Susceptibility to gut leakiness: a possible mechanism for endotoxaemia in non‐alcoholic steatohepatitis

Farhadi, Ashkan; Gundlapalli, Sushama; Shaikh, Maliha; Frantzides, Constantine T.; Harrell, Laura; Kwasny, Mary; Keshavarzian, Ali

doi:10.1111/j.1478-3231.2008.01723.x

Cited by 202 publications

(195 citation statements)

References 20 publications

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“…Endotoxemia derived from enterobacteria is related to the pathogenesis of NASH (Wigg et al, 2001; Farhadi et al, 2008). Moreover, Imajo et al reported that upregulation of CD14 by leptin‐STAT3 led hyperreactivity against low‐dose lipopolysaccharide in fatty liver induced by HFD (Imajo et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…Then, “the second hit” by various factors related to liver injury induces hepatic inflammation and fibrosis in the fatty liver. In recent years, the effects of endotoxin derived from enterobacteria have been reported, and it is known that hyperreactivity against lipopolysaccharide is led in fatty liver in cases of obesity (Wigg, Roberts‐Thomson, Dymock, McCarthy, Grose, & Cummins, 2001; Farhadi et al, 2008). …”

Section: Introductionmentioning

confidence: 99%

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Porphyromonas gingivalis induced periodontitis exacerbates progression of non‐alcoholic steatohepatitis in rats

Kuraji

Fujita

et al. 2016

Clinical & Exp Dental Res

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Non‐alcoholic steatohepatitis (NASH) is a chronic liver disease that can develop into hepatocirrhosis and hepatic carcinoma. In recent years, epidemiological and animal studies have reported that Porphyromonas gingivalis (P. gingivalis), a known periodontopathic bacteria, is closely related to NASH. However, previous studies could not demonstrate a direct relationship between periodontitis, P. gingivalis infection, and NASH. The purpose of the present study was to examine the impact of P. gingivalis‐associated periodontitis on the onset and progression of NASH. Forty‐two male Wistar rats were used in this study. Rats were fed a high‐fat diet (HFD) for 12 weeks in order to induce fatty liver. At 4 weeks from the start of feeding, the animals were performed ligature placement around the maxillary first molar tooth in order to induce experimental periodontitis, and then a P. gingivalis slurry was applied around the ligature twice in a week for 8 weeks (HFD/Pg(+) group). Controls were given the slurry without P. gingivalis after ligature placement using the same protocol (HFD/Pg(−) group). Significant increases in alveolar bone resorption and inflammation in periodontal tissue around the molar tooth in the HFD/Pg(+) group were observed when compared with the HFD/Pg(−) group. Moreover, histological images showing NASH characterized by perivenular lipid deposition including big fatty drops, ballooning degeneration, and focal necrosis with inflammatory cells were confirmed in the liver of rats in the HFD/Pg(+) group. Significant increases in alanine aminotransaminase, aspartate aminotransferase, and C‐reactive protein levels were observed in the HFD/Pg(+) group. Furthermore, endotoxin levels in serum in the HFD/Pg(+) group were significantly higher than those in the HFD/Pg(−) group. The present study demonstrated that experimental periodontitis induced by P. gingivalis led to the progression of NASH in rats with fatty liver. Increased levels of endotoxin derived from P. gingivalis infection appear to play a considerable role in the progression of NASH.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Porphyromonas gingivalis induced periodontitis exacerbates progression of non‐alcoholic steatohepatitis in rats

Kuraji

Fujita

et al. 2016

Clinical & Exp Dental Res

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“…11 We could show that subjects with MetS have increased gastroduodenal and small intestinal permeability compared with normal controls by using a differential sugar absorption method and by determination of DAO levels in serum. Saccharose (a disaccharide) is an accepted marker for gastroduodenal permeability because normally it is not able to cross the intestinal wall and is rapidly hydrolyzed in the upper part of the small intestine.…”

Section: Discussionmentioning

confidence: 99%

“…10 Patients with fatty liver also revealed a susceptibility to increased gut permeability, possibly related to increased endotoxin levels. 11 Those increased endotoxin levels may further trigger inflammatory reactions and/or immune dysfunction. 12 This is also underlined by impaired cell-mediated immune responses in vivo and in vitro and a reduced intracellular killing by neutrophils.…”

Section: Introductionmentioning

confidence: 99%

The influence of probiotic supplementation on gut permeability in patients with metabolic syndrome: an open label, randomized pilot study

et al. 2012

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BACKGROUND/OBJECTIVES: Obesity and metabolic disorders are linked to inflammation via gut microbiota and/or gut permeability. Gut-derived endotoxin triggers inflammation leading to metabolic syndrome (MetS) and contributing to oxidative stress. We intended to investigate the effect of Lactobacillus casei Shirota on gut permeability, presence of endotoxin and neutrophil function in MetS. SUBJECTS/METHODS: Patients with MetS were randomized to receive 3 Â 6.5 Â 10 9 CFU L. casei Shirota (probiotic group) or not for 3 months. Gut permeability was assessed by a differential sugar absorption method and by determination of diaminooxidase serum levels, endotoxin by an adapted limulus amoebocyte lysate assay, neutrophil function and toll-like receptor (TLR) expression by flow cytometry and ELISA was used to detect lipopolysaccharide-binding protein (LBP) and soluble CD14 (sCD14) levels. RESULTS: Twenty-eight patients and 10 healthy controls were included. Gut permeability was significantly increased in MetS compared with controls but did not differ between patient groups. None of the patients were positive for endotoxin. LBP and sCD14 levels were not significantly different from healthy controls. High-sensitive C-reactive protein and LBP levels slightly but significantly increased after 3 months within the probiotics group. Neutrophil function and TLR expression did not differ from healthy controls or within the patient groups. CONCLUSIONS: Gut permeability of MetS patients was increased significantly compared with healthy controls. L. casei Shirota administration in the MetS patients did not have any influence on any parameter tested possibly due to too-short study duration or underdosing of L. casei Shirota.

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“…[9] This susceptibility was also demonstrated in non-alcoholic steatohepatitis. [10] In patients with cirrhosis and severe sepsis, high production of proinflammatory cytokines seems to cause a deterioration in liver function and predisposes to the development of shock, renal failure, acute lung injury or acute respiratory distress syndrome, coagulopathy, or hepatic encephalopathy. Variants of the NOD2 gene (100fs and G908R) appear to increase bacterial translocation in cirrhotics and have been associated with spontaneous bacterial peritonitis in a recent study.…”

Section: Sepsis In Liver Cirrhosismentioning

confidence: 99%

Sepsis, the Liver and the Gut

Azzopardi¹,

Fenech²,

Piscopo³

2012

Sepsis - An Ongoing and Significant Challenge

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Susceptibility to gut leakiness: a possible mechanism for endotoxaemia in non‐alcoholic steatohepatitis

Cited by 202 publications

References 20 publications

Porphyromonas gingivalis induced periodontitis exacerbates progression of non‐alcoholic steatohepatitis in rats

Porphyromonas gingivalis induced periodontitis exacerbates progression of non‐alcoholic steatohepatitis in rats

The influence of probiotic supplementation on gut permeability in patients with metabolic syndrome: an open label, randomized pilot study

Sepsis, the Liver and the Gut

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