DJ-1 (Park7) affects the gut microbiome, metabolites and the development of innate lymphoid cells (ILCs)
Abstract The proper communication between gut and brain is pivotal for the maintenance of health and, dysregulation of the gut-brain axis can lead to several clinical disorders. In Parkinson’s disease (PD) 85% of all patients experienced constipation many years before showing any signs of motor phen...
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2020
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oai:doaj.org-article:297b1457494e463d9c3a7180902847052021-12-02T18:51:27ZDJ-1 (Park7) affects the gut microbiome, metabolites and the development of innate lymphoid cells (ILCs)10.1038/s41598-020-72903-w2045-2322https://doaj.org/article/297b1457494e463d9c3a7180902847052020-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-72903-whttps://doaj.org/toc/2045-2322Abstract The proper communication between gut and brain is pivotal for the maintenance of health and, dysregulation of the gut-brain axis can lead to several clinical disorders. In Parkinson’s disease (PD) 85% of all patients experienced constipation many years before showing any signs of motor phenotypes. For differential diagnosis and preventive treatment, there is an urgent need for the identification of biomarkers indicating early disease stages long before the disease phenotype manifests. DJ-1 is a chaperone protein involved in the protection against PD and genetic mutations in this protein have been shown to cause familial PD. However, how the deficiency of DJ-1 influences the risk of PD remains incompletely understood. In the present study, we provide evidence that DJ-1 is implicated in shaping the gut microbiome including; their metabolite production, inflammation and innate immune cells (ILCs) development. We revealed that deficiency of DJ-1 leads to a significant increase in two specific genera/species, namely Alistipes and Rikenella. In DJ-1 knock-out (DJ-1-/-) mice the production of fecal calprotectin and MCP-1 inflammatory proteins were elevated. Fecal and serum metabolic profile showed that malonate which influences the immune system was significantly more abundant in DJ-1−/− mice. DJ-1 appeared also to be involved in ILCs development. Further, inflammatory genes related to PD were augmented in the midbrain of DJ-1−/− mice. Our data suggest that metabolites and inflammation produced in the gut could be used as biomarkers for PD detection. Perhaps, these metabolites and inflammatory mediators could be involved in triggering inflammation resulting in PD pathology.Yogesh SinghChristoph TrautweinAchal DhariwalMadhuri S. SalkerMd AlauddinLaimdota ZizmareLisann PelzlMartina FegerJakob AdmardNicolas CasadeiMichael FöllerVivek PachauriDavid S. ParkTak W. MakJulia-Stefanie FrickDiethelm WallwienerSara Y. BruckerFlorian LangOlaf RiessNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-19 (2020) |
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Medicine R Science Q Yogesh Singh Christoph Trautwein Achal Dhariwal Madhuri S. Salker Md Alauddin Laimdota Zizmare Lisann Pelzl Martina Feger Jakob Admard Nicolas Casadei Michael Föller Vivek Pachauri David S. Park Tak W. Mak Julia-Stefanie Frick Diethelm Wallwiener Sara Y. Brucker Florian Lang Olaf Riess DJ-1 (Park7) affects the gut microbiome, metabolites and the development of innate lymphoid cells (ILCs) |
| description |
Abstract The proper communication between gut and brain is pivotal for the maintenance of health and, dysregulation of the gut-brain axis can lead to several clinical disorders. In Parkinson’s disease (PD) 85% of all patients experienced constipation many years before showing any signs of motor phenotypes. For differential diagnosis and preventive treatment, there is an urgent need for the identification of biomarkers indicating early disease stages long before the disease phenotype manifests. DJ-1 is a chaperone protein involved in the protection against PD and genetic mutations in this protein have been shown to cause familial PD. However, how the deficiency of DJ-1 influences the risk of PD remains incompletely understood. In the present study, we provide evidence that DJ-1 is implicated in shaping the gut microbiome including; their metabolite production, inflammation and innate immune cells (ILCs) development. We revealed that deficiency of DJ-1 leads to a significant increase in two specific genera/species, namely Alistipes and Rikenella. In DJ-1 knock-out (DJ-1-/-) mice the production of fecal calprotectin and MCP-1 inflammatory proteins were elevated. Fecal and serum metabolic profile showed that malonate which influences the immune system was significantly more abundant in DJ-1−/− mice. DJ-1 appeared also to be involved in ILCs development. Further, inflammatory genes related to PD were augmented in the midbrain of DJ-1−/− mice. Our data suggest that metabolites and inflammation produced in the gut could be used as biomarkers for PD detection. Perhaps, these metabolites and inflammatory mediators could be involved in triggering inflammation resulting in PD pathology. |
| format |
article |
| author |
Yogesh Singh Christoph Trautwein Achal Dhariwal Madhuri S. Salker Md Alauddin Laimdota Zizmare Lisann Pelzl Martina Feger Jakob Admard Nicolas Casadei Michael Föller Vivek Pachauri David S. Park Tak W. Mak Julia-Stefanie Frick Diethelm Wallwiener Sara Y. Brucker Florian Lang Olaf Riess |
| author_facet |
Yogesh Singh Christoph Trautwein Achal Dhariwal Madhuri S. Salker Md Alauddin Laimdota Zizmare Lisann Pelzl Martina Feger Jakob Admard Nicolas Casadei Michael Föller Vivek Pachauri David S. Park Tak W. Mak Julia-Stefanie Frick Diethelm Wallwiener Sara Y. Brucker Florian Lang Olaf Riess |
| author_sort |
Yogesh Singh |
| title |
DJ-1 (Park7) affects the gut microbiome, metabolites and the development of innate lymphoid cells (ILCs) |
| title_short |
DJ-1 (Park7) affects the gut microbiome, metabolites and the development of innate lymphoid cells (ILCs) |
| title_full |
DJ-1 (Park7) affects the gut microbiome, metabolites and the development of innate lymphoid cells (ILCs) |
| title_fullStr |
DJ-1 (Park7) affects the gut microbiome, metabolites and the development of innate lymphoid cells (ILCs) |
| title_full_unstemmed |
DJ-1 (Park7) affects the gut microbiome, metabolites and the development of innate lymphoid cells (ILCs) |
| title_sort |
dj-1 (park7) affects the gut microbiome, metabolites and the development of innate lymphoid cells (ilcs) |
| publisher |
Nature Portfolio |
| publishDate |
2020 |
| url |
https://doaj.org/article/297b1457494e463d9c3a718090284705 |
| work_keys_str_mv |
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| _version_ |
1718377375577669632 |