Microbial Urolithin Consortia for Complete Metabotype Profiles

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Solution Overview

Problem

Existing technologies fail to produce a complete profile of urolithins associated with human metabotypes A and B, and there is a need for natural strategies to convert non-urolithin-producing individuals into producers of these metabolites for health benefits.

Innovation Solution

A novel bacterial strain from the Enterocloster genus, combined with other bacteria from the Gordonibacter, Ellagibacter, and Slackia genera, is used to produce a customized urolithin profile in vitro and in vivo, including novel urolithin G, to mimic metabotypes A and B, and convert non-producers into producers.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If pure cultures of Gordonibacter and Ellagibacter are used, then some Uros are produced, but the complete Uro profile including intermediates and final Uros cannot be obtained

Engineering Contradiction:
ImproveUrolithin productionVSAvoidUrolithin profile completeness
Core Design Contradiction:
Quantity of substanceVSAdaptability or versatility

Solution Approach 1:

The patent combines multiple bacterial strains (Gordonibacter, Ellagibacter, and other enteric bacteria) into a consortium that functions together to produce the complete urolithin profile. Each strain contributes specific metabolic capabilities, and their combined action enables the full catabolic pathway from ellagic acid through intermediates to final urolithins, resolving the limitation of pure cultures.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The bacterial consortium is designed to perform multiple functions simultaneously: producing intermediate Uros, producing final Uros, and mimicking both metabotype A and B profiles. This multi-functional system overcomes the single-function limitation of individual strains.

Inventive Principle:
Principle #6Universality (Multi-functionality)

2Quantity of substance

If chemical synthesis methods are used, then Uro-A can be produced, but public acceptance is poor and complete metabotype profiles cannot be achieved

Engineering Contradiction:
ImproveUrolithin productionVSAvoidPublic acceptance and natural production
Core Design Contradiction:
Quantity of substanceVSEase of manufacture

Solution Approach 1:

The bacterial consortium performs self-service by naturally metabolizing ellagic acid and ellagitannins into the complete urolithin profile through their inherent metabolic pathways. This biological self-processing eliminates the need for chemical synthesis interventions and provides a naturally accepted production method.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The patent replaces chemical synthesis mechanisms with biological metabolic mechanisms. Instead of using chemical reagents and synthesis protocols, the system uses bacterial enzymatic pathways to convert precursors into urolithins, providing a more acceptable and sustainable production approach.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

3Adaptability or versatility

If UM-0 individuals are treated with bacterial consortia, then Urolithin production is activated, but the complexity of converting non-producers to producers increases

Engineering Contradiction:
ImproveMetabotype conversion capabilityVSAvoidBacterial consortium composition
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The conversion process is segmented into manageable components: the bacterial consortium is divided into specific strains with defined roles, and the metabolic pathway is broken down into sequential steps from ellagic acid through various intermediates to final urolithins. This segmentation makes the complex conversion process more controllable and reproducible.

Inventive Principle:
Principle #1Segmentation

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 bacterial consortia effectively produce urolithins in vitro and in vivo, enabling the production of urolithin profiles characteristic of metabotypes A and B, offering potential health benefits and applications in pharmaceuticals, cosmetics, and food industries.

Implementation Method 1

EA is released through the hydrolysis of ET's ester bonds by the enzyme known as ellagitannase

Methodology Applied
Scientific EffectHydrolysis: Hydrolysis

Implementation Method 2

which is then decarboxylated to pentahydroxy-Uro (Uro-M5)

Methodology Applied
Scientific EffectDecarboxylation:

Implementation Method 3

Next, consecutive dehydroxylations convert it to tetrahydroxy-Uros (Uro-D, Uro-E, and Uro-M6)

Methodology Applied
Scientific EffectDehydroxylation:

Implementation Method 4

The human gut microbiota is responsible for converting these polyphenols into Uros

Methodology Applied
Scientific EffectFermentation: Fermentation

Data Source

PatentUS20250327022A1Microbial method for reproducing the human urolithin metabotypes in vitro and in vivo
Publication Date: 2025.10.23 CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS (CSIC)
  • US20250327022A1 patent drawing
  • US20250327022A1 patent drawing
  • US20250327022A1 patent drawing

AI summary

The present invention relates to a new bacterial strain and a new urolithin named urolithin G. The new strain of the invention is Enterocloster bolteae CEBAS S4A9 DSM 34392 and can customize urolithin production to mimic metabotype A and metabotype B in vitro and in vivo if combined with at least one bacterial strain belonging to the Gordonibacter and/or Ellagibacter and/or Slackia genera. The invention also refers to methods or uses of E. bolteae CEBAS S4A9 DSM 34392 or the consortium that comprises E. bolteae CEBAS S4A9 DSM 34392 and at least one bacterial strain belonging to the Gordonibacter and/or Ellagibacter and/or Slackia genera for producing urolithins. The invention also refers to compositions or food products that contain E. bolteae CEBAS S4A9 DSM 34392, the aforementioned consortium, or the new urolithin G.