FERULIC ACID METABOLISM IN THE GUT: IDENTIFICATION OF METABOTYPES AND THEIR MICROBIAL ASSOCIATIONS

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60460709%3A41210%2F25%3A102241" target="_blank" >RIV/60460709:41210/25:102241 - isvavai.cz</a>

Výsledek na webu

<a href="https://plus.cobiss.net/cobiss/si/en/data/cobib/239652867" target="_blank" >https://plus.cobiss.net/cobiss/si/en/data/cobib/239652867</a>

DOI - Digital Object Identifier

—

Jazyk výsledku

čeština

Název v původním jazyce

FERULIC ACID METABOLISM IN THE GUT: IDENTIFICATION OF METABOTYPES AND THEIR MICROBIAL ASSOCIATIONS

Popis výsledku v původním jazyce

Background Dietary (poly)phenols support cardiovascular health, but their effects vary due to metabotypes, distinct gut metabolic phenotypes that influence polyphenol bioactivation based on microbiota composition. While daidzein-equol and ellagitannin-urolithin metabotypes are well studied, those for other polyphenols, such as ferulic acid (FA), remain largely unexplored. As a key hydroxycinnamic acid found in whole grains, seeds, and vegetables, FA metabolism may impact disease risk and personalized nutrition, highlighting the need for further research. This study aims to identify and characterize FA metabotypes and their relationship with gut microbiota composition and associated fermentation profiles. Methods FA (20 µg/mL) was anaerobically incubated in batch fermentation models with stool from 18 healthy donors (18–80 years). Samples were collected at 0, 2, 4, 8, and 24 hours, and microbial profilling (16S rRNA) and metabolomics analyses (LC-MS and 1H NMR) were performed. Untargeted LC-MS analysis identified FA, five major FA-derived metabolites, and two unknown compounds that differed between control and FA-treated samples. Donors were classified based on metabolite kinetics, specifically FA disappearance or metabolite production, considering both timing (early/late) and quantity (high/low). Associations between metabolite variations and corresponding changes in microbiome and metabolome composition were assessed using the Wilcoxon test (p < 0.05) with FDR correction (q < 0.05). Results FA metabolism followed individual-specific variations, with major metabolites including dihydroferulic acid (dHFA), 4-hydroxyphenylpropionic acid (4HPPA), 3-(3-hydroxyphenyl)propionic acid (3,3HPPA), and benzoic acid (BA). Individuals with early dHFA formation (67%) exhibited a higher abundance of Faecalibacterium CM04.06 (p = 0.003, q = 0.41). Similarly, early 4HPPA producers (50%) showed increased levels of Faecalibacterium CM04.06 (p = 0.013, q = 0.86) and decreased levels of Blautia faecis (p = 0.013, q = 0.86). Individuals with early 3,3HPPA production (50%) had a higher abundance of Holdemania filiformis (p = 0.028, q = 0.82), Parabacteroides distasonis (p = 0.028, q = 0.82), and Blautia massiliensis (p = 0.037, q = 0.82). Additionally, three donors (17%) displayed a distinct trend, characterized by high BA abundance as a final metabolite, forming a potential BA metabotype. These individuals exhibited lower levels of Parabacteroides johnsonii (p = 0.018, q = 0.79) and higher levels of Alistipes putredinis (p = 0.024, q = 0.79). Among the distinct taxa, Parabacteroides, Alistipes, and Blautia species are known to contribute to (poly)phenol metabolism, whereas the role of Holdemania sp. remains unclear. Early 3,3HPPA production, together with rapid FA degradation, was associated with higher microbial fermentation capacity, lower amino acid levels, and increased SCFA production. Conclusion Colon metabolism of FA did not result in clearly defined metabotypes associated with the production of major metabolites. Instead, it exhibited a gradient in metabolite production in terms of quantity and timing. However, a small subset of donors, representing 17% of the population, displayed high BA production and formed a distinct metabotype that merits further investigation. Notably, fast FA degraders also showed early 3,3HPPA formation alongside SCFA production, which may have positive health implications.

Název v anglickém jazyce

FERULIC ACID METABOLISM IN THE GUT: IDENTIFICATION OF METABOTYPES AND THEIR MICROBIAL ASSOCIATIONS

Popis výsledku anglicky

Background Dietary (poly)phenols support cardiovascular health, but their effects vary due to metabotypes, distinct gut metabolic phenotypes that influence polyphenol bioactivation based on microbiota composition. While daidzein-equol and ellagitannin-urolithin metabotypes are well studied, those for other polyphenols, such as ferulic acid (FA), remain largely unexplored. As a key hydroxycinnamic acid found in whole grains, seeds, and vegetables, FA metabolism may impact disease risk and personalized nutrition, highlighting the need for further research. This study aims to identify and characterize FA metabotypes and their relationship with gut microbiota composition and associated fermentation profiles. Methods FA (20 µg/mL) was anaerobically incubated in batch fermentation models with stool from 18 healthy donors (18–80 years). Samples were collected at 0, 2, 4, 8, and 24 hours, and microbial profilling (16S rRNA) and metabolomics analyses (LC-MS and 1H NMR) were performed. Untargeted LC-MS analysis identified FA, five major FA-derived metabolites, and two unknown compounds that differed between control and FA-treated samples. Donors were classified based on metabolite kinetics, specifically FA disappearance or metabolite production, considering both timing (early/late) and quantity (high/low). Associations between metabolite variations and corresponding changes in microbiome and metabolome composition were assessed using the Wilcoxon test (p < 0.05) with FDR correction (q < 0.05). Results FA metabolism followed individual-specific variations, with major metabolites including dihydroferulic acid (dHFA), 4-hydroxyphenylpropionic acid (4HPPA), 3-(3-hydroxyphenyl)propionic acid (3,3HPPA), and benzoic acid (BA). Individuals with early dHFA formation (67%) exhibited a higher abundance of Faecalibacterium CM04.06 (p = 0.003, q = 0.41). Similarly, early 4HPPA producers (50%) showed increased levels of Faecalibacterium CM04.06 (p = 0.013, q = 0.86) and decreased levels of Blautia faecis (p = 0.013, q = 0.86). Individuals with early 3,3HPPA production (50%) had a higher abundance of Holdemania filiformis (p = 0.028, q = 0.82), Parabacteroides distasonis (p = 0.028, q = 0.82), and Blautia massiliensis (p = 0.037, q = 0.82). Additionally, three donors (17%) displayed a distinct trend, characterized by high BA abundance as a final metabolite, forming a potential BA metabotype. These individuals exhibited lower levels of Parabacteroides johnsonii (p = 0.018, q = 0.79) and higher levels of Alistipes putredinis (p = 0.024, q = 0.79). Among the distinct taxa, Parabacteroides, Alistipes, and Blautia species are known to contribute to (poly)phenol metabolism, whereas the role of Holdemania sp. remains unclear. Early 3,3HPPA production, together with rapid FA degradation, was associated with higher microbial fermentation capacity, lower amino acid levels, and increased SCFA production. Conclusion Colon metabolism of FA did not result in clearly defined metabotypes associated with the production of major metabolites. Instead, it exhibited a gradient in metabolite production in terms of quantity and timing. However, a small subset of donors, representing 17% of the population, displayed high BA production and formed a distinct metabotype that merits further investigation. Notably, fast FA degraders also showed early 3,3HPPA formation alongside SCFA production, which may have positive health implications.

Druh

O - Ostatní výsledky

CEP obor

—

OECD FORD obor

30308 - Nutrition, Dietetics

Projekt

—

Návaznosti

S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů