol relapse in patients with alcoholic hepatitis undergoing stool transplant or corticosteroid therapy. Indian J Gastroenterol 42, 724–730 (2023). https://doi.org/10.1007/s12664-023-01401-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12664-023-01401-4

Keywords

Search

Navigation