Engineered Gut Bacteria for Stronger Microbiome Engraftment

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Solution Overview

Problem

Existing probiotic strains have limited engraftment and persistence in the human gut, limiting their efficacy in modulating the microbiome and addressing adverse health outcomes.

Innovation Solution

Utilizing bacterial cells or populations with specific modifications, such as heterologous ECF-type sigma factors or deletions of anti-sigma factors, to enhance engraftment and persistence in the gut microbiome, potentially administered with BcpT or BSAP-3 to increase bacterial populations and treat infections or reverse adverse health outcomes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional probiotic strains are administered, then daily supplementation is required, but engraftment and persistence in the gut are limited

Engineering Contradiction:

Improveengraftment and persistenceVSAvoidefficacy in modulating microbiome

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent modifies bacterial strain parameters by introducing heterologous ECF-type sigma factors and deleting anti-sigma factors, fundamentally changing the bacterial physiology to achieve superior engraftment and persistence in the gut microbiome, thereby resolving the contradiction between reliability of establishment and productivity of modulatory efficacy

Inventive Principle:

Principle #35Parameter changes

2Ease of operation

If most probiotic strains are used, then daily intake is necessary, but clinical improvements are not causally linked to microbiota changes

Engineering Contradiction:

Improvedaily supplementation requirementVSAvoidcausal link to clinical improvement

Core Design Contradiction:

Ease of operationVSReliability

Solution Approach 1:

The patent performs preliminary genetic modification of the probiotic strain before administration, equipping it with enhanced engraftment capabilities through heterologous sigma factors and anti-sigma factor deletions. This preliminary action ensures that when the strain is introduced to the gut, it automatically achieves robust establishment and persistent modulation of the microbiome, eliminating the need for daily supplementation and establishing causal links to clinical improvements

Inventive Principle:

Principle #10Preliminary action

Data Source

PatentUS20260014211A1Methods and compositions for increasing bacterial engraftment and populations in the gut microbiome

Publication Date: 2026.01.15 UNIVERSITY OF CHICAGO

AI summary

The disclosure relates to methods and compositions that provide for bacterial populations with increased potential for engraftment into the gut of mammalian systems. Accordingly, aspects of the disclosure relate to a bacterial cell or population of cells that comprise at least one of: i) a heterologous nucleic acid encoding a ECF-type sigma factor of the family identified above based on the structure and sequence of cognate anti-sigma factor, or a functional fragment thereof; ii) deletion of a functional ECF-type-associated anti-sigma factor; or iii) a heterologous nucleic acid encoding a ECF-type sigma factor-induced gene and/or an O-antigen inducing gene.