Human-Derived Bifidobacterium dentium Modulates the Mammalian Serotonergic System and Gut–Brain AxisSummary
Background & Aims: The human gut microbiota can regulate production of serotonin (5-hydroxytryptamine [5-HT]) from enterochromaffin cells. However, the mechanisms underlying microbial-induced serotonin signaling are not well understood. Methods: Adult germ-free mice were treated with sterile...
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| Format: | Article |
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Elsevier
2021-01-01
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| Series: | Cellular and Molecular Gastroenterology and Hepatology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352345X20301260 |
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| author | Melinda A. Engevik Berkley Luck Chonnikant Visuthranukul Faith D. Ihekweazu Amy C. Engevik Zhongcheng Shi Heather A. Danhof Alexandra L. Chang-Graham Anne Hall Bradley T. Endres Sigmund J. Haidacher Thomas D. Horvath Anthony M. Haag Sridevi Devaraj Kevin W. Garey Robert A. Britton Joseph M. Hyser Noah F. Shroyer James Versalovic |
| author_facet | Melinda A. Engevik Berkley Luck Chonnikant Visuthranukul Faith D. Ihekweazu Amy C. Engevik Zhongcheng Shi Heather A. Danhof Alexandra L. Chang-Graham Anne Hall Bradley T. Endres Sigmund J. Haidacher Thomas D. Horvath Anthony M. Haag Sridevi Devaraj Kevin W. Garey Robert A. Britton Joseph M. Hyser Noah F. Shroyer James Versalovic |
| author_sort | Melinda A. Engevik |
| collection | DOAJ |
| description | Background & Aims: The human gut microbiota can regulate production of serotonin (5-hydroxytryptamine [5-HT]) from enterochromaffin cells. However, the mechanisms underlying microbial-induced serotonin signaling are not well understood. Methods: Adult germ-free mice were treated with sterile media, live Bifidobacterium dentium, heat-killed B dentium, or live Bacteroides ovatus. Mouse and human enteroids were used to assess the effects of B dentium metabolites on 5-HT release from enterochromaffin cells. In vitro and in vivo short-chain fatty acids and 5-HT levels were assessed by mass spectrometry. Expression of tryptophan hydroxylase, short-chain fatty acid receptor free fatty acid receptor 2, 5-HT receptors, and the 5-HT re-uptake transporter (serotonin transporter) were assessed by quantitative polymerase chain reaction and immunostaining. RNA in situ hybridization assessed 5-HT–receptor expression in the brain, and 5-HT–receptor–dependent behavior was evaluated using the marble burying test. Results: B dentium mono-associated mice showed increased fecal acetate. This finding corresponded with increased intestinal 5-HT concentrations and increased expression of 5-HT receptors 2a, 4, and serotonin transporter. These effects were absent in B ovatus-treated mice. Application of acetate and B dentium–secreted products stimulated 5-HT release in mouse and human enteroids. In situ hybridization of brain tissue also showed significantly increased hippocampal expression of 5-HT–receptor 2a in B dentium–treated mice relative to germ-free controls. Functionally, B dentium colonization normalized species-typical repetitive and anxiety-like behaviors previously shown to be linked to 5-HT–receptor 2a. Conclusions: These data suggest that B dentium, and the bacterial metabolite acetate, are capable of regulating key components of the serotonergic system in multiple host tissues, and are associated with a functional change in adult behavior. |
| first_indexed | 2024-12-21T14:25:49Z |
| format | Article |
| id | doaj.art-104cb38cf9ef42919922904300f90cbe |
| institution | Directory Open Access Journal |
| issn | 2352-345X |
| language | English |
| last_indexed | 2024-12-21T14:25:49Z |
| publishDate | 2021-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cellular and Molecular Gastroenterology and Hepatology |
| spelling | doaj.art-104cb38cf9ef42919922904300f90cbe2022-12-21T19:00:38ZengElsevierCellular and Molecular Gastroenterology and Hepatology2352-345X2021-01-01111221248Human-Derived Bifidobacterium dentium Modulates the Mammalian Serotonergic System and Gut–Brain AxisSummaryMelinda A. Engevik0Berkley Luck1Chonnikant Visuthranukul2Faith D. Ihekweazu3Amy C. Engevik4Zhongcheng Shi5Heather A. Danhof6Alexandra L. Chang-Graham7Anne Hall8Bradley T. Endres9Sigmund J. Haidacher10Thomas D. Horvath11Anthony M. Haag12Sridevi Devaraj13Kevin W. Garey14Robert A. Britton15Joseph M. Hyser16Noah F. Shroyer17James Versalovic18Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas; Department of Pathology, Texas Children’s Hospital, Houston, TexasDepartment of Pathology and Immunology, Baylor College of Medicine, Houston, Texas; Department of Pathology, Texas Children’s Hospital, Houston, TexasDepartment of Pathology and Immunology, Baylor College of Medicine, Houston, Texas; Department of Pathology, Texas Children’s Hospital, Houston, Texas; Department of Pediatrics, Pediatric Nutrition Special Task Force for Activating Research (STAR), Faculty of Medicine, Chulalongkorn University, Bangkok, ThailandPediatric Gastroenterology, Hepatology and Nutrition, Texas Children’s Hospital, Baylor College of Medicine, Houston, TexasDepartment of Surgical Sciences, Vanderbilt University Medical Center, Nashville TennesseeDepartment of Pathology and Immunology, Baylor College of Medicine, Houston, Texas; Department of Pathology, Texas Children’s