Rifaximin has minor effects on bacterial composition, inflammation, and bacterial translocation in cirrhosis: A randomized trial

Kimer, Nina; Pedersen, Julie Steen; Tavenier, Juliette; Christensen, Jeffrey E.; Busk, Troels M.; Hobolth, Lise; Krag, Aleksander; Al‐Soud, Waleed Abu; Mortensen, Martin Steen; Sørensen, Søren J.; Möller, Sören; Bendtsen, Flemming

doi:10.1111/jgh.13852

Cited by 58 publications

(66 citation statements)

References 50 publications

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“…However, the use of these medications is so widely implemented in patients with cirrhosis that it would be extremely difficult to find patients with advanced cirrhosis without any of these confounders, and such patients would be an anomaly not reflecting the reality of patients with decompensated cirrhosis in terms of microbiota composition. Furthermore, recent studies suggest that several of these treatments do not have the anticipated major impact on microbiota composition, suggesting that the abnormalities in the cirrhosis microbiota are more related to the disease itself than to the medications received by these patients. Indeed, in our present study the severity of disease was more informative than treatment with antibiotics, lactulose or PPIs in explaining the variation in composition of the samples, or the changes in SCFAs production, but our small sample size does not allow us to answer this question.…”

Section: Discussionsupporting

confidence: 90%

Faecal microbiota from patients with cirrhosis has a low capacity to ferment non‐digestible carbohydrates into short‐chain fatty acids

Jin

Kalainy

Baskota

et al. 2019

Liver International

112

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Background and Aims:Cirrhosis is associated with dysbiosis, but its functional consequences are still largely unknown. Short-chain fatty acids (SCFAs) account for physiological interactions between the gut microbiota and host. Our aim was to assess the impact of cirrhotic dysbiosis on the production of SCFAs. Methods: Seventeen patients with cirrhosis and 17 controls were selected. Microbiota composition in faecal samples was assessed by next-generation 16S rRNA gene sequencing. SCFAs were measured with GC-MS in faecal samples and after in vitro batch fermentations using arabinoxylan, resistant starch, pectin, and lactulose as substrates.Results: Among the 17 cirrhotic patients (mean age 58, eight males), six, nine and two were, respectively, Child-Pugh class A, B and C. Eleven patients were on oral antibiotics, 11 on lactulose and 13 on proton pump inhibitors. Cirrhotic patients showed marked differences in the composition and diversity of gut microbiome when compared to controls, that were more pronounced with increased severity. Stool samples from cirrhotic patients showed lower SCFAs content and reduced capacity to produce SCFAs in batch fermentations, with butyrate production being the most abnormal. These functional aberrancies were more pronounced with greater liver disease severity. Abundance of Ruminococcus faecis (in family Ruminococcaceae), Faecalicatena fissicatena and Fusicatenibacter saccharivorans (in family Lachnospiraceae) was positively correlated with the SCFAs production. Conclusion:Cirrhotic dysbiosis is associated with a decreased capacity to ferment non-digestible carbohydrates into SCFAs, especially into butyrate. These functional abnormalities are more pronounced as disease progresses. These results might inform the design of gut-targeted therapies for cirrhosis. K E Y W O R D Scirrhosis, microbiota, short-chain fatty acids

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Section: Discussionsupporting

confidence: 90%

Faecal microbiota from patients with cirrhosis has a low capacity to ferment non‐digestible carbohydrates into short‐chain fatty acids

Jin

Kalainy

Baskota

et al. 2019

Liver International

112

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“…However, the findings remain unconvincing to date. In some studies, rifaximin showed a major preventive effect [62,63], while in others, this effect could not be determined or was only minor [64,65]. Thus, while there is some evidence that some patients might benefit from rifaximin, a better selection and stratification of patients is required in the clinical setting.…”

Section: Poorly Absorbable Antibiotics As Gut-liver Axis Interventionmentioning

confidence: 99%

Gut-Liver Axis Links Portal Hypertension to Acute-on-Chronic Liver Failure

2018

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Acute-on-chronic liver failure (ACLF) is considered a distinct syndrome in patients with liver disease, with systemic inflammation playing a central role. Portal hypertension (PHT) is also aggravated by inflammation and may subsequently impact the course of ACLF. PHT is more than just an increase in portal pressure in the portal venous system; it aggravates the course of liver disease and, thus, also facilitates the development of acute decompensation and ACLF. A critical mechanistic link between PHT and ACLF might be the gut-liver axis, which is discussed in this review.

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“…Of note, a doubleblinded randomized control trial with 54 patients could not confirm these beneficial effects [29••]. Furthermore, Rifaximin seems to have only minor effects on bacterial composition, inflammation, and bacterial translocation [30]. Nevertheless, a combination of Rifaximin and Propanolol seem to be promising, probably due to additive effects of Rifaximin compared with NSBB monotherapy with decreased incidence of side effects due to lower NSBB dose than used normally as shown by an open-label randomized (2:1) trial in 73 patients [31].…”

Section: Current Concepts In the Clinicsmentioning

confidence: 99%

Novel Targets and Drug Development in Portal Hypertension

Schierwagen

Klein

Uschner

et al. 2019

Curr Hepatology Rep

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Purpose of the Review This review aims to introduce animal models of portal hypertension in which targets and drugs can be tested and presents current advances in the field of preclinical and early clinical settings. Recent Findings The interest in this field has risen in recent years and many promising targets and potential drugs have been tested in preclinical and early clinical studies. Most of these targets are intrahepatic and aim to decrease hepatic stellate cell activity, as this cell type mediates both fibrosis and portal hypertension. Summary Liver cirrhosis with portal hypertension is a global health burden due to their complications. Besides that, there are only a few therapies available, those are ineffective in a large part of the patients. Therefore, novel targets and treatment options are vastly needed.

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Rifaximin has minor effects on bacterial composition, inflammation, and bacterial translocation in cirrhosis: A randomized trial

Abstract: Four weeks of treatment with rifaximin had no impact on the inflammatory state and only minor effects on BT and intestinal bacterial composition in stable, decompensated cirrhosis (NCT01769040).

Cited by 58 publications

References 50 publications

Faecal microbiota from patients with cirrhosis has a low capacity to ferment non‐digestible carbohydrates into short‐chain fatty acids

Faecal microbiota from patients with cirrhosis has a low capacity to ferment non‐digestible carbohydrates into short‐chain fatty acids

Gut-Liver Axis Links Portal Hypertension to Acute-on-Chronic Liver Failure

Novel Targets and Drug Development in Portal Hypertension

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