Live Biotherapeutics Drug Discovery Services for Inflammatory Bowel Disease (IBD)

Inflammatory bowel disease (IBD) describes disorders that involve chronic inflammation of the digestive tract. A prevailing hypothesis is that immune disturbances and intestinal dysbiosis are central players in this disease pathogenesis, therefore, therapies aiming at modulating intestinal microbial composition may represent a promising strategy in IBD control. As a leader in the development of next-generation probiotics (NGPs), Creative Biolabs has explored a live biotherapeutics drug discovery platform to deepen our understanding of the role of microbiota in IBD and discover novel NGPs for IBD treatment.

Introduction of IBD

IBD is a group of multifactorial and inflammatory infirmities of the gastrointestinal tract that cause significant morbidity. IBD consists of two main types: Ulcerative colitis (UC) and Crohn’s disease (CD). Symptoms of IBD include patchy, transmural inflammation of the gastrointestinal tract, diarrhea, and are complicated by fever and fatigue, strictures, abscesses, and fistulae. Classic strategies to treat IBD are based on pharmacological approaches to decrease inflammation and reduce disease relapse. But these approaches have been reported with some limitations, such as low responsiveness, excessive immunosuppression, and refractoriness. NGPs administration aiming to re-establish the microbial balance has been a promising strategy.

Gut microbiota alteration and immune responses in IBD. Fig.1 Gut microbiota alteration and immune responses in IBD. (Zuo, 2018)

NGPs for IBD Treatment

Dysbiosis has been explored as a causative agent of IBD and correcting dysbiosis by NGPs is a promising strategy to alleviate and cure this inflammatory disease. NGPs could induce anti-inflammatory effects, improve (or restore) barrier function, and beneficially modulate the composition of the microbiome by inhibiting the growth of detrimental bacteria and promoting the growth of beneficial species to promote IBD treatment.

The abundance of Akkermansia muciniphila (A. muciniphila) reduces many folds in IBD patients. A. muciniphila improves the gut barrier partially via its outer membrane protein Amuc_1100 that interacts with Toll-like receptor 2 (TLR2). Besides, A. muciniphila induces homeostatic IgG production and antigen-specific T cell responses to modulate human immunological homeostasis.

Individuals with IBD show a significantly lower percentage of the Bacteroides spp. population, especially B. fragilis. Bacteroides spp. can produce polysaccharide A (PSA) that directs the development of CD4+ T cells and induces the anti-inflammatory function of Tregs in IBD patients. Moreover, sphingolipids produced by B. fragilis regulate homeostasis of host intestinal natural killer T cells and confer protection.

Probiotic Lactobacillus spp. (Lactobacillus reuteri, Lactobacillus rhamnosus) are associated with decreased intestinal inflammation in patients with UC and showed efficacy in the treatment of UC.

The amount of Faecalibacterium prausnitzii (F. prausnitzii) was reported to be decreased significantly in patients with IBD. F. prausnitzii can stimulate peripheral blood mononuclear cells, leading to significantly lower IL-12 and IFN-γ production levels and higher secretion of the anti-inflammatory cytokine IL-10. These researches suggest the anti-inflammatory role of F. prausnitzii in IBD.

Clostridium spp. strains that lack toxins and virulence factors have immunosuppressive activity in IBD demonstrated by inducing Treg cells in intestine in a TGF-β-, IL-10- or butyrate-dependent manner.

Escherichia coli (E. coli) was shown to play a role in maintaining remission in UC patients in two independent relatively large trials. Tryptophan-metabolizing pathways in E. coli can convert tryptophan to bioactive indole-containing molecules that activate the aryl hydrocarbon receptor and down-regulates inflammation in IBD.

Our Capacity of NGPs Development

Capacity of NGPs DevelopmentWith advances in high-throughput sequencing, Creative Biolabs is committed to fully understand the interactions between microbiota and the host immune system, to accurately guide our NGP development. Our comprehensive services include but not limited to:

  • NGP strain isolation and definition to select “superior microbial strains” for probiotic applications;
  • NGPs' metabolic profiling, antibiotic susceptibility/resistance, viability assays, biological safety, etc.;
  • GMP scale-up services;
  • Host-microbe interaction tests to optimize NGPs therapeutic efficiency;
  • Master and working cell bank preparation, validation, and storage;
  • Fermentation and subsequent downstream purification.

NGPs represents a revolutionary approach to the prevention and treatment of IBD. With years of experience in probiotics discovery, Creative Biolabs is dedicated to helping our customers accelerate live biotherapeutics projects. We will work with you at all stages of the NGPs development process from the initiation of your project to the large-scale production of your microbes.

If you are interested in our services, please feel free to contact us.

Reference

  1. Zuo, T.; Ng, S. C. The gut microbiota in the pathogenesis and therapeutics of inflammatory bowel disease. Frontiers in microbiology. 2018, 9: 2247.

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