Brain Microbiota in Huntington’s Disease Patients
One of the most important challenges facing medical science is to better understand the cause of neuronal pathology in neurodegenerative diseases. Such is the case for Huntington’s disease (HD), a genetic disorder primarily caused by a triplet expansion in the Huntingtin gene (HTT). Although aberran...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-11-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fmicb.2019.02622/full |
| _version_ | 1828791202816720896 |
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| author | Ruth Alonso Diana Pisa Luis Carrasco |
| author_facet | Ruth Alonso Diana Pisa Luis Carrasco |
| author_sort | Ruth Alonso |
| collection | DOAJ |
| description | One of the most important challenges facing medical science is to better understand the cause of neuronal pathology in neurodegenerative diseases. Such is the case for Huntington’s disease (HD), a genetic disorder primarily caused by a triplet expansion in the Huntingtin gene (HTT). Although aberrant HTT is expressed from embryogenesis, it remains puzzling as to why the onset of disease symptoms manifest only after several decades of life. In the present study, we investigated the possibility of microbial infection in brain tissue from patients with HD, reasoning that perhaps mutated HTT could be deleterious for immune cells and neural tissue, and could facilitate microbial colonization. Using immunohistochemistry approaches, we observed a variety of fungal structures in the striatum and frontal cortex of seven HD patients. Some of these fungi were found in close proximity to the nucleus, or even as intranuclear inclusions. Identification of the fungal species was accomplished by next-generation sequencing (NGS). Interestingly, some genera, such as Ramularia, appeared unique to HD patients, and have not been previously described in other neurodegenerative diseases. Several bacterial species were also identified both by PCR and NGS. Notably, a curved and filamentous structure that immunoreacts with anti-bacterial antibodies was characteristic of HD brains and has not been previously observed in brain tissue from neurodegenerative patients. Prevalent bacterial genera included Pseudomonas, Acinetobacter, and Burkholderia. Collectively, our results represent the first attempt to identify the brain microbiota in HD. Our observations suggest that microbial colonization may be a risk factor for HD and might explain why the onset of the disease appears after several decades of life. Importantly, they may open a new field of investigation and could help in the design of new therapeutic strategies for this devastating disorder. |
| first_indexed | 2024-12-12T02:46:42Z |
| format | Article |
| id | doaj.art-9481a29714ac44b0a2209f469ebc908b |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-12T02:46:42Z |
| publishDate | 2019-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-9481a29714ac44b0a2209f469ebc908b2022-12-22T00:41:01ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2019-11-011010.3389/fmicb.2019.02622485954Brain Microbiota in Huntington’s Disease PatientsRuth AlonsoDiana PisaLuis CarrascoOne of the most important challenges facing medical science is to better understand the cause of neuronal pathology in neurodegenerative diseases. Such is the case for Huntington’s disease (HD), a genetic disorder primarily caused by a triplet expansion in the Huntingtin gene (HTT). Although aberrant HTT is expressed from embryogenesis, it remains puzzling as to why the onset of disease symptoms manifest only after several decades of life. In the present study, we investigated the possibility of microbial infection in brain tissue from patients with HD, reasoning that perhaps mutated HTT could be deleterious for immune cells and neural tissue, and could facilitate microbial colonization. Using immunohistochemistry approaches, we observed a variety of fungal structures in the striatum and frontal cortex of seven HD patients. Some of these fungi were found in close proximity to the nucleus, or even as intranuclear inclusions. Identification of the fungal species was accomplished by next-generation sequencing (NGS). Interestingly, some genera, such as Ramularia, appeared unique to HD patients, and have not been previously described in other neurodegenerative diseases. Several bacterial species were also identified both by PCR and NGS. Notably, a curved and filamentous structure that immunoreacts with anti-bacterial antibodies was characteristic of HD brains and has not been previously observed in brain tissue from neurodegenerative patients. Prevalent bacterial genera included Pseudomonas, Acinetobacter, and Burkholderia. Collectively, our results represent the first attempt to identify the brain microbiota in HD. Our observations suggest that microbial colonization may be a risk factor for HD and might explain why the onset of the disease appears after several decades of life. Importantly, they may open a new field of investigation and could help in the design of new therapeutic strategies for this devastating disorder.https://www.frontiersin.org/article/10.3389/fmicb.2019.02622/fullHuntington’s diseaseneurodegenerative diseasespolymicrobial infectionsendomycosomesfungal infectionnext generation sequencing |
| spellingShingle | Ruth Alonso Diana Pisa Luis Carrasco Brain Microbiota in Huntington’s Disease Patients Frontiers in Microbiology Huntington’s disease neurodegenerative diseases polymicrobial infections endomycosomes fungal infection next generation sequencing |
| title | Brain Microbiota in Huntington’s Disease Patients |
| title_full | Brain Microbiota in Huntington’s Disease Patients |
| title_fullStr | Brain Microbiota in Huntington’s Disease Patients |
| title_full_unstemmed | Brain Microbiota in Huntington’s Disease Patients |
| title_short | Brain Microbiota in Huntington’s Disease Patients |
| title_sort | brain microbiota in huntington s disease patients |
| topic | Huntington’s disease neurodegenerative diseases polymicrobial infections endomycosomes fungal infection next generation sequencing |
| url | https://www.frontiersin.org/article/10.3389/fmicb.2019.02622/full |
| work_keys_str_mv | AT ruthalonso brainmicrobiotainhuntingtonsdiseasepatients AT dianapisa brainmicrobiotainhuntingtonsdiseasepatients AT luiscarrasco brainmicrobiotainhuntingtonsdiseasepatients |