Selection of agents modulating gastrointestinal pain
Inventors
Conolly, Eamonn • Kunze, Wolfgang • Bienenstock, John
Assignees
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Publication Number
US-10656141-B2
Publication Date
2020-05-19
Expiration Date
Abstract
The present embodiments relate to selection of agents effective in reducing or preventing gastrointestinal pain in a subject. Such an agent is selected and identified if it is capable of reducing spontaneous and/or induced transient receptor potential vanilloid 1 (TRPV1) activation.
Core Innovation
The invention relates to selecting a lactic acid bacterial strain for reducing gastrointestinal pain locally in a subject. The method includes contacting a cell expressing transient receptor potential vanilloid 1 (TRPV1) with the bacterial strain, and measuring spontaneous and/or induced TRPV1 activation in the cell following the contacting.
The selected bacterial strain is effective in reducing gastrointestinal pain locally when the measured spontaneous and/or induced TRPV1 activation is lower than control TRPV1 activation. TRPV1 activation is measured as spontaneous and/or induced activation, including Ca2+ influx and stimuli such as capsaicin, pH change, and/or heat, or by temperature-gated ion-channel activity.
Preferred lactic acid bacteria include Lactobacillus reuteri, including Lactobacillus reuteri DSM 17938 (DSMZ Accession No. DSM 17938). The disclosure also describes using conditioned medium, including freeze-dried conditioned medium, and local gastrointestinal delivery and formulation/use for reducing or preventing gastrointestinal pain, with emphasis on limiting systemic TRPV1 modulation.
Claims Coverage
The partial document provides one independent claim with dependent claims that refine the TRPV1 activation measurement and narrow the bacterial strain identity. Across the claim set, the inventive elements include contacting TRPV1-expressing cells with a lactic acid bacterial strain, selecting based on reduced spontaneous and/or induced TRPV1 activation relative to control, and narrowing the bacterial strain to Lactobacillus reuteri and specifically Lactobacillus reuteri DSM 17938.
Selecting lactic acid bacteria by reduced TRPV1 activation
Contacting a cell expressing transient receptor potential vanilloid 1 (TRPV1) with the bacterial strain, measuring spontaneous and/or induced TRPV1 activation in said cell following the contacting, and selecting said bacterial strain effective in reducing gastrointestinal pain locally when said measured spontaneous and/or induced TRPV1 activation is lower than control TRPV1 activation.
Measuring TRPV1 activation by Ca2+ influx after stimulation
Measuring spontaneous and/or induced TRPV1 activation by measuring Ca2+ influx in a cell induced by capsaicin, pH change, and/or heat.
Measuring TRPV1 activation by temperature-gated ion-channel activity
Measuring spontaneous and/or induced TRPV1 activation by measuring temperature-gated ion-channel activity in the cell.
Using Lactobacillus reuteri as the bacterial strain
Carrying out the method using a Lactobacillus reuteri bacterial strain.
Using Lactobacillus reuteri DSM 17938 (DSMZ Accession No. DSM 17938)
Using the Lactobacillus reuteri bacterial strain identified as Lactobacillus reuteri DSM 17938 deposited under DSMZ Accession No. DSM 17938.
Overall, the claim coverage centers on selecting a lactic acid bacterial strain by contacting TRPV1-expressing cells and selecting for strains that reduce measured spontaneous and/or induced TRPV1 activation relative to control, with dependent refinements specifying Ca2+ influx, temperature-gated ion-channel activity readouts, and narrowing to Lactobacillus reuteri and specifically Lactobacillus reuteri DSM 17938.
Stated Advantages
Reduces gastrointestinal pain locally.
Documented Applications
No documented applications found
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