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Predicting microbiota response to dietary fibers

A technology of dietary fiber and microbiota, applied in computer software products and devices of reaction, to prove functional heterogeneity in the fermentative capacity of healthy human gut microbiota, able to solve problems such as no short-chain fatty acid diagnostic solutions available

Pending Publication Date: 2022-07-08
MYOTA GMBH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0012] There are still no diagnostically available solutions for measuring or predicting short-chain fatty acid (SCFA) production (and intermediate fermentation metabolites such as oligosaccharides, monosaccharides, lactate, formate, and succinate) in response to different dietary compounds

Method used

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  • Predicting microbiota response to dietary fibers
  • Predicting microbiota response to dietary fibers
  • Predicting microbiota response to dietary fibers

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0215] In vitro measurement of SCFA production

[0216] To measure in vitro SCFA production in response to different dietary polysaccharides, feces from 40 healthy human participants were homogenized into slurries under anaerobic conditions and supplemented with inulin, pectin or cellulose (see Methods section). The slurries were then allowed to evolve over time and samples were taken at regular time intervals to quantify the SCFA content at each time point ( figure 1 ). To determine an appropriate sampling frequency, Applicants conducted a pilot experiment in which Applicants analyzed the trajectories of each SCFA concentration over a 24-hour period. Applicants found that only a small fraction of participants appeared to converge to final SCFA concentrations before the 24-hour time point, but all participants exhibited a linear rate of production over the 0 to 4-hour time window ( figure 2 ). These data are in good agreement with inulin concentrations measured from fece...

Embodiment 2

[0219] Predicting microbial metabolic phenotypes from community composition

[0220] Applicants then asked the question whether Applicants could predict participants' MMPs, defined here as the relative abundance of 97% de novoOTUs obtained from 16S rRNA sequencing of feces prior to incubation with different fibers, from community composition alone. Spend. Applicants trained a random forest classifier (RFC) to predict whether the production rate of a given SCFA for a given microbiota in response to a given fiber was high or low, the production rate being high or low, respectively, by ≥ 0 or less than 0. Production rate z-score is defined. Performance varied by SCFA, with the highest accuracy obtained in predicting butyrate production in response to inulin (AUC=0.87) and pectin (AUC=0.79) Figure 4 ).

[0221] Applicants also tested whether straight fecal SCFA content could be predicted by 16S rRNA sequencing and found moderate predictive power for acetate and butyrate (AUC...

Embodiment 3

[0223] Stability of individual MMPs over time

[0224] While it is known that an individual's gut microbiota can be relatively stable over time without large perturbations, it is unclear whether an individual's MMPs would be equally stable over time. Therefore, applicants repeated the experiment with eight participants at time points spaced at least 6 months apart ( Image 6 a). Although some variability between time points was observed, the extreme values ​​of the MMP for each individual were generally conserved ( Image 6 b). Fisher's test on a contingency table derived from pairwise comparisons of each SCFA:fiber pair for all individuals at both time points indicated that this stability was statistically significant (p=0.003; two-sided Fisher's test ). These results are consistent with the fact that MMPs correlate with the relative abundance of specific members of the microbiota: individuals with higher relative abundances of the above-mentioned Prevotella OTUs may The...

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Abstract

The present invention relates to human gut microbiota and its metabolic capability. The invention particularly relates to a method for proving functional heterogeneity in the aspect of fermentation capacity of healthy human intestinal microbiota. More specifically, the present invention provides a computer simulation (insilo) method for predicting response to different dietary fibers based on analysis and measurement of fermentation or metabolic capability of a subject's intestinal microbiota, as well as a computer software product and apparatus for predicting a subject's response to different dietary fibers.

Description

technical field [0001] The present invention relates to the human gut microbiota and its metabolic capacity. In particular, a method to demonstrate functional heterogeneity in the fermentative capacity of the healthy human gut microbiota. More specifically, the present invention provides an in silico or in vitro method for predicting responses to different dietary fibers based on analysis and measurement of the fermentative or metabolic capacity of a subject's gut microbiota. ) method, and a computer software product and apparatus for predicting a subject's response to different dietary fibers. Background technique [0002] The symbiotic relationship between the host and gut microbiota is closely related to the host diet. For example, most of the calories consumed by ruminants come from microbial fermentation of otherwise indigestible polysaccharides in their diets. In humans, the fermentation of dietary fiber and other microbiota-available carbohydrates (MACs) constitute...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G16H20/60
CPCG16H50/20G16H50/70G16H20/60G16B40/20G16B20/00G16H10/40G16B5/00C12Q1/689
Inventor T·J·古里
Owner MYOTA GMBH
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