Probiotic Microbiota Modulation for Genome Instability Therapy
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Solution Overview
Problem
Current therapies are inadequate for preventing or treating ataxia-telangiectasia (A-T) associated conditions, lymphoma, and radiation-induced toxicity, as they fail to address genome instability and related mortalities effectively.
Innovation Solution
The use of specific combinations of pre-biotics, pro-biotics, and anti-biotics to alter the intestinal microbiota, particularly by administering Lactobacillus johnsonii, to modulate the immune response and reduce genotoxicity, inflammation, and oxidative stress, thereby delaying disease onset and improving lifespan.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional therapies are used for A-T patients, then treatment is provided, but they fail to prevent cancer or progressive neurodegeneration effectively
Solution Approach 1:
The patent applies preliminary action by administering probiotic compositions (containing Lactobacillus johnsonii and other beneficial microbes) to A-T patients before disease manifestation or progression. This preventive approach modifies the intestinal microbiota composition in advance to reduce genotoxicity, inflammation, and oxidative stress, thereby delaying lymphoma onset and neurodegeneration without waiting for disease symptoms to appear.
Solution Approach 2:
The patent uses the intestinal microbiota as an intermediary system to mediate the therapeutic effect. Rather than directly treating A-T symptoms, the probiotic composition modifies the microbiota composition, which in turn produces metabolites and immune modulating effects that indirectly reduce genotoxicity and delay disease onset. The microbiota acts as a biological mediator between the administered probiotics and the host's genomic stability.
2Object-affected harmful factors
If intestinal microbiota is modified using probiotic compositions, then genotoxicity and inflammation are reduced, but the mechanism involves complex microbial interactions
Solution Approach 1:
The patent applies parameter changes by specifically modifying the composition and abundance of bacterial species in the intestinal microbiota. The probiotic composition contains defined ratios of beneficial microbes (e.g., Lactobacillus johnsonii at ≥10^8 CFU/g, Bifidobacterium species at ≥10^7 CFU/g) to shift the microbiota from a pro-inflammatory state to an anti-inflammatory state, thereby reducing genotoxicity through controlled changes in microbial parameters.
Solution Approach 2:
The patent uses a composite probiotic composition containing multiple beneficial bacterial species (Lactobacillus johnsonii, Bifidobacterium animalis, Bifidobacterium longum, Lactobacillus rhamnosus, and other clostridia) working synergistically. Each species contributes different functions: some produce short-chain fatty acids, others modulate immune responses, and some compete with pathogenic bacteria. This composite approach achieves greater reduction in genotoxicity than single-strain probiotics.
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
This approach effectively delays the onset of A-T associated conditions, reduces systemic genotoxicity, and extends lifespan by modifying the intestinal microbiota, offering a non-invasive method for treating or preventing genome instability-related diseases.
Implementation Method 1
The use of specific combinations of pre-biotics, pro-biotics, and anti-biotics to alter the intestinal microbiota, particularly by administering Lactobacillus johnsonii, to modulate the immune response and reduce genotoxicity, inflammation, and oxidative stress
Data Source
AI summary
Inoculation of ATM-deficient mice with probiotic microorganisms, such as L. johnsonii, changed immune parameters, decreased a marker of DNA damage and increased the lifespan of the mice. Compositions and methods described herein are useful for the treatment and prevention of Ataxia telangiectasia and other cancer-prone disease, such as p53 deficiency-associated cancers. Compositions and methods of the present invention are also useful for treating and preventing radiation-induced toxicity to normal tissue in a subject being exposed to radiation. Compositions and methods of the invention can increase lifespans in a simple, non-invasive manner.