title: Probiotics VSL#3 protect against development of visceral pain in murine model of irritable bowel syndrome.
abstract: OBJECTIVE
  Irritable bowel syndrome (IBS) is linked to post-inflammatory and stress-correlated factors that cause changes in the perception of visceral events. Probiotic bacteria may be effective in treating IBS symptoms. Here, we have investigated whether early life administration of VSL#3, a mixture of 8 probiotic bacteria strains, protects against development of visceral hypersensitivity driven by neonatal maternal separation (NMS), a rat model of IBS.
  
  
  METHODS
  Male NMS pups were treated orally with placebo or VSL#3 from days 3 to 60, while normal, not separated rats were used as controls. After 60 days from birth, perception of painful sensation induced by colorectal distension (CRD) was measured by assessing the abdominal withdrawal reflex (score 0-4). The colonic gene expression was assessed by using the Agilent Whole Rat Genome Oligo Microarrays platform and confirmed by real time PCR.
  
  
  RESULTS
  NMS rats exhibited both hyperalgesia and allodynia when compared to control rats. VSL#3 had a potent analgesic effect on CRD-induced pain without changing the colorectal compliance. The microarray analysis demonstrated that NMS induces a robust change in the expression of subsets of genes (CCL2, NOS3, THP1, NTRK1, CCR2, BDRKRB1, IL-10, TNFRSF1B, TRPV4, CNR1 and OPRL1) involved in pain transmission and inflammation. TPH1, tryptophan hydroxylase 1, a validated target gene in IBS treatment, was markedly upregulated by NMS and this effect was reversed by VSL#3 intervention.
  
  
  CONCLUSIONS
  Early life administration of VSL#3 reduces visceral pain perception in a model of IBS and resets colonic expression of subsets of genes mediating pain and inflammation.
  Accession number of repository for expression microarray data is GSE38942 (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE38942).
authors.affiliation: S.C. di Gastroenterologia ed Epatologia, Azienda Ospedaliera di Perugia, Perugia, Italy. eleonoradistrutti@katamail.com
authors.forename: Eleonora
authors.initials: E
authors.lastname: Distrutti
authors.forename: Sabrina
authors.initials: S
authors.lastname: Cipriani
authors.forename: Andrea
authors.initials: A
authors.lastname: Mencarelli
authors.forename: Barbara
authors.initials: B
authors.lastname: Renga
authors.forename: Stefano
authors.initials: S
authors.lastname: Fiorucci
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D004195:Disease Models, Animal; D043183:Irritable Bowel Syndrome / Q000150:complications*; D008297:Male; D051379:Mice; D010919:Placebos; D019936:Probiotics; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D059265:Visceral Pain / Q000209:etiology / Q000517:prevention & control*
chemical_list: D017931:DNA Primers; D010919:Placebos