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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.
SUBMITTER: Bajaj JS
PROVIDER: S-EPMC9998342 | biostudies-literature | 2023 Apr
REPOSITORIES: biostudies-literature
Bajaj Jasmohan S JS Peña-Rodriguez Marcela M La Reau Alex A Phillips Wendy W Fuchs Michael M Davis Brian C BC Sterling Richard K RK Sikaroodi Masoumeh M Fagan Andrew A Shamsaddini Amirhossein A Henseler Zachariah Z Ward Tonya T Puri Puneet P Lee Hannah H Gillevet Patrick M PM
Gut 20221107 4
<h4>Objective</h4>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.<h4>Design</h4>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, ...[more]