NASH Target Development Service for Gut Microbiota

The change of intestinal microbiome is closely related to the occurrence of nonalcoholic steatohepatitis (NASH). It has been reported that small intestinal bacterial overgrowth (SIBO) exert a role in the pathogenesis of NASH. Creative Biolabs, as a pioneer in the development of drugs against NASH, provides a comprehensive one-stop service to help global customers with the screening, structural characterization and functional profiling of targets related to gut microbiota based on our powerful technical platform, target identification for drug discovery.

Introduction of Gut Microbiota in NASH

Accumulating evidence suggests that dysregulation of microbiota components is associated with various liver diseases, including nonalcoholic fatty liver disease (NAFLD) and NASH, through obesity predisposition, metabolic alterations, and liver inflammation. Gut microbiota generates additional energy for the host, processing polysaccharides into short-chain fatty acids and stimulating lipogenesis. Aberrant microbiota could induce triglyceride accumulation and promote NASH both reducing choline and increasing methylamines. Small intestinal bacterial overgrowth (SIBO), a condition characterized by excessive gram-negative aerobic and anaerobic bacteria in the proximal small bowel, plays a role in the pathogenesis of NASH via increasing intestinal permeability and promoting the absorption of endotoxin or other enteric bacterial products. Moreover, SIBO has also been revealed to interact with TLR-4 and induce the pro-inflammatory cytokine IL-8, thereby promoting the progression of NASH.

Fig.1 Dysbiosis for the effect of gut microbiome in NAFLD development and progression to NASH. (Marra, 2018)

IgG-Enhanced Bovine-Derived Colostrum

Bovine colostrum (BC) is the milk secreted by mammals during the first 72h after birth. It contains abundant bioactive components including growth factors, lysozyme, lactoferrin, nucleosides, Igs, lactoperoxidase, vitamins, peptides, and oligosaccharides, which are significantly associated with human health. BC has been shown to play anti-infection effects in a variety of chronic infections. Moreover, oral administration of IgG-enhanced colostrum fractions derived from cows immunized against LPS from intestinal bacteria (Escherichia coli) could relieve chronic inflammation, liver injury and insulin resistance associated with NASH.

Fig.2 Effect of Imm124-E (an anti-LPS hyperimmune BC) on insulin resistance, as measured on days 1 and 30. (Meir, 2012)

Lipase Inhibitor

Lipase inhibitor initially is used for weight loss. The major role of it is to reduce the activity of lipases and further decrease the gastrointestinal absorption of fats. But a study has implicated that a gastrointestinal lipase inhibitor, Orlistat, improves serum alanine transaminase (ALT) level and characterization of steatosis in NAFLD patients.

Other Agents Targeting the Microbiome

Other agents targeting the microbiome include a macrolide antibiotic, solithromycin may also exert therapeutic effects in NASH. Currently, these agents are in a phase II trial.

Features

• Excellent technical team which has engaged in the research of NASH therapy for many years
• Powerful technologies which facilitate target screening and identification as well as drug discovery
• One-stop service relieves your scientific research pressure
• Best after-sale service

Creative Biolabs is a leading service provider that focuses on the discovery of drugs targeting a variety of diseases. Our service portfolio includes not only target screening, structural characterization, and functional profiling but also covers antibody development (e.g. Phage Display & Antibody Library Services, Antibody Analysis Services, Antibody Engineering Services) and the one-stop service of drug discovery. If you are interested in our service list, please feel free to contact us for more details.

References

1. Marra, F., Svegliati-Baroni, G. Lipotoxicity and the gut-liver axis in NASH pathogenesis. Journal of Hepatology. 2018, 68(2): 280-295.
2. Meir, M.; et al. Alleviation of insulin resistance and liver damage by oral administration of Imm124-E is mediated by increased Tregs and associated with increased serum GLP-1 and adiponectin: results of a phase I/II clinical trial in NASH. JInflamm Res. 2012, 5: 141-150.