Engineered Microbes Secrete Peptide Hormones for NAFLD

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Solution Overview

Problem

Current treatments for non-alcoholic fatty liver disease (NAFLD) are limited, particularly in maintaining sustained levels of peptide hormones like FGF-19, Aldafermin, and IGF-1 in the gastrointestinal tract, which are crucial for regulating peptide hormone homeostasis and addressing metabolic disorders.

Innovation Solution

A composition comprising a genetically engineered non-pathogenic microorganism, such as E. coli Nissle 1917, that expresses and secretes polypeptide hormones like FGF-19, Aldafermin, and IGF-1 in the gastrointestinal tract, overcoming the challenges of chemical modification and degradation of these hormones.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If peptide hormones are administered to treat NAFLD, then therapeutic effect is improved, but sustained delivery and stability in the gastrointestinal tract deteriorates due to chemical modification and degradation

Engineering Contradiction:
Improvetherapeutic effectVSAvoidhormone stability
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent uses genetically engineered microorganisms as intermediaries to deliver peptide hormones. The microorganisms express and secrete hormones like FGF-19, Aldafermin, and IGF-1 directly in the gastrointestinal tract, protecting them from degradation and enabling sustained delivery without chemical modification

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The microorganisms serve themselves by autonomously expressing and secreting the therapeutic hormones in response to physiological conditions in the GI tract. The engineered bacteria function as living factories that continuously produce and release hormones, eliminating the need for external administration and chemical stabilization

Inventive Principle:
Principle #25Self-service

2Duration of action of moving object

If genetically engineered microorganisms are used to deliver hormones, then sustained delivery is improved, but device complexity increases

Engineering Contradiction:
Improvedelivery durationVSAvoidsystem complexity
Core Design Contradiction:
Duration of action of moving objectVSDevice complexity

Solution Approach 1:

The patent modifies parameters of microorganisms through genetic engineering to enable hormone expression. By changing the genetic parameters of simple, well-characterized bacteria like E. coli Nissle 1917, the system achieves complex sustained delivery functionality without requiring complex device structures

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The engineered microorganisms perform multiple functions: they colonize the GI tract, respond to physiological conditions, express hormones, and secrete them sustainably. This multi-functionality in a single biological system simplifies the overall delivery architecture compared to mechanical or chemical delivery systems

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

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 composition effectively reduces liver fat content, ameliorates NAFLD, and modulates peptide hormone homeostasis, providing a sustained and constant delivery of these hormones, which is beneficial for treating NAFLD and related metabolic disorders.

Implementation Method 1

a composition comprising a system for secreting peptide hormones in the gastrointestinal tract, wherein the system comprises engineered non-pathogenic microorganism expressing a polypeptide comprising a polypeptide hormone

Methodology Applied
Scientific EffectSecretion:

Data Source

PatentUS20250108076A1Methods for treatment of non-alcoholic fatty liver diseases (NAFLD) using advanced microbiome therapeutics
Publication Date: 2025.04.03 DANMARKS TEKNISKE UNIV
  • US20250108076A1 patent drawing
  • US20250108076A1 patent drawing
  • US20250108076A1 patent drawing

AI summary

The present invention relates to a composition comprising a genetically engineered non-pathogenic microorganism expressing one or more polypeptide comprising polypeptide hormones. The composition is preferably for use in the treatment of non-alcoholic fat liver disease (NAFLD).