title: Lactobacillus bulgaricus OLL1181 activates the aryl hydrocarbon receptor pathway and inhibits colitis.
abstract: Increasing evidence suggests that the aryl hydrocarbon receptor (AhR) pathway has an important role in the regulation of inflammatory responses. Most recently, we have shown that the activation of the AhR pathway by a potent AhR agonist inhibits the development of dextran sodium sulfate (DSS)-induced colitis, a model of human ulcerative colitis, by the induction of prostaglandin E2 (PGE2) in the large intestine. Because several strains of probiotic lactic acid bacteria have been reported to inhibit DSS-induced colitis by unidentified mechanisms, we hypothesized that particular strains of lactic acid bacterium might have the potential to activate the AhR pathway, thereby inhibiting DSS-induced colitis. This study investigated whether there are specific lactic acid bacterial strains that can activate the AhR pathway, and if so, whether this AhR-activating potential is associated with suppression of DSS-induced colitis. By using AhR signaling reporter cells, we found that Lactobacillus bulgaricus OLL1181 had the potential to activate the AhR pathway. OLL1181 also induced the mRNA expression of cytochrome P450 family 1A1 (CYP1A1), a target gene of the AhR pathway, in human colon cells, which was inhibited by the addition of an AhR antagonist, α-naphthoflavon (αNF). In addition, mice treated orally with OLL1181 showed an increase in CYP1A1 mRNA expression in the large intestine and amelioration of DSS-induced colitis. Thus, OLL1181 can induce activation of the intestinal AhR pathway and inhibit DSS-induced colitis in mice. This strain of lactic acid bacterium has therefore the potential to activate the AhR pathway, which may be able to suppress colitis.
authors.affiliation: Department of Immunology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
authors.forename: Takeyuki
authors.initials: T
authors.lastname: Takamura
authors.forename: Daisuke
authors.initials: D
authors.lastname: Harama
authors.forename: Suguru
authors.initials: S
authors.lastname: Fukumoto
authors.forename: Yuki
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Naomi
authors.initials: N
authors.lastname: Shimokawa
authors.forename: Kayoko
authors.initials: K
authors.lastname: Ishimaru
authors.forename: Shuji
authors.initials: S
authors.lastname: Ikegami
authors.forename: Seiya
authors.initials: S
authors.lastname: Makino
authors.forename: Masanori
authors.initials: M
authors.lastname: Kitamura
authors.forename: Atsuhito
authors.initials: A
authors.lastname: Nakao
mesh_terms: D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology; D045744:Cell Line, Tumor; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D003106:Colon / Q000378:metabolism / Q000382:microbiology; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism*; D016264:Dextran Sulfate / Q000494:pharmacology; D005260:Female; D006801:Humans; D007778:Lactobacillus / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019936:Probiotics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D001571:Benzoflavones; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; C011512:alpha-naphthoflavone; D016264:Dextran Sulfate; D019363:Cytochrome P-450 CYP1A1