Co-administration of Lactobacillus gasseri KBL697 and tumor necrosis factor-alpha inhibitor infliximab improves colitis in mice
Abstract Inflammatory bowel disease (IBD) refers to disorders involving chronic inflammation of the gastrointestinal tract. Well-established treatments for IBD have not yet to be suggested. To address this gap, we investigated the effects of co-administration of Lactobacillus gasseri (L. gasseri) KB...
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| Format: | Article |
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Nature Portfolio
2022-06-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-13753-6 |
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| author | Dae Hee Han Woon-ki Kim Cheonghoon Lee SungJun Park Kiuk Lee Sung Jae Jang GwangPyo Ko |
| author_facet | Dae Hee Han Woon-ki Kim Cheonghoon Lee SungJun Park Kiuk Lee Sung Jae Jang GwangPyo Ko |
| author_sort | Dae Hee Han |
| collection | DOAJ |
| description | Abstract Inflammatory bowel disease (IBD) refers to disorders involving chronic inflammation of the gastrointestinal tract. Well-established treatments for IBD have not yet to be suggested. To address this gap, we investigated the effects of co-administration of Lactobacillus gasseri (L. gasseri) KBL697 and infliximab (IFX), the first approved tumor necrosis factor (TNF)-alpha inhibitor, on the dextran sodium sulfate-induced colitis mouse model. 2 × 109 colony-forming units/g of L. gasseri KBL697 were administered to seven-week-old female C57BL/6J mice daily by oral gavage. On day three, IFX (5 mg/kg) suspended in 1 × PBS (200 µL) was intravenously injected in the IFX-treated group and all mice were sacrificed on day nine. Co-administration of L. gasseri KBL697 and IFX improved colitis symptoms in mice, including body weight, disease activity index, colon length, and histology score. Additionally, pro-inflammatory cytokines, such as interferon-gamma, interleukin (IL)-2, IL-6, IL-17A, and TNF were significantly decreased, while IL-10, an anti-inflammatory cytokine, was increased. Expression levels of tight junction genes and CD4 + CD25 + Foxp3 + T regulatory cells in the mesenteric lymph nodes were synergistically upregulated with the combined treatment. Furthermore, co-administered mice displayed altered cecum microbial diversity and composition with increases in the genus Prevotella. Related changes in the predicted amino and nucleic acid metabolic pathways were also evident, along with increased acetate and butyrate level. Therefore, the synergistic effect of L. gasseri KBL697 and IFX co-administration is a possible method of prevention and treatment for IBD. |
| first_indexed | 2024-12-12T16:35:58Z |
| format | Article |
| id | doaj.art-3a728122eb0e4d32911e533ee7d291c7 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-12T16:35:58Z |
| publishDate | 2022-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-3a728122eb0e4d32911e533ee7d291c72022-12-22T00:18:40ZengNature PortfolioScientific Reports2045-23222022-06-011211910.1038/s41598-022-13753-6Co-administration of Lactobacillus gasseri KBL697 and tumor necrosis factor-alpha inhibitor infliximab improves colitis in miceDae Hee Han0Woon-ki Kim1Cheonghoon Lee2SungJun Park3Kiuk Lee4Sung Jae Jang5GwangPyo Ko6Department of Environmental Health Sciences, Graduate School of Public Health, Seoul National UniversityDepartment of Environmental Health Sciences, Graduate School of Public Health, Seoul National UniversityDepartment of Environmental Health Sciences, Graduate School of Public Health, Seoul National UniversityDepartment of Environmental Health Sciences, Graduate School of Public Health, Seoul National UniversityKoBioLabs, IncDepartment of Environmental Health Sciences, Graduate School of Public Health, Seoul National UniversityDepartment of Environmental Health Sciences, Graduate School of Public Health, Seoul National UniversityAbstract Inflammatory bowel disease (IBD) refers to disorders involving chronic inflammation of the gastrointestinal tract. Well-established treatments for IBD have not yet to be suggested. To address this gap, we investigated the effects of co-administration of Lactobacillus gasseri (L. gasseri) KBL697 and infliximab (IFX), the first approved tumor necrosis factor (TNF)-alpha inhibitor, on the dextran sodium sulfate-induced colitis mouse model. 2 × 109 colony-forming units/g of L. gasseri KBL697 were administered to seven-week-old female C57BL/6J mice daily by oral gavage. On day three, IFX (5 mg/kg) suspended in 1 × PBS (200 µL) was intravenously injected in the IFX-treated group and all mice were sacrificed on day nine. Co-administration of L. gasseri KBL697 and IFX improved colitis symptoms in mice, including body weight, disease activity index, colon length, and histology score. Additionally, pro-inflammatory cytokines, such as interferon-gamma, interleukin (IL)-2, IL-6, IL-17A, and TNF were significantly decreased, while IL-10, an anti-inflammatory cytokine, was increased. Expression levels of tight junction genes and CD4 + CD25 + Foxp3 + T regulatory cells in the mesenteric lymph nodes were synergistically upregulated with the combined treatment. Furthermore, co-administered mice displayed altered cecum microbial diversity and composition with increases in the genus Prevotella. Related changes in the predicted amino and nucleic acid metabolic pathways were also evident, along with increased acetate and butyrate level. Therefore, the synergistic effect of L. gasseri KBL697 and IFX co-administration is a possible method of prevention and treatment for IBD.https://doi.org/10.1038/s41598-022-13753-6 |
| spellingShingle | Dae Hee Han Woon-ki Kim Cheonghoon Lee SungJun Park Kiuk Lee Sung Jae Jang GwangPyo Ko Co-administration of Lactobacillus gasseri KBL697 and tumor necrosis factor-alpha inhibitor infliximab improves colitis in mice Scientific Reports |
| title | Co-administration of Lactobacillus gasseri KBL697 and tumor necrosis factor-alpha inhibitor infliximab improves colitis in mice |
| title_full | Co-administration of Lactobacillus gasseri KBL697 and tumor necrosis factor-alpha inhibitor infliximab improves colitis in mice |
| title_fullStr | Co-administration of Lactobacillus gasseri KBL697 and tumor necrosis factor-alpha inhibitor infliximab improves colitis in mice |
| title_full_unstemmed | Co-administration of Lactobacillus gasseri KBL697 and tumor necrosis factor-alpha inhibitor infliximab improves colitis in mice |
| title_short | Co-administration of Lactobacillus gasseri KBL697 and tumor necrosis factor-alpha inhibitor infliximab improves colitis in mice |
| title_sort | co administration of lactobacillus gasseri kbl697 and tumor necrosis factor alpha inhibitor infliximab improves colitis in mice |
| url | https://doi.org/10.1038/s41598-022-13753-6 |
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