Quantitative Microbiota Profiling for Inflammation Diagnosis

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Solution Overview

Problem

Current methods for diagnosing and managing inflammation-associated disorders such as inflammatory bowel disease, primary sclerosing cholangitis, and multiple sclerosis lack sensitivity and specificity, particularly in detecting gut microbiota dysbiosis, which is linked to inflammation severity.

Innovation Solution

A diagnostic method utilizing quantitative microbiota profiling (QMP) that combines flow cytometry and metagenomics to quantify bacterial loads and determine the relative abundance of specific genera like Bacteroides and Faecalibacterium in stool samples, identifying a Bacteroides2 enterotype associated with inflammation, allowing for the detection and potential treatment of inflammatory disorders.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional microbiota analysis methods are used, then the analysis is simpler and faster, but the measurement precision and reliability of detecting dysbiosis is insufficient

Engineering Contradiction:

Improvedetection accuracy of dysbiosisVSAvoidcomplexity of microbiota profiling method

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent combines flow cytometry and metagenomics into a unified quantitative microbiota profiling system. Flow cytometry provides total bacterial load measurement while metagenomics provides compositional data, and their integration enables precise detection of dysbiosis by correlating absolute cell counts with relative abundance data, resolving the technical contradiction between measurement precision and method complexity.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The patent transitions from relative abundance measurements to absolute quantification by measuring total bacterial load through flow cytometry. This parameter change from relative to absolute measurements fundamentally improves the precision of dysbiosis detection, as it allows for accurate assessment of bacterial population changes rather than just compositional shifts.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If quantitative microbiota profiling combining flow cytometry and metagenomics is used, then the detection reliability is improved, but the device complexity and operational complexity increase

Engineering Contradiction:

Improvereliability of inflammation diagnosisVSAvoidease of microbiota analysis operation

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The patent performs preliminary quantification of total bacterial load using flow cytometry before conducting metagenomic analysis. This preliminary action establishes a baseline for absolute abundance that guides subsequent relative abundance interpretation, improving diagnostic reliability while structuring the operational workflow to manage complexity systematically.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent uses total bacterial load measurement as an intermediary parameter that bridges flow cytometry and metagenomics data. This intermediary enables the correlation of absolute cell counts with relative abundance profiles, providing a reliable diagnostic marker for inflammation-associated disorders while integrating two complex methodologies through a common quantitative framework.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Quantity of substance

If relative microbiota composition analysis is used, then the method is simpler to implement, but the ability to quantify complex microbial ecosystems and detect dysbiosis is insufficient

Engineering Contradiction:

Improvequantification of bacterial loadVSAvoidcomplexity of quantification method

Core Design Contradiction:

Quantity of substanceVSDevice complexity

Solution Approach 1:

The patent replaces traditional culturing-based quantification methods with flow cytometry, which uses optical detection principles to count and characterize bacterial cells. This substitution enables accurate measurement of total bacterial load and cell size distribution without requiring bacterial cultivation, thereby achieving precise quantification while managing technical complexity through non-culturing-based detection.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

This approach provides a non-invasive, reliable method for diagnosing inflammatory disorders by correlating bacterial load and composition with inflammatory markers, enabling targeted anti-inflammatory therapy to reduce inflammation severity.

Implementation Method 1

combining microbial load assessments by flow cytometry and metagenomics

Methodology Applied

Scientific EffectFlow cytometry:

Implementation Method 2

16S rRNA gene sequencing was performed with Illumina MiSeq technology

Methodology Applied

Scientific Effect16S rRNA gene sequencing:

Data Source

PatentUS11649508B2Inflammation associated, low cell count enterotype

Publication Date: 2023.05.16 VLAAMS INTERUNIVERSITAIR INST VOOR BIOTECHNOLOGIE VZW

AI summary

The present invention relates to the field of inflammation-associated disorders or conditions, more particularly to gut inflammation. Provided herein are means and methods to diagnose and treat or reduce the severity of inflammation-associated disorders or conditions in a subject in need thereof.