Method for selection of agents influencing intestinal motility disorders and pain

Abstract

A method is provided for evaluating agents for the treatment of different intestinal motility disorders, using distinct methodological parts related to musculature and nerves of the GI tract which communicate with the brain. In particular, the present invention provides a method for the selection of an agent effective for the treatment of an intestinal motility disorder, wherein said method comprises: a) a step of spatiotemporal (ST) mapping carried out on a gastrointestinal segment to analyse the effect of said agent on gastrointestinal motility; and b) a step of ex vivo nerve bundle recording carried out on a gastrointestinal segment to analyse the effect of said agent on mesenteric afferent nerve firing. Bacterial strains selected by the methods of the invention and the use of said bacterial strains in the treatment of intestinal motility disorders are also provided.

1 . A method of treating poor nutritional uptake without increasing the risk for constipation in a subject having poor nutritional uptake, the method comprising administering to the subject a  Lactobacillus reuteri  bacterial strain that has differential effects on transit time in the jejunum and in the colon, wherein the  L. reuteri  bacterial strain decreases MMC frequency and MMC velocity in the jejunum, increases MMC frequency and MMC velocity in the colon, thereby increasing transit time of material through the jejunum, resulting in increased nutritional uptake in the jejunum and decreasing the transit time of material through the colon, resulting in reduced risk for constipation, thereby treating poor nutritional uptake without increasing the risk for constipation. 
     
     
         2 . The method of  claim 1 , wherein the  L. reuteri  bacterial strain decreases mesenteric afferent nerve firing in both jejunum and colon, thereby decreasing pain signalling in the jejunum and colon. 
     
     
         3 . The method of  claim 1 , wherein decreasing MMC frequency and MMC velocity in the jejunum of the subject reduces jejunum motility and increasing MMC frequency and MMC velocity in the colon of the subject increases colon motility. 
     
     
         4 . The method according to  claim 1 , wherein said  L. reuteri  bacterial strain is  L. reuteri  DSM 17938, having been deposited under DSMZ Accession No. DSM 17938. 
     
     
         5 . The method of  claim 1 , wherein the subject having or at risk of having poor nutritional uptake is a newborn, an infant, a toddler or a child. 
     
     
         6 . The method of  claim 1 , wherein the subject having or at risk of having poor nutritional uptake is an elderly subject. 
     
     
         7 . A method of decreasing migrating motor complex (MMC) frequency and MMC velocity in the jejunum and increasing MMC frequency and MMC velocity in the colon of a subject diagnosed with poor nutritional uptake, the method comprising administering to said subject diagnosed with poor nutritional uptake a  Lactobacillus reuteri  bacterial strain that has differential effects on MMC frequency and velocity in the jejunum and colon, wherein the  L. reuteri  bacterial strain decreases MMC frequency and MMC velocity in the jejunum of the subject and increases MMC frequency and MMC velocity in the colon of the subject, thereby increasing transit time of material through the jejunum and decreasing transit time of material through the colon. 
     
     
         8 . The method of  claim 7 , wherein decreasing MMC frequency and MMC velocity in the jejunum of the subject reduces jejunum motility and increasing MMC frequency and MMC velocity in the colon of the subject increases colon motility. 
     
     
         9 . The method of  claim 7 , wherein increasing transit time results in increased nutritional uptake in the jejunum and decreasing transit time of material through the colon reduces the risk for constipation. 
     
     
         10 . The method of  claim 7 , wherein the  L. reuteri  bacterial strain decreases mesenteric afferent nerve firing in both jejunum and colon, thereby decreasing pain signalling in the jejunum and colon. 
     
     
         11 . The method according to  claim 7 , wherein said  L. reuteri  bacterial strain is  L. reuteri  DSM 17938, having been deposited under DSMZ Accession No. DSM 17938. 
     
     
         12 . The method of  claim 7 , wherein the subject diagnosed with poor nutritional uptake is a newborn, an infant, a toddler or a child. 
     
     
         13 . The method of  claim 7 , wherein the subject diagnosed with poor nutritional uptake is an elderly subject.