Anti-TNF Therapy Response in Patients with Ulcerative Colitis Is Associated with Colonic Antimicrobial Peptide Expression and Microbiota Composition

Magnusson, Maria K.; Strid, Hans; Sapnara, Maria; Lasson, Anders; Bajor, Antal; Ung, Kjell-Arne; Öhman, Lena

doi:10.1093/ecco-jcc/jjw051

Cited by 139 publications

(152 citation statements)

References 54 publications

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“…In particular, a lower dysbiosis index and higher amount of Faecalibacterium prausnitzii (Firmicutes) in responders compared with nonresponders at baseline was found. F. prausnitzii increased also during induction therapy in responders, indicating this species as a biomarker of treatment effectiveness . Consistent with several studies, F. prausnitzii contributes to the reduction of disease activity by producing butyrate, a SCFA, which inhibits the differentiation of Th17 cells and increases Treg cells …”

Section: Role Of Microbiota and Efficacy Of Therapeutics In Ibdsupporting

confidence: 85%

“…F. prausnitzii increased also during induction therapy in responders, indicating this species as a biomarker of treatment effectiveness. 57 Consistent with several studies, F. prausnitzii contributes to the reduction of disease activity by producing butyrate, a SCFA, which inhibits the differentiation of Th17 cells and increases Treg cells. 58 Recently, Yilmaz and collaborators published a similar paper focused on the role of microbiota composition in two independent long-term IBD cohorts (cohort 1 = 346 patients; cohort 2 = 156 patients).…”

Section: Intestinal Microbiota and Immunosuppresant Drugssupporting

confidence: 84%

“…Microbiota analysis of fecal samples derived by 56 patients with ulcerative colitis responsive or poorly responsive to anti‐TNF therapy (infliximab and adalimumab) revealed a separate profile of gut microbiota before treatment start . In particular, a lower dysbiosis index and higher amount of Faecalibacterium prausnitzii (Firmicutes) in responders compared with nonresponders at baseline was found.…”

Section: Role Of Microbiota and Efficacy Of Therapeutics In Ibdmentioning

confidence: 98%

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Emerging Insights on the Interaction Between Anticancer and Immunosuppressant Drugs and Intestinal Microbiota in Pediatric Patients

Lucafò

Franzin

Lagatolla

et al. 2019

Clinical Translational Sci

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Diseases affecting the immune system, such as inflammatory bowel disease (IBD), juvenile idiopathic arthritis (JIA), and acute lymphoblastic leukemia (ALL), are pathological conditions affecting the pediatric population and are often associated with alterations in the intestinal microbiota, such as a decrease in bacterial diversity. Growing evidence suggests that gut microbiota can interfere with chemotherapeutic and immunosuppressant drugs, used in the treatment of these diseases, reducing or facilitating drug efficacy. In particular, the effect of intestinal microflora through translocation, immunomodulation, metabolism, enzymatic degradation, and reduction of bacterial diversity seems to be one of the reasons of interindividual variability in the therapeutic response. Although the extent of the role of intestinal microflora in chemotherapy and immunosuppression remains still unresolved, current evidence on bacterial compositional shifts will be taken in consideration together with clinical response to drugs for a better and personalized therapy. This review is focused on the effect of the intestinal microbiota on the efficacy of pharmacological therapy of agents used to treat IBD, JIA, and ALL.

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Section: Role Of Microbiota and Efficacy Of Therapeutics In Ibdsupporting

confidence: 85%

Section: Intestinal Microbiota and Immunosuppresant Drugssupporting

confidence: 84%

Section: Role Of Microbiota and Efficacy Of Therapeutics In Ibdmentioning

confidence: 98%

See 1 more Smart Citation

Emerging Insights on the Interaction Between Anticancer and Immunosuppressant Drugs and Intestinal Microbiota in Pediatric Patients

Lucafò

Franzin

Lagatolla

et al. 2019

Clinical Translational Sci

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“…Week two concentrations of FC (AUC 0.82 and 0.61), faecal lactoferrin (AUC 0.84 and 0.80) and the dimeric M2 isoform of pyruvate kinase (AUC 0.88 and 0.78) could accurately predict both clinical and endoscopic response to IFX induction treatment . Finally, several authors have reported the association between low post‐induction FC levels and the decrease between baseline and post‐induction FC values and subsequent sustained response …”

Section: Resultsmentioning

confidence: 96%

Systematic review: predictive biomarkers of therapeutic response in inflammatory bowel disease—personalised medicine in its infancy

Stevens

Matheeuwsen

Lönnkvist

et al. 2018

Aliment Pharmacol Ther

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Summary Background Inflammatory bowel disease (IBD) is characterised by substantial heterogeneity in treatment response. With an expanding number of therapeutic agents, identifying optimal treatment at the patient level remains a major challenge. Aim To systematically review the available literature on predictive biomarkers of therapeutic response in IBD. Methods An electronic literature search was performed on 30 January 2018 using MEDLINE, EMBASE and the Cochrane Library. Retrospective, prospective, uncontrolled and controlled studies reporting on biomarkers predicting therapeutic response in paediatric and adult IBD populations were eligible for inclusion. The methodological quality of the included studies was assessed using the QUIPS tool. Due to anticipated heterogeneity and limited data, a qualitative, rather than quantitative, assessment was planned. Results Of the 10 638 citations identified, 92 articles met the inclusion criteria. Several potential DNA, mRNA and protein markers were evaluated as predictive biomarkers. Most studies focused on predicting response to anti‐TNF agents. Substantial between‐study heterogeneity was identified with respect to both the biomarkers studied and the definition of response. None of the included studies received a low risk of bias rating for all six domains. Currently, none of the biomarkers is sufficiently predictive for clinical use. Conclusions The search for predictive biomarkers is still in its infancy and current evidence is limited. Future research efforts should take into account the high patient heterogeneity within prospective trials with objective response assessment. Predictive models will most likely comprise a combination of several molecular markers from integrated omics‐levels and clinical characteristics.

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“…Recent evidence, however, shows that mucosal expression patterns of certain defensins can be used to predict the potential efficacy of anti-TNF treatment. More specifically, it was found that a positive response to anti-TNF therapy was associated with increased mucosal expression of HD5 (Magnusson et al, 2016). …”

Section: Clinical Applicationsmentioning

confidence: 99%

Guardians of the Gut: Enteric Defensins

2017

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Enteric defensins likely play a key role in the management of the human microbiome throughout development. The functional and mechanistic diversity of defensins is much greater than was initially thought. Defensin expression and overall Paneth cell physiology likely plays a key role in the development of colitis and other inflammatory or dysbiotic diseases of the gut. As our understanding of enteric defensins grows, their potential as tools of clinical intervention becomes more apparent. In this review, we focus on the function and activity of Paneth Cell defensins and highlight their role in disease.

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Anti-TNF Therapy Response in Patients with Ulcerative Colitis Is Associated with Colonic Antimicrobial Peptide Expression and Microbiota Composition

Abstract: Anti-TNF therapy responders and non-responders display distinctly separate patterns of mucosal AMP expression and gut microbiota before treatment start. This indicates that intestinal antimicrobial/microbial composition can influence treatment outcome.

Cited by 139 publications

References 54 publications

Emerging Insights on the Interaction Between Anticancer and Immunosuppressant Drugs and Intestinal Microbiota in Pediatric Patients

Emerging Insights on the Interaction Between Anticancer and Immunosuppressant Drugs and Intestinal Microbiota in Pediatric Patients

Systematic review: predictive biomarkers of therapeutic response in inflammatory bowel disease—personalised medicine in its infancy

Guardians of the Gut: Enteric Defensins

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