Host genetics and gut microbiota influence lipid metabolism and inflammation: potential implications for ALS pathophysiology in SOD1G93A mice
Abstract Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disorder characterized by the progressive loss of motor neurons, with genetic and environmental factors contributing to its complex pathogenesis. Dysregulated immune responses and altered energetic metabolism are key fea...
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BMC
2024-11-01
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| Series: | Acta Neuropathologica Communications |
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| Online Access: | https://doi.org/10.1186/s40478-024-01877-x |
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| author | Elena Niccolai Leandro Di Gloria Maria Chiara Trolese Paola Fabbrizio Simone Baldi Giulia Nannini Cassandra Margotta Claudia Nastasi Matteo Ramazzotti Gianluca Bartolucci Caterina Bendotti Giovanni Nardo Amedeo Amedei |
| author_facet | Elena Niccolai Leandro Di Gloria Maria Chiara Trolese Paola Fabbrizio Simone Baldi Giulia Nannini Cassandra Margotta Claudia Nastasi Matteo Ramazzotti Gianluca Bartolucci Caterina Bendotti Giovanni Nardo Amedeo Amedei |
| author_sort | Elena Niccolai |
| collection | DOAJ |
| description | Abstract Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disorder characterized by the progressive loss of motor neurons, with genetic and environmental factors contributing to its complex pathogenesis. Dysregulated immune responses and altered energetic metabolism are key features, with emerging evidence implicating the gut microbiota (GM) in disease progression. We investigated the interplay among genetic background, GM composition, metabolism, and immune response in two distinct ALS mouse models: 129Sv_G93A and C57Ola_G93A, representing rapid and slow disease progression, respectively. Using 16 S rRNA sequencing and fecal metabolite analysis, we characterized the GM composition and metabolite profiles in non-transgenic (Ntg) and SOD1G93A mutant mice of both strains. Our results revealed strain-specific differences in GM composition and functions, particularly in the abundance of taxa belonging to Erysipelotrichaceae and the levels of short and medium-chain fatty acids in fecal samples. The SOD1 mutation induces significant shifts in GM colonization in both strains, with C57Ola_G93A mice showing changes resembling those in 129 Sv mice, potentially affecting disease pathogenesis. ALS symptom progression does not significantly alter microbiota composition, suggesting stability. Additionally, we assessed systemic immunity and inflammatory responses revealing strain-specific differences in immune cell populations and cytokine levels. Our findings underscore the substantial influence of genetic background on GM composition, metabolism, and immune response in ALS mouse models. These strain-specific variations may contribute to differences in disease susceptibility and progression rates. Further elucidating the mechanisms underlying these interactions could offer novel insights into ALS pathogenesis and potential therapeutic targets. |
| format | Article |
| id | doaj-art-d31341825a604a139ea3623daa340017 |
| institution | Kabale University |
| issn | 2051-5960 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj-art-d31341825a604a139ea3623daa3400172025-01-12T12:43:59ZengBMCActa Neuropathologica Communications2051-59602024-11-0112111510.1186/s40478-024-01877-xHost genetics and gut microbiota influence lipid metabolism and inflammation: potential implications for ALS pathophysiology in SOD1G93A miceElena Niccolai0Leandro Di Gloria1Maria Chiara Trolese2Paola Fabbrizio3Simone Baldi4Giulia Nannini5Cassandra Margotta6Claudia Nastasi7Matteo Ramazzotti8Gianluca Bartolucci9Caterina Bendotti10Giovanni Nardo11Amedeo Amedei12Department of Experimental and Clinical Medicine, University of FlorenceDepartment of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of FlorenceLaboratory of Molecular Neurobiology and Preclinical Therapy, Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCSLaboratory of Molecular Neurobiology and Preclinical Therapy, Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCSDepartment of Experimental and Clinical Medicine, University of FlorenceDepartment of Experimental and Clinical Medicine, University of FlorenceLaboratory