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In-vitro high-throughput screening platform for acting effect of drug candidates on intestinal flora

A technology for intestinal flora and candidates, which can be used in measurement devices, color/spectral property measurement, material analysis by electromagnetic means, etc. Reduced adverse reactions, high-throughput effects

Inactive Publication Date: 2020-06-19
INST OF MICROBIOLOGY - CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, animal models are mostly used to evaluate the interaction between drugs and intestinal flora, and there is a lack of high-throughput rapid screening methods similar to in vitro cell-based screening platforms

Method used

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  • In-vitro high-throughput screening platform for acting effect of drug candidates on intestinal flora
  • In-vitro high-throughput screening platform for acting effect of drug candidates on intestinal flora
  • In-vitro high-throughput screening platform for acting effect of drug candidates on intestinal flora

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Experimental program
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Effect test

Embodiment 1

[0027] In this implementation case, we choose inosine (Inosine) as the drug to be screened. Inosine, also known as inosine, is a biological fermentation product, which can be used for adjuvant treatment of acute and chronic hepatitis in medical treatment, for various reasons The leukopenia and thrombocytopenia caused by it are also used for heart diseases such as cor pulmonale and the treatment of heart or liver toxicity caused by anti-schistosomiasis drugs. The effect of this compound on intestinal flora is unknown, and it is hoped that through this screening, the effect on its effect on intestinal flora in people with liver damage will be studied. It was determined that the intestinal flora environment to be simulated in vitro was the intestines of the non-alcoholic fatty liver population, and then by analyzing the high-throughput sequencing data of 324 non-alcoholic fatty liver human intestinal flora, the bacterial species in the population samples were determined Relative ...

Embodiment 2

[0041] In this implementation case, we choose salicin as the drug to be screened. Salicin has the effect of treating colds, fever and infection, and relieving arthritis pain and low back pain. The mechanism of action between the compound and the intestinal flora is unknown, and it is hoped that through this screening, the effect of the compound on the intestinal flora of the Asian healthy population will be studied. It was determined that the intestinal flora environment to be simulated in vitro was the intestinal tract of healthy Chinese people, and then by analyzing the high-throughput sequencing data of 516 healthy human intestinal flora, it was determined that the relative abundance of bacteria in the population samples was >0.1%. 30 genera Alistipes, Bacteroides, Bifidobacterium, Blautia, Butyricicoccus, Clostridium, Collinsella, Coprococcus, Dysosmobacter, Eubacterium, Faecalibacillus, Faecalibacterium, Intestinibacter, Lactobacillus, Novgen_2710, Odoribacter, Oscil with ...

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Abstract

The invention discloses an in-vitro high-throughput screening platform for the acting effect of drug candidates on intestinal flora. According to the characteristics of the drug candidates and the intestinal flora of a target population, a plurality of representative intestinal strains areselected to simulate a simplified human intestinal microbial environment. The intestinal strains are diluted in a microorganism culture medium and then the diluted intestinal strains are put into an integrated pore plate. The initial concentration of the bacterial suspension of the intestinal strain should bekept between 0.2 and 1.0 in absorbance value. The growth phenotype of the intestinal tract strains is detected and the microbial metabolite of a target compound is detected; according to the in-vitrohigh-throughput screening method disclosed by the invention, the defects of high cost, long period, low flux and possible poor repeatability of a method for evaluating the drug-intestinal microorganism effect based on an animal model are overcome, and the in-vitro high-throughput screening method has considerable high flux, stability and repeatability.

Description

technical field [0001] The invention relates to the technical field of biological detection, in particular to an in vitro high-throughput screening platform for the effect of drug candidates on intestinal flora. Background technique [0002] In past studies, the screening methods for new drugs and new drug candidates are more commonly used in vitro screening methods based on in vitro cell culture and drug activity screening based on targets (including enzyme targets, GPCR targets, ion channel targets, etc.) , nuclear receptor targets, etc.). However, in recent years, with the in-depth research on intestinal microbes, it has been found that a considerable part of the drug’s mechanism of action on the body is not only absorbed into the blood and directly interacts with the host or acts on the target of the host cell, but also through The human intestinal flora interacts to exert the medicinal effect indirectly. In recent studies, two teams have published articles in Nature a...

Claims

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Application Information

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IPC IPC(8): G01N30/02G01N27/62G01N21/31
CPCG01N30/02G01N27/62G01N21/31
Inventor 刘双江刘畅周楠姜成英
Owner INST OF MICROBIOLOGY - CHINESE ACAD OF SCI