| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Glickman, Jonathan N. Kim, Jason H. Kulakauskas, Saulius Garrett, Wendy S. Fenn, Kathrin Ballal, Sonia A. Van Hylckama Vlieg, Johan Béal, Chloé Gallini, Carey Ann Quéré, Gaëlle Courtin, Pascal Derrien, Muriel Veiga, Patrick Garault, Peggy Michaud, Monia Chapot-chartier, Marie-pierre |
| Description |
Author Affiliation: Ballal SA ( Division of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital, Boston, MA 02115); Veiga P ( Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115); Fenn K ( Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115); Michaud M ( Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115); Kim JH ( Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115); Gallini CA ( Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115); Glickman JN ( Department of Pathology, Harvard Medical School, Boston, MA 02115); Quéré G ( Danone Nutricia Research, 91767 Palaiseau, France); Garault P ( Danone Nutricia Research, 91767 Palaiseau, France); Béal C ( Danone Nutricia Research, 91767 Palaiseau, France); Derrien M ( Danone Nutricia Research, 91767 Palaiseau, France); Courtin P ( Institut National de la Recherche Agronomique, UMR 1319 Micalis, 78352 Jouy-en-Josas, France); Kulakauskas S ( Institut National de la Recherche Agronomique, UMR 1319 Micalis, 78352 Jouy-en-Josas, France); Chapot-Chartier MP ( Institut National de la Recherche Agronomique, UMR 1319 Micalis, 78352 Jouy-en-Josas, France); van Hylckama Vlieg J ( Danone Nutricia Research, 91767 Palaiseau, France); Garrett WS ( Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115); |
| Abstract |
Beneficial microbes that target molecules and pathways, such as oxidative stress, which can negatively affect both host and microbiota, may hold promise as an inflammatory bowel disease therapy. Prior work showed that a five-strain fermented milk product (FMP) improved colitis in $T-bet^{−/−}$ $Rag2^{−/−}$ mice. By varying the number of strains used in the FMP, we found that Lactococcus lactis I-1631 was sufficient to ameliorate colitis. Using comparative genomic analyses, we identified genes unique to L. lactis I-1631 involved in oxygen respiration. Respiration of oxygen results in reactive oxygen species (ROS) generation. Also, ROS are produced at high levels during intestinal inflammation and cause tissue damage. L. lactis I-1631 possesses genes encoding enzymes that detoxify ROS, such as superoxide dismutase (SodA). Thus, we hypothesized that lactococcal SodA played a role in attenuating colitis. Inactivation of the sodA gene abolished L. lactis I-1631’s beneficial effect in the $T-bet^{−/−}$ $Rag2^{−/−}$ model. Similar effects were obtained in two additional colonic inflammation models, $Il10^{−/−}$ mice and dextran sulfate sodium-treated mice. Efforts to understand how a lipophobic superoxide anion $(O_{2}^{−})$ can be detoxified by cytoplasmic lactoccocal SodA led to the finding that host antimicrobial-mediated lysis is a prerequisite for SodA release and SodA’s extracytoplasmic $O_{2}^{−}$ scavenging. L. lactis I-1631 may represent a promising vehicle to deliver antioxidant, colitis-attenuating SodA to the inflamed intestinal mucosa, and host antimicrobials may play a critical role in mediating SodA’s bioaccessibility. |
| ISSN |
00278424 |
| e-ISSN |
10916490 |
| Journal |
Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number |
25 |
| Volume Number |
112 |
| Language |
English |
| Publisher |
National Academy of Sciences |
| Publisher Date |
2015-06-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Colitis Metabolism Lactococcus Lactis Muramidase Superoxide Dismutase Animals Enzymology Microbiology Intestinal Mucosa Mice Reactive Oxygen Species Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Multidisciplinary |