Hospital, Houston, TexasDepartment of Virology and Microbiology, Baylor College of Medicine, Houston, TexasDepartment of Virology and Microbiology, Baylor College of Medicine, Houston, TexasDepartment of Pathology and Immunology, Baylor College of Medicine, Houston, Texas; Department of Pathology, Texas Children’s Hospital, Houston, Texas; Department of Virology and Microbiology, Baylor College of Medicine, Houston, TexasDepartment of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, TexasDepartment of Pathology and Immunology, Baylor College of Medicine, Houston, Texas; Department of Pathology, Texas Children’s Hospital, Houston, TexasDepartment of Pathology and Immunology, Baylor College of Medicine, Houston, Texas; Department of Pathology, Texas Children’s Hospital, Houston, TexasDepartment of Pathology and Immunology, Baylor College of Medicine, Houston, Texas; Department of Pathology, Texas Children’s Hospital, Houston, TexasDepartment of Pathology and Immunology, Baylor College of Medicine, Houston, Texas; Department of Pathology, Texas Children’s Hospital, Houston, TexasDepartment of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, TexasDepartment of Virology and Microbiology, Baylor College of Medicine, Houston, TexasDepartment of Virology and Microbiology, Baylor College of Medicine, Houston, TexasSection of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TexasDepartment of Pathology and Immunology, Baylor College of Medicine, Houston, Texas; Department of Pathology, Texas Children’s Hospital, Houston, Texas; Correspondence Address correspondence to: James Versalovic, MD, PhD, Department of Pathology and Immunology, Baylor College of Medicine, 1102 Bates Avenue, Suite 830, Houston, Texas 7703. fax: (832) 825-1165.Background & Aims: The human gut microbiota can regulate production of serotonin (5-hydroxytryptamine [5-HT]) from enterochromaffin cells. However, the mechanisms underlying microbial-induced serotonin signaling are not well understood. Methods: Adult germ-free mice were treated with sterile media, live Bifidobacterium dentium, heat-killed B dentium, or live Bacteroides ovatus. Mouse and human enteroids were used to assess the effects of B dentium metabolites on 5-HT release from enterochromaffin cells. In vitro and in vivo short-chain fatty acids and 5-HT levels were assessed by mass spectrometry. Expression of tryptophan hydroxylase, short-chain fatty acid receptor free fatty acid receptor 2, 5-HT receptors, and the 5-HT re-uptake transporter (serotonin transporter) were assessed by quantitative polymerase chain reaction and immunostaining. RNA in situ hybridization assessed 5-HT–receptor expression in the brain, and 5-HT–receptor–dependent behavior was evaluated using the marble burying test. Results: B dentium mono-associated mice showed increased fecal acetate. This finding corresponded with increased intestinal 5-HT concentrations and increased expression of 5-HT receptors 2a, 4, and serotonin transporter. These effects were absent in B ovatus-treated mice. Application of acetate and B dentium–secreted products stimulated 5-HT release in mouse and human enteroids. In situ hybridization of brain tissue also showed significantly increased hippocampal expression of 5-HT–receptor 2a in B dentium–treated mice relative to germ-free controls. Functionally, B dentium colonization normalized species-typical repetitive and anxiety-like behaviors previously shown to be linked to 5-HT–receptor 2a. Conclusions: These data suggest that B dentium, and the bacterial metabolite acetate, are capable of regulating key components of the serotonergic system in multiple host tissues, and are associated with a functional change in adult behavior.http://www.sciencedirect.com/science/article/pii/S2352345X20301260SerotoninSerotonin TransporterBifidobacteriumProbioticsEnteroidsOrganoids |
| spellingShingle | Melinda A. Engevik Berkley Luck Chonnikant Visuthranukul Faith D. Ihekweazu Amy C. Engevik Zhongcheng Shi Heather A. Danhof Alexandra L. Chang-Graham Anne Hall Bradley T. Endres Sigmund J. Haidacher Thomas D. Horvath Anthony M. Haag Sridevi Devaraj Kevin W. Garey Robert A. Britton Joseph M. Hyser Noah F. Shroyer James Versalovic Human-Derived Bifidobacterium dentium Modulates the Mammalian Serotonergic System and Gut–Brain AxisSummary Cellular and Molecular Gastroenterology and Hepatology Serotonin Serotonin Transporter Bifidobacterium Probiotics Enteroids Organoids |
| title | Human-Derived Bifidobacterium dentium Modulates the Mammalian Serotonergic System and Gut–Brain AxisSummary |
| title_full | Human-Derived Bifidobacterium dentium Modulates the Mammalian Serotonergic System and Gut–Brain AxisSummary |
| title_fullStr | Human-Derived Bifidobacterium dentium Modulates the Mammalian Serotonergic System and Gut–Brain AxisSummary |
| title_full_unstemmed | Human-Derived Bifidobacterium dentium Modulates the Mammalian Serotonergic System and Gut–Brain AxisSummary |
| title_short | Human-Derived Bifidobacterium dentium Modulates the Mammalian Serotonergic System and Gut–Brain AxisSummary |
| title_sort | human derived bifidobacterium dentium modulates the mammalian serotonergic system and gut brain axissummary |
| topic | Serotonin Serotonin Transporter Bifidobacterium Probiotics Enteroids Organoids |
| url | http://www.sciencedirect.com/science/article/pii/S2352345X20301260 |
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