Bacteroides ovatus as Next Generation Probiotics

The ability to engineer commensal bacteria to produce immunomodulatory molecules offers the potential of providing a more measured, specific, and controlled therapy for chronic gut disorders. This approach could be used to deliver a variety of biologically relevant molecules, including enzymes, cytokines, and vaccines, with applications in the treatment and prevention of a variety of disorders. Armed with rich experience in disease treatment and live biotherapeutics drug discovery, Creative Biolabs has developed novel systems for the controlled in vivo delivery of biologically active ingredients by genetically modified Bacteroides ovatus (B. ovatus).

B. ovatus Introduction

B. ovatus is a major human commensal colonic gram-negative anaerobe and is normally considered for use in molecular-based methods as a general fecal indicator. It is a member of the genus Bacteroides which are anaerobic, bile-resistant, non-spore-forming, gram-negative rods. Fig.1 indicates the percentages of anaerobic infections that involve particular species of Bacteroides.

In many cases, drugs or bioactive ingredients are delivered systemically and are not targeted to the inflamed or damaged sites. Problems such as protein instability in the acid- and protease-rich environment of the upper gastrointestinal tract make it difficult to achieve therapeutic levels of recombinant proteins following oral delivery of naked protein. B. ovatus offers an alternative to develop improved live biotherapeutics for disease treatments.

Fig.1 Proportions of Bacteroides species seen clinically. (Wexler, 2007)

B. ovatus and Disease Treatments

Bacteroides can utilize xylan as a sole energy source and have been identified within the mucin layer coating the colonic mucosa, making them ideally suited for therapeutic protein delivery directly to the injured epithelium. Since the anaerobic nature of B. ovatus provides an inherent biosafety feature, approaches that overcome the current therapeutic limitations have emerged in the generation of recombinant B. ovatus -based drug delivery systems.

Inflammatory Bowel Disease (IBD)

Scientists have developed a new live bacteria drug-delivery system using the B. ovatus engineered to secrete human keratinocyte growth factor-2 (KGF-2). B. ovatus strains expressing KGF-2 were generated by homologous recombination and evaluated using the dextran sodium sulfate (DSS)-induced model of intestinal epithelial injury and colitis. In DSS treated mice, administration of xylan and BO-KGF had a significant therapeutic effect in improving stool consistency, reducing weight loss and rectal bleeding, reducing inflammation and neutrophil infiltration, reducing expression of pro-inflammatory cytokines, accelerating healing of damaged epithelium, and accelerating production of goblet cells. This live bacterial drug delivery system may apply to treat IBD.

Similarly, B. ovatus was engineered to produce murine interleukin-2 (MuIL2) intracellularly in response to xylan in culture media by inserting the MuIL2 gene into the xylanase operon of the organism, leading to the development of new long-term immunotherapies for inflammatory gut diseases.

Cancer

The tumor-specific Thomsen-Friedenreich antigen, also known as CD176, is an attractive target for a cancer vaccine but synthetic vaccines have not overcome the low intrinsic immunogenicity of CD176. Since natural CD176-directed antibodies present in human sera are generated in response to microbes found in the gastrointestinal tract, microbial CD176 structures are more immunogenic than synthetic TF. A new strain of the B. ovatus, B. ovatus D-6, carries the true CD176 antigen. B. ovatus D-6 presents unique CD176-specific immunogenicity based on a combination of several inherent properties such as intrinsic adjuvant properties, expression of the true CD176 antigen, presentation of CD176 as repetitive side chains on a capsular polysaccharide. Therefore, B. ovatus D-6 is a promising candidate for the development of the first adjuvant-free anti-CD176-specific cancer vaccine.

Equipped with advanced drug discovery platform and in-depth researches in next-generation probiotics (NGPs), Creative Biolabs provides customized B. ovatus based live biotherapeutics drug discovery services and products for global clients. If you are interested in our services or products, please feel free to contact us for more information.

References

Wexler, H. M. Bacteroides: the good, the bad, and the nitty-gritty. Clinical microbiology reviews. 2007, 20(4), 593-621.
O'Toole, P. W.; et al. Next-generation probiotics: the spectrum from probiotics to live biotherapeutics. Nature microbiology. 2017, 2(5), 1-6.

CAT	Product Name	Product Overview
LBST-027FG	Bacteroides ovatus; 24398	Bacteroides ovatus is an anaerobe, mesophilic bacterium. Thalli were rod-shaped, single or paired, Gram-negative.
LBST-028FG	Bacteroides ovatus; 359491	Bacteroides ovatus is an anaerobe, mesophilic bacterium. Thalli were rod-shaped, single or paired, Gram-negative.