Regulation of oxytocin receptor gene expression in obsessive–compulsive disorder: a possible role for the microbiota-host epigenetic axis
Background Obsessive–compulsive disorder (OCD) is a prevalent and severe clinical condition. Robust evidence suggests a gene-environment interplay in its etiopathogenesis, yet the underlying molecular clues remain only partially understood. In order to further deepen our understanding of OCD, it is...
Ausführliche Beschreibung
Autor*in: |
D’Addario, Claudio [verfasserIn] |
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E-Artikel |
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Englisch |
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2022 |
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Anmerkung: |
© The Author(s) 2022 |
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Übergeordnetes Werk: |
Enthalten in: Clinical epigenetics - [S.l.] : BioMed Central, 2010, 14(2022), 1 vom: 31. März |
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Übergeordnetes Werk: |
volume:14 ; year:2022 ; number:1 ; day:31 ; month:03 |
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DOI / URN: |
10.1186/s13148-022-01264-0 |
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Katalog-ID: |
SPR050607081 |
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520 | |a Background Obsessive–compulsive disorder (OCD) is a prevalent and severe clinical condition. Robust evidence suggests a gene-environment interplay in its etiopathogenesis, yet the underlying molecular clues remain only partially understood. In order to further deepen our understanding of OCD, it is essential to ascertain how genes interact with environmental risk factors, a cross-talk that is thought to be mediated by epigenetic mechanisms. The human microbiota may be a key player, because bacterial metabolites can act as epigenetic modulators. We analyzed, in the blood and saliva of OCD subjects and healthy controls, the transcriptional regulation of the oxytocin receptor gene and, in saliva, also the different levels of major phyla. We also investigated the same molecular mechanisms in specific brain regions of socially isolated rats showing stereotyped behaviors reminiscent of OCD as well as short chain fatty acid levels in the feces of rats. Results Higher levels of oxytocin receptor gene DNA methylation, inversely correlated with gene expression, were observed in the blood as well as saliva of OCD subjects when compared to controls. Moreover, Actinobacteria also resulted higher in OCD and directly correlated with oxytocin receptor gene epigenetic alterations. The same pattern of changes was present in the prefrontal cortex of socially-isolated rats, where also altered levels of fecal butyrate were observed at the beginning of the isolation procedure. Conclusions This is the first demonstration of an interplay between microbiota modulation and epigenetic regulation of gene expression in OCD, opening new avenues for the understanding of disease trajectories and for the development of new therapeutic strategies. | ||
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700 | 1 | |a Sergi, Manuel |4 aut | |
700 | 1 | |a Maccarrone, Mauro |4 aut | |
700 | 1 | |a Buzzelli, Valeria |4 aut | |
700 | 1 | |a Trezza, Viviana |4 aut | |
700 | 1 | |a Dell’Osso, Bernardo |0 (orcid)0000-0001-9370-5365 |4 aut | |
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10.1186/s13148-022-01264-0 doi (DE-627)SPR050607081 (SPR)s13148-022-01264-0-e DE-627 ger DE-627 rakwb eng D’Addario, Claudio verfasserin aut Regulation of oxytocin receptor gene expression in obsessive–compulsive disorder: a possible role for the microbiota-host epigenetic axis 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Background Obsessive–compulsive disorder (OCD) is a prevalent and severe clinical condition. Robust evidence suggests a gene-environment interplay in its etiopathogenesis, yet the underlying molecular clues remain only partially understood. In order to further deepen our understanding of OCD, it is essential to ascertain how genes interact with environmental risk factors, a cross-talk that is thought to be mediated by epigenetic mechanisms. The human microbiota may be a