Browsing by Author "Mancilla, Viviana J."
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Item A Synthetic Formula Amino Acid Diet Leads to Microbiome Dysbiosis, Reduced Colon Length, Inflammation, and Altered Locomotor Activity in C57BL/6J Mice(MDPI, 2023-11-25) Mancilla, Viviana J.; Braden-Kuhle, Paige N.; Brice, Kelly N.; Mann, Allison E.; Williams, Megan T.; Zhang, Yan; Chumley, Michael J.; Barber, Robert C.; White, Sabrina N.; Boehm, Gary W.; Allen, Michael S.The effects of synthetic, free-amino acid diets, similar to those prescribed as supplements for (phenylketonuria) PKU patients, on gut microbiota and overall health are not well understood. In the current, multidisciplinary study, we examined the effects of a synthetically-derived, low-fiber, amino acid diet on behavior, cognition, gut microbiome composition, and inflammatory markers. A cohort of 20 male C57BL/6J mice were randomly assigned to either a standard or synthetic diet (n = 10) at post-natal day 21 and maintained for 13 weeks. Sequencing of the 16S rRNA gene from fecal samples revealed decreased bacterial diversity, increased abundance of bacteria associated with disease, such as Prevotella, and a downward shift in gut microbiota associated with fermentation pathways in the synthetic diet group. Furthermore, there were decreased levels of short chain fatty acids and shortening of the colon in mice consuming the synthetic diet. Finally, we measured TNF-alpha, IL-6, and IL-10 in serum, the hippocampus, and colon, and found that the synthetic diet significantly increased IL-6 production in the hippocampus. These results demonstrate the importance of a multidisciplinary approach to future diet and microbiome studies, as diet not only impacts the gut microbiome composition but potentially systemic health as well.Item Effects of a Synthetic Amino Acid Diet: Insights from the Guy Microbiome, Inflammation, and Behavior(2021-05) Mancilla, Viviana J.; Allen, Michael S.; Jones, Harlan P.; Phillips, Nicole R.; Planz, John V.; Ellis, DorettePhenylketonuria (PKU) is an inborn error of phenylalanine metabolism primarily treated through a phenylalanine-restrictive diet and frequently supplemented with an amino acid formula to maintain proper nutrition. PKU patients often report high levels of anxiety along with symptoms of gastrointestinal distress (i.e., chronic diarrhea, constipation, cramps); symptoms previously associated with gut microbiome dysbiosis. Little is known of the effects of these dietary interventions on the gut microbiome of PKU patients, particularly in adults. The gut microbiome is a collection of microbes residing primarily in the large intestine. The colon is a major production site for short chain fatty acids (SCFAs) through anaerobic fermentation by commensal bacteria. SCFAs provide a source of energy for the colonocytes, as well as provide anti-inflammatory benefits. The production of SCFA appears to be dependent on the availability of soluble fibers and members of the gut microbiota capable of fermentation. We characterized the gut microbiome of adults with PKU for the first time and identified signs of dysbiosis. We then focused on the synthetic, low fiber, nature of the amino acid diet in a murine model. In this interdisciplinary study, we monitored the effect of a consuming synthetic diet on the composition of the murine gut microbiome over the course of 13 weeks, beginning at weaning. At the conclusion of the feeding period, mice we observed for anxiolytic behavior, locomotion, and cognition. We also searched for markers of inflammation through colon shrinkage, changes in cytokine levels within several tissues, and determined the concentration of SCFAs in the colon at the conclusion of the feeding period. The gut microbiome of mice fed the synthetic diet experienced significant deviation from the control group which affected relative abundance of beneficial bacteria. Mice on the synthetic diet were found to have shorter colons, lower concentration of SCFAs in the colon, and demonstrated elevated exploratory behavior.Item Gut Microbiome of Phenylketonuria Patients(2017-03-14) Zhang, Yan; Durrer, Katherine; Allen, Michael; Mancilla, Viviana J.Background: Phenylketonuria (PKU) is a metabolic disease caused by a mutation in the phenylalanine hydroxylase (PAH) gene, resulting in the inability to metabolize phenylalanine. Currently, the main treatment for PKU is dietary Phe restriction. Numerous studies on the gut microbiome have demonstrated impacts on overall health, and both diet and genetics have been shown to impact the composition of the