Evidence that the loss of colonic anti-microbial peptides may promote dysbiotic Gram-negative inflammaging-associated bacteria in aging mice
Introduction: Aging studies in humans and mice have played a key role in understanding the intestinal microbiome and an increased abundance of “inflammaging” Gram-negative (Gn) bacteria. The mechanisms underlying this inflammatory profile in the aging microbiome are unknown. We tested the hypothesis...
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| Format: | Article |
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Frontiers Media S.A.
2024-03-01
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| Series: | Frontiers in Aging |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fragi.2024.1352299/full |
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| author | Christopher B. Forsyth Christopher B. Forsyth Christopher B. Forsyth Maliha Shaikh Phillip A. Engen Fabian Preuss Ankur Naqib Ankur Naqib Breanna A. Palmen Stefan J. Green Stefan J. Green Lijuan Zhang Zlata R. Bogin Kristi Lawrence Deepak Sharma Garth R. Swanson Garth R. Swanson Garth R. Swanson Faraz Bishehsari Faraz Bishehsari Faraz Bishehsari Robin M. Voigt Robin M. Voigt Robin M. Voigt Ali Keshavarzian Ali Keshavarzian Ali Keshavarzian Ali Keshavarzian |
| author_facet | Christopher B. Forsyth Christopher B. Forsyth Christopher B. Forsyth Maliha Shaikh Phillip A. Engen Fabian Preuss Ankur Naqib Ankur Naqib Breanna A. Palmen Stefan J. Green Stefan J. Green Lijuan Zhang Zlata R. Bogin Kristi Lawrence Deepak Sharma Garth R. Swanson Garth R. Swanson Garth R. Swanson Faraz Bishehsari Faraz Bishehsari Faraz Bishehsari Robin M. Voigt Robin M. Voigt Robin M. Voigt Ali Keshavarzian Ali Keshavarzian Ali Keshavarzian Ali Keshavarzian |
| author_sort | Christopher B. Forsyth |
| collection | DOAJ |
| description | Introduction: Aging studies in humans and mice have played a key role in understanding the intestinal microbiome and an increased abundance of “inflammaging” Gram-negative (Gn) bacteria. The mechanisms underlying this inflammatory profile in the aging microbiome are unknown. We tested the hypothesis that an aging-related decrease in colonic crypt epithelial cell anti-microbial peptide (AMP) gene expression could promote colonic microbiome inflammatory Gn dysbiosis and inflammaging.Methods: As a model of aging, C57BL/6J mice fecal (colonic) microbiota (16S) and isolated colonic crypt epithelial cell gene expression (RNA-seq) were assessed at 2 months (mth) (human: 18 years old; yo), 15 mth (human: 50 yo), and 25 mth (human: 84 yo). Informatics examined aging-related microbial compositions, differential colonic crypt epithelial cell gene expressions, and correlations between colonic bacteria and colonic crypt epithelial cell gene expressions.Results: Fecal microbiota exhibited significantly increased relative abundances of pro-inflammatory Gn bacteria with aging. Colonic crypt epithelial cell gene expression analysis showed significant age-related downregulation of key AMP genes that repress the growth of Gn bacteria. The aging-related decrease in AMP gene expressions is significantly correlated with an increased abundance in Gn bacteria (dysbiosis), loss of colonic barrier gene expression, and senescence- and inflammation-related gene expression.Conclusion: This study supports the proposed model that aging-related loss of colonic crypt epithelial cell AMP gene expression promotes increased relative abundances of Gn inflammaging-associated bacteria and gene expression markers of colonic inflammaging. These data may support new targets for aging-related therapies based on intestinal genes and microbiomes. |
| first_indexed | 2024-03-07T16:18:07Z |
| format | Article |
| id | doaj.art-acec46e9e49b44de8ff3f353d34caeb6 |
| institution | Directory Open Access Journal |
| issn | 2673-6217 |
| language | English |
| last_indexed | 2024-03-07T16:18:07Z |
| publishDate | 2024-03-01 |
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| series | Frontiers in Aging |
| spelling | doaj.art-acec46e9e49b44de8ff3f353d34caeb62024-03-04T10:12:40ZengFrontiers Media S.A.Frontiers in Aging2673-62172024-03-01510.3389/fragi.2024.13522991352299Evidence that the loss of colonic anti-microbial peptides may promote dysbiotic Gram-negative inflammaging-associated bacteria in aging miceChristopher B. Forsyth0Christopher B. Forsyth1Christopher B. Forsyth2Maliha Shaikh3Phillip A. Engen4Fabian Preuss5Ankur Naqib6Ankur Naqib7Breanna A. Palmen8Stefan J. Green9Stefan J. Green10Lijuan Zhang11Zlata R. Bogin12Kristi Lawrence13Deepak Sharma14Garth R. Swanson15Garth R. Swanson16Garth R. Swanson17Faraz Bishehsari18Faraz Bishehsari19Faraz Bishehsari20Robin M. Voigt21Robin M. Voigt22Robin M. Voigt23Ali Keshavarzian24Ali Keshavarzian25Ali Keshavarzian26Ali Keshavarzian27Department of Internal Medicine, Rush University Medical Center, Chicago, IL, United StatesRush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL, United StatesDepartment of Anatomy and Cell Biology, Rush University Medical Center, Chicago, IL, United StatesRush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL, United StatesRush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL, United StatesDepartment of Biological Sciences, University of Wisconsin Parkside, Kenosha, WI, United StatesRush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL, United StatesGenomics and Microbiome Core Facility, Rush University Medical Center, Chicago, IL, United StatesDepartment of Biological