key player, because bacterial metabolites can act as epigenetic modulators. We analyzed, in the blood and saliva of OCD subjects and healthy controls, the transcriptional regulation of the oxytocin receptor gene and, in saliva, also the different levels of major phyla. We also investigated the same molecular mechanisms in specific brain regions of socially isolated rats showing stereotyped behaviors reminiscent of OCD as well as short chain fatty acid levels in the feces of rats. Results Higher levels of oxytocin receptor gene DNA methylation, inversely correlated with gene expression, were observed in the blood as well as saliva of OCD subjects when compared to controls. Moreover, Actinobacteria also resulted higher in OCD and directly correlated with oxytocin receptor gene epigenetic alterations. The same pattern of changes was present in the prefrontal cortex of socially-isolated rats, where also altered levels of fecal butyrate were observed at the beginning of the isolation procedure. Conclusions This is the first demonstration of an interplay between microbiota modulation and epigenetic regulation of gene expression in OCD, opening new avenues for the understanding of disease trajectories and for the development of new therapeutic strategies. Oxytocin receptor (dpeaa)DE-He213 DNA methylation (dpeaa)DE-He213 Gene expression (dpeaa)DE-He213 Obsessive–compulsive disorder (dpeaa)DE-He213 Microbiota (dpeaa)DE-He213 Saliva (dpeaa)DE-He213 Pucci, Mariangela aut Bellia, Fabio aut Girella, Antonio aut Sabatucci, Annalaura aut Fanti, Federico aut Vismara, Matteo aut Benatti, Beatrice aut Ferrara, Luca aut Fasciana, Federica aut Celebre, Laura aut Viganò, Caterina aut Elli, Luca aut Sergi, Manuel aut Maccarrone, Mauro aut Buzzelli, Valeria aut Trezza, Viviana aut Dell’Osso, Bernardo (orcid)0000-0001-9370-5365 aut Enthalten in Clinical epigenetics [S.l.] : BioMed Central, 2010 14(2022), 1 vom: 31. März (DE-627)626459028 (DE-600)2553921-8 1868-7083 nnns volume:14 year:2022 number:1 day:31 month:03 https://dx.doi.org/10.1186/s13148-022-01264-0 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2022 1 31 03 |
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10.1186/s13148-022-01264-0 doi (DE-627)SPR050607081 (SPR)s13148-022-01264-0-e DE-627 ger DE-627 rakwb eng D’Addario, Claudio verfasserin aut Regulation of oxytocin receptor gene expression in obsessive–compulsive disorder: a possible role for the microbiota-host epigenetic axis 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Background Obsessive–compulsive disorder (OCD) is a prevalent and severe clinical condition. Robust evidence suggests a gene-environment interplay in its etiopathogenesis, yet the underlying molecular clues remain only partially understood. In order to further deepen our understanding of OCD, it is essential to ascertain how genes interact with environmental risk factors, a cross-talk that is thought to be mediated by epigenetic mechanisms. The human microbiota may be a key player, because bacterial metabolites can act as epigenetic modulators. We analyzed, in the blood and saliva of OCD subjects and healthy controls, the transcriptional regulation of the oxytocin receptor gene and, in saliva, also the different levels of major phyla. We also investigated the same molecular mechanisms in specific brain regions of socially isolated rats showing stereotyped behaviors reminiscent of OCD as well as short chain fatty acid levels in the feces of rats. Results Higher levels of oxytocin receptor gene DNA methylation, inversely correlated with gene expression, were observed in the blood as well as saliva of OCD subjects when compared to controls. Moreover, Actinobacteria also resulted higher in OCD and directly correlated with oxytocin receptor gene epigenetic alterations. The same pattern of changes was present in the prefrontal cortex of socially-isolated rats, where also altered levels of fecal butyrate were observed at the beginning of the isolation procedure. Conclusions This is the first demonstration of an interplay between microbiota modulation and epigenetic regulation of gene expression in OCD, opening new avenues for the understanding of disease trajectories and for the