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Gut microbiota involvement in the alteration of inflammatory cell infiltration and gut barrier integrity in liver cirrhosis

  • Authors:
    • Kaiduan Xie
    • Yiwang Zhang
    • Shuyan Tan
    • Jiajie Luo
    • Xingtong Ou
    • Siwei Tan
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China, Department of Pathology, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China
    Copyright: © Xie et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 193
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    Published online on: October 20, 2025
       https://doi.org/10.3892/br.2025.2071
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Abstract

The gut microbiota is essential for the development and regulation of the immune and intestinal homeostasis of the host. The present study aimed to investigate the composition, diversity and functional features of the microbiota in patients with liver cirrhosis. and healthy volunteers using high‑throughput sequencing of the 16S rRNA gene, and evaluated inflammatory cell infiltration and the gut barrier in both the colonic mucosa and liver sections using histological analysis. Diversity and metagenome function of the gut microbiota significantly differed between healthy volunteers and patients with liver cirrhosis. Patients with cirrhosis showed decreased microbial richness, evenness, and diversity, with functional prediction indicating enrichment of phosphotransferase and membrane transport pathways, while amino acid and energy metabolism pathways were predominant in healthy controls. Furthermore, gut microbial dysbiosis associated with liver cirrhosis augmented inflammatory cell infiltration in the colonic mucosa and liver sections, impaired gut barrier function and enhanced intestinal permeability and bacterial translocation. The gut microbiota contributes to the pathophysiology of liver cirrhosis, which may impact prevention and treatment strategies for patients with liver cirrhosis.
View Figures

Figure 1

Characteristics of the gut microbiota
in healthy volunteers and patients with liver cirrhosis. (A)
Rarefaction (Chao and Shannon index) and rank abundance
distribution curves, based on the 16S rRNA gene sequencing of fecal
samples from healthy volunteers and patients with liver cirrhosis.
(B) Rank dissimilarity revealed that the between-group difference
was greater than the within-group difference. Chao and Shannon
index measures of diversity suggested that patients with liver
cirrhosis had significantly decreased microbial index compared with
healthy volunteers. (C) PC analysis plots of β index (based on OTU,
left) and unweighted (middle) and weighted UniFrac distances
(right). PC, principal component; OTU, operational taxonomic unit;
ANOSIM, analysis of similarity.

Figure 2

Bacterial community structures. (A)
Heatmap of the core genera in healthy volunteers and patients with
cirrhosis. (B) Relative abundance at the family level. (C) Relative
abundance at the genus level in terms of total effective bacterial
sequences.

Figure 3

Microbial taxa composition in healthy
volunteers and patients with liver cirrhosis. (A) Cladogram of the
fecal microbiota taxa associated with healthy volunteers and
patients with liver cirrhosis. (B) Association of specific
microbiota taxa with the healthy and liver cirrhosis groups based
on LDA effect size. LDA, linear discriminant analysis.

Figure 4

Taxonomic and functional
classification of microbiota between healthy volunteers and
patients with liver cirrhosis. (A) Differential abundance of fecal
microbiota genera between healthy volunteers and patients with
liver cirrhosis. (B) Functional classification differences of gut
microbiota determined by Kyoto Encyclopedia of Genes and Genomes
analysis of healthy volunteers and patients with liver cirrhosis.
*P<0.05; **P<0.01;
***P<0.001 vs. healthy.

Figure 5

Gut microbiota in liver cirrhosis is
associated with environmental information processing. (A) Cladogram
representation of the gut microbiota functional classification
using the KEGG orthology revealed that liver cirrhosis was
associated with ‘membrane transport’ and ‘phosphotransferase system
(PTS)’ of environmental information processing. (B) Association
between environmental information processing and gut microbiota of
liver cirrhosis using LDA effect size. (C) Functional
classification differences in the gut microbiota between healthy
volunteers and cirrhotic patients. KEGG, Kyoto Encyclopedia of
Genes and Genome; LDA, linear discriminant analysis; Class B/Z,
internal confidence level classification labels.

