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

Abstract

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.

Intestinal bacteria and colorectal cancer: etiology and treatment

“…that promote anti-tumor immunity or directly induce cancer cell apoptosis. 156 , 157 Similar anti-tumorigenic effects have been observed after colonization by other LAB such as Bifidobacterium longum ( B. longum ) 158 and Streptococcus thermophilus ( S. thermophilus ) 159 ( Figure 3 ).

Figure 3.

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“…For example, oral administration of a high dose of B. longum (four 14-day cycles with 7 days between, 1.5 × 10 10 CFU) inhibited tumor initiation in rats treated with AOM/DSS and consequently ameliorated Lactobacillus depletion observed in AOM/DSS rats not gavaged with B. longum . 158 Similarly, daily gavage with Lactobacillus gallinarium ( L. gallinarium ) reduced tumor number and size in both Apc Min/+ and AOM/DSS mouse models, with a concomitant increase in other probiotic species like L. reuteri . 160 While these findings suggest that colonization with LAB promotes the proliferation or persistence of other probiotic species, the underlying mechanism remains unclear ( Figure 3 ).…”

Genetically engineered bacteria: a new frontier in targeted drug delivery

“…119 In addition, it has been demonstrated that the utilization of a secure strain of B. longum as a mode of transportation for the delivery of endostatin to the gastrointestinal tract has a relieving effect on epithelium injury, loss of body weight, diarrhea, and colon shortening of DSS-induced colitis model. 120 The results of this investigation imply that the delivery of recombinant B. longum -Endo strain through oral administration holds potential as a promising therapeutic approach for the treatment of IBD and colitis-associated cancers. 120 Looking ahead, the promising findings from the research on engineered probiotics for the treatment of IBD offer exciting possibilities for the future of gastroenterology and personalized medicine.…”

“…120 The results of this investigation imply that the delivery of recombinant B. longum -Endo strain through oral administration holds potential as a promising therapeutic approach for the treatment of IBD and colitis-associated cancers. 120 Looking ahead, the promising findings from the research on engineered probiotics for the treatment of IBD offer exciting possibilities for the future of gastroenterology and personalized medicine. The development and utilization of probiotic strains such as Bifidobacterium bifidum BGN4-SK and B. bifidum BGN4-pBESIL10, along with recombinant B. longum-Endo , represent innovative strategies that could transform IBD management.…”

Atox1 regulates macrophage polarization in intestinal inflammation via ROS-NLRP3 inflammasome pathway

“…Mice were examined daily for diarrhea and rectal bleeding. Disease activity index (DAI) was determined by scoring changes in body weight, presence of blood in stool, and stool consistency, as described previously [ 26 ]. After 72–96 h of TNBS instillation, the mice were euthanized, and the colon tissues were collected.…”