development of new therapeutic strategies. Oxytocin receptor (dpeaa)DE-He213 DNA methylation (dpeaa)DE-He213 Gene expression (dpeaa)DE-He213 Obsessive–compulsive disorder (dpeaa)DE-He213 Microbiota (dpeaa)DE-He213 Saliva (dpeaa)DE-He213 Pucci, Mariangela aut Bellia, Fabio aut Girella, Antonio aut Sabatucci, Annalaura aut Fanti, Federico aut Vismara, Matteo aut Benatti, Beatrice aut Ferrara, Luca aut Fasciana, Federica aut Celebre, Laura aut Viganò, Caterina aut Elli, Luca aut Sergi, Manuel aut Maccarrone, Mauro aut Buzzelli, Valeria aut Trezza, Viviana aut Dell’Osso, Bernardo (orcid)0000-0001-9370-5365 aut Enthalten in Clinical epigenetics [S.l.] : BioMed Central, 2010 14(2022), 1 vom: 31. März (DE-627)626459028 (DE-600)2553921-8 1868-7083 nnns volume:14 year:2022 number:1 day:31 month:03 https://dx.doi.org/10.1186/s13148-022-01264-0 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2022 1 31 03 |
allfields_unstemmed |
10.1186/s13148-022-01264-0 doi (DE-627)SPR050607081 (SPR)s13148-022-01264-0-e DE-627 ger DE-627 rakwb eng D’Addario, Claudio verfasserin aut Regulation of oxytocin receptor gene expression in obsessive–compulsive disorder: a possible role for the microbiota-host epigenetic axis 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Background Obsessive–compulsive disorder (OCD) is a prevalent and severe clinical condition. Robust evidence suggests a gene-environment interplay in its etiopathogenesis, yet the underlying molecular clues remain only partially understood. In order to further deepen our understanding of OCD, it is essential to ascertain how genes interact with environmental risk factors, a cross-talk that is thought to be mediated by epigenetic mechanisms. The human microbiota may be a key player, because bacterial metabolites can act as epigenetic modulators. We analyzed, in the blood and saliva of OCD subjects and healthy controls, the transcriptional regulation of the oxytocin receptor gene and, in saliva, also the different levels of major phyla. We also investigated the same molecular mechanisms in specific brain regions of socially isolated rats showing stereotyped behaviors reminiscent of OCD as well as short chain fatty acid levels in the feces of rats. Results Higher levels of oxytocin receptor gene DNA methylation, inversely correlated with gene expression, were observed in the blood as well as saliva of OCD subjects when compared to controls. Moreover, Actinobacteria also resulted higher in OCD and directly correlated with oxytocin receptor gene epigenetic alterations. The same pattern of changes was present in the prefrontal cortex of socially-isolated rats, where also altered levels of fecal butyrate were observed at the beginning of the isolation procedure. Conclusions This is the first demonstration of an interplay between microbiota modulation and epigenetic regulation of gene expression in OCD, opening new avenues for the understanding of disease trajectories and for the development of new therapeutic strategies. Oxytocin receptor (dpeaa)DE-He213 DNA methylation (dpeaa)DE-He213 Gene expression (dpeaa)DE-He213 Obsessive–compulsive disorder (dpeaa)DE-He213 Microbiota (dpeaa)DE-He213 Saliva (dpeaa)DE-He213 Pucci, Mariangela aut Bellia, Fabio aut Girella, Antonio aut Sabatucci, Annalaura aut Fanti, Federico aut Vismara, Matteo aut Benatti, Beatrice aut Ferrara, Luca aut Fasciana, Federica aut Celebre, Laura aut Viganò, Caterina aut Elli, Luca aut Sergi, Manuel aut Maccarrone, Mauro aut Buzzelli, Valeria aut Trezza, Viviana aut Dell’Osso, Bernardo (orcid)0000-0001-9370-5365 aut Enthalten in Clinical epigenetics [S.l.] : BioMed Central, 2010 14(2022), 1 vom: 31. März (DE-627)626459028 (DE-600)2553921-8 1868-7083 nnns volume:14 year:2022 number:1 day:31 month:03 https://dx.doi.org/10.1186/s13148-022-01264-0 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2022 1 31 03 |
allfieldsGer |
