Alteration of Gut Microbiota Composition in the Progression of Liver Damage in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a complex disorder whose prevalence is rapidly growing in South America. The disturbances in the microbiota-gut-liver axis impact the liver damaging processes toward fibrosis. Gut microbiota status is shaped by dietary and lifestyle factors, depending on geographic location. We aimed to identify microbial signatures in a group of Chilean MASLD patients. Forty subjects were recruited, including healthy controls (HCs), overweight/obese subjects (Ow/Ob), patients with MASLD without fibrosis (MASLD/F-), and MASLD with fibrosis (MASLD/F+). Both MASLD and fibrosis were detected through elastography and/or biopsy, and fecal microbiota were analyzed through deep sequencing. Despite no differences in α- and β-diversity among all groups, a higher abundance of Bilophila and a lower presence of Defluviitaleaceae, Lachnospiraceae ND3007, and Coprobacter was found in MASLD/F- and MASLD/F+, compared to HC. Ruminococcaceae UCG-013 and Sellimonas were more abundant in MASLD/F+ than in Ow/Ob; both significantly differed between MASLD/F- and MASLD/F+, compared to HC. Significant positive correlations were observed between liver stiffness and Bifidobacterium, Prevotella, Sarcina, and Acidaminococcus abundance. Our results show that MASLD is associated with changes in bacterial taxa that are known to be involved in bile acid metabolism and SCFA production, with some of them being more specifically linked to fibrosis.

Keywords: MASLD; gut–liver axis; intestinal microbiota; liver fibrosis; obesity.

Figure 1

Boxplots of alpha-diversity indices. Alpha-diversity comparisons of the gut microbiota of the healthy controls (HCs), overweight/obese without MASLD (Ow/Ob), MASLD without fibrosis (MASLD/F−), and MASLD with fibrosis (MASLD/F+). (A) Observed species. (B) Shannon index. p < 0.05 (Kruskal–Wallis).

Figure 2

Canonical correspondence analysis (CCA) shows the correlation between the gut microbiota compositions at the species level of healthy control (HC), overweight/obese without MASLD (Ow/Ob), MASLD without fibrosis (MASLD/F−), and MASLD with fibrosis (MASLD/F+).

Figure 3

Heatmap showing the abundance difference of the gut microbiota at the genus level among healthy controls (HCs), overweight/obese without MASLD (Ow/Ob), MASLD patients, MASLD without fibrosis (MASLD/F−), and MASLD with fibrosis (MASLD/F+). For each heatmap row, values with different superscripts are significantly different (p < 0.05 (Kruskal–Wallis test among groups and post hoc Dunn’s test)). The scale was normalized for better visualization of the data.

Figure 4

Correlations between the relative abundance of different bacterial taxa and fibrosis severity (KPa) (Pearson correlation). (A) Actinobacteria phylum. (B) Bifidobacteriaceae family. (C) Bifidobacterium genus. (D) Prevotella 2 genus. (E) Sarcina genus. (F) Acidaminococcus genus.