Affiliation:
1. University of Milan
2. University of Pisa
3. National Research Council
4. ASST Santi Paolo e Carlo
Abstract
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. CDD patients 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 CDD patients and their healthy relatives. Notably, differences in intestinal bacterial diversity and composition were identified in CDD patients. We further investigated microbiota changes based on the severity of GI issues, seizure frequency, sleep disorders, food intake type, impairment in neuro-behavioral features (assessed through the RTT Behaviour Questionnaire - RSBQ), and ambulation capacity. Our findings hint at a potential connection between CDD, microbiota, and symptom severity. This study marks the first exploration of the gut-microbiota-brain axis in CDD patients. 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 CDD patients.
Publisher
Research Square Platform LLC
Reference84 articles.
1. Jakimiec, M., Paprocka, J. & Śmigiel, R. CDKL5 Deficiency Disorder—A Complex Epileptic Encephalopathy. Brain Sciences vol. 10 107 Preprint at https://doi.org/10.3390/brainsci10020107 (2020).
2. Prevalence and onset of comorbidities in the CDKL5 disorder differ from Rett syndrome;Mangatt M;Orphanet J. Rare Dis.,2016
3. Leoncini, S. et al. Cytokine Dysregulation in MECP2- and CDKL5-Related Rett Syndrome: Relationships with Aberrant Redox Homeostasis, Inflammation, and ω-3 PUFAs. Oxid. Med. Cell. Longev. 2015, 421624 (2015).
4. Leoncini, S. et al. Cytokine Dysregulation in MECP2- and CDKL5-Related Rett Syndrome: Relationships with Aberrant Redox Homeostasis, Inflammation, and ω-3 PUFAs. Oxid. Med. Cell. Longev. 2015, 421624 (2015).
5. Rett Syndrome: A Focus on Gut Microbiota;Borghi E;Int. J. Mol. Sci.,2017