title: Probiotic Lactobacillus casei strain Shirota prevents indomethacin-induced small intestinal injury: involvement of lactic acid.
abstract: Inflammatory responses triggered by activation of the lipopolysaccharide (LPS)/Toll-like receptor (TLR) 4 signaling pathway are a key mechanism in nonsteroidal anti-inflammatory drug-induced enteropathy. The aim of this study was to investigate the probiotic effect of Lactobacillus casei strain Shirota (LcS) on indomethacin-induced small intestinal injury. Rats pretreated with viable LcS or heat-killed LcS once or once daily for a week were administered indomethacin by gavage to induce injury. Anti-inflammatory effects of L-lactic acid (1-15 mM) were evaluated in vitro by use of THP-1 cells. One-week treatment with viable LcS prevented indomethacin-induced intestinal injury with increase in the concentration of lactic acid in small intestinal content and inhibited increases in myeloperoxidase activity and expression of mRNA for tumor necrosis factor-alpha (TNF-alpha) while affecting neither TLR4 expression nor the number of gram-negative bacteria in intestinal content, whereas neither heat-killed LcS nor a single dose of viable LcS inhibited intestinal injury. Prevention of this injury was also observed in rats given l-lactic acid in drinking water. Both L-lactic acid and LcS culture supernatant containing 10 mM lactic acid inhibited NF-kappaB activation and increases in TNF-alpha mRNA expression and TNF-alpha protein secretion in THP-1 cells treated with LPS. Western blot analyses showed that both L-lactic acid and LcS culture supernatants suppressed phosphorylation and degradation of I-kappaB-alpha induced by LPS without affecting expression of TLR4. These findings suggest that LcS exhibits a prophylactic effect on indomethacin-induced enteropathy by suppressing the LPS/TLR4 signaling pathway and that this probiotic effect of LcS may be mediated by L-lactic acid.
authors: Dept. of Gastroenterology, Osaka City Univ. Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan. watanabet@med.osaka-cu.ac.jp
authors: Toshio
authors: T
authors: Watanabe
authors: Hikaru
authors: H
authors: Nishio
authors: Tetsuya
authors: T
authors: Tanigawa
authors: Hirokazu
authors: H
authors: Yamagami
authors: Hirotoshi
authors: H
authors: Okazaki
authors: Kenji
authors: K
authors: Watanabe
authors: Kazunari
authors: K
authors: Tominaga
authors: Yasuhiro
authors: Y
authors: Fujiwara
authors: Nobuhide
authors: N
authors: Oshitani
authors: Takashi
authors: T
authors: Asahara
authors: Koji
authors: K
authors: Nomoto
authors: Kazuhide
authors: K
authors: Higuchi
authors: Koji
authors: K
authors: Takeuchi
authors: Tetsuo
authors: T
authors: Arakawa
mesh_terms: D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007213:Indomethacin; D007410:Intestinal Diseases / Q000139:chemically induced / Q000378:metabolism / Q000382:microbiology / Q000517:prevention & control*; D007421:Intestine, Small / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D019344:Lactic Acid / Q000008:administration & dosage / Q000378:metabolism*; D007780:Lacticaseibacillus casei / Q000302:isolation & purification / Q000378:metabolism*; D008297:Male; D009000:Monocytes / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D010766:Phosphorylation; D019936:Probiotics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C000606206:Nfkbia protein, rat; D012333:RNA, Messenger; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D019344:Lactic Acid; D009195:Peroxidase; D007213:Indomethacin