Figure 6

Gut microbiota of patients with
cirrhosis participates in the regulation of colonic and hepatic
immune response. (A) Colonoscopic images and H&E and related
inflammatory cell staining, including T lymphocytes (CD4), B
lymphocytes (CD19), macrophages (CD68) and neutrophils (MPO) of the
colon mucosa of healthy volunteers and patients with liver
cirrhosis. (B) Cell indices were analyzed using histopathological
staining. (C) H&E and (D) α-SMA, CD4, CD19, CD68 and MPO
histopathological staining were performed on liver sections of
healthy volunteers and patients with liver cirrhosis.
*P<0.05 vs. healthy. H&E, hematoxylin-eosin
staining; MPO, myeloperoxidase; SMA, smooth muscle actin.

Figure 7

Gut microbiota from patients with
liver cirrhosis influences the gut barrier and intestinal
permeability. (A) Colonoscopic images and histopathological
staining of claudin-1, ZO-1 and E-cadherin in healthy volunteers
and patients with liver cirrhosis. Collagen deposition was
determined by Sirius red staining of liver tissue sections. (B)
Claudin-1 and ZO-1. (C) E-cadherin and Sirius red staining. (D)
Intestinal permeability analysis based on blood DAO detection and
bacterial translocation analysis based on blood endotoxin detection
were performed using ELISA. (E) Positive correlation between the
blood DAO levels and collagen deposition (determined by Sirius red
staining), endotoxin levels and collagen deposition. (F) Schematic
diagram of gut microbiota involves in liver cirrhosis.
*P<0.05 vs. healthy. ZO-1, zonula occludens-1; DAO,
diamine oxidase.
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Xie K, Zhang Y, Tan S, Luo J, Ou X and Tan S: Gut microbiota involvement in the alteration of inflammatory cell infiltration and gut barrier integrity in liver cirrhosis. Biomed Rep 23: 193, 2025.
APA
Xie, K., Zhang, Y., Tan, S., Luo, J., Ou, X., & Tan, S. (2025). Gut microbiota involvement in the alteration of inflammatory cell infiltration and gut barrier integrity in liver cirrhosis. Biomedical Reports, 23, 193. https://doi.org/10.3892/br.2025.2071
MLA
Xie, K., Zhang, Y., Tan, S., Luo, J., Ou, X., Tan, S."Gut microbiota involvement in the alteration of inflammatory cell infiltration and gut barrier integrity in liver cirrhosis". Biomedical Reports 23.6 (2025): 193.
Chicago
Xie, K., Zhang, Y., Tan, S., Luo, J., Ou, X., Tan, S."Gut microbiota involvement in the alteration of inflammatory cell infiltration and gut barrier integrity in liver cirrhosis". Biomedical Reports 23, no. 6 (2025): 193. https://doi.org/10.3892/br.2025.2071
Copy and paste a formatted citation
x
Spandidos Publications style
Xie K, Zhang Y, Tan S, Luo J, Ou X and Tan S: Gut microbiota involvement in the alteration of inflammatory cell infiltration and gut barrier integrity in liver cirrhosis. Biomed Rep 23: 193, 2025.
APA
Xie, K., Zhang, Y., Tan, S., Luo, J., Ou, X., & Tan, S. (2025). Gut microbiota involvement in the alteration of inflammatory cell infiltration and gut barrier integrity in liver cirrhosis. Biomedical Reports, 23, 193. https://doi.org/10.3892/br.2025.2071
MLA
Xie, K., Zhang, Y., Tan, S., Luo, J., Ou, X., Tan, S."Gut microbiota involvement in the alteration of inflammatory cell infiltration and gut barrier integrity in liver cirrhosis". Biomedical Reports 23.6 (2025): 193.
Chicago
Xie, K., Zhang, Y., Tan, S., Luo, J., Ou, X., Tan, S."Gut microbiota involvement in the alteration of inflammatory cell infiltration and gut barrier integrity in liver cirrhosis". Biomedical Reports 23, no. 6 (2025): 193. https://doi.org/10.3892/br.2025.2071
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