gut microbiome. The gut microbiome in adult PKU patients has not yet been systematically investigated, and the ramifications of dietary Phe restriction are unknown. Objective: Characterize the gut microbiome of PKU patients. Materials and Methods: Gut microbial composition of 16 adult PKU patients were compared to 15 healthy adults by sequencing the 16S RNA gene v4 region using the Illumina MiSeq instrument. Results: The dominant genera found in the gut microbiome of PKU and healthy control were Blautia and Bacteroides. When comparing the microbiome composition of healthy individuals and PKU patients, the abundance of Blautia, Corpococcus, Subdoligranulum, and Psuedonomas were increased in PKU patients, while Bacteriodes, Alistipes, SMB53, Faecalibacterium, and members of the Enterobacteriaceae family were shown to decrease in abundance in PKU patients. Conclusions: The compositions of the PKU gut microbiome showed differences compared to that of healthy controls. This study provides valuable background information on the gut microbiome of PKU patients, which could be beneficial to the development of future treatments.Item Natural Product Drug Discovery Through Crowd-Sourcing and Crowd-Funding(2016-03-23) Patel, Rinkal; Liu, Xiangyang; Cheng, Yi-Qiang; Mancilla, Viviana J.Natural products continue to be a major source of human medicines. We hypothesize that the diverse geographic features and soil types of Texas harbor diverse microorganisms (bacteria and fungi), from which potent natural products may be discovered for the development of new drugs to treat cancer, infectious diseases, parasites or other medical conditions. We designed a crowd-sourcing and crowd-funding project to test this hypothesis. We have conducted a Phase I Feasibility Study using 5 soil samples collected by us within the Tarrant County and the preliminary results are encouraging. For a Phase II Pilot Study, we are reaching out to a high school in each of the carefully selected 11 counties in Texas. We request interested high school science teachers and students to collect 4 to 5 distinctive soil samples within the boundary of their respective counties and send the samples to UNTHSC for processing. In the future Phase III Comprehensive Study, we hope to cover all 254 counties in Texas. Thousands of distinctive microbial isolates will be obtained from those soil samples and will be fermented in different media to produce natural product crude extracts. Those crude extracts will be fractionated through flash chromatography. Tens of thousands of natural product fractions will be arranged systematically in 96-deep well plates to constitute a natural product fraction library. Subsequent screening of this library is predicted to generate dozens of natural product drug leads that possess activities against cancer cells, pathogenic bacteria or fungi, parasites or other medical conditions. An interactive website will be created to provide an effective communication platform between citizen scientists and campus researchers and to solicit donations to support this innovative research project.Item The Adult Phenylketonuria (PKU) Gut Microbiome(MDPI, 2021-03-04) Mancilla, Viviana J.; Mann, Allison E.; Zhang, Yan; Allen, Michael S.Phenylketonuria (PKU) is an inborn error of phenylalanine metabolism primarily treated through a phenylalanine-restrictive diet that is frequently supplemented with an amino acid formula to maintain proper nutrition. Little is known of the effects of these dietary interventions on the gut microbiome of PKU patients, particularly in adults. In this study, we sequenced the V4 region of the 16S rRNA gene from stool samples collected from adults with PKU (n = 11) and non-PKU controls (n = 21). Gut bacterial communities were characterized through measurements of diversity and taxa abundance. Additionally, metabolic imputation was performed based on detected bacteria. Gut community diversity was lower in PKU individuals, though this effect was only statistically suggestive. A total of 65 genera across 5 phyla were statistically differentially abundant between PKU and control samples (p < 0.001). Additionally, we identified six metabolic pathways that differed between groups (p < 0.05), with four enriched in PKU samples and two in controls. While the child PKU gut microbiome has been previously investigated, this is the first study to explore the gut microbiome of adult PKU patients. We find that microbial diversity in PKU children differs from PKU adults and highlights the need for further studies to understand the effects of dietary restrictions.