Publicação
Natural phenolic compounds - gut microbiota dynamics: a mutual relationship
| Resumo: | Phenolic compounds (PCs) represent one of the most structurally diverse classes of plant secondary metabolites, with more than 10,000 different structures identified in nature. These bioactive compounds are widely distributed and commonly found in the human diet, particularly in vegetables and fruits. With several recognized biological activities (such as antioxidant, anti-inflammatory, anti-cancer, anti-microbial among others), their presence in dietary products has been correlated with multiple beneficial effects on human health. However, the biological activities of dietary PCs are affected by several factors, including chemical structure, content in the human diet and bioavailability. The behavior of these compounds along the gastrointestinal tract appears to be crucial for their human health effects, as PCs may undergo various transformations induced by gastrointestinal enzymes or gut microbiota (GM), into lower molecular weight compounds. Conversely, GM community, which plays a pivotal role in human health, and its composition is influenced by a number of different factors (e.g. age, gender, diet, the use of drugs and environmental factors), can be modulated by dietary PCs. These compounds have the potential to inhibit or stimulate specific intestinal bacteria - both beneficial and/or pathogenic ones - acting as prebiotic and/or antibacterial agents. Therefore, this mutual relationship between PCs and GM has been widely studied by the scientific community. However, most of these studies have employed food matrices, which impede a comprehensive understanding of the metabolites resulting from each of the PCs present in such matrices, and the individual modulatory effect on GM. Hence, the objective of this thesis was to study the mutual relationship between individual dietary PCs and GM. Initially, a total of 2,921 indexed scientific articles were analyzed to achieve a comprehensive understanding of the structure-activity relationship (SAR) between PCs and their antioxidant activity, with the compilation of results from approximately 350 articles. The presence of OH groups demonstrated a predominant positive influence on antioxidant activity of most PCs classes, whereas their substitution exhibited a negative effect. Subsequently, the bioaccessibility and intestinal absorption of ten PCs representative of the major classes, namely quercetin, rutin, naringenin, naringin, epigallocatechin-gallate, apigenin, daidzein, phloretin, phloroglucinol and ellagic acid were evaluated in an in vitro simulated gastrointestinal digestion (INFOGEST), and the collected samples were analyzed by ultra-high-performance liquid chromatography coupled with diode-array detection and tandem mass spectrometry (UHPLC-DAD-MSn). Most of the studied PCs were found along the gastrointestinal tract, exhibiting no enzymatic transformations and bioaccessibilities above 50%. They showed highly levels of absorption under simulated intestine conditions. In light of the results obtained in the previous works, the lack of information in literature on microbiota modulation, and the previously determined antimicrobial and prebiotic properties of certain compounds, three phenolic compounds (ellagic acid (EA), naringenin (NAR) and phloroglucinol (PG)) were individually subjected to an in vitro batch fecal fermentation, in order to identify the metabolites produced by GM and also to ascertain the modulatory effect of these PCs and their respective metabolites on the GM community composition. Through UHPLC-DAD-MSn analysis, 8-hydroxyurolithin was identified for the first time as an EA metabolite produced by GM and isomers of 4-hydroxybenzoic, 3,4-dihydroxybenozic and p-coumaric acids as NAR metabolites. The lower molecular weight metabolites of PG were detected by UHPLC-DAD-MSn and gas chromatography coupled with mass spectrometry (GC-MS) analysis, being identified for the first time phloroglucinic, 2-hydroxy-3-phenylpropanoic, 3-phenylpropanoic and 2-phenylacetic acids. Regarding their impact on the composition of GM, EA and PG demonstrated prebiotic properties, promoting the growth of beneficial Lactobacillus and Bifidobacterium genera, and stimulating the production of health-promoting specific short-chain fatty acids (SCFAs) (such as acetic, propionic and butyric acids). In contrast, NAR seemed to stimulate the growth of potentially pathogenic genera, including Escherichia and Salmonella. Furthermore, to comprehend the impact of these PCs’ metabolism on their biological activities, the antioxidant activity of EA, NAR and PG and their respective metabolites antioxidant activity was evaluated through two in chemico assay (DPPH and ABTS). The complete transformation of EA appeared to result in a reduction in antioxidant activity, whereas some of the NAR metabolites seemed to have a higher antioxidant activity than the precursor compound. With regard to PG and the most active metabolite phloroglucinic acid, it was not possible to establish a SAR between the two compounds, due to the lack of agreement in the results obtained from the DPPH and ABTS assays. In this vein, the results presented in this thesis contribute to the understanding of the potential beneficial effects of dietary PCs on human health. Additionally, these findings may represent a significant contribution for developing food supplements, novel prebiotics or functional foods. In the future, this knowledge could be used to evaluate the combination of PCs in order to create a more diverse and well-balanced GM ecosystem. Furthermore, when combined with emerging methodologies for drug delivery or bioactive compound encapsulation, this knowledge may prove instrumental in developing new nutraceutical and pharmaceutical formulations, as well as personalized nutrition strategies based on microbiota profiling, which could advance the control and/or prevention of certain diseases. |
|---|---|
| Autores principais: | Pais, Adriana Cabrita Sousa |
| Assunto: | Phenolic compounds Gut microbiota Metabolites Mutual relationship Bioactive compounds Biological activities Antioxidant activity Composition modulation |
