Selection and use of melatonin supporting bacteria to reduce infantile colic
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Publication Number
US-11911424-B2
Publication Date
2024-02-27
Expiration Date
Abstract
The present invention relates to lactic acid bacterial strains which are capable of producing or inducing the production of melatonin, for use in the production of melatonin in a subject. Preferred strains for such uses are capable of producing or inducing the production of adenosine. Therapeutic uses of such strains include the treatment or prevention of diseases associated with melatonin deficiency, for example infantile colic. Novel strains are also provided.
Core Innovation
The invention relates to lactic acid bacterial strains, preferably Lactobacillus reuteri, selected for the ability to produce or induce adenosine and thereby increase melatonin. The disclosed therapeutic focus is on melatonin-deficiency-associated conditions, especially infantile colic. The approach links adenosine generation to downstream melatonin production rather than treating melatonin alone.
A mechanistic pathway is described in which extracellular adenosine activates adenosine receptor/cAMP signaling to upregulate AANAT, characterized as the rate-limiting enzyme for melatonin synthesis. Adenosine is generated extracellularly through cell-surface or supernatant 5′-nucleotidase, described as CD73, converting AMP to adenosine.
Strain selection and evaluation are disclosed based on screening for a 5′-nucleotidase gene and/or activity and quantifying activity and/or adenosine production, with optional assessment of melatonin in intestinal enteroid models. Comparative results are described in a human intestinal enteroid model, where supernatant plus AMP markedly increases melatonin production compared to control and to a comparator strain supernatant.
Claims Coverage
The partial claim set includes one independent claim directed to specified Lactobacillus reuteri strains by DSM accession and dependent claims that extend coverage to dried forms, combination products, administration concepts, and induction thresholds for melatonin or adenosine production. The inventive features include strain identity by DSM accession, formulation state, combination-product inclusion of additional melatonin or adenosine sources or inducing substrate components or agents, and quantified fold increases upon administration.
Specified Lactobacillus reuteri strain by DSM accession
A bacterial strain that is Lactobacillus reuteri selected from DSM 32846, DSM 32847, DSM 32849, or DSM 33198.
Dried form of the specified Lactobacillus reuteri strain
The bacterial strain of the specified Lactobacillus reuteri is provided in a dried form.
Combination product to increase melatonin or adenosine production
A combination product that increases melatonin or adenosine production in a subject by including Lactobacillus reuteri plus either additional melatonin or adenosine sources or substrate components or agents that enhance or induce production of melatonin or adenosine by the bacterial strain.
Optional co-administration of additional substrate components or agents
Further administering additional substrate components or agents to increase or enhance production or induction of melatonin or adenosine in a subject, where the additional agent or agents can be given combined with Lactobacillus reuteri or separately.
Inducing melatonin or adenosine by fold-thresholds
Administering a therapeutically effective amount of a Lactobacillus reuteri strain that induces production of melatonin or adenosine at least 1.5-fold, at least 2-fold, or at least 5-fold versus levels before administration.
Across the independent and dependent claims provided, the coverage centers on specific Lactobacillus reuteri DSM strains and their use to induce melatonin or adenosine, including dried formulations, combination products with additional melatonin or adenosine sources or inducing substrate components or agents, optional combined versus separate administration of such agents, and quantified induction thresholds versus pre-administration levels.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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