Fecal Microbiota Homogenization for Bacterial Viability

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Solution Overview

Problem

Current fecal microbiota transplantation methods lack reproducibility and homogeneity, leading to variability in bacterial diversity and viability, which is crucial for effective treatment of intestinal dysbiosis and associated pathologies.

Innovation Solution

A method involving the collection of fecal microbiota samples from preselected donors, followed by oxygen-tight storage, qualitative control, addition of a cryoprotective agent, filtration, pooling, and homogenization to create a homogeneous mixture with high bacterial diversity and viability, ensuring intra-batch and inter-batch homogeneity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If fecal microbiota samples are collected and processed using current empirical methods, then the procedure is simple and quick, but the bacterial diversity and viability are insufficient and variable

Engineering Contradiction:
Improvebacterial diversity and viabilityVSAvoidprocessing procedure complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The processing procedure is divided into distinct sequential steps: sample collection, qualitative control, addition of cryoprotective agent, filtration, pooling, and homogenization. Each step serves a specific function to preserve bacterial diversity and viability, transforming the empirical one-step approach into a systematic multi-stage process that ensures reliability.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The method implements preliminary actions by collecting samples from preselected donors meeting specific criteria before processing, and by adding cryoprotective agents immediately within 5 minutes of collection. These preliminary measures prevent degradation of bacterial diversity and viability before the main processing occurs.

Inventive Principle:
Principle #10Preliminary action

2Manufacturing precision

If fecal microbiota samples are processed without strict quality control, then the procedure is faster and simpler, but homogeneity between batches varies significantly

Engineering Contradiction:
Improvehomogeneity between batchesVSAvoidprocessing time
Core Design Contradiction:
Manufacturing precisionVSLoss of time

Solution Approach 1:

The method incorporates qualitative control at multiple stages with defined exclusion criteria for samples that do not meet standards. This feedback mechanism ensures only qualifying samples proceed to pooling and homogenization, guaranteeing batch homogeneity while maintaining efficient processing by avoiding rework of不合格 samples.

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The method standardizes processing parameters including the addition of cryoprotective agents within 5 minutes of collection, specific filtration steps, and controlled homogenization. These standardized parameter changes ensure consistent results across batches while maintaining reasonable processing times through optimized parameters.

Inventive Principle:
Principle #35Parameter changes

3Reliability

If fecal microbiota samples are not preserved with cryoprotective agents, then the processing is simpler and faster, but bacterial viability decreases significantly

Engineering Contradiction:
Improvebacterial viabilityVSAvoidprocessing simplicity
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

Cryoprotective agents are added within 5 minutes of sample collection as a preliminary action before filtration and pooling. This timing is critical to preserve bacterial viability while minimizing the added complexity, as the agent is simply mixed with the sample in a controlled manner.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

Cryoprotective agents act as intermediaries between the fecal sample and the final processed product. These agents protect the bacteria during processing and storage, maintaining viability without requiring complex preservation systems, thus balancing reliability with ease of manufacture.

Inventive Principle:
Principle #24Intermediary (Mediator)

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

The method produces fecal microbiota samples with high bacterial diversity and viability, ensuring consistent treatment efficacy for conditions like graft-versus-host disease, Clostridium difficile infection, and inflammatory bowel disease, by maintaining bacterial stability and homogeneity throughout the process.

Implementation Method 1

adding to each of the samples retained after control step c) an aqueous saline solution comprising at least one cryoprotective agent and/or a bulking agent

Methodology Applied
Scientific EffectCryoprotection:

Implementation Method 2

filtering the samples obtained at the end of step d) to form a series of inocula

Methodology Applied
Scientific EffectFiltration: Filter (physical)

Implementation Method 3

homogenizing said mixture obtained in step f), in particular by manual stirring or using a stirring device

Methodology Applied
Scientific EffectHomogenization:

Data Source

PatentEP3762001B1Stool collecting procedure and process of preparation of sample for fecal transplantation
Publication Date: 2024.08.21 MAAT PHARMA
  • EP3762001B1 patent drawingFigure 1
  • EP3762001B1 patent drawingFigure 2
  • EP3762001B1 patent drawingFigure 3

AI summary

The present invention relates to a method for preparing a homogeneous mixture of fecal microbiota from at least two preselected donors. The homogeneous mixture of fecal microbiota thus obtained has a bacterial diversity and an increased viability. The homogeneous mixture of fecal microbiota may be used for treating intestinal dysbiosis and for treating pathologies associated with such dysbiosis.