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

Nina Kimer, Julie S Pedersen, Juliette Tavenier, Jeffrey E Christensen, Troels Malte Busk, Lise Hobolth, Aleksander Krag, Waleed Abu Al-Soud, Martin S Mortensen, Søren J. Sørensen, Søren Møller, Flemming Bendtsen, And members of the CoRif study group

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Resumé

Background and Aim: Decompensated cirrhosis is characterized by disturbed hemodynamics, immune dysfunction, and high risk of infections. Translocation of viable bacteria and bacterial products from the gut to the blood is considered a key driver in this process. Intestinal decontamination with rifaximin may reduce bacterial translocation (BT) and decrease inflammation. A randomized, placebo-controlled trial investigated the effects of rifaximin on inflammation and BT in decompensated cirrhosis. Methods: Fifty-four out-patients with cirrhosis and ascites were randomized, mean age 56 years (± 8.4), and model for end-stage liver disease score 12 (± 3.9). Patients received rifaximin 550-mg BD (n = 36) or placebo BD (n = 18). Blood and fecal (n = 15) sampling were conducted at baseline and after 4 weeks. Bacterial DNA in blood was determined by real-time qPCR 16S rRNA gene quantification. Bacterial composition in feces was analyzed by 16S rRNA gene sequencing. Results: Circulating markers of inflammation, including tumor necrosis factor alpha, interleukins 6, 10, and 18, stromal cell-derived factor 1-α, transforming growth factor β-1, and high sensitivity C-reactive protein, were unaltered by rifaximin treatment. Rifaximin altered abundance of bacterial taxa in blood marginally, only a decrease in Pseudomonadales was observed. In feces, rifaximin decreased bacterial richness, but effect on particular species was not observed. Subgroup analyses on patients with severely disturbed hemodynamics (n = 34) or activated lipopolysaccharide binding protein (n = 37) revealed no effect of rifaximin. Conclusion: 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).

OriginalsprogEngelsk
TidsskriftJournal of Gastroenterology and Hepatology
Vol/bind33
Udgave nummer1
Sider (fra-til)307–314
ISSN0815-9319
DOI
StatusUdgivet - jan. 2018

Fingeraftryk

Bacterial Translocation
rRNA Genes
Feces
Placebos
Bacterial DNA
Interleukin-18
Decontamination
Interleukin-10
Interleukin-6
Outpatients
Randomized Controlled Trials
Tumor Necrosis Factor-alpha

