Ketogenic diet restrains herpes simplex encephalitis via gut microbes |
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| Institution: | 1. Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, PR China;2. Infectious Diseases Institute, Guangzhou Eighth People''s Hospital, Guangdong, China;3. School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen, China;1. Division of Pharmacy Practice and Administration, University of Missouri-Kansas City School of Pharmacy, Kansas City, Missouri, USA;2. Department of Pharmacy, Centerpoint Medical Center, Independence, Missouri, USA;1. Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, United States;2. Animal Resource Program, Atrium Health Wake Forest Baptist, Winston Salem, NC, United States;3. Department of Comparative Medicine, Worldwide Research, Development, and Medical, Pfizer, Cambridge, MA, United States;4. Novartis Institutes for BioMedical Research, Cambridge, MA, United States;5. Merck Research Laboratories, Merck, South San Francisco, CA, United States;6. Department of Medicine, Columbia University, New York, NY, United States;7. Division of Neonatology, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, United States;8. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, United States;1. Laboratório de Entomologia I, Fiocruz Rondônia – Fundação Oswaldo Cruz, Lagoa, 76812-245, Porto Velho, Rondônia State, Brazil;2. Programa de Pós-Graduação em Biologia Experimental – PGBIOEXP, Fundação Universidade Federal de Rondônia – UNIR, BR-364, km 9.5, 76801-059, Porto Velho, Rondônia State, Brazil;3. Laboratório de Ecologia de Doenças Transmissíveis na Amazônia, Instituto Leônidas e Maria Deane – Fiocruz Amazônia, Adrianópolis, 69057-070, Manaus, Amazonas State, Brazil;4. Programa de Pós-Graduação em Biologia Celular e Molecular, Instituto Oswaldo Cruz, Fiocruz, Manguinhos, 21040-360, Rio de Janeiro State, Brazil;5. Programa de Pós-Graduação em Biologia da Interação Patógeno-Hospedeiro, Instituto Leônidas e Maria Deane – Fiocruz Amazônia, Adrianópolis, 69057-070, Manaus, Amazonas State, Brazil;6. Laboratório de Virologia Molecular, Fiocruz Rondônia – Fundação Oswaldo Cruz, Lagoa, 76812-245, Porto Velho, Rondônia State, Brazil;7. Instituto Nacional de Epidemiologia da Amazônia Ocidental – INCT-EpiAmO, Lagoa, 76812-245, Porto Velho, Rondônia State, Brazil;1. Department of Pharmacy, Guangdong Second Provincial General Hospital, No.466 Middle Xingang Road, Guangzhou, 510317, China;2. Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, No. 1838 Shatai South Road, Baiyun District, Guangzhou, 510515, China;3. Department of Pharmacy, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-sen University, No.23 Haipang Street, North Street, Jiangmen, 529030, China;1. Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, Jiangsu, China;2. Institute of Oceanology and Marine Fisheries, Nantong, 226007, Jiangsu, China;3. Guangxi Key Laboratory for Polysaccharide Materials and Modifications, School of Marine Sciences and Biotechnology, Guangxi University for Nationalities, Nanning, 530008, Guangxi, China;1. Departamento de Medicina Veterinária, Faculdade de Zootecnia e Medicina Veterinária, Universidade Federal de Lavras, Lavras, Minas Gerais, Brazil;2. Departamento de Genética, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil;3. Centro de Ciência da Saúde - Medicina - Araguaína, Universidade Federal de Tocantins, Tocantins, Brazil;4. Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, United Kingdom;5. IVBIC, INSERM, Universite de Montpellier, Nimes, France;6. CNR Brucella, Laboratoire de Microbiologie, CHU Nimes, Nimes, France;7. Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, USA;8. Departamento de Microbiologia, Imunologia e Parasitologia, Instituto de Ciências Biológicas e Ciências Naturais, Universidade Federal Do Triângulo Mineiro, Uberaba, Minas Gerais, Brazil;9. Instituto de Ciências Biológicas, Centro de Genômica e Biologia de Sistemas, Universidade Federal Do Pará, Belém, Pará, Brazil;10. Universidade Federal Do Vale Do São Francisco, Departamento de Zootecnia, Petrolina, Pernambuco, Brazil;11. Departamento de Medicina Veterinária Preventiva, Escola de Veterinária, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil |
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| Abstract: | Herpes simplex virus type 1 (HSV-1) infection-associated herpes simplex encephalitis (HSE) is an occasionally but severe neuronal disease that causes behavioral disorder and impairs cognition. Herein, we demonstrate that the consumption of ketogenic diet (KD), a low-carbohydrate high-fat diet, restricts the neurotropic infection of HSV-1 and HSE progression in mice. KD reduced weight loss, neurodegenerative symptoms, virus production and neuroinflammation, resulting in the enhanced survival rate of HSE mice. Notably, depletion of gut microbes by antibiotics attenuated the protective function of KD on HSV-1-related neuroinflammation and HSE development. Therefore, KD represents as an alternative therapeutic strategy to alleviate or prevent HSE via gut microbiota. |
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| Keywords: | Herpes simplex encephalitis Ketogenic diet Gut microbes Inflammation Herpes simplex virus type 1 |
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