Journal Article

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

Kang, Sini, Lin, Zhaoyan, Xu, Yang, Park, Minju, Ji, Geun Eog, Park, Myeong Soo, Ku, Seockmo, Johnston, Tony V.

2022

Overview

Background 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. Results 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. Conclusions 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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Analysis / Antioxidants / Applied Microbiology / Bacteria / Bifidobacterium bifidum / Biotechnology / Care and treatment / Catalase / Chemistry / Chemistry and Materials Science / Colitis / Cytokines / Dextran / Dextrans / Diagnosis / Diarrhea / E coli / Enzymes / Enzymology / Gastrointestinal diseases / Gene expression / Genetic Engineering / Genetic modification / Glutathione / Glutathione peroxidase / Human interleukin-10 / IL-1β / Inflammation / Inflammatory bowel disease / Inflammatory bowel diseases / Interleukin 10 / Interleukin 6 / Interleukin 8 / Interleukins / Intestine / Lipopolysaccharides / Microbial Genetics and Genomics / Microbiology / Oral administration / Oxidative stress / Peroxidase / Probiotics / Production processes / Risk factors / Signs and symptoms / Sodium sulfate / Streptococcus / Superoxide / Superoxide dismutase / Superoxide peroxidase / Synergistic effect / Tumor necrosis factor / Tumor necrosis factor-TNF / Tumor necrosis factor-α / Weight loss / Zonula occludens-1 protein