Citer dette

Kimer, N., Pedersen, J. S., Tavenier, J., Christensen, J. E., Busk, T. M., Hobolth, L., ... And members of the CoRif study group (2018). Rifaximin has minor effects on bacterial composition, inflammation and bacterial translocation in cirrhosis: A randomized trial. Journal of Gastroenterology and Hepatology, 33(1), 307–314. https://doi.org/10.1111/jgh.13852
Kimer, Nina ; Pedersen, Julie S ; Tavenier, Juliette ; Christensen, Jeffrey E ; Busk, Troels Malte ; Hobolth, Lise ; Krag, Aleksander ; Al-Soud, Waleed Abu ; Mortensen, Martin S ; Sørensen, Søren J. ; Møller, Søren ; Bendtsen, Flemming ; And members of the CoRif study group. / Rifaximin has minor effects on bacterial composition, inflammation and bacterial translocation in cirrhosis : A randomized trial. I: Journal of Gastroenterology and Hepatology. 2018 ; Bind 33, Nr. 1. s. 307–314.
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title = "Rifaximin has minor effects on bacterial composition, inflammation and bacterial translocation in cirrhosis: A randomized trial",
abstract = "Background and Aim: Decompensated cirrhosis is characterized by disturbed hemodynamics, immune dysfunction, and high risk of infections. Translocation of viable bacteria and bacterial products from the gut to the blood is considered a key driver in this process. Intestinal decontamination with rifaximin may reduce bacterial translocation (BT) and decrease inflammation. A randomized, placebo-controlled trial investigated the effects of rifaximin on inflammation and BT in decompensated cirrhosis. Methods: Fifty-four out-patients with cirrhosis and ascites were randomized, mean age 56 years (± 8.4), and model for end-stage liver disease score 12 (± 3.9). Patients received rifaximin 550-mg BD (n = 36) or placebo BD (n = 18). Blood and fecal (n = 15) sampling were conducted at baseline and after 4 weeks. Bacterial DNA in blood was determined by real-time qPCR 16S rRNA gene quantification. Bacterial composition in feces was analyzed by 16S rRNA gene sequencing. Results: Circulating markers of inflammation, including tumor necrosis factor alpha, interleukins 6, 10, and 18, stromal cell-derived factor 1-α, transforming growth factor β-1, and high sensitivity C-reactive protein, were unaltered by rifaximin treatment. Rifaximin altered abundance of bacterial taxa in blood marginally, only a decrease in Pseudomonadales was observed. In feces, rifaximin decreased bacterial richness, but effect on particular species was not observed. Subgroup analyses on patients with severely disturbed hemodynamics (n = 34) or activated lipopolysaccharide binding protein (n = 37) revealed no effect of rifaximin. Conclusion: 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).",
keywords = "Journal Article, portal hypertension, inflammation, bacterial translocation, cytokines, cirrhosis, Humans, Middle Aged, Liver Cirrhosis/drug therapy, Male, Intestines/microbiology, Anti-Infective Agents/administration & dosage, Bacterial Translocation/drug effects, DNA, Bacterial/blood, Rifamycins/administration & dosage, Feces/microbiology, Adult, Biomarkers/blood, Female, Aged, Rifaximin, Hemodynamics",
author = "Nina Kimer and Pedersen, {Julie S} and Juliette Tavenier and Christensen, {Jeffrey E} and Busk, {Troels Malte} and Lise Hobolth and Aleksander Krag and Al-Soud, {Waleed Abu} and Mortensen, {Martin S} and S{\o}rensen, {S{\o}ren J.} and S{\o}ren M{\o}ller and Flemming Bendtsen and {And members of the CoRif study group}",
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year = "2018",
month = "1",
doi = "10.1111/jgh.13852",
language = "English",
volume = "33",
pages = "307–314",
journal = "Journal of Gastroenterology and Hepatology",
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Kimer, N, Pedersen, JS, Tavenier, J, Christensen, JE, Busk, TM, Hobolth, L, Krag, A, Al-Soud, WA, Mortensen, MS, Sørensen, SJ, Møller, S, Bendtsen, F & And members of the CoRif study group 2018, 'Rifaximin has minor effects on bacterial composition, inflammation and bacterial translocation in cirrhosis: A randomized trial', Journal of Gastroenterology and Hepatology, bind 33, nr. 1, s. 307–314. https://doi.org/10.1111/jgh.13852

Rifaximin has minor effects on bacterial composition, inflammation and bacterial translocation in cirrhosis : A randomized trial. / Kimer, Nina; Pedersen, Julie S; Tavenier, Juliette; Christensen, Jeffrey E; Busk, Troels Malte; Hobolth, Lise; Krag, Aleksander; Al-Soud, Waleed Abu; Mortensen, Martin S; Sørensen, Søren J.; Møller, Søren; Bendtsen, Flemming; And members of the CoRif study group.

I: Journal of Gastroenterology and Hepatology, Bind 33, Nr. 1, 01.2018, s. 307–314.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Rifaximin has minor effects on bacterial composition, inflammation and bacterial translocation in cirrhosis

T2 - A randomized trial

AU - Kimer, Nina

AU - Pedersen, Julie S

AU - Tavenier, Juliette

AU - Christensen, Jeffrey E

AU - Busk, Troels Malte

AU - Hobolth, Lise

AU - Krag, Aleksander

AU - Al-Soud, Waleed Abu

AU - Mortensen, Martin S

AU - Sørensen, Søren J.

AU - Møller, Søren

AU - Bendtsen, Flemming

AU - And members of the CoRif study group

N1 - This article is protected by copyright. All rights reserved.

