RETRACTED ARTICLE: Rifaximin alters gut microbiota profile, but does not affect systemic inflammation - a randomized controlled trial in common variable immunodeficiency

Jørgensen, Silje Fjellgård; Macpherson, Magnhild Eide; Bjørnetrø, Tonje; Holm, Kristian; Kummen, Martin; Rashidi, Azita; Michelsen, Annika; Lekva, Tove; Halvorsen, Bente; Trøseid, Marius; Mollnes, Tom Eirik; Berge, Rolf K.; Yndestad, Arne; Ueland, Thor; Karlsen, Tom H.; Aukrust, Pål; Hov, Johannes Espolin Roksund; Fevang, Børre

doi:10.1038/s41598-018-35367-7

Cited by 40 publications

(52 citation statements)

References 28 publications

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“…Additionally, variations in global bacterial communities resulting from rifaximin instillation were assessed by 16S sequencing. All rifaximin formulations caused less bacterial disruption of gut microbiota populations in the chemostat models than observed with other antibiotics, [19-21, 24] which agrees with previous rifaximin studies [2, 11, 12, 15, 35]. Rifaximin formulations α, β and κ caused similar alterations in the gut microbiota, with some obligate ( Bacteroides spp.…”

Section: Discussionsupporting

confidence: 88%

“…This is similar to the variations of the Bacteroides genus shown by the 16S sequencing data, particularly for models A and B. In the literature, Bacteroides abundance has been reported as unchanged [15] or increased [10, 12] after rifaximin dosing, however no testing was performed in those studies during antibiotic dosing. We observed that genus Bacteroides populations were affected by rifaximin but recovered within few days, showing similar results pre and post-antibiotic period.…”

Section: Discussionsupporting

confidence: 80%

“…A decline in colonic bacterial diversity has been reported during rifaximin use, [10-12] with bacterial populations recovering following antibiotic treatment. However, studies have mostly investigated variations in faecal samples from particular patient groups with gastrointestinal or immune diseases [10, 12-14], who may already have a depleted gut microbiota, therefore giving only a partial insight into the effects of rifaximin on the gut microbiome. Sampling during in vivo studies is usually done via faecal microbiota profiling which limits the time points available for analysis and does not always reflect disruptive effects in the colon and, providing only partial data on the antibiotic effects in the intestinal microbiome.…”

Section: Introductionmentioning

confidence: 99%

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Profiling the effects of rifaximin on the healthy human colonic microbiota using a chemostat model

Buckley

Ewin

et al. 2019

Preprint

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27Rifaximin is a low solubility antibiotic with activity against a wide range of bacterial 28 pathogens. It accumulates in the intestine and is suitable for prolonged use. Three chemostat 29 models (A, B and C) were used to investigate the effects of three rifaximin formulations (α, β 30 and κ, respectively) on the gut microbiome. Bacterial populations were monitored by 31 bacterial culture and 16S rRNA gene amplicon (16S) sequencing. Limited disruption of 32 bacterial populations was observed for rifaximin α, β and κ. All formulations caused declines 33 in total spores (~2 log10 cfu ml -1 ), Enterococcus spp. (~2 log10 cfu ml -1 in models A and C, 34 and ~1 log10 cfu ml -1 in model B), and Bacteroides spp. populations (~3 log10 cfu ml -1 in 35 models A and C, and ~4 log10 cfu ml -1 in model B). Bacterial populations fully recovered 36 during antibiotic dosing in model C, and before the end of the experiment in models A and B. 37According to the taxonomic analysis, prior to rifaximin exposure, Bifidobacteriaceae, 38 Ruminococcaceae, Acidaminococcaceae, Lachnospiraceae and Rikenellaceae families 39 represented >92% of the total relative abundance, in all models. Within these families, 15 40 bacterial genera represented >99% of the overall relative abundance. Overall, the 16S 41 sequencing and culture data showed similar variations in the bacterial populations studied. 42 Among the three formulations, rifaximin κ appeared to have the least disruptive effect on the 43 colonic microbiota, with culture populations showing recovery in a shorter period and the 44 taxonomic analysis revealing the least global variation in relative abundance of prevalent 45 groups. 46 Rifaximin is an oral antibiotic with low solubility and in vitro bactericidal activity reported 48 against a wide range of facultative and obligate aerobes such as, Escherichia coli, 49 Clostridioides difficile, Staphylococcus spp., and Streptococcus spp., among others [1-3]. Its 50 chemical structure is a derivative of rifamycin and contains a supplementary pyridoimidazole 51 ring that limits the absorption of the drug in the intestine [3]. Rifaximin is considered suitable 52 for prolonged use due to its poor solubility and subsequent low systemic side effects [2, 4]. It 53 is FDA approved for the treatment of traveller's diarrhoea and irritable bowel syndrome 54 (IBS), and has been shown effective in clinical trials as therapeutic agent in small bowel 55 bacterial overgrowth, inflammatory bowel disease and in C. difficile infection [2, 4-8]. 56 Rifaximin is also used to reduce the risk of hepatic encephalopathy in patients with impaired 57 liver function and portosystemic shunting [9]. 58 A decline in colonic bacterial diversity has been reported during rifaximin use, [10-12] with 59 bacterial populations recovering following antibiotic treatment. However, studies have 60 mostly investigated variations in faecal samples from particular patient groups with 61 gastrointestinal or immune diseases [10, 12-14], who may already have a depleted gut 62 microb...

