Reg3α Polypeptide Protects Oxygen-Sensitive Bacteria

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Solution Overview

Problem

Current approaches to managing gut microbiota imbalance, which can lead to various diseases, are inadequate in effectively protecting oxygen-sensitive gram-positive bacteria and promoting their growth, leading to dysbiosis and related disorders.

Innovation Solution

A Reg3α polypeptide, comprising a specific amino acid sequence or variants thereof, is used to protect oxygen-sensitive gram-positive bacteria by promoting their growth and survival, thereby maintaining gut microbiota balance and reducing inflammation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current approaches are used to manage gut microbiota imbalance, then general microbiota management is attempted, but oxygen-sensitive gram-positive bacteria cannot be effectively protected and promoted, leading to dysbiosis

Engineering Contradiction:
Improveprotection of oxygen-sensitive gram-positive bacteriaVSAvoidgrowth promotion of oxygen-sensitive gram-positive bacteria
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent introduces Reg3α polypeptide as an intermediary substance that mediates between the host environment and oxygen-sensitive gram-positive bacteria. This polypeptide acts as a protective mediator that enables these bacteria to survive in oxygen-containing environments without requiring strict anaerobic conditions, thus resolving the contradiction between protecting the bacteria and promoting their growth.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention changes the oxygen sensitivity parameter of gram-positive bacteria by introducing Reg3α polypeptide. The bacteria transform from being strictly anaerobic to being able to tolerate and grow in oxygenated environments, fundamentally altering their oxygen requirement parameter and enabling growth promotion under conditions previously incompatible with their survival.

Inventive Principle:
Principle #35Parameter changes

2Productivity

If oxygen-sensitive gram-positive bacteria are exposed to oxygen environments, then ex vivo growth is attempted, but the bacteria cannot survive due to oxygen sensitivity

Engineering Contradiction:
Improveex vivo growth of oxygen-sensitive bacteriaVSAvoidoxygen toxicity to gram-positive bacteria
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent converts the harmful effect of oxygen on gram-positive bacteria into a beneficial condition for their growth. By introducing Reg3α polypeptide, the previously toxic oxygen environment becomes a suitable growth medium, allowing ex vivo cultivation and expansion of these bacteria without requiring complex anaerobic infrastructure.

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

3Stability of the object's composition

If gut microbiota balance is not effectively maintained, then dysbiosis occurs, but current approaches fail to specifically protect beneficial gram-positive bacteria

Engineering Contradiction:
Improvegut microbiota balanceVSAvoidsurvival of beneficial gram-positive bacteria
Core Design Contradiction:
Stability of the object's compositionVSReliability

Solution Approach 1:

The Reg3α polypeptide performs multiple functions simultaneously: it protects gram-positive bacteria from oxygen toxicity, promotes their growth, and thereby maintains overall gut microbiota balance. This multi-functional approach addresses both the survival of specific bacteria and the stability of the entire microbiota system.

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

Data Source

PatentEP3651787B1Reg3alpha for for promoting ex vivo growth of oxygen sensitive gram-positive bacteria
Publication Date: 2024.09.04 THE HEALTHY AGING CO
  • EP3651787B1 patent drawingFigure 1
  • EP3651787B1 patent drawingFigure 2
  • EP3651787B1 patent drawingFigure 3~4

AI summary

The invention concerns a Reg3α polypeptide (also known as Hepatocarcinoma-Intestine- Pancreas/Pancreatitis Associated Protein (HIP/PAP)) for use in the protection of oxygen sensitive gram-positive bacteria, compositions comprising the polypeptide and their use. The inventors have shown that an increase in the concentration of the h Reg3α lectin into the gastrointestinal tract (GIT) lumen of hReg3α-transgenic mice induced significant changes in the composition of the gut microbiota, and dramatically improved host resistance to intestinal inflammation. hReg3α exerted a potent antioxidant activity on intestinal epithelial cells during colitis, and in particular the ROS scavenging activity, in particular, by promoting the survival of highly oxygen sensitive bacteria. Inventors also showed that h Reg3α-transgenic mice resist better to DSS-induced colitis after antibiotherapy. Thus, the invention concerns a Reg3α polypeptide for use in the protection of oxygen sensitive gram-positive bacteria, notably the Ruminococcaceae, such as Faecalibacterium prausnitzii, and/or the Lachnospiraceae, such as Roseburia intestinalis; pharmaceutical compositions comprising the polypeptide and their use; and the use of this polypeptide for promoting ex vivo growth of oxygen sensitive gram-positive bacteria. The Reg3α polypeptide may be used for preventing or treating microbiota-related disease and/or disorder, particularly selected from inflammatory bowel disease (IBD), colitis, gastrointestinal infections, irritable bowel syndrome and other gastrointestinal functional diseases, gastrointestinal tract cancer, metabolic syndrome and obesity, diabetes, liver diseases, allergic diseases, neurodegenerative diseases and psychological disorders.