Co-administration of Lactobacillus gasseri KBL697 and tumor necrosis factor-alpha inhibitor infliximab improves colitis in mice

• Published in: Scientific reports Vol. 12; no. 1; pp. 9640 - 9
• Main Authors: Han, Dae Hee, Kim, Woon-ki, Lee, Cheonghoon, Park, SungJun, Lee, Kiuk, Jang, Sung Jae, Ko, GwangPyo
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10.06.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 631/250; 631/326; 692/700; Acetic acid; Animals; Body weight; CD25 antigen; CD4 antigen; Cecum; Colitis; Colitis - chemically induced; Colitis - drug therapy; Colitis - metabolism; Colon - pathology; Combined treatment; Cytokines - metabolism; Dextran; Dextran Sulfate - toxicity; Disease Models, Animal; Female; Foxp3 protein; Gastrointestinal tract; Histology; Humanities and Social Sciences; Immunologic Factors - pharmacology; Immunoregulation; Inflammatory bowel disease; Inflammatory bowel diseases; Inflammatory Bowel Diseases - pathology; Infliximab; Interleukin 10; Interleukin 6; Lactobacillus gasseri; Lymph nodes; Lymphocytes T; Metabolic pathways; Mice; Mice, Inbred C57BL; Monoclonal antibodies; multidisciplinary; Necrosis; Nucleic acids; Science; Science (multidisciplinary); Sodium sulfate; Synergistic effect; TNF inhibitors; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; Tumor necrosis factor-α; γ-Interferon
• DOI: 10.1038/s41598-022-13753-6
• ISSN: 2045-2322

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 × 10 9 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.