Butyrate-Producing Bacteria for C. difficile Prevention

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Solution Overview

Problem

Clostridium difficile infections are exacerbated by antibiotic-induced gut dysbiosis, leading to bacterial overgrowth and intestinal inflammation, with current treatments involving further antibiotic therapy, which is ineffective in preventing recurrence.

Innovation Solution

Supplementation with Faecalibacterium prausnitzii, a butyrate-producing bacterium, and potato starch, a prebiotic, during antibiotic exposure to enhance innate immune responses and protect gut integrity, thereby preventing bacterial overgrowth and colonization by Clostridium difficile.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Object-affected harmful factors

If antibiotic therapy is used to treat Clostridium difficile infection, then bacterial infection is suppressed, but gut microbiota dysbiosis is exacerbated and recurrence is prevented

Engineering Contradiction:

ImproveClostridium difficile infectionVSAvoidgut microbiota composition

Core Design Contradiction:

Object-affected harmful factorsVSStability of the object's composition

Solution Approach 1:

The patent applies preliminary anti-action by administering butyrate-producing bacteria and prebiotics before or during antibiotic treatment to prevent the harmful effects of antibiotic-induced dysbiosis. This proactive approach counteracts the disruption to gut microbiota composition before it can lead to C. difficile overgrowth and infection recurrence.

Inventive Principle:

Principle #9Preliminary anti-action

Solution Approach 2:

The patent uses butyrate-producing bacteria and prebiotics as intermediary agents that mediate between antibiotic treatment and gut microbiota stability. These intermediaries protect the microbiota ecosystem from antibiotic damage while allowing the antibiotics to maintain their therapeutic effect against C. difficile.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Object-affected harmful factors

If further antibiotic therapy is administered to treat CDI, then bacterial growth is inhibited, but colonization resistance is compromised and recurrence increases

Engineering Contradiction:

Improvebacterial overgrowthVSAvoidcolonization resistance

Core Design Contradiction:

Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent employs self-service by introducing butyrate-producing bacteria that naturally restore colonization resistance through their own metabolic activities. These bacteria produce butyrate, which reinforces the intestinal barrier and competes with pathogenic bacteria for resources, thereby self-regulating the microbial ecosystem without requiring additional therapeutic intervention.

Inventive Principle:

Principle #25Self-service

Solution Approach 2:

The patent applies parameter changes by modifying the gut microbiota ecosystem through the introduction of butyrate-producing bacteria and prebiotics. This changes the chemical and biological parameters of the intestinal environment, increasing butyrate levels and altering the microbial composition to favor beneficial bacteria over pathogenic C. difficile.

Inventive Principle:

Principle #35Parameter changes

3Reliability

If butyrate-producing bacteria are supplemented during antibiotic exposure, then innate immune responses are enhanced and gut integrity is protected, but the complexity of treatment increases

Engineering Contradiction:

Improvegut integrityVSAvoidtreatment regimen

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies merging by combining butyrate-producing bacteria and prebiotics into a single therapeutic formulation that can be administered together. This integration simplifies the treatment regimen despite the multiple mechanisms of action, as patients receive a unified supplement that simultaneously restores microbiota, produces butyrate, and enhances gut barrier function.

Inventive Principle:

Principle #5Merging (Combining)

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 supplementation with Faecalibacterium prausnitzii and potato starch effectively reduces bacterial overgrowth, enhances immune responses, and preserves intestinal integrity, demonstrating therapeutic benefits in preventing Clostridium difficile colonization and associated intestinal damage.

Implementation Method 1

Prebiotics are indigestible carbohydrates, which upon fermentation beneficially alter gut microbiota composition as well as produce substrate specific amounts of SCFA acetate, propionate and butyrate.

Methodology Applied

Scientific EffectFermentation: Fermentation

Implementation Method 2

Gut microbiota provide colonization resistance to pathogenic bacteria.

Methodology Applied

Scientific EffectColonization resistance:

Data Source

PatentUS11491192B2Treatment and prevention of pathogenic bacterial overgrowth using butyrate-producing bacteria

Publication Date: 2022.11.08 THE CLEVELAND CLINIC FOUND

AI summary

A method of treating or preventing overgrowth by pathogenic bacteria in a subject deficient in butyrate and/or butyrate-producing bacteria in their gut microbiota by administering a therapeutically effective amount of a butyrate-producing bacteria to the subject is described. A prebiotic can be included with the butyrate-producing bacteria. Overgrowth by pathogenic bacteria is commonly caused by antibiotic administration.