| Ano: | 2025 |
| País: | Portugal |
| Tipo de documento: | tese de doutoramento |
| Tipo de acesso: | acesso embargado |
| Instituição associada: | Universidade de Aveiro |
| Idioma: | inglês |
| Origem: | RIA - Repositório Institucional da Universidade de Aveiro |
| Resumo: | Phenolic compounds (PCs) represent one of the most structurally diverse classes of plant secondary metabolites, with more than 10,000 different structures identified in nature. These bioactive compounds are widely distributed and commonly found in the human diet, particularly in vegetables and fruits. With several recognized biological activities (such as antioxidant, anti-inflammatory, anti-cancer, anti-microbial among others), their presence in dietary products has been correlated with multiple beneficial effects on human health. However, the biological activities of dietary PCs are affected by several factors, including chemical structure, content in the human diet and bioavailability. The behavior of these compounds along the gastrointestinal tract appears to be crucial for their human health effects, as PCs may undergo various transformations induced by gastrointestinal enzymes or gut microbiota (GM), into lower molecular weight compounds. Conversely, GM community, which plays a pivotal role in human health, and its composition is influenced by a number of different factors (e.g. age, gender, diet, the use of drugs and environmental factors), can be modulated by dietary PCs. These compounds have the potential to inhibit or stimulate specific intestinal bacteria - both beneficial and/or pathogenic ones - acting as prebiotic and/or antibacterial agents. Therefore, this mutual relationship between PCs and GM has been widely studied by the scientific community. However, most of these studies have employed food matrices, which impede a comprehensive understanding of the metabolites resulting from each of the PCs present in such matrices, and the individual modulatory effect on GM. Hence, the objective of this thesis was to study the mutual relationship between individual dietary PCs and GM. Initially, a total of 2,921 indexed scientific articles were analyzed to achieve a comprehensive understanding of the structure-activity relationship (SAR) between PCs and their antioxidant activity, with the compilation of results from approximately 350 articles. The presence of OH groups demonstrated a predominant positive influence on antioxidant activity of most PCs classes, whereas their substitution exhibited a negative effect. Subsequently, the bioaccessibility and intestinal absorption of ten PCs representative of the major classes, namely quercetin, rutin, naringenin, naringin, epigallocatechin-gallate, apigenin, daidzein, phloretin, phloroglucinol and ellagic acid were evaluated in an in vitro simulated gastrointestinal digestion (INFOGEST), and the collected samples were analyzed by ultra-high-performance liquid chromatography coupled with diode-array detection and tandem mass spectrometry (UHPLC-DAD-MSn). Most of the studied PCs were found along the gastrointestinal tract, exhibiting no enzymatic transformations and bioaccessibilities above 50%. They showed highly levels of absorption under simulated intestine conditions. In light of the results obtained in the previous works, the lack of information in literature on microbiota modulation, and the previously determined antimicrobial and prebiotic properties of certain compounds, three phenolic compounds (ellagic acid (EA), naringenin (NAR) and phloroglucinol (PG)) were individually subjected to an in vitro batch fecal fermentation, in order to identify the metabolites produced by GM and also to ascertain the modulatory effect of these PCs and their respective metabolites on the GM community composition. Through UHPLC-DAD-MSn analysis, 8-hydroxyurolithin was identified for the first time as an EA metabolite produced by GM and isomers of 4-hydroxybenzoic, 3,4-dihydroxybenozic and p-coumaric acids as NAR metabolites. The lower molecular weight metabolites of PG were detected by UHPLC-DAD-MSn and gas chromatography coupled with mass spectrometry (GC-MS) analysis, being identified for the first time phloroglucinic, 2-hydroxy-3-phenylpropanoic, 3-phenylpropanoic and 2-phenylacetic acids. Regarding their impact on the composition of GM, EA and PG demonstrated prebiotic properties, promoting the growth of beneficial Lactobacillus and Bifidobacterium genera, and stimulating the production of health-promoting specific short-chain fatty acids (SCFAs) (such as acetic, propionic and butyric acids). In contrast, NAR seemed to stimulate the growth of potentially pathogenic genera, including Escherichia and Salmonella. Furthermore, to comprehend the impact of these PCs’ metabolism on their biological activities, the antioxidant activity of EA, NAR and PG and their respective metabolites antioxidant activity was evaluated through two in chemico assay (DPPH and ABTS). The complete transformation of EA appeared to result in a reduction in antioxidant activity, whereas some of the NAR metabolites seemed to have a higher antioxidant activity than the precursor compound. With regard to PG and the most active metabolite phloroglucinic acid, it was not possible to establish a SAR between the two compounds, due to the lack of agreement in the results obtained from the DPPH and ABTS assays. In this vein, the results presented in this thesis contribute to the understanding of the potential beneficial effects of dietary PCs on human health. Additionally, these findings may represent a significant contribution for developing food supplements, novel prebiotics or functional foods. In the future, this knowledge could be used to evaluate the combination of PCs in order to create a more diverse and well-balanced GM ecosystem. Furthermore, when combined with emerging methodologies for drug delivery or bioactive compound encapsulation, this knowledge may prove instrumental in developing new nutraceutical and pharmaceutical formulations, as well as personalized nutrition strategies based on microbiota profiling, which could advance the control and/or prevention of certain diseases. |
|---|