Gut Bacterial Composition for Steroid-Refractory GVHD
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current treatments for graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation are limited, with adrenocorticosteroid hormones being only partially effective, and there is a lack of established secondary therapies.
Innovation Solution
A prophylactic or therapeutic composition comprising specific bacteria from the genera Blautia, Clostridium, Actinomyces, Parabacteroides, Lachnoclostridium, and others, identified through fecal microbiota transplantation (FMT), which are effective in preventing or treating GVHD.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If adrenocorticosteroid hormones are used for GVHD treatment, then GVHD symptoms can be suppressed in about half of patients, but no secondary therapy is established and efficacy is limited
Solution Approach 1:
The patent introduces fecal microbiota transplantation as an intermediary therapeutic approach between the donor and recipient. The microbiota acts as a mediator that modulates the immune system, providing a mechanism for GVHD treatment that is distinct from direct immunosuppression by steroids. This intermediary approach enables treatment in patients who are steroid-refractory or require steroid-sparing therapy.
Solution Approach 2:
The patent changes the therapeutic parameter from pharmacological immunosuppression (steroid hormones) to biological modulation (microbiota transplantation). By altering the treatment modality from chemical to biological, the patent addresses the limitation of steroid efficacy and establishes a new therapeutic paradigm for GVHD management.
2Reliability
If fecal microbiota transplantation is used for GVHD treatment, then GVHD can be prevented or treated, but the relationship between GVHD and FMT is not clearly established
Solution Approach 1:
The patent segments the complex fecal microbiota into specific bacterial genera that are associated with GVHD protection. By identifying and isolating specific bacterial groups (such as Clostridium, Bacteroides, Faecalibacterium, and others), the patent creates a more manageable and mechanism-understandable therapeutic composition while maintaining the protective effects of whole FMT.
Solution Approach 2:
The patent creates a simplified model of the protective microbiota composition that can be reproduced and standardized. By copying the beneficial bacterial profile from donor feces into a defined composition containing specific genera, the patent enables consistent therapeutic application while facilitating further research into the mechanisms of action.
3Manufacturing precision
If specific bacterial genera are identified and isolated from fecal microbiota, then the composition can be standardized for therapy, but the complexity of characterizing and validating multiple bacterial genera increases
Solution Approach 1:
The patent applies partial action by focusing on a specific subset of bacterial genera that are most associated with GVHD protection, rather than attempting to characterize and validate every possible bacterial species in the fecal microbiota. This selective approach to composition standardization maintains manufacturing precision while reducing the complexity of characterization and validation processes.
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 identified bacterial composition effectively prevents or treats acute gut GVHD, including steroid-refractory and steroid-dependent cases, by modulating the gut microbiota, thereby improving patient outcomes.
Implementation Method 1
by modulating the gut microbiota, thereby improving patient outcomes
Data Source
AI summary
The present invention provides a prophylactic or therapeutic composition for graft-versus-host disease (GVHD). There is provided a prophylactic or therapeutic composition for GVHD, which comprises bacteria belonging to any genus selected from the group consisting of the following genera: Blautia, Clostridium, unclassified Clostridiales, Actinomyces, Parabacteroides, Lachnoclostridium, Bacteroides, Faecalibacterium, unclassified Lachnospiraceae, Roseburia, Ruminococcus, unclassified Firmicutes, Dorea, Phascolarctobacterium, Sutterella, Megamonas, Collinsella, Eubacterium, and Coprococcus, etc., or any combination of bacteria belonging to these genera.