4.6 Article

Recombinant Bifidobacterium longum Carrying Endostatin Protein Alleviates Dextran Sodium Sulfate-Induced Colitis and Colon Cancer in Rats

Journal

FRONTIERS IN MICROBIOLOGY
Volume 13, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fmicb.2022.927277

Keywords

inflammatory bowel disease; Bifidobacterium; endostatin; colon cancer; gut microbiota

Categories

Funding

  1. Chinese National Natural Sciences Foundation [82130106, 81773099]
  2. National Key R&D Program of China [2017YFA0506002]
  3. Jiangsu Province Natural Sciences Foundation [BK2019 2005]

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This study demonstrates that using Bifidobacterium longum as a delivery system for endostatin can effectively alleviate symptoms of inflammatory bowel disease and colitis-associated cancer. The combination of endostatin and B. longum also reduces tumor formation and alters the gut microbiota, suggesting a promising therapeutic strategy.
Bifidobacterium has been widely administrated orally as probiotics to prevent pathogen colonization and modulate the gut microbiome balance. Endostatin is an endogenous inhibitor of angiogenesis and has been shown to inhibit tumor growth, invasion, and metastasis. At present, the combination of endostatin and chemotherapeutic drugs has been regarded as a promising antitumor treatment strategy. In this study, we selected a safe strain of Bifidobacterium longum as a delivery system to transport endostatin to the gastrointestinal tract and explored their combined effect on inflammatory bowel disease (IBD) and colitis-associated cancer. The results indicated that B. longum-Endo relieved dextran sulfate sodium-induced body weight loss, diarrhea, colon shortening, and epithelium damage. Long-term oral administration of B. longum-Endo significantly decreased tumor formation rate, tumor number, and tumor size. Moreover, the effect of B. longum-Endo on gut microbiota dysbiosis was also confirmed by 16S rRNA sequencing analysis. The levels of potentially beneficial bacteria, such as Lactobacillus, Bifidobacterium, Allobaculum, and Parabateroides, were increased in the B. longum-Endo group compared to the model and B. longum groups. Meanwhile, levels of potentially pathogenic bacteria including Desulfovibrio, Helicobacter, and Enterorhabdus were decreased. Taken together, these results suggested that oral administration of recombinant B. longum-Endo strain may be a promising therapeutic strategy for IBD and colitis-associated cancer.

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