10.1186/s13148-022-01264-0 doi (DE-627)SPR050607081 (SPR)s13148-022-01264-0-e DE-627 ger DE-627 rakwb eng D’Addario, Claudio verfasserin aut Regulation of oxytocin receptor gene expression in obsessive–compulsive disorder: a possible role for the microbiota-host epigenetic axis 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Background Obsessive–compulsive disorder (OCD) is a prevalent and severe clinical condition. Robust evidence suggests a gene-environment interplay in its etiopathogenesis, yet the underlying molecular clues remain only partially understood. In order to further deepen our understanding of OCD, it is essential to ascertain how genes interact with environmental risk factors, a cross-talk that is thought to be mediated by epigenetic mechanisms. The human microbiota may be a key player, because bacterial metabolites can act as epigenetic modulators. We analyzed, in the blood and saliva of OCD subjects and healthy controls, the transcriptional regulation of the oxytocin receptor gene and, in saliva, also the different levels of major phyla. We also investigated the same molecular mechanisms in specific brain regions of socially isolated rats showing stereotyped behaviors reminiscent of OCD as well as short chain fatty acid levels in the feces of rats. Results Higher levels of oxytocin receptor gene DNA methylation, inversely correlated with gene expression, were observed in the blood as well as saliva of OCD subjects when compared to controls. Moreover, Actinobacteria also resulted higher in OCD and directly correlated with oxytocin receptor gene epigenetic alterations. The same pattern of changes was present in the prefrontal cortex of socially-isolated rats, where also altered levels of fecal butyrate were observed at the beginning of the isolation procedure. Conclusions This is the first demonstration of an interplay between microbiota modulation and epigenetic regulation of gene expression in OCD, opening new avenues for the understanding of disease trajectories and for the development of new therapeutic strategies. Oxytocin receptor (dpeaa)DE-He213 DNA methylation (dpeaa)DE-He213 Gene expression (dpeaa)DE-He213 Obsessive–compulsive disorder (dpeaa)DE-He213 Microbiota (dpeaa)DE-He213 Saliva (dpeaa)DE-He213 Pucci, Mariangela aut Bellia, Fabio aut Girella, Antonio aut Sabatucci, Annalaura aut Fanti, Federico aut Vismara, Matteo aut Benatti, Beatrice aut Ferrara, Luca aut Fasciana, Federica aut Celebre, Laura aut Viganò, Caterina aut Elli, Luca aut Sergi, Manuel aut Maccarrone, Mauro aut Buzzelli, Valeria aut Trezza, Viviana aut Dell’Osso, Bernardo (orcid)0000-0001-9370-5365 aut Enthalten in Clinical epigenetics [S.l.] : BioMed Central, 2010 14(2022), 1 vom: 31. März (DE-627)626459028 (DE-600)2553921-8 1868-7083 nnns volume:14 year:2022 number:1 day:31 month:03 https://dx.doi.org/10.1186/s13148-022-01264-0 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2022 1 31 03 |
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10.1186/s13148-022-01264-0 doi (DE-627)SPR050607081 (SPR)s13148-022-01264-0-e DE-627 ger DE-627 rakwb eng D’Addario, Claudio verfasserin aut Regulation of oxytocin receptor gene expression in obsessive–compulsive disorder: a possible role for the microbiota-host epigenetic axis 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Background Obsessive–compulsive disorder (OCD) is a prevalent and severe clinical condition. Robust evidence suggests a gene-environment interplay in its etiopathogenesis, yet the underlying molecular clues remain only partially understood. In order to further deepen our understanding of OCD, it is essential to ascertain how genes interact with environmental risk factors, a cross-talk that is thought to be mediated by epigenetic mechanisms. The human microbiota may be a key player, because bacterial metabolites can act as epigenetic modulators. We analyzed, in the blood and saliva of OCD subjects and healthy controls, the transcriptional regulation of the oxytocin receptor gene and, in saliva, also the different levels of major phyla. We also investigated the same molecular mechanisms in specific brain regions of socially isolated rats showing stereotyped behaviors reminiscent of OCD as well as short chain fatty acid levels in the feces of rats. Results Higher levels of oxytocin receptor gene DNA methylation, inversely correlated with gene expression, were observed in the blood as well as saliva of OCD subjects when compared to controls. Moreover, Actinobacteria also resulted higher in OCD and directly correlated with