Serotonin producing bacteria
Inventors
GRASSET, Estelle • Khan, Muhammed • Möllstam, Bo • Roos, Stefan
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12295975-B2
Publication Date
2025-05-13
Expiration Date
Abstract
The invention relates to selection of bacterial strain for use in treating serotonin deficiency and/or a disease related to serotonin deficiency by culturing bacteria of a lactic acid producing bacterial strain, under aerobic conditions, in a culture medium comprising tryptophan. Any serotonin produced by the bacteria of the lactic acid producing bacterial strain in the culture medium is detected and the lactic acid producing bacterial strain is selected as effective in treating serotonin deficiency and/or a disease related to serotonin deficiency in a subject if serotonin is detected in the culture medium.
Core Innovation
The invention provides Lactobacillus reuteri strains that are selected for producing and extracellularly releasing serotonin when exposed to aerobic conditions in a tryptophan-containing media. Serotonin production is evaluated by culturing under aerobic conditions and detecting serotonin in culture medium and/or samples, with comparison to serotonin production under anaerobic conditions described as an aerobic/anaerobic relationship. The approach uses defined Lactobacillus reuteri strains including DSM 33509, DSM 33632, DSM 33633, DSM 33634, and DSM 33635.
The invention further describes using a germ-free Tph1−/− in vivo model to confirm that serotonin produced by administered lactic acid bacteria results in increased serotonin in body samples. In this model, administration with serotonin-producing strains restores serum serotonin and is associated with increased enteric nervous system maturation and serotonin-positive ENS/crypt innervation markers. Human-derived serotonin-producing isolates are also described as increasing serotonin in the germ-free Tph1−/− model.
In addition, the invention emphasizes selecting strains suited to oxygenated mucosal niches, including via mucus adhesion and close proximity to intestinal epithelium, and describes bioactivity and systemic transport connected to serotonin delivery. Embodiments include oxygen-tolerant and/or storage-stable L. reuteri strains and include non-limiting medicament and product formats such as lyophilized or dried strains and tablet or oil-based formulations for treating serotonin-deficiency-related diseases.
Claims Coverage
The independent claims include 3 main inventive claim groups: (i) a selected Lactobacillus reuteri strain set defined by specific DSM deposits, (ii) the same strain set provided in dried/frozen/lyophilized form, and (iii) a method of treating serotonin deficiency and/or diseases related to serotonin deficiency by administering the specified Lactobacillus reuteri DSM strains. Across these claims, 3 independent claim inventive features are identified.
Selected Lactobacillus reuteri DSM strains
A Lactobacillus reuteri strain selected from the group consisting of L. reuteri strain DSM 33509, L. reuteri strain DSM 33632, L. reuteri strain DSM 33633, L. reuteri strain DSM 33634, and L. reuteri strain DSM 33635.
Selected Lactobacillus reuteri DSM strains in dried, frozen or lyophilized form
A Lactobacillus reuteri strain selected from the group consisting of L. reuteri strain DSM 33509, L. reuteri strain DSM 33632, L. reuteri strain DSM 33633, L. reuteri strain DSM 33634, and L. reuteri strain DSM 33635 in a dried, frozen or lyophilized form.
Method for treating serotonin deficiency with selected Lactobacillus reuteri DSM strains
A method for treating a serotonin deficiency and/or a disease related to serotonin deficiency in a subject in need thereof, the method comprising administering to the subject a Lactobacillus reuteri bacterial strain selected from the group consisting of L. reuteri DSM 33509, L. reuteri DSM 33632, L. reuteri DSM 33633, L. reuteri DSM 33634, and L. reuteri DSM 33635.
Overall, the claims cover specific Lactobacillus reuteri DSM-deposited strains, provide them in dried/frozen/lyophilized form in one independent claim, and define a treatment method for serotonin deficiency and serotonin-deficiency-related diseases by administering the specified DSM strains.
Stated Advantages
Restores serum serotonin in a germ-free Tph1−/− in vivo model.
Increases enteric nervous system maturation and serotonin-positive ENS/crypt innervation markers.
Increases serotonin in germ-free Tph1−/− mice using human-derived serotonin-producing isolates.
Documented Applications
Treating serotonin deficiency and/or a disease related to serotonin deficiency in a subject in need thereof.
Treating central nervous system disorders selected from anxiety, depressed mood, aggression, poor memory, eating disorders, obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder, and social anxiety disorder.
Treating gastrointestinal system disorders consisting of a gastrointestinal motility disorder, IBS, or IBD.
Treating cardiovascular disease and APECED as serotonin-deficiency-related diseases.
Treating osteoporosis, osteopenia, and bone loss conditions, including glucocorticoid-associated bone loss.
Interested in licensing this patent?