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Project #13458
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#13458 : Assessing the role of gut microbiota in spondyloarthritis patients and impact of anti-TNF treament on its composition
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Name of Applicant : Corinne RICHARD-MICELI
Date of application : 09-08-2019
Unit : Immunoregulation
Location : Metchnikoff 5eme étage 22
Phone : 0612929487
@ Mail : corinne.miceli@aphp.fr

Project context and summary :

Our hypothesis is that gut microbiota could define predictive markers of response and tolerance to biologics. A. Preliminary results: gut bacteria predicting response to TNF blockers. A proof-of-concept study has been performed on 58 patients who were recruited according to the following criteria: active disease despite NSAIDs intake; no history of inflammatory bowel disease; no antibiotics intake within 3 months prior recruitment. Bacterial 16S rRNA gene sequencing region was performed on stools samples before and after TNF-blocker treatment. Diversity metrics and custom LefSe were used to explore the relationship between the composition of the intestinal microbiota and the efficacy of TNF-blockers. A lower alpha diversity at baseline was unexpectedly associated with better treatment response, HLA-B27 genotype and smoking behavior. Meanwhile, beta diversity was associated with smoking behavior and HLA-B27 genotype before and after treatment. Beta diversity at baseline was associated with the BASDAI index after treatment, and the response to the treatment. These results indicate a potential regulatory role for the gut microbiota on the underlying mechanisms involved in the response to TNF-blockers. Moreover, a LefSe-like approach identified 6 bacterial species as potential biomarkers for the treatment response, despite the absence of global changes (beta diversity) in the microbiota composition following a 3-month TNF-blockers intake. B. Current project: ITS2 fungal rDNA sequencing analyses In order to establish a causal link between host-microbe interactions and clinical efficacy of anti-TNF, we expect the following research endpoints from our experimental and translation approach (cohorts/clinical trials): 1. Defining the impact of anti-TNF on fungal microbiota and on the relative representation of fungal/bacterial components 2. Defining correlations between gut fungal composition and clinical outcome, with the aim of identifying stool microbial fingerprint of durable responses and/or primary resistance to anti-TNFα in SpA patients. The analyses will be performed on the same 58 SpA patients that were previously analyzed for their 16S bacterial component. These patients perfectly described regarding their disease characteristics, demographics, ongoing treatments, response to anti-TNF after a 3-month treatment period.


Related team publications :
THE RESPONSE TO TNF-BLOCKERS TREATMENT OF SPA PATIENTS IS INFLUENCED BY THE INTERPLAY BETWEEN HLA-B27 AND GUT MICROBIOTA COMPOSITION AT BASELINE. Manuscript in redaction (16S part)
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Project Manager : amine.ghozlane@pasteur.fr
Status : Pending


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