Probiotic Strains Sequestering Cholesterol via BSH Activity

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Solution Overview

Problem

Current methods for treating hypercholesterolemia have undesirable side effects, and there is a need for more natural and effective ways to reduce serum cholesterol levels using probiotic strains that can efficiently absorb and sequester cholesterol in the intestinal tract.

Innovation Solution

The use of specific probiotic strains, such as Lactobacillus reuteri V3401 and Bifidobacterium breve BT820, which are capable of absorbing cholesterol, either in viable or heat-inactivated forms, and can be cultured under specific conditions to enhance their cholesterol-absorbing capacity, thereby reducing cholesterol absorption by intestinal epithelial cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If drug therapy is used to treat hypercholesterolemia, then serum cholesterol concentration is reduced, but undesirable side effects occur

Engineering Contradiction:
Improveserum cholesterol concentrationVSAvoidside effects
Core Design Contradiction:
Quantity of substanceVSObject-affected harmful factors

Solution Approach 1:

The patent uses probiotic bacteria (Lactobacillus and Bifidobacterium species) as intermediary agents to reduce serum cholesterol. These bacteria colonize the gastrointestinal tract and bind bile salts through BSH activity, creating an indirect mechanism to lower cholesterol without the direct toxic effects of pharmaceutical drugs. The bacteria act as a biological mediator between the host's metabolic system and cholesterol homeostasis.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces the mechanical/chemical action of pharmaceutical drugs with a biological system (probiotic bacteria). Instead of using synthetic compounds that directly interfere with cholesterol metabolism pathways, the invention employs living organisms that naturally produce BSH enzymes to deconjugate bile salts, thereby substituting a biological mechanism for a pharmacological one to avoid side effects.

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

2Quantity of substance

If lactic acid bacteria are used to reduce cholesterol, then cholesterol absorption is reduced, but the mechanism is not fully understood and effectiveness varies

Engineering Contradiction:
Improvecholesterol absorptionVSAvoideffectiveness consistency
Core Design Contradiction:
Quantity of substanceVSReliability

Solution Approach 1:

The patent optimizes specific parameters of the probiotic bacteria to enhance cholesterol-reducing effectiveness. This includes selecting strains with high BSH activity, optimizing culture conditions (pH, temperature, incubation time), and determining appropriate dosages. By systematically adjusting these parameters, the invention achieves more consistent and reliable cholesterol absorption reduction compared to previous studies that did not standardize these factors.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent employs in vitro assays using Caco-2 enterocytes and in vivo animal models to measure and evaluate the cholesterol absorption inhibition effect of different probiotic strains. This feedback mechanism allows for the selection and optimization of strains that demonstrate the most effective and consistent cholesterol-reducing properties, thereby improving reliability.

Inventive Principle:
Principle #23Feedback

3Quantity of substance

If probiotic strains are used to sequester cholesterol, then cholesterol absorption by intestinal cells is reduced, but more natural and effective methods are still needed

Engineering Contradiction:
Improvecholesterol absorption by intestinal cellsVSAvoidcholesterol reduction efficiency
Core Design Contradiction:
Quantity of substanceVSProductivity

Solution Approach 1:

The patent uses probiotic bacteria that colonize the gastrointestinal tract in advance and continuously bind bile salts through BSH activity. This preliminary and ongoing action prevents cholesterol from being absorbed in the first place, rather than attempting to remove or reverse cholesterol after absorption has occurred. The bacteria are established in the gut beforehand to create a sustained cholesterol-sequestering effect.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent combines multiple probiotic strains (Lactobacillus and Bifidobacterium species) with complementary properties to create a synergistic effect. By using a composite probiotic formulation rather than a single strain, the invention enhances overall cholesterol reduction efficiency and addresses the limitation of individual strains having variable effectiveness.

Inventive Principle:
Principle #40Composite materials

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

These strains effectively reduce the absorption of cholesterol by intestinal cells, demonstrating their potential in treating hypercholesterolemia and dyslipidemias by sequestering cholesterol from the intestinal tract, as shown in in vitro and in vivo assays.

Implementation Method 1

Strains of Lactobacillus acidophilus and bifidobacteria have been reported to assimilate cholesterol from laboratory media. Miremandi F. et al assesses the ability of 14 probiotic strains of lactobacilli and bifidobacteria, either growing or non-growing (resting or heat-killed), to remove cholesterol. All strains were found to assimilate cholesterol at varying degrees.

Methodology Applied
Scientific EffectAbsorption: Absorption (physical)

Data Source

PatentEP3230479B1Probiotic strains having cholesterol absorbing capacity, methods and uses thereof
Publication Date: 2021.10.06 BIOSEARCH SA
  • EP3230479B1 patent drawingFigure 1~2B
  • EP3230479B1 patent drawingFigure 3~4
  • EP3230479B1 patent drawingFigure 5~7

AI summary

The invention relates to a probiotic strain selected from Lactobacillus reuteri V340 with accession number CECT 8605 and Bifidobacterium breve BT820 with accession number CECT 8606, or a variantof said probiotic strain having cholesterol-absorbing capacity, and to methods and therapeutic uses thereof. The invention also relates to compositions, pharmaceutical compositions, feeds or nutritional products comprising a probiotic strain selected from Lactobacillus reuteri V3401 with accession number CECT 8605 and Bifidobacterium breve BT820 with accession number CECT 8606, or a variant of said probiotic strain having cholesterol-absorbing capacity.