oxytocin receptor gene epigenetic alterations. The same pattern of changes was present in the prefrontal cortex of socially-isolated rats, where also altered levels of fecal butyrate were observed at the beginning of the isolation procedure. Conclusions This is the first demonstration of an interplay between microbiota modulation and epigenetic regulation of gene expression in OCD, opening new avenues for the understanding of disease trajectories and for the development of new therapeutic strategies. Oxytocin receptor (dpeaa)DE-He213 DNA methylation (dpeaa)DE-He213 Gene expression (dpeaa)DE-He213 Obsessive–compulsive disorder (dpeaa)DE-He213 Microbiota (dpeaa)DE-He213 Saliva (dpeaa)DE-He213 Pucci, Mariangela aut Bellia, Fabio aut Girella, Antonio aut Sabatucci, Annalaura aut Fanti, Federico aut Vismara, Matteo aut Benatti, Beatrice aut Ferrara, Luca aut Fasciana, Federica aut Celebre, Laura aut Viganò, Caterina aut Elli, Luca aut Sergi, Manuel aut Maccarrone, Mauro aut Buzzelli, Valeria aut Trezza, Viviana aut Dell’Osso, Bernardo (orcid)0000-0001-9370-5365 aut Enthalten in Clinical epigenetics [S.l.] : BioMed Central, 2010 14(2022), 1 vom: 31. März (DE-627)626459028 (DE-600)2553921-8 1868-7083 nnns volume:14 year:2022 number:1 day:31 month:03 https://dx.doi.org/10.1186/s13148-022-01264-0 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2022 1 31 03 |
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Regulation of oxytocin receptor gene expression in obsessive–compulsive disorder: a possible role for the microbiota-host epigenetic axis Oxytocin receptor (dpeaa)DE-He213 DNA methylation (dpeaa)DE-He213 Gene expression (dpeaa)DE-He213 Obsessive–compulsive disorder (dpeaa)DE-He213 Microbiota (dpeaa)DE-He213 Saliva (dpeaa)DE-He213 |
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regulation of oxytocin receptor gene expression in obsessive–compulsive disorder: a possible role for the microbiota-host epigenetic axis |
title_auth |
Regulation of oxytocin receptor gene expression in obsessive–compulsive disorder: a possible role for the microbiota-host epigenetic axis |
abstract |
Background Obsessive–compulsive disorder (OCD) is a prevalent and severe clinical condition. Robust evidence suggests a gene-environment interplay in its etiopathogenesis, yet the underlying molecular clues remain only partially understood. In order to further deepen our understanding of OCD, it is essential to ascertain how genes interact with environmental risk factors, a cross-talk that is thought to be mediated by epigenetic mechanisms. The human microbiota may be a key player, because bacterial metabolites can act as epigenetic modulators. We analyzed, in the blood and saliva of OCD subjects and healthy controls, the transcriptional regulation of the oxytocin receptor gene and, in saliva, also the different levels of major phyla. We also investigated the same molecular mechanisms in specific brain regions of socially isolated rats showing stereotyped behaviors reminiscent of OCD as well as short chain fatty acid levels in the feces of rats. Results Higher levels of oxytocin receptor gene DNA methylation, inversely correlated with gene expression, were observed in the blood as well as saliva of OCD subjects when compared to controls. Moreover, Actinobacteria also resulted higher in OCD and directly correlated with oxytocin receptor gene epigenetic alterations. The same pattern of changes was present in the prefrontal cortex of socially-isolated rats, where also altered levels of fecal butyrate were observed at the beginning of the isolation procedure. Conclusions This is the first demonstration of an interplay between microbiota modulation and epigenetic regulation of gene expression in OCD, opening new avenues for the understanding of disease trajectories and for the development of new therapeutic strategies. © The Author(s) 2022 |
abstractGer |