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Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

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Profiling the effects of rifaximin on the healthy human colonic microbiota using a chemostat model

Buckley

Ewin

et al. 2019

Preprint

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“…So far, only few investigations of the CVID microbiome have been published (21)(22)(23)(24)(25)(26). The diversity of microbiota within one individual or its sample (alpha diversity) and the differences in distribution of different microbiota among samples or individuals (beta diversity) can be described.…”

Section: Introductionmentioning

confidence: 99%

Altered Microbiota, Impaired Quality of Life, Malabsorption, Infection, and Inflammation in CVID Patients With Diarrhoea

Schewick

Nöltner²,

Abel

et al. 2020

Front. Immunol.

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Background: Diarrhoea is the commonest gastrointestinal symptom in patients with common variable immunodeficiency (CVID). Objective: The aim of this study was to describe the prevalence and clinical presentation of chronic and recurrent diarrhoea in the Royal-Free-Hospital (RFH) London CVID cohort, including symptoms, infections, level of inflammation, and microbial diversity. Methods: A cross-sectional study of adult CVID patients (139 out of 172 diagnosed with CVID completed the screening questionnaire). Those with diarrhoea ≥6 days/month had stool and blood samples analysed and completed the short Inflammatory Bowel Disease Questionnaire (sIBDQ). BMI, spleen-size, lymphocytes and gut-microbial diversity were compared. Due to logistical and clinical restraints, not all patients could be analysed on all measures. Results: 46/139 (33.1%) patients had current significant diarrhoea. In patients with past or present diarrhoea, BMI was lower (median 23.7 vs. 26, p = 0.005), malabsorption more common (57.97 vs. 35.71%, p = 0.011). CD4+ lymphocytes were higher in patients with diarrhoea (p = 0.028; n = 138), but CD4+ naïve lymphocytes were significantly higher in non-diarrhoea patients (p = 0.009, N = 28). Nine patients had confirmed or probable current gastrointestinal infections. Calprotectin was >60 µg/g in 13/29 with significant diarrhoea including 9 without infection. SIBDQ revealed a low median score of 4.74. Microbial alpha diversity was significantly lower in CVID patients compared to healthy household controls. There was no significant difference in alpha diversity in relation to antibiotic intake during the 6 weeks prior to providing samples. Conclusion: Patients with CVID and significant diarrhoea had infections, raised calprotectin, malabsorption, a lower BMI, an impaired quality of life (comparable van Schewick et al. Longstanding Diarrhoea in CVID to active IBD), and they differed from non-diarrhoea patients in their lymphocyte phenotyping. Furthermore, microbial diversity was altered. These findings strongly imply that there may be an inflammatory nature and a systemic predisposition to diarrhoea in CVID, which necessitates further investigation.

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“…In fact, it does not affect the overall microbiome biodiversity [104], inducing selective depletion of a few taxa (Streptococcus and Veillonella) that may play a key role in the regulation of inflammation and mucosal barrier functionality [105]. These microbiome alterations do not affect systemic inflammation, but have relevance only for the gastrointestinal district [106]. Thus, the beneficial effects of rifaximin administration in SUDD and recurrent acute diverticulitis may depend on targeted antibiotic effects on the intestinal microbial communities, probably also inducing shifts in the functionality of bacteria [19,21,107].…”

Section: Rifaximinmentioning

confidence: 99%

Diverticular Disease: a Gut Microbiota Perspective

Ticinesi

Nouvenne

Corrente

et al. 2019

JGLD

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Gut microbiota composition and functionality are involved in the pathophysiology of several intestinal andextraintestinal diseases, and are increasingly considered a modulator of local and systemic inflammation.However, the involvement of gut microbiota in diverticulosis and in diverticular disease is still poorlyinvestigated. In this review, we critically analyze the existing evidence on the fecal and mucosa-associatedmicrobiota composition and functionality across different stages of diverticular disease. We also explorethe influence of risk factors for diverticulosis on gut microbiota composition, and speculate on the possiblerelevance of these associations for the pathogenesis of diverticula. We overview the current treatments ofdiverticular disease targeting the intestinal microbiome, highlighting the current areas of uncertainty andthe need for future studies. Although no conclusive remarks on the relationship between microbiota anddiverticular disease can be made, preliminary data suggest that abdominal symptoms are associated withreduced representation of taxa with a possible anti-inflammatory effect, such as Clostridium cluster IV, andovergrowth of Enterobacteriaceae, Bifidobacteria and Akkermansia. The role of the microbiota in the earlystages of the disease is still very uncertain. Future studies should help to disentangle the role of the microbiomein the pathogenesis of diverticular disease and its progression towards more severe forms.

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RETRACTED ARTICLE: Rifaximin alters gut microbiota profile, but does not affect systemic inflammation - a randomized controlled trial in common variable immunodeficiency

Cited by 40 publications

References 28 publications

Profiling the effects of rifaximin on the healthy human colonic microbiota using a chemostat model

Profiling the effects of rifaximin on the healthy human colonic microbiota using a chemostat model

Altered Microbiota, Impaired Quality of Life, Malabsorption, Infection, and Inflammation in CVID Patients With Diarrhoea

Diverticular Disease: a Gut Microbiota Perspective

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