| Autor: |
Bose, Sujoy, Bose, Moumita, Basumatary, Tarun Kumar, Bose, Purabi Deka, Baruah, Vargab, Saikia, Anjan Kumar |
| Předmět: |
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| Zdroj: |
Gut & Liver; Nov2019, Vol. 13 Issue 6(suppl. 1), p86-86, 1/4p |
| Abstrakt: |
Background/Aims Present study focused on alterations in gut-microbiota and its clinical relevance with nonalcoholic fatty liver disease (NAFLD) pathogenesis in tribal cases enrolled from northeast India. Methods Clinically characterized NAFLD cases (n=36) with clinical details and fibroscan based liver stiffness measurement (LSM)-score were enrolled along with healthy controls (n=52). Decidual aspirations based microbiome load and diversity analysis was performed by standard culture and microbial metagenomics methods for NAFLD and representative HC cases. Serum endotoxin levels were estimated using standard kit. Differential sCD14, mCD14, CD40, sTLR2, TLR2, TLR4, NK/NKT expression and cytokine panels were analyzed by enzyme-linked immunosorbent assay /flowcytometry. HepG2 cell line based microbial stimulation studies were performed for specificity of differential monocyte, cytokine and HSC activation. Results Increased total and gram negative bacterial load was observed in NAFLD cases compared to HC. Metagenomic diversity profile data indicated a sharp difference in microbiota between NAFLD and HC subjects. Serum endotoxin and sCD14 levels were higher in NAFLD cases. Monocyte CD14 (p=0.019) and activation marker CD40 (p=0.043) was significantly increased in NAFLD cases. Average TLR4 (p=0.071) and TLR2 expression (p=0.137) on blood cells was also higher in NAFLD cases, while sTLR2 expression was significantly reduced in NAFLD cases (p=0.031) compared to HC. The CD40 and TLR4 levels significantly positively correlated with higher LSM scores. NK cell expression was higher in NAFLD. Distinct up-regulation of NFkBp65, tumor necrosis factor-α, interleukin (IL)-12 combined with significant downregulation of anti-inflammatory cytokine IL-10 and IL-4 was found to be significantly correlating with NAFLD pathogenesis and higher LSM-score (p<0.001). The hepG2 cell line (naïve and oleic acid stimulated) with NAFLD and HC microbial antigen stimulation and coculture study also indicated the increased monocyte activation, inflammatory cytokine expression and HSC activation markers on stimulation with microbes of NAFLD patient's origin. Conclusions Dysbiosis and resulting altered monocytosis and hyper-immunomodulation is specific and detrimental to NAFLD pathogenesis. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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