Gut microbiota profile in CDKL5 deficiency disorder patients
Abstract CDKL5 deficiency disorder (CDD) is a neurodevelopmental condition characterized by global developmental delay, early-onset seizures, intellectual disability, visual and motor impairments. Unlike Rett Syndrome (RTT), CDD lacks a clear regression period. Patients with CDD frequently encounter...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-03-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-56989-0 |
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| author | Elisa Borghi Ornella Xynomilakis Emerenziana Ottaviano Camilla Ceccarani Ilaria Viganò Paola Tognini Aglaia Vignoli |
| author_facet | Elisa Borghi Ornella Xynomilakis Emerenziana Ottaviano Camilla Ceccarani Ilaria Viganò Paola Tognini Aglaia Vignoli |
| author_sort | Elisa Borghi |
| collection | DOAJ |
| description | Abstract CDKL5 deficiency disorder (CDD) is a neurodevelopmental condition characterized by global developmental delay, early-onset seizures, intellectual disability, visual and motor impairments. Unlike Rett Syndrome (RTT), CDD lacks a clear regression period. Patients with CDD frequently encounter gastrointestinal (GI) disturbances and exhibit signs of subclinical immune dysregulation. However, the underlying causes of these conditions remain elusive. Emerging studies indicate a potential connection between neurological disorders and gut microbiota, an area completely unexplored in CDD. We conducted a pioneering study, analyzing fecal microbiota composition in individuals with CDD (n = 17) and their healthy relatives (n = 17). Notably, differences in intestinal bacterial diversity and composition were identified in CDD patients. In particular, at genus level, CDD microbial communities were characterized by an increase in the relative abundance of Clostridium_AQ, Eggerthella, Streptococcus, and Erysipelatoclostridium, and by a decrease in Eubacterium, Dorea, Odoribacter, Intestinomonas, and Gemmiger, pointing toward a dysbiotic profile. We further investigated microbiota changes based on the severity of GI issues, seizure frequency, sleep disorders, food intake type, impairment in neuro-behavioral features and ambulation capacity. Enrichment in Lachnoclostridium and Enterobacteriaceae was observed in the microbiota of patients with more severe GI symptoms, while Clostridiaceae, Peptostreptococcaceae, Coriobacteriaceae, Erysipelotrichaceae, Christensenellaceae, and Ruminococcaceae were enriched in patients experiencing daily epileptic seizures. Our findings suggest a potential connection between CDD, microbiota and symptom severity. This study marks the first exploration of the gut-microbiota-brain axis in subjects with CDD. It adds to the growing body of research emphasizing the role of the gut microbiota in neurodevelopmental disorders and opens doors to potential interventions that target intestinal microbes with the aim of improving the lives of patients with CDD. |
| first_indexed | 2024-04-24T16:19:38Z |
| format | Article |
| id | doaj.art-5076cb12f9cd4b8c93cb0121aa6fc6ae |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-24T16:19:38Z |
| publishDate | 2024-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-5076cb12f9cd4b8c93cb0121aa6fc6ae2024-03-31T11:17:08ZengNature PortfolioScientific Reports2045-23222024-03-0114111510.1038/s41598-024-56989-0Gut microbiota profile in CDKL5 deficiency disorder patientsElisa Borghi0Ornella Xynomilakis1Emerenziana Ottaviano2Camilla Ceccarani3Ilaria Viganò4Paola Tognini5Aglaia Vignoli6Department of Health Sciences, Università Degli Studi di MilanoDepartment of Health Sciences, Università Degli Studi di MilanoDepartment of Health Sciences, Università Degli Studi di MilanoInstitute of Biomedical Technologies, National Research CouncilEpilepsy Center-Child Neuropsychiatric Unit, ASST Santi Paolo e CarloDepartment of Translational Research and New Technologies in Medicine and Surgery, University of PisaDepartment of Health Sciences, Università Degli Studi di MilanoAbstract CDKL5 deficiency disorder (CDD) is a neurodevelopmental condition characterized by global developmental delay, early-onset seizures, intellectual disability, visual and motor impairments. Unlike Rett Syndrome (RTT), CDD lacks a clear regression period. Patients with CDD frequently encounter gastrointestinal (GI) disturbances and exhibit signs of subclinical immune dysregulation. However, the underlying causes of these conditions remain elusive. Emerging studies indicate a potential connection between neurological disorders and gut microbiota, an area completely unexplored in CDD. We conducted a pioneering study, analyzing fecal microbiota composition in individuals with CDD (n = 17) and their healthy relatives (n = 17). Notably, differences in intestinal bacterial diversity and composition were identified in CDD patients. In particular, at genus level, CDD microbial communities were characterized by an increase in the relative abundance of Clostridium_AQ, Eggerthella, Streptococcus, and Erysipelatoclostridium, and by a decrease in Eubacterium, Dorea, Odoribacter, Intestinomonas, and Gemmiger, pointing toward a dysbiotic profile. We further investigated microbiota changes based on the severity of GI issues, seizure frequency, sleep disorders, food intake type, impairment in neuro-behavioral features and ambulation capacity. Enrichment in Lachnoclostridium and Enterobacteriaceae was observed in the microbiota of patients with more severe GI symptoms, while Clostridiaceae, Peptostreptococcaceae, Coriobacteriaceae, Erysipelotrichaceae, Christensenellaceae, and Ruminococcaceae were enriched in patients experiencing daily epileptic seizures. Our findings suggest a potential connection between CDD, microbiota and symptom severity. This study marks the first exploration of the gut-microbiota-brain axis in subjects with CDD. It adds to the growing body of research emphasizing the role of the gut microbiota in neurodevelopmental disorders and opens doors to potential interventions that target intestinal microbes with the aim of improving the lives of patients with CDD.https://doi.org/10.1038/s41598-024-56989-0CDKL5 deficiency disorderGastrointestinal disturbancesGut microbiotaGut-brain-axis |
| spellingShingle | Elisa Borghi Ornella Xynomilakis Emerenziana Ottaviano Camilla Ceccarani Ilaria Viganò Paola Tognini Aglaia Vignoli Gut microbiota profile in CDKL5 deficiency disorder patients Scientific Reports CDKL5 deficiency disorder Gastrointestinal disturbances Gut microbiota Gut-brain-axis |
| title | Gut microbiota profile in CDKL5 deficiency disorder patients |
| title_full | Gut microbiota profile in CDKL5 deficiency disorder patients |
| title_fullStr | Gut microbiota profile in CDKL5 deficiency disorder patients |
| title_full_unstemmed | Gut microbiota profile in CDKL5 deficiency disorder patients |
| title_short | Gut microbiota profile in CDKL5 deficiency disorder patients |
| title_sort | gut microbiota profile in cdkl5 deficiency disorder patients |
| topic | CDKL5 deficiency disorder Gastrointestinal disturbances Gut microbiota Gut-brain-axis |
| url | https://doi.org/10.1038/s41598-024-56989-0 |
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