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Original research
Longitudinal transkingdom gut microbial approach towards decompensation in outpatients with cirrhosis
  1. Jasmohan S Bajaj1,2,
  2. Marcela Peña-Rodriguez3,
  3. Alex La Reau4,
  4. Wendy Phillips4,
  5. Michael Fuchs1,2,
  6. Brian C Davis1,2,
  7. Richard K Sterling1,2,
  8. Masoumeh Sikaroodi5,
  9. Andrew Fagan2,
  10. Amirhossein Shamsaddini5,
  11. Zachariah Henseler4,
  12. Tonya Ward4,
  13. Puneet Puri1,2,
  14. Hannah Lee1,2,
  15. Patrick M Gillevet5
  1. 1Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University Health System, Richmond, Virginia, USA
  2. 2GI Section, Central Virginia Veterans Healthcare System, Richmond, Virginia, USA
  3. 3University of Guadalajara, Guadalajara, Mexico
  4. 4Diversigen Inc, New Brighton, Minnesota, USA
  5. 5Microbiome Analysis Center, George Mason University, Manassas, Virginia, USA
  1. Correspondence to Dr Jasmohan S Bajaj, Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University Health System, Richmond, VA 23298, USA; jasmohan{at}gmail.com

Abstract

Objective First decompensation development is a critical milestone that needs to be predicted. Transkingdom gut microbial interactions, including archaeal methanogens, may be important targets and predictors but a longitudinal approach is needed.

Design Cirrhosis outpatients who provided stool twice were included. Group 1: compensated, group 2: 1 decompensation (decomp), group 3: >1 decompensationwere followed and divided into those who remained stable or decompensated. Bacteria, viral and archaeal presence, α/β diversity and taxa changes over time adjusted for clinical variables were analysed. Correlation networks between kingdoms were analysed.

Results 157 outpatients (72 group 1, 33 group 2 and 52 group 3) were followed and 28%–47% developed outcomes. Baseline between those who remained stable/developed outcome: While no α/β diversity differences were seen, commensals were lower and pathobionts were higher in those who decompensated. After decompensation: those experiencing their first decompensation showed greater decrease in α/β-diversity, bacterial change (↑Lactobacillus spp, Streptococcus parasanguinis and ↓ beneficial Lachnospiraceae and Eubacterium hallii) and viral change (↑Siphoviridae, ↓ Myoviridae) versus those with further decompensation. Archaea: 19% had Methanobacter brevii, which was similar between/within groups. Correlation networks: Baseline archaeal-viral-bacterial networks were denser and more homogeneous in those who decompensated versus the rest. Archaea-bacterial correlations collapsed post first decompensation. Lactobacillus phage Lc Nu and C2-like viruses were negatively linked with beneficial bacteria.

Conclusion In this longitudinal study of cirrhosis outpatients, the greatest transkingdom gut microbial changes were seen in those reaching the first decompensation, compared with subsequent decompensating events. A transkingdom approach may refine prediction and provide therapeutic targets to prevent cirrhosis progression.

  • HEPATIC ENCEPHALOPATHY
  • ENTERIC BACTERIAL MICROFLORA
  • CIRRHOSIS
  • ASCITES

Data availability statement

No data are available. Metadata are not available due to IRB restrictions.

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Data availability statement

No data are available. Metadata are not available due to IRB restrictions.

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Footnotes

  • Twitter @jasmohanbajaj

  • Presented at AASLD Liver meeting 2022 in Washington DC as an oral presentation

  • Contributors JSB conceptualised the study and participated in all aspects. AF, MF, BCD, RKS, HL and PP were involved in study conduct, remaining authors were involved in microbial and bioinformatics analysis. JSB is the guarantor of the study

  • Funding VA Merit Review 2I0CX001076, AHRQ RO1HS025412, NCATS R21TR003095, Investigator-initiated grant from Bausch Health and from McGuire Research Institute.

  • Competing interests Dr Bajaj’s institution received an investigator-initiated grant from BauschZH, WP, ALR and TW are employees of DiversigenNo other competing interests.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Provenance and peer review Not commissioned; externally 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.