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Letter
Impact of acute alcohol consumption on circulating microbiome in asymptomatic alcohol-related liver disease
  1. Mads Israelsen1,
  2. Camila Alvarez-Silva2,
  3. Bjørn Stæhr Madsen1,
  4. Camilla Dalby Hansen1,
  5. Nikolaj Christian Torp1,3,
  6. Stine Johansen1,3,
  7. Johanne Kragh Hansen1,3,
  8. Katrine Prier Lindvig1,3,
  9. Jeanlouis Insonere4,
  10. Virginie Riviere4,
  11. Helene Bæk Juel2,
  12. Asker Brejnrod5,
  13. Lars Juhl Jensen6,
  14. Maja Thiele1,3,
  15. Benjamin Lelouvier4,
  16. Torben Hansen2,
  17. Manimozhiyan Arumugam2,
  18. Aleksander Krag1,3,
  19. MicrobLiver consortium
  20. GALAXY consortium
      1. 1 Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark
      2. 2 Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
      3. 3 Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
      4. 4 Vaiomer, Labège, France
      5. 5 Department of Health Technology, Technical University of Denmark, Lyngby, Hovedstaden, Denmark
      6. 6 Faculty of Health and Medical Sciences, University of Copenhagen, Kobenhavn, Denmark
      1. Correspondence to Dr Aleksander Krag, Department of Gastroenterology, Odense University Hospital, Odense, Syddanmark, Denmark; Aleksander.Krag{at}rsyd.dk; Dr Manimozhiyan Arumugam, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark; arumugam{at}sund.ku.dk

      https://doi.org/10.1136/gutjnl-2023-330360

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        We read with great interest the review by Tranah et al,1 which highlighted that alcohol consumption, alterations in the gut microbiome and impairment of the gut barrier function were linked to the development of alcohol-related liver disease (ALD). However, the impact of acute alcohol consumption on the circulating microbiome in patients with ALD remains unclear.

        To address this gap, we conducted a controlled acute alcohol intervention in healthy controls (n=8), individuals with ALD (n=14) and non-alcoholic fatty liver disease (NAFLD) (n=14). Ethanol (2.5 mL of 40% EtOH per kg body weight) was instilled via a nasogastric tube over 30 min by infusion pump. To sample hepatic and systemic venous blood simultaneously, we placed a catheter in a hepatic vein via a transjugular access and another catheter in the right internal jugular vein. Blood was sampled at eight time points over 3 hours (figure 1A).2 3 We performed 16S rRNA gene amplicon sequencing (16S sequencing) and measurement of 16S rRNA gene copy number using qPCR (16S qPCR) in 576 blood samples. Circulating microbial DNA quantities were significantly higher in hepatic/systemic circulation compared with negative controls, indicating that microbial contamination was well contained and had a negligible impact on the results (figure 1B).

        Figure 1

        Experimental design and bioinformatic workflow. (A) Experimental design: The 36 participants had three distinct hepatic phenotypes: 8 healthy controls, 14 with ALD, and 14 with NAFLD. At baseline, blood was sampled first, and alcohol subsequently instilled over 30 minutes. Blood was sampled at 0, 15, 30, 60, 90, 120, 150, 180. (B) 16S rRNA gene amplicon analysis workflow: We characterised the microbial …

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        Footnotes

        • X @IsraelsenMads, @mariacalvarezs1, @Camilla_Dalby, @NikolajTorp_, @microbiomix

        • MI and CA-S contributed equally.

        • Correction notice This article has been corrected since it published Online First. The author contribution statement has been added.

        • Collaborators MicrobLiver consortium: Peer Bork, Mathias Mann, Jelle Matthijnssens, Aleksander Krag, Torben Hansen; GALAXY consortium: Ema Anastasiadou, Manimozhian Arumugam, Peer Bork, Torben Hansen, Roland Henrar, Hans Israelsen, Morten Karsdal, Cristina Legido-Quigley, Hans Olav Melberg, Maja Thiele, Jonel Trebicka, Aleksander Krag.

        • Contributors Conceptualisation and methodology: MI, CA-S, TH, AK and MA. Data collection: MI, BSM CDH, NCT, SJ, JKH and KPL. Data generation: JI, VR and BL. Formal analysis: MI, CA-S and MA. Investigation: MI, CA-S, AK and MA. Resources: AK, TH and MA. Writing—original draft. MI, CA-S and MA. Visualisation: MI, CA-S and MA. Supervision: AK and MA. All authors contributed to the manuscript with important intellectual content and approved the final version.

        • Funding Challenge Grant 'MicrobLiver' grant number NNF15OC0016692 from the Novo Nordisk Foundation. Novo Nordisk Foundation Center for Basic Metabolic Research is an independent research centre, based at the University of Copenhagen, Denmark, and partially funded by an unconditional donation from the Novo Nordisk Foundation (www.cbmr.ku.dk) (grant number NNF18CC0034900). CA-S was supported by Novo Nordisk Foundation (grant NNF16CC0020896). LJJ was supported by Novo Nordisk Foundation (grant NNF14CC0001).

        • Competing interests LJJ owns shares in Amgen and Novo Nordisk A/S and is a member of the Scientific Advisory Board of ZS Associates. MT has received speaker’s fee from Echosens, Siemens Healthcare, Norgine, Tillotts Pharma and advisory fee from GE Healthcare. MA has received speaking and/or consulting fees from Roche A/S, Lundbeck Pharma A/S and SNIPR Biome ApS. AK has served as speaker for Norgine, Siemens and Nordic Bioscience and participated in advisory boards for Norgine and Siemens, all outside the submitted work.

        • Provenance and peer review Not commissioned; internally peer reviewed.

        • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.