Alterations in the Intestinal Microbiome (Dysbiosis) as a Predictor of Relapse After Infliximab Withdrawal in Crohnʼs Disease

Rajca, Sylvie; Grondin, Virginie; Louis, Édouard; Vernier‐Massouille, Gwénola; Grimaud, Jean-Charle; Bouhnik, Yoram; Laharie, David; Dupas, Jean‐Louis; Pillant, Hélène; Picon, Laurence; Veyrac, M.; Flamant, Mathurin; Savoye, Guillaume; Jian, Raymond; Devos, M.; Paintaud, Gilles; Piver, Éric; Allez, Matthieu; Mary, Jean Yves; Sokol, Harry; Colombel, Jean–Frédéric; Seksik, Philippe

doi:10.1097/mib.0000000000000036

Cited by 157 publications

(168 citation statements)

References 36 publications

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“…29 Thus, the finding of sibling dysbiosis including reduced abundance of F. prausnitzii is robust, having been demonstrated in analyses using different techniques (454 pyrosequencing and qPCR), and in both mucosa-associated and faecal microbiota There has been intense speculation regarding the role of F. prausnitzii in CD pathogenesis as it is the only microbial factor shown to be predictive of the natural history of CD 30 and of the response to treatment. 31 It may be speculated that loss of F. prausnitzii could result in the loss of key functions that contribute to gut health, for example the production of short-chain fatty acids, in particular butyrate, 32 and NFkB-mediated effects. 33 However, we would be cautious in constructing pathogenic hypotheses based on the functions of this particular species, rather interpreting these data as implicating that loss of F. prausnitzii is a sensitive indicator of a broader change in the gut microbiota.…”

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confidence: 99%

The gut microbiota of siblings offers insights into microbial pathogenesis of inflammatory bowel disease

et al. 2017

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Siblings of patients with Crohn's disease (CD) have elevated risk of developing CD and display aspects of disease phenotype, including faecal dysbiosis. In our recent article we have used 16S rRNA gene targeted high-throughput sequencing to comprehensively characterize the mucosal microbiota in healthy siblings of CD patients, and determine the influence of genotypic and phenotypic factors on the gut microbiota (dysbiosis). We have demonstrated that the core microbiota of both patients with CD and healthy siblings is significantly less diverse than controls. Faecalibacterium prausnitzii contributed most to core metacommunity dissimilarity between both patients and controls and between siblings and controls. Phenotype/genotype markers of CD risk significantly influenced microbiota variation between and within groups, of which genotype had the largest effect. Individuals with elevated CD-risk display mucosal dysbiosis characterized by reduced diversity of core microbiota and lower abundance of F. prausnitzii. The presence of this dysbiosis in healthy people at-risk of CD implicates microbiological processes in CD pathogenesis.

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confidence: 99%

The gut microbiota of siblings offers insights into microbial pathogenesis of inflammatory bowel disease

et al. 2017

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“…Such understanding will in turn lead us to robust approaches focussed on when and how to influence the microbiome by probiotic supplementation or by nutrient or antimicrobial means. More and more studies are exploring how the microbiome can predict outcomes, including following fecal transplant, probiotic, dietary, and drug treatment (David et al 2014;Kwak et al 2014;Rajca et al 2014;Seekatz et al 2014). Such work will require carefully designed studies with high quality clinical documentation, and samples that are processed using some of the methods described herein.…”

Section: Discussionmentioning

confidence: 99%

Compositional analysis: a valid approach to analyze microbiome high-throughput sequencing data

2016

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Abstract:A workshop held at the 2015 annual meeting of the Canadian Society of Microbiologists highlighted compositional data analysis methods and the importance of exploratory data analysis for the analysis of microbiome data sets generated by high-throughput DNA sequencing. A summary of the content of that workshop, a review of new methods of analysis, and information on the importance of careful analyses are presented herein. The workshop focussed on explaining the rationale behind the use of compositional data analysis, and a demonstration of these methods for the examination of 2 microbiome data sets. A clear understanding of bioinformatics methodologies and the type of data being analyzed is essential, given the growing number of studies uncovering the critical role of the microbiome in health and disease and the need to understand alterations to its composition and function following intervention with fecal transplant, probiotics, diet, and pharmaceutical agents.

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“…Th ese studies are still in their infancy, but data suggest that Faecalibacterium prausnitzii abundance may be associated with disease recurrence in CD ( 30 ). In addition, results from a pediatric inception cohort suggest that increased Enterobacteriaceae, Pasturellaceae, Veillonellaceae, and Fusobacteriaceae together with decreased Erysipelotrichales, Bacteroidales, and Clostridiales were not only associated with CD but also with disease severity ( 31 ).…”

Section: Th E Microbiome In CDmentioning

confidence: 99%

Using Markers in IBD to Predict Disease and Treatment Outcomes: Rationale and a Review of Current Status

Lichtenstein¹,

McGovern²

2016

Am J Gastroenterol Suppl

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Biomarkers, radiology fi ndings, and endoscopic studies, together with clinical assessment of patients with infl ammatory bowel disease, can be used to help determine prognosis, assess disease activity, and increasingly to inform treatment decision-making. This article reviews the current "state of the science" regarding the multitude of different tests that can be performed and how these can be used in the clinic to guide management. Initially, when patients present with symptoms suggestive of infl ammatory bowel disease (IBD), standard endoscopic studies and radiographic studies should be performed and the use of combinations of serologic and fecal markers may additionally be incorporated into patient assessment. Once the patient has a formal diagnosis, prognosis should be assessed and serologic evaluation may be used, but in conjunction with endoscopic and radiographic studies. Within the context of evaluating clinical predictors of disease (e.g., disease location, nutritional status, routine blood tests), early mucosal healing has been linked to better outcomes, and failure to heal the mucosa has been associated with poorer outcomes. Evaluation of response to therapy can be approximated with the use of biomarkers (e.g., C-reactive protein, fecal calprotectin, lactoferrin), and therapeutic drug monitoring has enabled us to assess levels of drug metabolites, drug levels, and antidrug antibodies to guide the ongoing management. Although there is not yet universal adoption of biomarkers to determine treatment choices (e.g., the use of anti-tumor necrosis factor therapy), biomarkers have enabled us to "fi ne tune" treatment of some patients with IBD. Establishing mechanisms of communicating these risks/benefi ts to patients will be a considerable challenge and remains a priority area of research.

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Alterations in the Intestinal Microbiome (Dysbiosis) as a Predictor of Relapse After Infliximab Withdrawal in Crohnʼs Disease

Cited by 157 publications

References 36 publications

The gut microbiota of siblings offers insights into microbial pathogenesis of inflammatory bowel disease

The gut microbiota of siblings offers insights into microbial pathogenesis of inflammatory bowel disease

Compositional analysis: a valid approach to analyze microbiome high-throughput sequencing data

Using Markers in IBD to Predict Disease and Treatment Outcomes: Rationale and a Review of Current Status

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