Hepatic injury associated with small bowel bacterial overgrowth in rats is prevented by metronidazole and tetracycline

Lichtman, Steven N.; Keku, J; Schwab, John H.; Sartor, R. Balfour

doi:10.1016/0016-5085(91)90224-9

Cited by 163 publications

(123 citation statements)

References 26 publications

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“…Furthermore, there is evidence that hepatic inflammation can be reduced by means of changes to the gut microbiota induced by antibiotics and probiotics. [47][48][49][50][51][52][53][54][55][56] Under high levels of oxidative stress, which is a feature usu- …”

Section: Pathophysiologymentioning

confidence: 99%

Nonalcoholic fatty liver disease and bariatric surgery: a comprehensive review

2017

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CONTEXT AND OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) has been increasingly diagnosed worldwide and is now recognized as a source of public health concern. It comprises a wide spectrum of histological features that range from simple steatosis to severe forms of fibrosis, steatohepatitis and even cirrhosis. The impact of bariatric surgery on the course of NAFLD in individuals with obesity has been extensively studied. DESIGN AND SETTING: Narrative review; public university hospital. METHODS: A comprehensive review was conducted based on an online search on the electronic databases MEDLINE and LILACS using the MeSH terms "fatty liver" and "bariatric surgery". RESULTS:The exact mechanisms that lead to improvement in NAFLD following bariatric surgery are not completely understood. Since Roux-en-Y gastric bypass (RYGB) is the bariatric surgical procedure most performed worldwide, it is also the one from which the effects on NAFLD have been most studied, although there is also consistent evidence regarding the effects from gastric banding, sleeve gastrectomy and biliopancreatic diversions. CONCLUSION: According to the currently available evidence, bariatric surgery leads to significant improvement in NAFLD. Further research, especially by means of randomized controlled trials enrolling larger cohorts of individuals, is needed to determine the optimal procedure for this group of subjects. RESUMO CONTEXTO E OBJETIVO:A doença hepática gordurosa não alcoólica (DHGNA) tem sido diagnosticada com maior frequência em todo o mundo na atualidade, sendo agora reconhecida como motivo de preocupação em saúde pública. Abrange um amplo espectro de alterações histológicas que variam desde a simples esteatose até formas graves de fibrose, esteato-hepatite e até cirrose. O impacto da cirurgia bariátrica sobre o curso da DHGNA em indivíduos com obesidade tem sido profundamente estudado. TIPO DE ESTUDO E LOCAL: Revisão narrativa; hospital universitário público. MÉTODOS: Uma revisão abrangente da literatura foi conduzida baseada na pesquisa on-line nas bases de dados eletrônicas MEDLINE e LILACS por meio dos termos MeSH "fígado gorduroso" e "cirurgia bariátrica". RESULTADOS: Os mecanismos exatos que levam à melhora da DHGNA após a cirurgia bariátrica não são completamente conhecidos. Como o bypass gástrico em Y de Roux é a cirurgia bariátrica mais realizada em todo o mundo, é também o procedimento cujos efeitos sobre DHGNA foram mais estudados, embora haja também evidências consistentes sobre os efeitos de banda gástrica, gastrectomia vertical e derivações biliopancreáticas. CONCLUSÃO: De acordo com as evidências atualmente disponíveis, a cirurgia bariátrica leva à melhora significativa da DHGNA. Mais estudos, especialmente por meio de ensaios clínicos randomizados e controlados, recrutando coortes maiores de indivíduos, são necessários para determinar o melhor procedimento para esse grupo de pacientes.

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Section: Pathophysiologymentioning

confidence: 99%

Nonalcoholic fatty liver disease and bariatric surgery: a comprehensive review

2017

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“…25 No 2: 159-165 anaerobic bacteria in the proximal small bowel, has been shown to induce hepatic steatosis in animal models [13,14]. In humans, the presence of SIBO has been associated with an increased risk and severity of NAFLD in obese individuals [15], who are already at a high risk for hepatic steatosis.…”

Section: Introductionmentioning

confidence: 99%

Small Intestinal Bacterial Overgrowth Is Associated with Non- Alcoholic Fatty Liver Disease