PY - 2018/1

Y1 - 2018/1

N2 - Background and Aim: Decompensated cirrhosis is characterized by disturbed hemodynamics, immune dysfunction, and high risk of infections. Translocation of viable bacteria and bacterial products from the gut to the blood is considered a key driver in this process. Intestinal decontamination with rifaximin may reduce bacterial translocation (BT) and decrease inflammation. A randomized, placebo-controlled trial investigated the effects of rifaximin on inflammation and BT in decompensated cirrhosis. Methods: Fifty-four out-patients with cirrhosis and ascites were randomized, mean age 56 years (± 8.4), and model for end-stage liver disease score 12 (± 3.9). Patients received rifaximin 550-mg BD (n = 36) or placebo BD (n = 18). Blood and fecal (n = 15) sampling were conducted at baseline and after 4 weeks. Bacterial DNA in blood was determined by real-time qPCR 16S rRNA gene quantification. Bacterial composition in feces was analyzed by 16S rRNA gene sequencing. Results: Circulating markers of inflammation, including tumor necrosis factor alpha, interleukins 6, 10, and 18, stromal cell-derived factor 1-α, transforming growth factor β-1, and high sensitivity C-reactive protein, were unaltered by rifaximin treatment. Rifaximin altered abundance of bacterial taxa in blood marginally, only a decrease in Pseudomonadales was observed. In feces, rifaximin decreased bacterial richness, but effect on particular species was not observed. Subgroup analyses on patients with severely disturbed hemodynamics (n = 34) or activated lipopolysaccharide binding protein (n = 37) revealed no effect of rifaximin. Conclusion: 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).

AB - Background and Aim: Decompensated cirrhosis is characterized by disturbed hemodynamics, immune dysfunction, and high risk of infections. Translocation of viable bacteria and bacterial products from the gut to the blood is considered a key driver in this process. Intestinal decontamination with rifaximin may reduce bacterial translocation (BT) and decrease inflammation. A randomized, placebo-controlled trial investigated the effects of rifaximin on inflammation and BT in decompensated cirrhosis. Methods: Fifty-four out-patients with cirrhosis and ascites were randomized, mean age 56 years (± 8.4), and model for end-stage liver disease score 12 (± 3.9). Patients received rifaximin 550-mg BD (n = 36) or placebo BD (n = 18). Blood and fecal (n = 15) sampling were conducted at baseline and after 4 weeks. Bacterial DNA in blood was determined by real-time qPCR 16S rRNA gene quantification. Bacterial composition in feces was analyzed by 16S rRNA gene sequencing. Results: Circulating markers of inflammation, including tumor necrosis factor alpha, interleukins 6, 10, and 18, stromal cell-derived factor 1-α, transforming growth factor β-1, and high sensitivity C-reactive protein, were unaltered by rifaximin treatment. Rifaximin altered abundance of bacterial taxa in blood marginally, only a decrease in Pseudomonadales was observed. In feces, rifaximin decreased bacterial richness, but effect on particular species was not observed. Subgroup analyses on patients with severely disturbed hemodynamics (n = 34) or activated lipopolysaccharide binding protein (n = 37) revealed no effect of rifaximin. Conclusion: 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).

KW - Journal Article

KW - portal hypertension

KW - inflammation

KW - bacterial translocation

KW - cytokines

KW - cirrhosis

KW - Humans

KW - Middle Aged

KW - Liver Cirrhosis/drug therapy

KW - Male

KW - Intestines/microbiology

KW - Anti-Infective Agents/administration & dosage

KW - Bacterial Translocation/drug effects

KW - DNA, Bacterial/blood

KW - Rifamycins/administration & dosage

KW - Feces/microbiology

KW - Adult

KW - Biomarkers/blood

KW - Female

KW - Aged

KW - Rifaximin

KW - Hemodynamics

U2 - 10.1111/jgh.13852

DO - 10.1111/jgh.13852

M3 - Journal article

C2 - 28671712

VL - 33

SP - 307

EP - 314

JO - Journal of Gastroenterology and Hepatology

JF - Journal of Gastroenterology and Hepatology

SN - 0815-9319

IS - 1

ER -