Distinct Gut Microbial Signature and Host Genetic Variants in Association with Liver Fibrosis Severity in Patients with MASLD - PubMed (original) (raw)

Distinct Gut Microbial Signature and Host Genetic Variants in Association with Liver Fibrosis Severity in Patients with MASLD

Nantawat Satthawiwat et al. Nutrients. 2024.

Abstract

Gut microbiota might affect the severity and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to characterize gut dysbiosis and clinical parameters regarding fibrosis stages assessed by magnetic resonance elastography. This study included 156 patients with MASLD, stratified into no/mild fibrosis (F0-F1) and moderate/severe fibrosis (F2-F4). Fecal specimens were sequenced targeting the V4 region of the 16S rRNA gene and analyzed using bioinformatics. The genotyping of PNPLA3, TM6SF2, and HSD17B13 was assessed by allelic discrimination assays. Our data showed that gut microbial profiles between groups significantly differed in beta-diversity but not in alpha-diversity indices. Enriched Fusobacterium and Escherichia_Shigella, and depleted Lachnospira were found in the F2-F4 group versus the F0-F1 group. Compared to F0-F1, the F2-F4 group had elevated plasma surrogate markers of gut epithelial permeability and bacterial translocation. The bacterial genera, PNPLA3 polymorphisms, old age, and diabetes were independently associated with advanced fibrosis in multivariable analyses. Using the Random Forest classifier, the gut microbial signature of three genera could differentiate the groups with high diagnostic accuracy (AUC of 0.93). These results indicated that the imbalance of enriched pathogenic genera and decreased beneficial bacteria, in association with several clinical and genetic factors, were potential contributors to the pathogenesis and progression of MASLD.

Keywords: fibrosis; gut microbiota; magnetic resonance elastography (MRE); metabolic dysfunction-associated steatotic liver disease (MASLD).

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1

Gut microbial composition between the F0–F1 and F2–F4 groups. Alpha diversity: (a) Chao1 index, (b) Shannon index, (c) Simpson index, (d) beta diversity using principal coordinate analysis (PCoA) based on Bray–Curtis index between groups. Statistical significance was determined by pairwise PERMANOVA. (e) The Firmicutes/Bacteroidetes ratio. * _p_-value < 0.05.

Figure 2

The top 20 relative bacterial compositions at the genus level in the F0–F1 and F2–F4 groups.

Figure 3

Linear discriminant analysis (LDA) effect size (LEfSe) analysis of gut microbiota between the two groups at the genus level (LAD > 2, _p_-value < 0.05).

Figure 4

Functional pathways obtained with PICRUSt2 based on the MetaCyc Metabolic Pathway Database with a false discovery rate (FDR) < 0.05.

Figure 5

ROC curve analysis based on 3 significant bacteria by Random Forest.

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Distinct Gut Microbial Signature and Host Genetic Variants in Association with Liver Fibrosis Severity in Patients with MASLD - PubMed (original) (raw)