Gut Microbial Metabolism Of Aromatic Amino Acids Under Chemical And Microbiota Interventions
2021-08
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Gut Microbial Metabolism Of Aromatic Amino Acids Under Chemical And Microbiota Interventions
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2021-08
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The acceptance of gut microbiota as an important endocrine and metabolic organ is mainly based on the energy supply and regulatory functions of their microbial metabolites. Unabsorbed amino acids, including aromatic amino acids (AAAs), are the major substrates in the metabolism of gut microbiota. The aryl moieties of AAAs are more resistant to microbial degradation than the side chains of other amino acids, leading to the formation of various aryl metabolites with diverse bioactivities. Previous studies have shown that oxidation and reduction as well as lyase-mediated elimination and decarboxylation occur in the microbial metabolism of AAAs, but the contribution of individual metabolic pathways to the formation and distribution of microbial AAA metabolites as well as their responses to chemical and microbial interventions are not well examined. In this study, deuterated AAAs were used as the sole source of dietary AAAs to trace their metabolic fates in mouse. The results showed that besides dietary AAAs, endogenous AAAs are also the major contributor of microbial metabolites. Tyrosine and phenylalanine undergo both oxidative and elimination reactions, producing phenylacetate (PAA), 4-hydroxyphenylacetate (4HPAA), p-cresol, phenol, and their conjugates as their major microbial metabolites, while tryptophan is mainly degraded by elimination reaction, producing indoxyl sulfate as a major microbial metabolite. Modulation of microbial AAA metabolism by microbiota and chemical interventions were investigated by the treatments of antibiotics, fecal microbiota transplantation (FMT), and green tea polyphenols (GTP). In both humans and mice, the production of p-cresol is highly sensitive to antibiotics and FMT since urinary p-cresol sulfate was depleted by antibiotics and then quickly restored by FMT through drastic changes in the gut microbiota. In contrast, chronic GTP consumption in humans did not significantly alter the microbial composition, but decreased urinary hippuric acid, indoxyl sulfate, and phenylacetylglutamine, potentially through competitive inhibition in the microbial metabolism of GTP and AAAs. Overall, microbial metabolism of AAAs is dominated by oxidative and elimination reactions and these metabolic pathways are highly susceptible to microbiota and chemical interventions. Therefore, microbial metabolism of AAAs should be a target of investigation in future studies on dietary and therapeutic modulation of gut microbiota in humans and animals.
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University of Minnesota Ph.D. dissertation. August 2021. Major: Food Science. Advisor: CHI CHEN. 1 computer file (PDF); xii, 188 pages.
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Zhou, Yuyin. (2021). Gut Microbial Metabolism Of Aromatic Amino Acids Under Chemical And Microbiota Interventions. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/258909.
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