Methods for the diagnosis and treatment of inflammatory bowel disease
Inventors
STINTZI, Alain • Mack, David R. • FIGEYS, Joseph Michel Daniel • Mottawea, Walid Abdelfattah Elsayed • Abujamel, Turki Saleh A. • CHIANG, Cheng-kang
Assignees
Publication Number
US-11104965-B2
Publication Date
2021-08-31
Expiration Date
2034-03-14
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Abstract
There is provided methods and compositions to diagnose, classify and treat inflammatory bowel disease including ulcerative colitis and Crohn's disease by measuring the levels of certain bacterial taxa and proteins collected from the gut.
Core Innovation
The invention provides methods and compositions for the diagnosis, classification, and treatment of inflammatory bowel disease (IBD), specifically including ulcerative colitis (UC) and Crohn's disease (CD), by measuring levels of specific bacterial taxa and proteins collected from the gut microbiota. The methods enable distinguishing IBD patients from healthy individuals and further classifying patients as having UC or CD based on differences in the gut microbiota composition and protein expression.
The problem addressed is the difficulty in accurately diagnosing and differentiating between UC and CD due to the lack of reliable biomarkers. Conventional diagnostic tools such as endoscopy have limited accuracy, and existing serological markers fail to differentiate between subtypes effectively. Additionally, treatment responses differ considerably between CD and UC patients, emphasizing the need for improved diagnostic and prognostic assays to guide appropriate therapies.
The invention solves this problem by identifying diagnostic markers including increased levels of proteobacteria, H2S producing bacteria such as Atopobium parvulum, and decreased abundance of butyrate producing bacteria in gut microbiota samples from patients with IBD compared to healthy controls. It also identifies altered levels of mitochondrial proteins involved in H2S detoxification as markers of disease severity. The use of such bacterial and protein markers facilitates early and accurate diagnosis, classification of IBD subtypes, assessment of disease severity, and monitoring of treatment efficacy.
Claims Coverage
The patent contains one independent claim focused on a method of treating IBD, Crohn's disease, or ulcerative colitis based on detection of a specific bacterial marker and administration of particular compounds.
Method of diagnosing IBD based on Atopobium parvulum levels
Detecting an increased level of Atopobium parvulum in a gut microbiota sample of a human subject relative to a predetermined level to diagnose the subject as having IBD, Crohn's disease, or ulcerative colitis.
Treatment based on bacterial detection
Administering one or more of immunomodulators, aminocalycylates, anti-integrins, anti-cytokines, steroids, corticosteroids, antibiotics, anti-TNFa, and bismuth to a patient diagnosed through detection of increased A. parvulum.
Use of quantitative polymerase chain reaction for detection
Employing quantitative PCR to detect A. parvulum in the gut microbiota sample.
Primer sequences for specific detection of A. parvulum
Using a forward primer (SEQ ID 1) and reverse primer (SEQ ID 2) specific for A. parvulum in quantitative PCR assays.
Additional biomarkers for confirming presence of A. parvulum
Measuring levels of cytokines and/or GALT foci, where elevated cytokine levels or GALT foci above normal indicate presence of A. parvulum and disease; cytokines include CxcH, IL17a, IL-12, and IL-1β.
The claims revolve around a diagnostic method using detection of an increased level of the bacterium Atopobium parvulum coupled with administration of targeted treatments, with specific detection enhanced by quantitative PCR using designated primers and corroborated by host biomarkers such as cytokines and GALT foci.
Stated Advantages
Provides a method for distinguishing between patients with ulcerative colitis and Crohn's disease.
Allows for more accurate and early diagnosis of IBD and its subtypes using gut microbiota and protein markers.
Enables assessment of disease severity and progression through bacterial taxa and host protein profiling.
Supports personalized treatment selection and optimization based on microbial biomarker levels.
Offers a noninvasive assay using gut mucus or stool samples improving over current invasive diagnostics.
Documented Applications
Diagnosis of inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), by analyzing gut microbiota and protein biomarkers.
Classification of gut samples to differentiate IBD subtypes (UC versus CD) based on bacterial taxa and protein profiles.
Assessment of disease severity and progression in CD using levels of specific bacterial taxa and mitochondrial proteins.
Treatment of IBD guided by detection of bacterial levels, including administration of immunomodulators, antibiotics, anti-TNFα, bismuth, and other compounds.
Use of quantitative PCR assays with specific primers for detecting Atopobium parvulum to inform diagnosis and treatment.
Use of cytokine and GALT foci levels as biomarkers correlating with presence of A. parvulum and disease status.
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