Histamine-Producing Probiotic Strains for Inflammation Control
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Solution Overview
Problem
Current probiotic lactic acid bacteria strains do not effectively produce histamine, which has anti-inflammatory benefits, due to historical concerns about histamine production being harmful, and there is a need for specific strains that can locally produce histamine in mammals for therapeutic benefits.
Innovation Solution
Selecting lactic acid bacterial strains with an active histidine operon capable of producing histamine by screening for the presence of specific genes and measuring histamine production levels, particularly strains like Lactobacillus reuteri, to deliver histamine locally in the GI tract, GU tract, oral cavity, lungs, and skin.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If lactic acid bacteria are used as probiotics, then health benefits are provided, but histamine production capability is insufficient
Solution Approach 1:
The patent changes the genetic parameters of lactic acid bacteria by introducing and expressing the hdc gene (histidine decarboxylase) to enable histamine production. This parameter change transforms the bacteria from non-histamine producing to histamine-producing strains, directly resolving the contradiction between maintaining probiotic reliability and achieving sufficient histamine productivity.
2Object-affected harmful factors
If histamine-producing bacteria are selected, then anti-inflammatory effects are achieved, but historical concerns about harmful effects arise
Solution Approach 1:
The patent applies local quality by targeting histamine production to specific locations in the gastrointestinal tract where inflammatory conditions exist. The probiotic bacteria are designed to produce histamine locally at the site of inflammation rather than systemically, achieving anti-inflammatory effects while minimizing potential toxic effects through localized action.
Solution Approach 2:
The patent converts the historically harmful aspect of histamine production into a beneficial therapeutic effect. By carefully controlling histamine production through specific bacterial strains and conditions, the patent transforms what was previously considered a toxic byproduct into a therapeutic agent for treating inflammatory conditions, effectively converting harm into benefit.
3Reliability
If specific strains are selected for histamine production, then therapeutic benefits are provided, but strain selection complexity increases
Solution Approach 1:
The patent performs preliminary action by pre-selecting and characterizing specific lactic acid bacteria strains that possess the hdc gene and are capable of histamine production. These pre-validated strains are then ready for clinical application, eliminating the need for complex strain selection processes at the point of use and simplifying the overall therapeutic implementation while maintaining reliable therapeutic effects.
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 selected strains produce histamine effectively, providing anti-inflammatory effects and therapeutic benefits, such as reducing inflammation and potentially treating inflammatory conditions, colitis, and other diseases by activating H2 receptors and inhibiting TNF-alpha production.
Implementation Method 1
Lactic-acid producing bacteria are not only used for their beneficial effect on human or animal health... L. reuteri is considered an indigenous organism of the human gastrointestinal tract... When L. reuteri cells are grown under anaerobic conditions in the presence of glycerol, they produce the antimicrobial substance known as reuterin
Data Source
AI summary
A method is provided of selecting specific probiotic lactic acid bacteria producing histamine and the use of such strains for beneficial effects for mammals. The method includes selecting a lactic acid bacterial strain for use in the local production of histamine in a mammal, and further comprises screening bacteria for the presence of an active histidine operon and selecting a strain which has an active histidine operon and is capable of producing histamine. Preferably said strain is selected for its ability to produce histamine at a level of greater than 250 pg/ml. The present invention further provides products comprising the strains obtainable by the selection methods of the invention for use in the local production of histamine in a mammal, in particular for use in the treatment or prophylaxis of inflammatory conditions.