title: Small intestinal bacterial overgrowth and toll-like receptor signaling in patients with non-alcoholic fatty liver disease.
abstract: OBJECTIVE
  The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is multifactorial. There is sparse literature on the role of small intestinal bacterial overgrowth (SIBO) and toll-like receptor (TLR) signaling in NAFLD. The present study evaluated the relationship of SIBO with expression of TLR signaling genes in patients with NAFLD.
  
  
  METHODS
  A total of 142 subjects composed of NAFLD (n = 60, mean age 38.7 ± 10.4 years), chronic viral hepatitis (CVH) (n = 32, mean age 39.5 ± 10.6 years), and healthy volunteers (n = 50, mean age 36.56 ± 4.2 years) were enrolled in the study. Duodenal fluid was taken endoscopically in 32 prospective patients with NAFLD for evaluation of SIBO. Hepatic mRNA expression of TLR4, CD14, TLR2, NF-κβ, and MD2 and protein expression of TLR4 and TLR2 were studied in 64 patients (NAFLD = 32, CVH = 32) by RT-PCR and immunohistochemistry, respectively. Serum levels of TNF-α, adiponectin, insulin, and endotoxins were also evaluated.
  
  
  RESULTS
  Small intestinal bacterial overgrowth was present in 12 (37.5%) out of 32 patients with NAFLD with Escherichia coli as the predominant bacterium. In comparison with those without SIBO, patients with SIBO had significantly higher endotoxin levels and higher CD14 mRNA, nuclear factor kappa beta mRNA, and TLR4 protein expression. Patients with NASH had significantly higher endotoxin levels and higher intensity of TLR4 protein expression in comparison with patients without NASH. Serum levels of TNF-α, endotoxins, and insulin were significantly higher and of adiponectin lower in NAFLD in comparison with CVH and healthy volunteers.
  
  
  CONCLUSIONS
  Our study provides the first direct evidence of role of SIBO and endotoxemia and its relation with TLR signaling genes and liver histology in patients with NAFLD.
authors.affiliation: Department of Hepatology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
authors.forename: Shweta
authors.initials: S
authors.lastname: Kapil
authors.affiliation: Department of Hepatology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
authors.forename: Ajay
authors.initials: A
authors.lastname: Duseja
authors.affiliation: Department of Hepatology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
authors.forename: Bal Krishan
authors.initials: BK
authors.lastname: Sharma
authors.affiliation: Department of Hepatology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
authors.forename: Bhupesh
authors.initials: B
authors.lastname: Singla
authors.affiliation: Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
authors.forename: Anuradha
authors.initials: A
authors.lastname: Chakraborti
authors.affiliation: Department of Histopathology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
authors.forename: Ashim
authors.initials: A
authors.lastname: Das
authors.affiliation: Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
authors.forename: Pallab
authors.initials: P
authors.lastname: Ray
authors.affiliation: Department of Hepatology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
authors.forename: Radha K
authors.initials: RK
authors.lastname: Dhiman
authors.affiliation: Department of Hepatology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
authors.forename: Yogesh
authors.initials: Y
authors.lastname: Chawla
mesh_terms: D000328:Adult; D004386:Duodenum / Q000382:microbiology*; D004731:Endotoxins / Q000097:blood / Q000378:metabolism; D004926:Escherichia coli / Q000254:growth & development*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology* / Q000235:genetics / Q000382:microbiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics*; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D051193:Toll-Like Receptors / Q000235:genetics* / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D004731:Endotoxins; D007328:Insulin; D012333:RNA, Messenger; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha
keywords: NAFLD; NASH; PAMPS; SIBO; TLR; non-alcoholic steatohepatitis