title: Human-derived probiotic Lactobacillus reuteri strains differentially reduce intestinal inflammation.
abstract: Lactobacillus reuteri (L. reuteri) is a probiotic that inhibits the severity of enteric infections and modulates the immune system. Human-derived L. reuteri strains DSM17938, ATCC PTA4659, ATCC PTA 5289, and ATCC PTA 6475 have demonstrated strain-specific immunomodulation in cultured monocytoid cells, but information about how these strains affect inflammation in intestinal epithelium is limited. We determined the effects of the four different L. reuteri strains on lipopolysaccharide (LPS)-induced inflammation in small intestinal epithelial cells and in the ileum of newborn rats. IPEC-J2 cells (derived from the jejunal epithelium of a neonatal piglet) and IEC-6 cells (derived from the rat crypt) were treated with L. reuteri. Newborn rat pups were gavaged cow milk formula supplemented with L. reuteri strains in the presence or absence of LPS. Protein and mRNA levels of cytokines and histological changes were measured. We demonstrate that even though one L. reuteri strain (DSM 17938) did not inhibit LPS-induced IL-8 production in cultured intestinal cells, all strains significantly reduced intestinal mucosal levels of KC/GRO (∼IL-8) and IFN-γ when newborn rat pups were fed formula containing LPS ± L. reuteri. Intestinal histological damage produced by LPS plus cow milk formula was also significantly reduced by all four strains. Cow milk formula feeding (without LPS) produced mild gut inflammation, evidenced by elevated mucosal IFN-γ and IL-13 levels, a process that could be suppressed by strain 17938. Other cytokines and chemokines were variably affected by the different strains, and there was no toxic effect of L. reuteri on intestinal cells or mucosa. In conclusion, L. reuteri strains differentially modulate LPS-induced inflammation. Probiotic interactions with both epithelial and nonepithelial cells in vivo must be instrumental in modulating intrinsic anti-inflammatory effects in the intestine. We suggest that the terms anti- and proinflammatory be used only to describe the effects of a probiotic in the living host.
authors.affiliation: Department of Pediatrics, Division of Gastroenterology and Pediatric Research Institute, The University of Texas Health Science Center at Houston, Houston, Texas 7703, USA.
authors.forename: Yuying
authors.initials: Y
authors.lastname: Liu
authors.forename: Nicole Y
authors.initials: NY
authors.lastname: Fatheree
authors.forename: Nisha
authors.initials: N
authors.lastname: Mangalat
authors.forename: Jon Marc
authors.initials: JM
authors.lastname: Rhoads
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism / Q000382:microbiology*; D006801:Humans; D007082:Ileum / Q000378:metabolism / Q000382:microbiology*; D007249:Inflammation / Q000378:metabolism / Q000382:microbiology*; D016209:Interleukin-8 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism / Q000382:microbiology; D007583:Jejunum / Q000166:cytology / Q000378:metabolism / Q000382:microbiology*; D052200:Limosilactobacillus reuteri; D019936:Probiotics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine
chemical_list: D016209:Interleukin-8
references.citation: J Pediatr Gastroenterol Nutr. 2006 May;42(5):545-52
references.pmid: 16707979
references.citation: Pediatrics. 2007 Jan;119(1):e124-30
references.pmid: 17200238
references.citation: Clin Exp Allergy. 2010 May;40(5):811-9
references.pmid: 20067483
references.citation: Kansenshogaku Zasshi. 2007 Jul;81(4):387-93
references.pmid: 17695792
references.citation: J Surg Res. 2000 Jul;92(1):71-7
references.pmid: 10864485
references.citation: Pediatr Res. 2008 Feb;63(2):117-23
references.pmid: 18091350
references.citation: Clin Infect Dis. 2008 Feb 1;46 Suppl 2:S67-72; discussion S144-51
references.pmid: 18181726
references.citation: Curr Issues Intest Microbiol. 2001 Sep;2(2):43-53
references.pmid: 11721280
references.citation: J Immunol. 2001 Aug 1;167(3):1609-16
references.pmid: 11466383
references.citation: Antimicrob Agents Chemother. 1989 May;33(5):674-9
references.pmid: 2751282
references.citation: Digestion. 1994;55(3):179-84
references.pmid: 8174832
references.citation: Infect Immun. 2004 Sep;72(9):5308-14
references.pmid: 15322027
references.citation: Appl Environ Microbiol. 2004 Jan;70(1):558-68
references.pmid: 14711688
references.citation: J Clin Invest. 1997 Jul 1;100(1):6-10
references.pmid: 9202050
references.citation: J Allergy Clin Immunol. 2007 May;119(5):1174-80
references.pmid: 17349686
references.citation: J Pediatr Gastroenterol Nutr. 2009 Feb;48(2):126-41
references.pmid: 19179874
references.citation: Inflamm Bowel Dis. 2008 Aug;14(8):1068-83
references.pmid: 18425802
references.citation: BMC Microbiol. 2009 Feb 11;9:35
references.pmid: 19210794
references.citation: Gastroenterology. 1999 May;116(5):1107-14
references.pmid: 10220502
references.citation: Am J Physiol Gastrointest Liver Physiol. 2009 Sep;297(3):G442-50
references.pmid: 19608731
references.citation: Curr Opin Microbiol. 1999 Feb;2(1):99-105
references.pmid: 10047563
references.citation: Inflamm Bowel Dis. 2009 Feb;15(2):300-10
references.pmid: 18626975
references.citation: Am J Physiol Gastrointest Liver Physiol. 2004 Jun;286(6):G914-21
references.pmid: 14726310
references.citation: Appl Environ Microbiol. 2004 Feb;70(2):1176-81
references.pmid: 14766603
references.citation: Environ Health. 2005 Nov 07;4:25
references.pmid: 16274475
references.citation: J Pediatr Surg. 2006 Jan;41(1):144-9; discussion 144-9
references.pmid: 16410124
references.citation: Gastroenterology. 2004 Apr;126(4):1054-70
references.pmid: 15057745
references.citation: PLoS Pathog. 2008 Aug 01;4(8):e1000112
references.pmid: 18670628
references.citation: Infect Immun. 2003 Jun;71(6):3503-11
references.pmid: 12761135
references.citation: Histochem Cell Biol. 2006 Mar;125(3):293-305
references.pmid: 16215741
references.citation: Amino Acids. 2009 May;37(1):131-42
references.pmid: 19189199
references.citation: Surgery. 2005 Apr;137(4):393-5
references.pmid: 15800483
references.citation: Am J Gastroenterol. 2000 Jan;95(1 Suppl):S16-8
references.pmid: 10634223
references.citation: J Immunol. 2000 Jan 15;164(2):966-72
references.pmid: 10623846
references.citation: Pediatr Res. 2009 Apr;65(4):437-42
references.pmid: 19127210