Diet:gut microbiota interactions are likely to play a key role in influencing hepatic bile acids (BAs) neosynthesis and production of secondary and tertiary BAs in the intestine. There are few studies exploring how diet:microbe interactions can modulate BAs profile in human. Probiotic, polyphenols and prebiotic fibers like oat β-glucans has been shown to modulate the gut microbiota composition and consequently the BAs pool. On the other hand certain fibers, apple pectin, proanthocyanidins or condensed tannins, may sequester BAs, driving them distally into the colon where they may be excreted or transformed by microbiota. In this work developed an isotopic dilution LC–ESI-MS/MS method for a comprehensive analysis of BAs in human serum with application to kinetic study with Vaccinium corymbosum and Vaccinium myrtillus. We used a combination of quantitative (LC-TripleQuad) and qualitative (LC-HR-Orbitrap) analysis for discovery of BAs isomers. Their presence was confirmed thanks to fragmentation pattern similarities with analytical standards and mass accuracy measurements in full scan and MS/MS modes. This method was applied to study BAs levels in serum from a kinetic study over 6h postprandial after consumption of two types of berries. For the first time sulfates conjugated forms of BAs were measured and quantified using deuterated bile acids internal standards. With this method it was possible to separate forty nine bile acids and quantify them at trace nM levels. A strategy of scheduled/ unscheduled injections of real samples allowed us to find additional BAs isomers not a priori included in the method, while high resolution full scan and MS/MS fragmentation analysis confirmed their structural adherence to the bile acid family. The applicability of the proposed method was assessed by analysing serum samples from a nutrikinetic challenge study with two different types of berries, which showed high inter-individual differences both in the concentrations and composition of plasmatic BAs in fasting and postprandial state. We found differences in bile acids quantity and time reaching maximal BAs concentrations between males and females, suggesting higher BA concentrations in males. Despite high inter-individual variability in fasting and postprandial states, we found three possible subgroups thorough hierarchical clustering. Values regarding the variability among all study volunteers and proportional distribution of BAs were in agreement with previous data measured in independent populations. These findings open new perspectives in understanding the role of the diet, and give an important impact on understanding of bile acid homeostasis and on future personalized nutrition strategies

Ulaszewska, M.; Mancini, A.; Garcia-Aloy, M.; Del Bubba, M.; Tuohy, M.; Vrhovsek, U. (2019). The profile of bile acids and their sulfate metabolites in postprandial human serum suggest sex-related differences. In: 13th European nutrition conference: malnutrition in an obese world: European perspectives, Dublin, Ireland, 15-18 October 2019. url: https://app.oxfordabstracts.com/events/696/program-app/submission/126009 handle: http://hdl.handle.net/10449/57768

The profile of bile acids and their sulfate metabolites in postprandial human serum suggest sex-related differences

Ulaszewska, M
Primo
;
Mancini, A.;Garcia-Aloy, M.;Tuohy, M.;Vrhovsek, U.
Ultimo
2019-01-01

Abstract

Diet:gut microbiota interactions are likely to play a key role in influencing hepatic bile acids (BAs) neosynthesis and production of secondary and tertiary BAs in the intestine. There are few studies exploring how diet:microbe interactions can modulate BAs profile in human. Probiotic, polyphenols and prebiotic fibers like oat β-glucans has been shown to modulate the gut microbiota composition and consequently the BAs pool. On the other hand certain fibers, apple pectin, proanthocyanidins or condensed tannins, may sequester BAs, driving them distally into the colon where they may be excreted or transformed by microbiota. In this work developed an isotopic dilution LC–ESI-MS/MS method for a comprehensive analysis of BAs in human serum with application to kinetic study with Vaccinium corymbosum and Vaccinium myrtillus. We used a combination of quantitative (LC-TripleQuad) and qualitative (LC-HR-Orbitrap) analysis for discovery of BAs isomers. Their presence was confirmed thanks to fragmentation pattern similarities with analytical standards and mass accuracy measurements in full scan and MS/MS modes. This method was applied to study BAs levels in serum from a kinetic study over 6h postprandial after consumption of two types of berries. For the first time sulfates conjugated forms of BAs were measured and quantified using deuterated bile acids internal standards. With this method it was possible to separate forty nine bile acids and quantify them at trace nM levels. A strategy of scheduled/ unscheduled injections of real samples allowed us to find additional BAs isomers not a priori included in the method, while high resolution full scan and MS/MS fragmentation analysis confirmed their structural adherence to the bile acid family. The applicability of the proposed method was assessed by analysing serum samples from a nutrikinetic challenge study with two different types of berries, which showed high inter-individual differences both in the concentrations and composition of plasmatic BAs in fasting and postprandial state. We found differences in bile acids quantity and time reaching maximal BAs concentrations between males and females, suggesting higher BA concentrations in males. Despite high inter-individual variability in fasting and postprandial states, we found three possible subgroups thorough hierarchical clustering. Values regarding the variability among all study volunteers and proportional distribution of BAs were in agreement with previous data measured in independent populations. These findings open new perspectives in understanding the role of the diet, and give an important impact on understanding of bile acid homeostasis and on future personalized nutrition strategies
2019
Ulaszewska, M.; Mancini, A.; Garcia-Aloy, M.; Del Bubba, M.; Tuohy, M.; Vrhovsek, U. (2019). The profile of bile acids and their sulfate metabolites in postprandial human serum suggest sex-related differences. In: 13th European nutrition conference: malnutrition in an obese world: European perspectives, Dublin, Ireland, 15-18 October 2019. url: https://app.oxfordabstracts.com/events/696/program-app/submission/126009 handle: http://hdl.handle.net/10449/57768
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