A Synthetic Formula Amino Acid Diet Leads to Microbiome Dysbiosis, Reduced Colon Length, Inflammation, and Altered Locomotor Activity in C57BL/6J Mice

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...

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Main Authors: Viviana J. Mancilla, Paige N. Braden-Kuhle, Kelly N. Brice, Allison E. Mann, Megan T. Williams, Yan Zhang, Michael J. Chumley, Robert C. Barber, Sabrina N. White, Gary W. Boehm, Michael S. Allen
Format: Article
Language:English
Published: MDPI AG 2023-11-01
Series:Microorganisms
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Online Access:https://www.mdpi.com/2076-2607/11/11/2694
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author Viviana J. Mancilla
Paige N. Braden-Kuhle
Kelly N. Brice
Allison E. Mann
Megan T. Williams
Yan Zhang
Michael J. Chumley
Robert C. Barber
Sabrina N. White
Gary W. Boehm
Michael S. Allen
author_facet Viviana J. Mancilla
Paige N. Braden-Kuhle
Kelly N. Brice
Allison E. Mann
Megan T. Williams
Yan Zhang
Michael J. Chumley
Robert C. Barber
Sabrina N. White
Gary W. Boehm
Michael S. Allen
author_sort Viviana J. Mancilla
collection DOAJ
description 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 (<i>n</i> = 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 <i>Prevotella</i>, 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-α, 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.
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spelling doaj.art-8f158b55c7bb4b6e81550e121605f3812023-11-24T14:56:56ZengMDPI AGMicroorganisms2076-26072023-11-011111269410.3390/microorganisms11112694A Synthetic Formula Amino Acid Diet Leads to Microbiome Dysbiosis, Reduced Colon Length, Inflammation, and Altered Locomotor Activity in C57BL/6J MiceViviana J. Mancilla0Paige N. Braden-Kuhle1Kelly N. Brice2Allison E. Mann3Megan T. Williams4Yan Zhang5Michael J. Chumley6Robert C. Barber7Sabrina N. White8Gary W. Boehm9Michael S. Allen10Department of Microbiology, Immunology, and Genetics, School of Biomedical Sciences, University of North Texas Health Science Center, Fort Worth, TX 76107, USADepartment of Psychology, College of Science and Engineering, Texas Christian University, Fort Worth, TX 76109, USADepartment of Psychology, College of Science and Engineering, Texas Christian University, Fort Worth, TX 76109, USADepartment of Microbiology, Immunology, and Genetics, School of Biomedical Sciences, University of North Texas Health Science Center, Fort Worth, TX 76107, USADepartment of Microbiology, Immunology, and Genetics, School of Biomedical Sciences, University of North Texas Health Science Center, Fort Worth, TX 76107, USADepartment of Microbiology, Immunology, and Genetics, School of Biomedical Sciences, University of North Texas Health Science Center, Fort Worth, TX 76107, USADepartment of Biology, College of Science and Engineering, Texas Christian University, Fort Worth, TX 76109, USADepartment of Pharmacology and Neuroscience, School of Biomedical Sciences, University of North Texas Health Science Center, Fort Worth, TX 76107, USADepartment of Microbiology, Immunology, and Genetics, School of Biomedical Sciences, University of North Texas Health Science Center, Fort Worth, TX 76107, USADepartment of Psychology, College of Science and Engineering, Texas Christian University, Fort Worth, TX 76109, USADepartment of Microbiology, Immunology, and Genetics, School of Biomedical Sciences, University of North Texas Health Science Center, Fort Worth, TX 76107, USAThe 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 (<i>n</i> = 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 <i>Prevotella</i>, 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-α, 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.https://www.mdpi.com/2076-2607/11/11/2694SCFAinflammationmouse modelfibersynthetic dietgut-brain axis
spellingShingle Viviana J. Mancilla
Paige N. Braden-Kuhle
Kelly N. Brice
Allison E. Mann
Megan T. Williams
Yan Zhang
Michael J. Chumley
Robert C. Barber
Sabrina N. White
Gary W. Boehm
Michael S. Allen
A Synthetic Formula Amino Acid Diet Leads to Microbiome Dysbiosis, Reduced Colon Length, Inflammation, and Altered Locomotor Activity in C57BL/6J Mice
Microorganisms
SCFA
inflammation
mouse model
fiber
synthetic diet
gut-brain axis
title A Synthetic Formula Amino Acid Diet Leads to Microbiome Dysbiosis, Reduced Colon Length, Inflammation, and Altered Locomotor Activity in C57BL/6J Mice
title_full A Synthetic Formula Amino Acid Diet Leads to Microbiome Dysbiosis, Reduced Colon Length, Inflammation, and Altered Locomotor Activity in C57BL/6J Mice
title_fullStr A Synthetic Formula Amino Acid Diet Leads to Microbiome Dysbiosis, Reduced Colon Length, Inflammation, and Altered Locomotor Activity in C57BL/6J Mice
title_full_unstemmed A Synthetic Formula Amino Acid Diet Leads to Microbiome Dysbiosis, Reduced Colon Length, Inflammation, and Altered Locomotor Activity in C57BL/6J Mice
title_short A Synthetic Formula Amino Acid Diet Leads to Microbiome Dysbiosis, Reduced Colon Length, Inflammation, and Altered Locomotor Activity in C57BL/6J Mice
title_sort synthetic formula amino acid diet leads to microbiome dysbiosis reduced colon length inflammation and altered locomotor activity in c57bl 6j mice
topic SCFA
inflammation
mouse model
fiber
synthetic diet
gut-brain axis
url https://www.mdpi.com/2076-2607/11/11/2694
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