A recombinant Bifidobacterium bifidum BGN4 strain expressing the streptococcal superoxide dismutase gene ameliorates inflammatory bowel disease

• Published in: Microbial cell factories Vol. 21; no. 1; p. 113
• Main Authors: Kang, Sini, Lin, Zhaoyan, Xu, Yang, Park, Minju, Ji, Geun Eog, Johnston, Tony V, Ku, Seockmo, Park, Myeong Soo
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 07.06.2022; BioMed Central; BMC
• Subjects: Analysis; Animals; Anti-Inflammatory Agents - adverse effects; Antioxidants; Antioxidants - metabolism; Bacteria; Bifidobacterium bifidum; Bifidobacterium bifidum - genetics; Care and treatment; Catalase; Colitis; Colitis - drug therapy; Colitis - therapy; Cytokines; Cytokines - metabolism; Dextran; Dextran Sulfate - adverse effects; Dextran Sulfate - metabolism; Dextrans; Diagnosis; Diarrhea; Disease Models, Animal; E coli; Enzymes; Gastrointestinal diseases; Gene expression; Genetic modification; Glutathione; Glutathione peroxidase; Human interleukin-10; Humans; IL-1β; Inflammation; Inflammatory bowel disease; Inflammatory bowel diseases; Inflammatory Bowel Diseases - drug therapy; Interleukin 10; Interleukin 6; Interleukin 8; Interleukin-10 - metabolism; Interleukins; Intestine; Lipopolysaccharides; Mice; Oral administration; Oxidative stress; Pain; Peroxidase; Probiotics; Probiotics - therapeutic use; Production processes; Risk factors; Signs and symptoms; Sodium sulfate; Streptococcus; Superoxide; Superoxide dismutase; Superoxide Dismutase - adverse effects; Superoxide Dismutase - genetics; Superoxide Dismutase - metabolism; Superoxide peroxidase; Synergistic effect; Tumor necrosis factor; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Weight loss; Zonula occludens-1 protein; South Korea; United States > US; Inflammatory bowel disease; Superoxide peroxidase; Catalase; Bifidobacterium bifidum; Human interleukin-10
• ISSN: 1475-2859; 1475-2859
• DOI: 10.1186/s12934-022-01840-2

Inflammatory bowel disease (IBD) is a gastrointestinal disease characterized by diarrhea, rectal bleeding, abdominal pain, and weight loss. Recombinant probiotics producing specific proteins with IBD therapeutic potential are currently considered novel drug substitutes. In this study, a Bifidobacterium bifidum BGN4-SK strain was designed to produce the antioxidant enzymes streptococcal superoxide dismutase (SOD) and lactobacillus catalase (CAT), and a B. bifidum BGN4-pBESIL10 strain was proposed to generate an anti-inflammatory cytokine, human interleukin (IL)-10. In vitro and in vivo efficacy of these genetically modified Bifidobacterium strains were evaluated for colitis amelioration. In a lipopolysaccharide (LPS)-stimulated HT-29 cell model, tumor necrosis factor (TNF)-α and IL-8 production was significantly suppressed in the B. bifidum BGN4-SK treatment, followed by B. bifidum BGN4-pBESIL10 treatment, when compared to the LPS-treated control. Synergistic effects on TNF-α suppression were also observed. In a dextran sodium sulphate (DSS)-induced colitis mouse model, B. bifidum BGN4-SK treatment significantly enhanced levels of antioxidant enzymes SOD, glutathione peroxidase (GSH-Px) and CAT, compared to the DSS-only group. B. bifidum BGN4-SK significantly ameliorated the symptoms of DSS-induced colitis, increased the expression of tight junction genes (claudin and ZO-1), and decreased pro-inflammatory cytokines IL-6, IL-1β and TNF-α. These findings suggest that B. bifidum BGN4-SK ameliorated DSS-induced colitis by generating antioxidant enzymes, maintaining the epithelial barrier, and decreasing the production of pro-inflammatory cytokines. Although B. bifidum BGN4-pBESIL10 exerted anti-inflammatory effects in vitro, the enhancement of IL-10 production and alleviation of colitis were very limited.