HMO compositions reducing proteolytic metabolites

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Solution Overview

Problem

The human intestinal microbiota produces detrimental proteolytic metabolites such as ammonia and branched chain fatty acids, which can lead to inflammatory conditions, liver damage, and other health issues, and existing methods are inadequate in effectively reducing these metabolites.

Innovation Solution

Administration of human milk oligosaccharides (HMOs), particularly neutral HMOs, to promote the growth of beneficial saccharolytic bacteria like Bifidobacterium, thereby shifting the metabolic pathway from proteolytic to saccharolytic and reducing the production of harmful metabolites.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If proteolytic bacteria are allowed to ferment proteins in the large intestine, then protein degradation products are produced, but detrimental metabolites such as ammonia and branched chain fatty acids are generated which can cause inflammatory conditions and liver damage

Engineering Contradiction:
Improveprotein degradationVSAvoiddetrimental metabolites
Core Design Contradiction:
ProductivityVSObject-generated harmful factors

Solution Approach 1:

The patent converts the harmful proteolytic fermentation pathway into a beneficial saccharolytic pathway by introducing HMOs as substrate. HMOs are fermented by beneficial bacteria to produce useful metabolites, thereby replacing the harmful protein degradation pathway with a beneficial carbohydrate fermentation pathway, eliminating detrimental metabolites while maintaining productive fermentation

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

The patent changes the substrate parameter from proteins to HMOs (human milk oligosaccharides). This parameter change fundamentally alters the fermentation pathway from proteolytic to saccharolytic, transforming the metabolic output from harmful metabolites to beneficial metabolites, thus resolving the contradiction between productive protein degradation and harmful metabolite generation

Inventive Principle:
Principle #35Parameter changes

2Object-generated harmful factors

If saccharolytic bacteria are stimulated to ferment carbohydrates, then beneficial short-chain fatty acids are produced, but the concentration of detrimental proteolytic metabolites increases when protein availability is high

Engineering Contradiction:
Improvebeneficial metabolitesVSAvoiddetrimental metabolites
Core Design Contradiction:
Object-generated harmful factorsVSObject-affected harmful factors

Solution Approach 1:

HMOs serve as an intermediary substance that mediates between the available carbohydrates and the bacterial community. By introducing HMOs as a preferred substrate, the system redirects bacterial metabolism toward beneficial saccharolytic pathways while preventing direct access to proteins that would generate harmful metabolites, thus resolving the contradiction between producing beneficial and avoiding harmful metabolites

Inventive Principle:
Principle #24Intermediary (Mediator)

3Productivity

If the intestinal microbiota is allowed to ferment non-digested dietary compounds, then metabolic functions are performed, but the species composition is altered by the diet leading to imbalances

Engineering Contradiction:
Improvemetabolic functionsVSAvoidmicrobiota species composition
Core Design Contradiction:
ProductivityVSStability of the object's composition

Solution Approach 1:

The patent changes the dietary substrate parameter from general non-digested carbohydrates to specifically HMOs. This parameter change selectively promotes beneficial saccharolytic bacteria while suppressing proteolytic bacteria, thereby stabilizing the microbiota species composition and preventing diet-induced imbalances while maintaining essential metabolic functions

Inventive Principle:
Principle #35Parameter changes

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 use of HMOs decreases the concentration of ammonia and branched short chain fatty acids by 10-20% and increases butyrate production by 50-100% in the gastrointestinal tract, creating a more beneficial intestinal environment and reducing harmful compounds.

Implementation Method 1

In the large intestine, non-digested dietary compounds as well as secreted endogenous substrates can be fermented by the indigenous bacteria, and the substrate availability is a major driver for bacterial fermentation pathways

Methodology Applied
Scientific EffectFermentation: Fermentation

Implementation Method 2

selective stimulation of specific saccharolytic intestinal bacteria to promote their growth and metabolic activity, and inhibit the growth of unfavourable bacteria such as proteolytic bacteria could be a helpful approach in shifting the bacterial metabolism from a proteolytic to a saccharolytic metabolism

Methodology Applied
Scientific EffectMetabolic pathway shift: Fermentation

Data Source

PatentUS11541067B2HMO compositions and methods for reducing detrimental proteolytic metabolites
Publication Date: 2023.01.03 GLYCOM AS
  • US11541067B2 patent drawing

AI summary

A method and a composition comprising human milk oligosaccharides for decreasing the production of detrimental proteolytic metabolites such as ammonia and branched chain fatty acids in the intestinal microbiota of humans, which is useful for the treatment of brain-gut disorders like autism, stress, anxiety, and depressive disorders, are disclosed. Methods of treatment of colon cancer and liver damage are also disclosed.