Background Obsessive–compulsive disorder (OCD) is a prevalent and severe clinical condition. Robust evidence suggests a gene-environment interplay in its etiopathogenesis, yet the underlying molecular clues remain only partially understood. In order to further deepen our understanding of OCD, it is essential to ascertain how genes interact with environmental risk factors, a cross-talk that is thought to be mediated by epigenetic mechanisms. The human microbiota may be a key player, because bacterial metabolites can act as epigenetic modulators. We analyzed, in the blood and saliva of OCD subjects and healthy controls, the transcriptional regulation of the oxytocin receptor gene and, in saliva, also the different levels of major phyla. We also investigated the same molecular mechanisms in specific brain regions of socially isolated rats showing stereotyped behaviors reminiscent of OCD as well as short chain fatty acid levels in the feces of rats. Results Higher levels of oxytocin receptor gene DNA methylation, inversely correlated with gene expression, were observed in the blood as well as saliva of OCD subjects when compared to controls. Moreover, Actinobacteria also resulted higher in OCD and directly correlated with oxytocin receptor gene epigenetic alterations. The same pattern of changes was present in the prefrontal cortex of socially-isolated rats, where also altered levels of fecal butyrate were observed at the beginning of the isolation procedure. Conclusions This is the first demonstration of an interplay between microbiota modulation and epigenetic regulation of gene expression in OCD, opening new avenues for the understanding of disease trajectories and for the development of new therapeutic strategies. © The Author(s) 2022 |
abstract_unstemmed |
Background Obsessive–compulsive disorder (OCD) is a prevalent and severe clinical condition. Robust evidence suggests a gene-environment interplay in its etiopathogenesis, yet the underlying molecular clues remain only partially understood. In order to further deepen our understanding of OCD, it is essential to ascertain how genes interact with environmental risk factors, a cross-talk that is thought to be mediated by epigenetic mechanisms. The human microbiota may be a key player, because bacterial metabolites can act as epigenetic modulators. We analyzed, in the blood and saliva of OCD subjects and healthy controls, the transcriptional regulation of the oxytocin receptor gene and, in saliva, also the different levels of major phyla. We also investigated the same molecular mechanisms in specific brain regions of socially isolated rats showing stereotyped behaviors reminiscent of OCD as well as short chain fatty acid levels in the feces of rats. Results Higher levels of oxytocin receptor gene DNA methylation, inversely correlated with gene expression, were observed in the blood as well as saliva of OCD subjects when compared to controls. Moreover, Actinobacteria also resulted higher in OCD and directly correlated with oxytocin receptor gene epigenetic alterations. The same pattern of changes was present in the prefrontal cortex of socially-isolated rats, where also altered levels of fecal butyrate were observed at the beginning of the isolation procedure. Conclusions This is the first demonstration of an interplay between microbiota modulation and epigenetic regulation of gene expression in OCD, opening new avenues for the understanding of disease trajectories and for the development of new therapeutic strategies. © The Author(s) 2022 |
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title_short |
Regulation of oxytocin receptor gene expression in obsessive–compulsive disorder: a possible role for the microbiota-host epigenetic axis |
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https://dx.doi.org/10.1186/s13148-022-01264-0 |
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author2 |
Pucci, Mariangela Bellia, Fabio Girella, Antonio Sabatucci, Annalaura Fanti, Federico Vismara, Matteo Benatti, Beatrice Ferrara, Luca Fasciana, Federica Celebre, Laura Viganò, Caterina Elli, Luca Sergi, Manuel Maccarrone, Mauro Buzzelli, Valeria Trezza, Viviana Dell’Osso, Bernardo |
author2Str |
Pucci, Mariangela Bellia, Fabio Girella, Antonio Sabatucci, Annalaura Fanti, Federico Vismara, Matteo Benatti, Beatrice Ferrara, Luca Fasciana, Federica Celebre, Laura Viganò, Caterina Elli, Luca Sergi, Manuel Maccarrone, Mauro Buzzelli, Valeria Trezza, Viviana Dell’Osso, Bernardo |
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