Longitudinal transkingdom gut microbial approach towards decompensation in outpatients with cirrhosis

Abstract

ObjectiveFirst 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.DesignCirrhosis 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.Results157 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 (↑Lactobacillusspp,Streptococcus parasanguinisand ↓beneficial LachnospiraceaeandEubacterium hallii) and viral change (↑Siphoviridae, ↓ Myoviridae) versus those with further decompensation. Archaea: 19% hadMethanobacter brevii, which wassimilar 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.Lactobacillusphage Lc Nu and C2-like viruses were negatively linked with beneficial bacteria.ConclusionIn 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.

Higher Rate of SBP Recurrence with Secondary SBP Prophylaxis Compared to No Prophylaxis in Two National Cirrhosis Cohorts

“…The microbiome in patients with cirrhosis changes as liver disease progresses, with etiology of liver disease, and with medications given. Patients with decompensated cirrhosis have high rates of bacterial, fungal, and viral dysbiosis, which is worsened by antibiotic use, such as SBP prophylaxis, and leads to further enrichment of antibiotic resistance genes[5, 6, 7, 8]. The current preventive strategies for recurrence include daily antibiotic use, usually with fluoroquinolones or trimethoprim-sulfomethoxazole (TMP-SMX)[1].…”

Gut microbiome-brain-cirrhosis axis

“…[10] Changes in the intestinal milieu can affect brain function across several diseases through bacterial translocation of bacteria and products, the impact of other kingdoms such as viruses, fungi, and archaea, as well as direct changes through the vagus and the bloodstream. [11,12] Gut-brain axis changes in cirrhosis could play a major role in the development, propagation, and progression of clinical and subclinical liver injury. The understanding of specific changes in the gut-brain axis in cirrhosis and their role in the development of cirrhosis and associated comorbidities could be helpful to diagnose, prognosticate, and potentially individualize therapeutic options for the multidimensional changes in cirrhosis.…”

“…This worsens with advancing cirrhosis and depends on the underlying etiology, with a worse milieu in those with prior or continuing alcohol intake 10. Changes in the intestinal milieu can affect brain function across several diseases through bacterial translocation of bacteria and products, the impact of other kingdoms such as viruses, fungi, and archaea, as well as direct changes through the vagus and the bloodstream 11,12. Gut-brain axis changes in cirrhosis could play a major role in the development, propagation, and progression of clinical and subclinical liver injury.…”

Alterations in gut virome are associated with cognitive function and minimal hepatic encephalopathy cross-sectionally and longitudinally in cirrhosis

“… 6 Phages and viruses are major modulators of bacterial populations and can also directly affect the human hosts. 8 , 9 In prior studies of liver disease and cirrhosis, there are alterations in phage and viral gut microbial populations, which can in turn impact outcomes. 4 , 8 , 10 However, the effect of bacterial-viral linkages on specific cognitive impairments cross-sectionally and longitudinally needs to be investigated.…”

“… 8 , 9 In prior studies of liver disease and cirrhosis, there are alterations in phage and viral gut microbial populations, which can in turn impact outcomes. 4 , 8 , 10 However, the effect of bacterial-viral linkages on specific cognitive impairments cross-sectionally and longitudinally needs to be investigated. This integrated approach can shed light on the intricate dynamics of the gut ecosystem and help identify novel biomarkers for early detection and intervention in cognitive dysfunction.…”