interleukin-8 and Hepatitis--Autoimmune

The gut microbiota has recently been recognized to play a role in the pathogenesis of autoimmune liver disease (AILD), mainly primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH). This study aimed to analyze and compare the composition of the oral microbiota of 56 patients with AILD and 15 healthy controls (HCs) and to evaluate its association with salivary immunological biomarkers and gut microbiota. The subjects included 39 patients with PBC and 17 patients with AIH diagnosed at our hospital. The control population comprised 15 matched HCs. Salivary and fecal samples were collected for analysis of the microbiome by terminal restriction fragment length polymorphism of 16S rDNA. Correlations between immunological biomarkers measured by Bio-Plex assay (Bio-Rad) and the oral microbiomes of patients with PBC and AIH were assessed. Patients with AIH showed a significant increase in Veillonella with a concurrent decrease in Streptococcus in the oral microbiota compared with the HCs. Patients with PBC showed significant increases in Eubacterium and Veillonella and a significant decrease in Fusobacterium in the oral microbiota compared with the HCs. Immunological biomarker analysis showed elevated levels of inflammatory cytokines (IL-1β, IFN-γ, TNF-α, IL-8) and immunoglobulin A in the saliva of patients with AILD. The relative abundance of Veillonella was positively correlated with the levels of IL-1β, IL-8 and immunoglobulin A in saliva and the relative abundance of Lactobacillales in feces. Dysbiosis of the oral microbiota is associated with inflammatory responses and reflects changes in the gut microbiota of patients with AILD. Dysbiosis may play an important role in the pathogenesis of AILD.

Topics: Aged; Case-Control Studies; Dysbiosis; Eubacterium; Feces; Female; Fusobacterium; Gene Expression; Hepatitis, Autoimmune; Humans; Interferon-gamma; Interleukin-1beta; Interleukin-8; Lactobacillales; Liver Cirrhosis, Biliary; Male; Microbiota; Middle Aged; Mouth; Saliva; Streptococcus; Tumor Necrosis Factor-alpha; Veillonella

Topics: Adult; Aged; Cohort Studies; Cross-Sectional Studies; Cytokines; Female; Hepatitis, Autoimmune; Humans; Interleukin-6; Interleukin-8; Liver Cirrhosis, Biliary; Male; Middle Aged; Tumor Necrosis Factor-alpha

Lipopolysaccharide (LPS) is suspected to trigger primary biliary cirrhosis (PBC) in susceptible individuals, yet the precise mechanism of its effect in PBC remains largely unknown. The aim of this study was to investigate altered responses to LPS ligand for Toll-like receptors (TLRs) in pathogenesis of PBC in vivo and in vitro.. In vivo, we investigated levels of LPS and pro-inflammatory cytokines in sera and expression of LPS receptors in liver tissues from 162 patients with PBC, 325 patients with other liver diseases and 80 healthy controls. In vitro, altered responses to LPS on monocytes and cultured human biliary epithelial cells (BECs) from patients with PBC were determined.. Significantly higher levels of LPS in patients with PBC were detected, compared with patients with other liver diseases and healthy controls. Immunohistochemically, expression of TLR4, CD14, CD68 and NF-κB was significantly enhanced in liver tissues from patients with PBC. Before LPS stimulation, we found significantly higher serum levels of tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and IL-8 in patients with PBC than those in healthy controls. After LPS stimulation, TLR4 expression and pro-inflammatory cytokine production in CD14-positive monocytes and cultured BEC from patients with PBC increased significantly.. These results indicated that patients with PBC were prone to exhibit higher serum LPS level, hypersensitivity of monocytes and BEC to LPS, and enhanced production of pro-inflammatory cytokines. LPS altered expression of TLR4, CD14 and NF-κB on monocytes and BEC, which may be implicated in the pathogenesis and progression of PBC.

Topics: Adult; Alkaline Phosphatase; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Bilirubin; CD83 Antigen; Cells, Cultured; Cross-Sectional Studies; Epithelial Cells; Female; gamma-Glutamyltransferase; Hepatitis B, Chronic; Hepatitis, Autoimmune; Humans; Immunoglobulins; Inflammation; Interleukin-1beta; Interleukin-6; Interleukin-8; Lipopolysaccharide Receptors; Lipopolysaccharides; Liver Cirrhosis, Biliary; Liver Diseases, Alcoholic; Male; Membrane Glycoproteins; Middle Aged; Monocytes; NF-kappa B; Toll-Like Receptor 4; Toll-Like Receptors; Tumor Necrosis Factor-alpha