Production and use of bacterial histamine
Inventors
Versalovic, James • Thomas, Carissa Michelle • Connolly, Eamonn
Assignees
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Publication Number
US-10004770-B2
Publication Date
2018-06-26
Expiration Date
Abstract
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.
Core Innovation
The invention relates to a method of treating and/or reducing the risk of developing an inflammatory disease or condition in a mammal by administering a lactic acid bacterial strain that produces histamine. The method includes screening for a lactic acid bacterial strain in which the hdcA gene, the hdcB gene, and the histidine/histamine antiporter gene are present, and in which histamine is detected in a culture sample. The approach further includes detecting the presence of the hdcA gene, hdcB gene, and histidine/histamine antiporter gene, and detecting whether histamine is produced by detecting histamine in a culture sample.
The screening comprises culturing the lactic acid bacterial strain in media comprising glucose under anaerobic conditions at 37°C, and selecting the lactic acid bacterial strain that produces histamine and comprises the hdcA gene, the hdcB gene, and the histidine/histamine antiporter gene. The selected strain is then administered to a mammal in need thereof, thereby treating and/or reducing the risk of developing the inflammatory disease or condition in the mammal. In the disclosed embodiments, the lactic acid bacterial strain includes Lactobacillus reuteri, including Lactobacillus reuteri 6475 (ATCC PTA 6475).
The document additionally describes treatment and/or risk reduction of inflammatory diseases or conditions at multiple anatomical sites, with embodiments focused on local histamine production. It also describes formulations and therapeutic or nutritional agents that include histidine and/or histidine analog, and/or an appropriate carbon source that supports histamine production by the strain.
Claims Coverage
The partial content identifies one independent claim (clm-00001). The inventive features are centered on screening lactic acid bacteria for an active histidine operon and histamine production, followed by administering the selected strain to treat and/or reduce the risk of an inflammatory disease or condition in a mammal.
Screening lactic acid bacteria with hdcA, hdcB, and histidine/histamine antiporter genes plus detected histamine production
Screening for a lactic acid bacterial strain for administration in which the hdcA gene, the hdcB gene, and the histidine/histamine antiporter gene are present, and in which histamine is detected in a culture sample of the lactic acid bacterial strain.
Culturing under anaerobic glucose conditions and detecting histamine in culture
Culturing the lactic acid bacterial strain in media comprising glucose under anaerobic conditions at 37°C and detecting whether histamine is produced by detecting the presence of histamine in a culture sample from the lactic acid bacterial strain.
Selecting a histamine-producing strain comprising hdcA, hdcB, and histidine/histamine antiporter genes
Selecting the lactic acid bacterial strain that produces histamine and comprises the hdcA gene, the hdcB gene, and the histidine/histamine antiporter gene.
Administering the selected strain to treat and/or reduce risk of inflammatory disease
Administering to a mammal in need thereof the selected lactic acid bacterial strain, thereby treating and/or reducing the risk of developing an inflammatory disease or condition in the mammal.
Oral and/or topical administration for local histamine production
Administering orally and/or topically to provide local production of histamine.
Using Lactobacillus reuteri
Performing the method using a lactic acid bacterial strain identified as Lactobacillus reuteri.
Treating inflammatory conditions in specified anatomical sites
Applying the method to treat an inflammatory disease or condition located in gastrointestinal tract, genitourinary tract, oral cavity, lungs and/or airways, and/or the skin.
Treating selected inflammatory disease types
Characterizing the inflammatory disease or condition as selected from colitis, inflammatory bowel disease, irritable bowel syndrome, diverticulosis, gingivitis, vaginitis, or any combination thereof.
Co-administering histidine or a histidine analog and/or a carbon source supporting histamine production
Further specifying that the therapeutic or nutritional agent includes histidine or a histidine analog, and/or an appropriate carbon source that supports histamine production by the strain.
Across the identified claim set, coverage centers on identifying lactic acid bacterial strains with the hdcA and hdcB genes and a histidine/histamine antiporter gene, verifying histamine production in a culture sample, selecting the histamine-producing strain, and administering it to a mammal to treat and/or reduce risk of inflammatory disease, with dependent refinements specifying route, strain identity, anatomical site, disease type, and optional histidine or histidine analog and carbon-source components.
Stated Advantages
Treating an inflammatory disease or condition in a mammal
Reducing the risk of developing an inflammatory disease or condition in a mammal
Documented Applications
Treating and/or reducing the risk of developing inflammatory diseases or conditions in a mammal, including inflammatory diseases or conditions located in the gastrointestinal tract, genitourinary tract, oral cavity, lungs and/or airways, and/or the skin.
Treating inflammatory disease types selected from colitis, inflammatory bowel disease, irritable bowel syndrome, diverticulosis, gingivitis, vaginitis, or any combination thereof.
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