Probiotic Oral Compositions for Nitric Oxide Production

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Solution Overview

Problem

There is a need for enhancing nitric oxide (NO) production in the oral cavity to treat or prevent conditions associated with NO insufficiency, such as cardiovascular diseases, as the role of oral microbiota in NO production is not well defined and antiseptic mouthwash disrupts this natural process.

Innovation Solution

A probiotic composition comprising specific bacteria isolates or mixtures, including Neisseria, Veillonella, Haemophilus, Actinomyces, Granulicatella, Prevotella, Leptotrichia, Brevibacillus, Porphyromonas, Fusobacterium, and clade Gemellaceae, with minimal Lactobacillus, to enhance nitrate reduction and nitrite accumulation in the oral cavity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Object-affected harmful factors

If antiseptic mouthwash is used to clean the oral cavity, then hygiene is improved, but nitric oxide production is reduced

Engineering Contradiction:
Improveoral hygieneVSAvoidnitric oxide production
Core Design Contradiction:
Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent extracts and isolates specific nitrate-reducing bacteria from the oral microbiota that are responsible for converting nitrate to nitrite, which then leads to nitric oxide production. By focusing on these specific beneficial bacteria rather than the entire microbiota, the invention preserves NO production while allowing for hygiene measures.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent introduces probiotic compositions containing specific nitrate-reducing bacteria as intermediaries to restore and maintain the nitrate-nitrite-NO pathway. These probiotics act as mediators between oral hygiene practices and nitric oxide production, ensuring that cleaning activities do not eliminate the necessary bacterial function.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Object-affected harmful factors

If oral microbiota are disrupted to treat disease, then pathogen control is improved, but nitric oxide homeostasis is compromised

Engineering Contradiction:
Improvepathogen controlVSAvoidnitric oxide homeostasis
Core Design Contradiction:
Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent applies local quality by targeting specific functional properties of certain bacteria (nitrate reduction capability) rather than treating all oral bacteria uniformly. This allows selective preservation or introduction of bacteria that maintain NO homeostasis while permitting control of pathogenic species.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent changes the parameter composition of oral microbiota by introducing specific probiotic strains with known nitrate-reducing capabilities. This alters the bacterial community structure to ensure adequate nitrite production while allowing flexibility in managing pathogen levels through targeted approaches.

Inventive Principle:
Principle #35Parameter changes

3Reliability

If dietary nitrate is supplemented to enhance nitric oxide production, then cardiovascular health is improved, but dependency on external sources increases

Engineering Contradiction:
Improvenitric oxide productionVSAvoidendogenous production capability
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent applies preliminary action by establishing a robust population of nitrate-reducing bacteria in the oral cavity before nitrate is needed for NO production. This pre-established bacterial capability ensures that when nitrate becomes available (from diet or supplementation), it can be rapidly converted to nitrite and then to nitric oxide, reducing dependency on external nitrate sources.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent enables the oral microbiota to serve itself by maintaining a self-sustaining population of nitrate-reducing bacteria that can autonomously convert dietary nitrate to nitrite. This self-service capability reduces the need for external nitrate supplementation while maintaining endogenous nitric oxide production.

Inventive Principle:
Principle #25Self-service

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 probiotic composition promotes nitric oxide production, supporting cardiovascular health by reducing nitrate and accumulating nitrite, thereby addressing NO insufficiency-related disorders.

Implementation Method 1

Salivary nitrate is metabolized to nitrite via a two-electron reduction, a reaction that mammalian cells are unable to perform, during anaerobic respiration by nitrate reductases produced by facultative and obligate anaerobic commensal oral bacteria

Methodology Applied
Scientific EffectNitrate reduction: Reduction

Implementation Method 2

during anaerobic respiration by nitrate reductases produced by facultative and obligate anaerobic commensal oral bacteria

Methodology Applied
Scientific EffectAnaerobic respiration: Anaerobic Digestion

Implementation Method 3

The gaseous free radical NO, which is endogenously produced in vascular endothelial cells, neurons and immune cells, plays a critical role in various physiological processes

Methodology Applied
Scientific EffectNitrite to nitric oxide conversion: Oxidation

Data Source

PatentEP3868389B1Compositions and methods for promoting nitric oxide production through an oral delivery system
Publication Date: 2025.09.03 BOARD OF RGT THE UNIV OF TEXAS SYST
  • EP3868389B1 patent drawingFigure 1
  • EP3868389B1 patent drawingFigure 2A
  • EP3868389B1 patent drawingFigure 2B

AI summary

Probiotic compositions, particularly oral compositions, comprising one or more bacteria that are capable of producing nitrite and/or nitric oxide in a subject are provided. Some compositions further comprise nitrate/nitrate, such as a botanical source of nitrate. Some compositions further comprise botanical sources of nitrate reductase. Also, provided are methods of improving the oral and/or vascular health of a subject by orally administering a composition comprising one or more bacteria capable of producing nitric oxide. Methods of repopulating the nitric oxide producing microflora and bacterial environment in the oral cavity of a subject are also provided.