Gut–Liver Interactions in Patients with Nonalcoholic Fatty Liver Disease: Role of Intestinal Flora and Toll-like receptors

Background: There is a diverse community of micorganisms that supports the homeostasis of metabolic status and the balanced immune response in the host. Disturbed gut microbiome composition was found to be associated with multiple diseases in humans. Furthermore, there is an impaired balance between nutritional absorption and energy storage that is involved in the pathogenesis and progression of non-alcoholic fatty liver disease (NAFLD) . Objectives: Investigate whether the gut bacterial microbiome could have a role in the inflammatory process leading to NAFLD development and decipher their effect on the immune response represented by Toll like receptor-4 levels. Methodology : One hundred and five adult participates were enrolled in the study, 70 patients diagnosed with NAFLD , they were further subdivided into 32 cases with pure steatosis (SS), and 38 cases with non alcoholic steatohepatitis (NASH), as well as 35 healthy subjects, all matched for age, gender. Full history and clinical examination, Body mass index (BMI), abdominal ultrasonography and l iver biopsy were done . Liver function tests, lipid profile, blood sugar, insulin and C-peptide, fasting insulin, and serum levels of Toll like receptor (TLR-4) were measured. Fresh stool samples were homogenized and either used for immediate aerobic and anaerobic cultures of bacteria, or for measurement of bacterial flora levels using quantitative real time PCR of genes e ncoding 16S rRNA. Results: BMI, Fasting glucose, LDL Cholesterol, HOMA-IR, AST, ALT and GGT were significantly increased in NAFLD group when compared to control group. The serum levels of TLR-4 were significantly increased in NAFLD groups compared to normal control group, with SS having the lowest level than that detected in NASH group.  Levels of bacteroids and lactobacilli were significantly increased in NAFLD groups compared to control group and its level was significantly increased in NASH compared to simple steatosis. Clostridia, bifidobacteria, and E.coli showed no significant difference among groups. The increased copy numbers of bacteroids as well as lactobacilli were positively correlated with BMI, ALT, AST, fasting glucose, triglycerides and, TLR-4 serum levels. Conclusion: Gut microbiota play an important role in NAFLD-related pathophysiology . Further large-scale studies are recommended to understand the mechanism of such effect and to evaluate possible therapeutic targets for prevention and control of NAFLD.