of Molecular Neurobiology and Preclinical Therapy, Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCSUnit of Immunopharmacology, Department of Experimental Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCSDepartment of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of FlorenceDepartment of Neurosciences, Psychology, Drug Research and Child Health Section of Pharmaceutical and Nutraceutical Sciences, University of FlorenceLaboratory of Molecular Neurobiology and Preclinical Therapy, Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCSLaboratory of Molecular Neurobiology and Preclinical Therapy, Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCSDepartment of Experimental and Clinical Medicine, University of FlorenceAbstract Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disorder characterized by the progressive loss of motor neurons, with genetic and environmental factors contributing to its complex pathogenesis. Dysregulated immune responses and altered energetic metabolism are key features, with emerging evidence implicating the gut microbiota (GM) in disease progression. We investigated the interplay among genetic background, GM composition, metabolism, and immune response in two distinct ALS mouse models: 129Sv_G93A and C57Ola_G93A, representing rapid and slow disease progression, respectively. Using 16 S rRNA sequencing and fecal metabolite analysis, we characterized the GM composition and metabolite profiles in non-transgenic (Ntg) and SOD1G93A mutant mice of both strains. Our results revealed strain-specific differences in GM composition and functions, particularly in the abundance of taxa belonging to Erysipelotrichaceae and the levels of short and medium-chain fatty acids in fecal samples. The SOD1 mutation induces significant shifts in GM colonization in both strains, with C57Ola_G93A mice showing changes resembling those in 129 Sv mice, potentially affecting disease pathogenesis. ALS symptom progression does not significantly alter microbiota composition, suggesting stability. Additionally, we assessed systemic immunity and inflammatory responses revealing strain-specific differences in immune cell populations and cytokine levels. Our findings underscore the substantial influence of genetic background on GM composition, metabolism, and immune response in ALS mouse models. These strain-specific variations may contribute to differences in disease susceptibility and progression rates. Further elucidating the mechanisms underlying these interactions could offer novel insights into ALS pathogenesis and potential therapeutic targets.https://doi.org/10.1186/s40478-024-01877-xAmyotrophic lateral sclerosisGenetic backgroundSOD1Immune responseMicrobiomeMCFA |
| spellingShingle | Elena Niccolai Leandro Di Gloria Maria Chiara Trolese Paola Fabbrizio Simone Baldi Giulia Nannini Cassandra Margotta Claudia Nastasi Matteo Ramazzotti Gianluca Bartolucci Caterina Bendotti Giovanni Nardo Amedeo Amedei Host genetics and gut microbiota influence lipid metabolism and inflammation: potential implications for ALS pathophysiology in SOD1G93A mice Acta Neuropathologica Communications Amyotrophic lateral sclerosis Genetic background SOD1 Immune response Microbiome MCFA |
| title | Host genetics and gut microbiota influence lipid metabolism and inflammation: potential implications for ALS pathophysiology in SOD1G93A mice |
| title_full | Host genetics and gut microbiota influence lipid metabolism and inflammation: potential implications for ALS pathophysiology in SOD1G93A mice |
| title_fullStr | Host genetics and gut microbiota influence lipid metabolism and inflammation: potential implications for ALS pathophysiology in SOD1G93A mice |
| title_full_unstemmed | Host genetics and gut microbiota influence lipid metabolism and inflammation: potential implications for ALS pathophysiology in SOD1G93A mice |
| title_short | Host genetics and gut microbiota influence lipid metabolism and inflammation: potential implications for ALS pathophysiology in SOD1G93A mice |
| title_sort | host genetics and gut microbiota influence lipid metabolism and inflammation potential implications for als pathophysiology in sod1g93a mice |
| topic | Amyotrophic lateral sclerosis Genetic background SOD1 Immune response Microbiome MCFA |
| url | https://doi.org/10.1186/s40478-024-01877-x |
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