Valérie Petit

Commensal and probiotic bacteria influence intestinal barrier function and susceptibility to colitis in Nod1-/-; Nod2-/- mice.

Background: The intestinal microbiota regulates key host functions. It is unknown whether modulation of the microbiota can affect a genetically determined host phenotype. Polymorphisms in the Nucleotide oligomerization domain (Nod)‐like receptor family confer genetic risk for inflammatory bowel disease (IBD). We investigated whether the intestinal microbiota and the probiotic strain Bifidobacterium breve NCC2950 affect intestinal barrier function and responses to intestinal injury in Nod1−/−;Nod2−/− mice. Methods: Specific pathogen‐free (SPF) Nod1−/−;Nod2−/− mice and mice gnotobiotically derived with altered Schaedler flora (ASF) biota were used. SPF Nod1+/−;Nod2+/−littermates (generated by crossing SPF Nod1−/−;Nod2−/− and germ‐free C57BL/6 mice) and ASF Nod1+/−;Nod2+/− mice were used as controls. SPF mice were gavaged daily with 109‐CFU B. breve for 14 days before colitis induction. Denaturing gradient gel electrophoresis (DGGE) and real‐time polymerase chain reaction (PCR) were used to assess microbiota composition. Intestinal permeability was assessed by in vitro and in vivo techniques. Expressions of epithelial apical junction proteins, mucin, and antimicrobial proteins were assessed by quantitative reverse‐transcription PCR (qRT‐PCR) and immunofluorescence. Responses to intestinal injury were investigated using an acute experimental model of colitis. Results: Under SPF conditions, Nod1−/−;Nod2−/− mice had increased paracellular permeability, decreased E‐cadherin, and lower colonic antimicrobial RegIII‐&ggr; expression compared to Nod1+/−;Nod2+/− littermate controls. These changes were associated with increased susceptibility to colitis. ASF colonization or B. breve supplementation normalized RegIII‐&ggr; expression and decreased susceptibility to dextran sodium sulfate (DSS) colitis in Nod1−/−;Nod2−/− mice. Conclusions: The intestinal microbiota influences colitis severity in Nod1−/−;Nod2−/− mice. The results suggest that colonization strategies with defined commensals or exogenous specific probiotic therapy may prevent intestinal inflammation in a genetically predisposed host. (Inflamm Bowel Dis 2012)

Importance of the regiospecific distribution of long-chain saturated fatty acids on gut comfort, fat and calcium absorption in infants

Gastrointestinal tolerance and fat and calcium (Ca) absorption are different between breast-fed (BF) and formula-fed (FF) infants. Certain components and/or structural particularities in human milk (HM), can contribute to favorable outcomes in BF infants. In HM, the long-chain saturated fatty acid (LCSFA) palmitic acid has a different stereospecific distribution (sn-2 position) compared to most infant formula (IF) (primarily sn-1, 3 positions), which may contribute to unfavorable outcomes. Evidence suggests palmitic acid is important in the formation of stool FA-mineral (or FA-Ca) soaps, associated with harder stools in FF infants. Partial replacement by structured palmitic acid-rich triacylglycerols (TAGs) promotes palmitic acid absorption. However, evidence for stool softening, improved fat absorption and reduced Ca excretion in stools is inconsistent. IFs with less palmitic acid can improve fat and Ca absorption, and stool consistency. The presence of other LCSFAs (myristic and stearic acids) in sn-1, 3 positions may also contribute to reduced absorption of fat and Ca, and stool hardness, in FF infants. Nevertheless, little attention has been given to modifying these other LCSFAs in IF. We review literature comparing the effect of HM and IF with different lipid compositions on stool patterns and/or fat and Ca absorption in healthy, term infants. Based on available data, we estimate a maximum level for sn-1, 3 LCSFAs of 13% of TAGs, under which fat and Ca absorption and stool consistency are improved. IF designed according to this threshold could efficiently improve nutrient absorption and stool patterns in healthy infants who cannot be breast-fed.