title: Luminal contents from the gut of colicky infants induce visceral hypersensitivity in mice.
abstract: BACKGROUND
  The pathophysiology of infantile colic is poorly understood, though various studies report gut microbiota dysbiosis in colicky infants. We aimed to test the hypothesis that colic-related dysbiosis is associated with visceral hypersensitivity triggered by an altered luminal milieu.
  
  
  METHODS
  Fecal samples from seven colicky and seven non-colicky infants were studied. Fecal supernatants (FS) were infused into the colons of C57/Bl6 mice (n=10/specimen). Visceral sensitivity was subsequently assessed in the animals by recording their abdominal muscle response to colorectal distension (CRD) by electromyography (EMG). Serine and cysteine protease activities were assessed in FS with specific substrates. Infant fecal microbiota composition was analyzed by DNA extraction and 16S rRNA gene pyrosequencing.
  
  
  RESULTS
  FS from colicky infants triggered higher EMG activity than FS from non-colicky infants in response to both the largest CRD volumes and overall, as assessed by the area under the curve of the EMG across all CRD volumes. Infant crying time strongly correlated with mouse EMG activity. Microbiota richness and phylogenetic diversity were increased in the colicky group, without showing prominent microbial composition alterations. Only Bacteroides vulgatus and Bilophila wadsworthia were increased in the colicky group. Bacteroides vulgatus abundance positively correlated with visceral sensitivity. No differences were found in protease activities.
  
  
  CONCLUSIONS
  Luminal contents from colicky infants trigger visceral hypersensitivity, which may explain the excessive crying behavior of these infants. Additional studies are required to determine the nature of the compounds involved, their mechanism of action, and the potential implications of intestinal microbiota in their generation.
authors.affiliation: Neuro-Gastroenterology and Nutrition, Toxalim UMR 1331 INRA/INP/UPS, Toulouse, France.
authors.forename: H
authors.initials: H
authors.lastname: Eutamène
authors.affiliation: Nutrition and Health Research, Nestlé Research Center, Lausanne, Switzerland.
authors.forename: C L
authors.identifier: http://orcid.org/0000-0003-1685-5364
authors.initials: CL
authors.lastname: Garcia-Rodenas
authors.affiliation: Neuro-Gastroenterology and Nutrition, Toxalim UMR 1331 INRA/INP/UPS, Toulouse, France.
authors.forename: S
authors.initials: S
authors.lastname: Yvon
authors.affiliation: IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, Toulouse, France.
authors.forename: E
authors.initials: E
authors.lastname: d'Aldebert
authors.affiliation: Nutrition and Health Research, Nestlé Research Center, Lausanne, Switzerland.
authors.forename: F
authors.initials: F
authors.lastname: Foata
authors.affiliation: Nutrition and Health Research, Nestlé Research Center, Lausanne, Switzerland.
authors.forename: B
authors.initials: B
authors.lastname: Berger
authors.affiliation: Clinical Development Unit, Nestlé Research Center, Lausanne, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Sauser
authors.affiliation: Neuro-Gastroenterology and Nutrition, Toxalim UMR 1331 INRA/INP/UPS, Toulouse, France.
authors.forename: V
authors.initials: V
authors.lastname: Theodorou
authors.affiliation: Nutrition and Health Research, Nestlé Research Center, Lausanne, Switzerland.
authors.forename: G
authors.initials: G
authors.lastname: Bergonzelli
authors.affiliation: IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, Toulouse, France.|Unité de Gastroenterology, Hépatologie, Nutrition, Diabétologie et Maladies Héréditaires du Metabolism, Hôpital des Enfants, Toulouse, France.
authors.forename: E
authors.initials: E
authors.lastname: Mas
mesh_terms: D000818:Animals; D003085:Colic / Q000150:complications / Q000503:physiopathology*; D003106:Colon / Q000382:microbiology / Q000503:physiopathology; D004576:Electromyography / Q000379:methods; D005243:Feces / Q000382:microbiology; D041981:Gastrointestinal Tract / Q000382:microbiology / Q000503:physiopathology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D059265:Visceral Pain / Q000139:chemically induced* / Q000503:physiopathology*
keywords: colorectal distension; fecal microbiota; infantile colic; visceral sensitivity