UroAPROD The gut and bias benefits - the investigation on urolithin metabotypes. Producer strains isolation and multiomic-based description of ellagitannin biotransformation.

Summary

Ellagitannin-rich herbal remedies are used traditionally because of their anti-inflammatory activity. This is connected not to ellagitannins themselves but to their metabolites produced by the gut microbiota. Urolithin A (UroA) is recognized as the most significant of all ellagitannins’ metabolites. However, not everyone is able to have it produced in their gut. The UroA production is exclusive to the hosts of urolithin metabotype A (UM-A) and B (UM-B) and is most probably dependent on the gut microbiota composition and activity. Preliminary trials showed that UM-A hosts have a lower risk of cardiovascular disease. Moreover, the transition from UM-A to other metabotypes is also connected to aging, which might suggest losing certain beneficial abilities. The identity of microorganisms that differentiate UroA producers were not yet revealed. If recognized, new probiotics might be designed. Providing non-UM-A hosts with the possibility to produce UroA efficiently would grant them an advantage due to reports of a wide range of proven and indicated UroAs biological activities.

The project aims to isolate, characterize and preserve bacterial strains able to produce UroA from the fecal samples of UM-A and UM-B donors. This will be possible due to innovative substrate conversion screening strategies and novel metabolomic and sequencing techniques utilization. Results will provide missing insights about urolithin metabotypes for further explanatory studies focused on the elucidation of UM-dependant features. Moreover, bioinformatic tools will be developed to obtain multi-omic descriptions of the studied processes, combining metabolomic and targeted metagenomic data. The project will deliver protocols and data analysis methods that will enable us to run advanced projects in the field of natural products biotransformation research. The established pipelines will be suitable also for dysbiosis, xenobiotic-microbiome interaction and pre- and probiotic design studies.

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Web resources:	https://cordis.europa.eu/project/id/101106272
Start date:	01-02-2024
End date:	31-01-2026
Total budget - Public funding:	- 191 760,00 Euro

Cordis data

Original description

Ellagitannin-rich herbal remedies are used traditionally because of their anti-inflammatory activity. This is connected not to ellagitannins themselves but to their metabolites produced by the gut microbiota. Urolithin A (UroA) is recognized as the most significant of all ellagitannins metabolites. However, not everyone is able to have it produced in their gut. The UroA production is exclusive to the hosts of urolithin metabotype A (UM-A) and B (UM-B) and is most probably dependent on the gut microbiota composition and activity. Preliminary trials showed that UM-A hosts have a lower risk of cardiovascular disease. Moreover, the transition from UM-A to other metabotypes is also connected to aging, which might suggest losing certain beneficial abilities. The identity of microorganisms that differentiate UroA producers were not yet revealed. If recognized, new probiotics might be designed. Providing non-UM-A hosts with the possibility to produce UroA efficiently would grant them an advantage due to reports of a wide range of proven and indicated UroAs biological activities.

The project aims to isolate, characterize and preserve bacterial strains able to produce UroA from the fecal samples of UM-A and UM-B donors. This will be possible due to innovative substrate conversion screening strategies and novel metabolomic and sequencing techniques utilization. Results will provide missing insights about urolithin metabotypes for further explanatory studies focused on the elucidation of UM-dependant features. Moreover, bioinformatic tools will be developed to obtain multi-omic descriptions of the studied processes, combining metabolomic and targeted metagenomic data. The project will deliver protocols and data analysis methods that will enable us to run advanced projects in the field of natural products biotransformation research. The established pipelines will be suitable also for dysbiosis, xenobiotic-microbiome interaction and pre- and probiotic design studies.