Rodent Model Microbiome Quantification
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Solution Overview
Problem
Current rodent models fail to accurately mimic human gut microbiomes, especially for physiological and pathological conditions, limiting their reliability in investigating causal roles of microbiomes on host physiology and disease predisposition, as well as in drug pharmacokinetics and personalized medicine.
Innovation Solution
Customized rodent models with controlled gut microbiomes are developed by quantifying and modifying the presence, proportion, and total load of target prokaryotes using 16S rRNA amplification and sequencing, allowing for the creation of models with specific microbiome profiles similar to human gut microbiomes, and using devices like tail cups to prevent coprophagia.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional rodent models are used, then the model is simple to maintain and operate, but the microbiome does not accurately mimic human gut microbiomes, reducing reliability for research
Solution Approach 1:
The patent applies preliminary action by pre-quantifying the absolute abundance of target prokaryotes in the rodent microbiome before conducting experiments. This is achieved through a two-step process: first performing 16S rRNA gene amplicon sequencing to determine relative abundance, then using digital PCR to measure absolute abundance of the 16S rRNA gene. By establishing the baseline microbiome composition in advance, researchers can selectively modify the microbiome to more closely mimic human gut microbiomes while maintaining systematic control over the complexity of the modification process.
2Reliability
If the microbiome is modified to mimic human gut microbiomes, then the model becomes more reliable for drug pharmacokinetics and personalized medicine, but the complexity of microbiome quantification and modification increases
Solution Approach 1:
The patent replaces traditional mechanical or culture-based microbiome analysis methods with molecular biology techniques. Specifically, it substitutes conventional microbiological culturing and estimation methods with 16S rRNA gene sequencing and digital PCR. This substitution enables precise quantification of absolute abundance of target prokaryotes, allowing researchers to accurately characterize and modify the rodent microbiome to mimic human gut microbiomes, thereby improving reliability for drug pharmacokinetics and personalized medicine research.
3Manufacturing precision
If absolute quantification of prokaryotes is performed, then the microbiome profile can be precisely controlled, but the time and resources required for analysis increase
Solution Approach 1:
The patent applies preliminary action by performing absolute quantification of prokaryotes before microbiome modification experiments. The two-step workflow (16S rRNA amplicon sequencing followed by digital PCR) establishes a comprehensive baseline characterization of the rodent microbiome in advance. This preliminary quantification data enables researchers to precisely target specific prokaryotes for modification while avoiding unnecessary modifications, thereby reducing the overall time and resources required for achieving the desired microbiome profile.
Solution Approach 2:
The patent uses 16S rRNA gene sequencing as a molecular copy or proxy to represent the entire prokaryotic community structure. Instead of analyzing each prokaryote individually through time-consuming culturing methods, the approach sequences the conserved 16S rRNA gene region, which serves as a representative marker for all prokaryotes in the sample. This copying strategy enables rapid, high-throughput characterization of microbiome composition with high precision, significantly reducing the time required compared to traditional methods.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
These customized models provide more accurate testing of compounds and their effects on gastrointestinal disorders and other conditions, enhancing the reliability of drug testing and personalized medicine applications by mimicking specific human microbiomes.
Implementation Method 1
amplifying a 16S rRNA recognition segment comprising a 16S rRNA variable region specific for the target taxon flanked by target 16S rRNA conserved regions specific for the sample taxon, by performing amplification of nucleic acids extracted from the sample with primers comprising a primer target sequence specific for the target 16S rRNA conserved regions to quantitatively detect an absolute abundance of prokaryotes of the sample taxon in the sample
Implementation Method 2
sequencing the amplified 16S rRNA recognition segment with primers comprising the primer target sequence specific for the target 16S rRNA conserved region and the 16S rRNA variable regions to detect a relative abundance of the prokaryotes of the target taxon with respect to the prokaryotes of the sample taxon in the sample
Data Source
AI summary
Provided herein are methods and systems and related composition, to provide a rodent model having a target microbiome profile formed by a target presence, a target proportion and/or a target total load of a target prokaryote of a target taxon, based on absolute quantification of the target prokaryote. Further provided are rodents obtained by the methods herein described and related use in testing methods performed in connection with physiological or pathological conditions in an individual preferably a human individual. Also provided herein is a tailcup device and related use to prevent coprophagia in rodents.