Sciences, University of Wisconsin Parkside, Kenosha, WI, United StatesRush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL, United StatesGenomics and Microbiome Core Facility, Rush University Medical Center, Chicago, IL, United StatesRush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL, United StatesRush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL, United StatesRush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL, United StatesRush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL, United StatesDepartment of Internal Medicine, Rush University Medical Center, Chicago, IL, United StatesRush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL, United StatesDepartment of Anatomy and Cell Biology, Rush University Medical Center, Chicago, IL, United StatesDepartment of Internal Medicine, Rush University Medical Center, Chicago, IL, United StatesRush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL, United StatesDepartment of Anatomy and Cell Biology, Rush University Medical Center, Chicago, IL, United StatesDepartment of Internal Medicine, Rush University Medical Center, Chicago, IL, United StatesRush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL, United StatesDepartment of Anatomy and Cell Biology, Rush University Medical Center, Chicago, IL, United StatesDepartment of Internal Medicine, Rush University Medical Center, Chicago, IL, United StatesRush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL, United StatesDepartment of Anatomy and Cell Biology, Rush University Medical Center, Chicago, IL, United StatesDepartment of Physiology, Rush University Medical Center, Chicago, IL, United StatesIntroduction: Aging studies in humans and mice have played a key role in understanding the intestinal microbiome and an increased abundance of “inflammaging” Gram-negative (Gn) bacteria. The mechanisms underlying this inflammatory profile in the aging microbiome are unknown. We tested the hypothesis that an aging-related decrease in colonic crypt epithelial cell anti-microbial peptide (AMP) gene expression could promote colonic microbiome inflammatory Gn dysbiosis and inflammaging.Methods: As a model of aging, C57BL/6J mice fecal (colonic) microbiota (16S) and isolated colonic crypt epithelial cell gene expression (RNA-seq) were assessed at 2 months (mth) (human: 18 years old; yo), 15 mth (human: 50 yo), and 25 mth (human: 84 yo). Informatics examined aging-related microbial compositions, differential colonic crypt epithelial cell gene expressions, and correlations between colonic bacteria and colonic crypt epithelial cell gene expressions.Results: Fecal microbiota exhibited significantly increased relative abundances of pro-inflammatory Gn bacteria with aging. Colonic crypt epithelial cell gene expression analysis showed significant age-related downregulation of key AMP genes that repress the growth of Gn bacteria. The aging-related decrease in AMP gene expressions is significantly correlated with an increased abundance in Gn bacteria (dysbiosis), loss of colonic barrier gene expression, and senescence- and inflammation-related gene expression.Conclusion: This study supports the proposed model that aging-related loss of colonic crypt epithelial cell AMP gene expression promotes increased relative abundances of Gn inflammaging-associated bacteria and gene expression markers of colonic inflammaging. These data may support new targets for aging-related therapies based on intestinal genes and microbiomes.https://www.frontiersin.org/articles/10.3389/fragi.2024.1352299/fullagingtight junctionmicrobiotagene expressionanti-microbial peptidesdysbiosis |
| spellingShingle | Christopher B. Forsyth Christopher B. Forsyth Christopher B. Forsyth Maliha Shaikh Phillip A. Engen Fabian Preuss Ankur Naqib Ankur Naqib Breanna A. Palmen Stefan J. Green Stefan J. Green Lijuan Zhang Zlata R. Bogin Kristi Lawrence Deepak Sharma Garth R. Swanson Garth R. Swanson Garth R. Swanson Faraz Bishehsari Faraz Bishehsari Faraz Bishehsari Robin M. Voigt Robin M. Voigt Robin M. Voigt Ali Keshavarzian Ali Keshavarzian Ali Keshavarzian Ali Keshavarzian Evidence that the loss of colonic anti-microbial peptides may promote dysbiotic Gram-negative inflammaging-associated bacteria in aging mice Frontiers in Aging aging tight junction microbiota gene expression anti-microbial peptides dysbiosis |
| title | Evidence that the loss of colonic anti-microbial peptides may promote dysbiotic Gram-negative inflammaging-associated bacteria in aging mice |
| title_full | Evidence that the loss of colonic anti-microbial peptides may promote dysbiotic Gram-negative inflammaging-associated bacteria in aging mice |
| title_fullStr | Evidence that the loss of colonic anti-microbial peptides may promote dysbiotic Gram-negative inflammaging-associated bacteria in aging mice |
| title_full_unstemmed | Evidence that the loss of colonic anti-microbial peptides may promote dysbiotic Gram-negative inflammaging-associated bacteria in aging mice |
| title_short | Evidence that the loss of colonic anti-microbial peptides may promote dysbiotic Gram-negative inflammaging-associated bacteria in aging mice |
| title_sort | evidence that the loss of colonic anti microbial peptides may promote dysbiotic gram negative inflammaging associated bacteria in aging mice |
| topic | aging tight junction microbiota gene expression anti-microbial peptides dysbiosis |
| url | https://www.frontiersin.org/articles/10.3389/fragi.2024.1352299/full |
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