Fialho

André

Thota

et al. 2016

JGLD

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Background: Changes in gut bacteria play a role in type 2 diabetes mellitus (DM) and hepatic steatosis. There is a lack of studies evaluating the frequency and risk factors for non-alcoholic fatty liver disease (NAFLD) in patients tested for small intestinal bacterial overgrowth (SIBO). Aim: To evaluate the frequency of NAFLD and associated risk factors in patients tested for SIBO. Methods: In this case-control study, 372 eligible patients submitted to glucose hydrogen/methane breath test for SIBO who also had an abdominal imaging study were included. Patients were divided into SIBO-positive and SIBO-negative groups. Clinical, demographic and laboratory variables were evaluated in addition to the presence of NAFLD on abdominal imaging. Results: Of the 372 eligible patients, 141 (37.9%) were tested positive for SIBO (study group) and 231 (62.1%) were negative for it (control group). NAFLD occurred in 45.4% (64/141) of the study group compared to 17.3% (40/231) of the control group (p<0.001). Patients in the study group were found to have higher rates of elevated aspartate aminotransferase (AST) (20.6% vs. 11.3%; p=0.034) and alanine aminotransferase (ALT) levels (56.0% vs. 40.7%; p= 0.039), type 2 diabetes (23.4% vs. 13.9%; p=0.041), hypertension (54.6% vs. 40.3%; p=0.046) and metabolic syndrome (78.0% vs. 60.2%; p=0.020). In the multivariate analysis, SIBO (odds ratio [OR]: 1.95; 95% confidence interval [CI]: 1.14-3.31; p=0.014), type 2 DM (OR: 3.04; 95%CI: 1.57-5.90; p=0.001) and obesity (OR: 3.58; 95%CI: 1.70-7.54; p=0.001) remained associated with NAFLD.Conclusion: Patients with SIBO have an increased risk for hepatic steatosis and may benefit from aggressive control of the risk factors for NAFLD including metabolic syndrome. Abbreviations: ALT: alanine aminotransferase; AST: aspartate aminotransferase; BMI: body mass index; CTE: computed tomography enterography; DM: diabetes mellitus; ETOH: ethanol; IL: interleukin; LPS: lipopolysaccharide; NAFLD: non-alcoholic fatty liver disease; NASH: non-alcoholic steatohepatitis; PPI: proton pump inhibitor; SIBO: small intestinal bacterial overgrowth; TLR-4: toll-like receptor 4; TMAO: trimethylamine-N-oxide (TMAO); TNF-α: tumor necrosis factor alpha.

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“…6 In rats, overproduction of tumor necrosis factor has been associated with bile duct destruction and proliferation, 7,8 and the self-filling loops of the small bowel associated with bacterial overgrowth with Bacteroides species can lead to hepatobiliary injury resembling PSC in humans. 9 Liver damage can be prevented with metronidazole (MTZ) or tetracycline. 9 In humans, metronidazole has been shown to induce significant inhibition of the endotoxin-stimulated tumor necrosis factor alpha production of human peripheral blood mononuclear cells at therapeutic levels.…”

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confidence: 99%

“…9 Liver damage can be prevented with metronidazole (MTZ) or tetracycline. 9 In humans, metronidazole has been shown to induce significant inhibition of the endotoxin-stimulated tumor necrosis factor alpha production of human peripheral blood mononuclear cells at therapeutic levels. 10 Metronidazole also has beneficial effects in healing intestinal damage, reduces intestinal permeability, and has a direct protective effect on the uncoupling of mitochondrial oxidative phosphorylation caused by nonsteroidal anti-inflammatory drugs.…”

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confidence: 99%

Metronidazole and Ursodeoxycholic Acid for Primary Sclerosing Cholangitis: A Randomized Placebo–Controlled Trial

et al. 2004

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No effective medical therapy is currently available for primary sclerosing cholangitis (PSC). Ursodeoxycholic acid (UDCA) improves liver enzymes, but its effect on liver histology is controversial. Metronidazole (MTZ) prevents PSC-like liver damage in animal models and reduces intestinal permeability. We recruited 80 patients with PSC into a randomized placebo-controlled study to evaluate the effect of UDCA and MTZ (UDCA/MTZ) compared with UDCA/placebo on the progression of PSC. Patients (41 UDCA/placebo and 39 UDCA/ MTZ) were followed every third month. Assessment of liver function test, histological stage and grade, and cholangiography (via ERCP) at baseline showed no differences between the groups. After 36 months, serum aminotransferases ␥-glutamyltransferase, and alkaline phosphatase (ALP) decreased markedly in both groups, serum ALP more significantly in the UDCA/MTZ group (؊337 ؎ 54 U/L, P < .05) compared with the UDCA/placebo group. The New Mayo Risk Score decreased markedly only in the UDCA/MTZ group (؊0.50 ؎ 0.13, P < .01). The number of patients with improvement of stage (P < .05) and grade (P < .05) was higher in the combination group. ERCP findings showed no progression or improvement in 77% and 68% of patients on UDCA/MTZ and UDCA/placebo, respectively. In conclusion, combining MTZ with UDCA in PSC improved serum ALP levels and New Mayo Risk Score, but no statistically significant effect on disease progression as assessed via liver histology or ERCP was seen. Long-term studies using a higher dose of UDCA combined with MTZ in larger patient populations are indicated. (HEPATOLOGY 2004;40:1379 -1386

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Hepatic injury associated with small bowel bacterial overgrowth in rats is prevented by metronidazole and tetracycline

Cited by 163 publications

References 26 publications

Nonalcoholic fatty liver disease and bariatric surgery: a comprehensive review

Nonalcoholic fatty liver disease and bariatric surgery: a comprehensive review

Small Intestinal Bacterial Overgrowth Is Associated with Non- Alcoholic Fatty Liver Disease

Metronidazole and Ursodeoxycholic Acid for Primary Sclerosing Cholangitis: A Randomized Placebo–Controlled Trial

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