The gut-brain connection: Exploring the influence of the gut microbiota on neuroplasticity and neurodevelopmental disorders

Damiani, Francesca; Cornuti, Sara; Tognini, Paola

doi:10.1016/j.neuropharm.2023.109491

Cited by 19 publications

(10 citation statements)

References 337 publications

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“…Additional lifestyle factors, including poor or fragmented sleep and dietary habits, 29 , 30 have also been shown to influence microglia inflammation. More recent work implicates other biological mechanisms, including dysbiosis of the gut 31 , 32 and the role of the inflammasome, innate immune sensors that regulate inflammation in response to harmful stimuli. 33 Together, these studies solidify the fact that cognitive aging is a complex disease process and that much work remains to understand the relationship between lifestyle stressors/factors, microglia inflammation, and cognition.…”

Section: Discussionmentioning

confidence: 99%

Association between hippocampal microglia, AD and LATE‐NC, and cognitive decline in older adults

Kapasi,

Yu,

Leurgans

et al. 2024

Alzheimer's & Dementia

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INTRODUCTIONThis study investigates the relationship between microglia inflammation in the hippocampus, brain pathologies, and cognitive decline.METHODSParticipants underwent annual clinical evaluations and agreed to brain donation. Neuropathologic evaluations quantified microglial burden in the hippocampus, amyloid beta (Aβ), tau tangles, and limbic age‐related transactive response DNA‐binding protein 43 (TDP‐43) encephalopathy neuropathologic changes (LATE‐NC), and other common brain pathologies. Mixed‐effect and linear regression models examined the association of microglia with a decline in global and domain‐specific cognitive measures, and separately with brain pathologies. Path analyses estimated direct and indirect effects of microglia on global cognition.RESULTHippocampal microglia were associated with a faster decline in global cognition, specifically in episodic memory, semantic memory, and perceptual speed. Tau tangles and LATE‐NC were independently associated with microglia. Other pathologies, including Aβ, were not related. Regional hippocampal burden of tau tangles and TDP‐43 accounted for half of the association of microglia with cognitive decline.DISCUSSIONMicroglia inflammation in the hippocampus contributes to cognitive decline. Tau tangles and LATE‐NC partially mediate this association.

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Section: Discussionmentioning

confidence: 99%

Association between hippocampal microglia, AD and LATE‐NC, and cognitive decline in older adults

Kapasi,

Yu,

Leurgans

et al. 2024

Alzheimer's & Dementia

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“…The disruption of the microbiota-gut-brain axis, attributed to disturbances in gut microbiota (i.e., dysbiosis), is considered a potential contributing factor to various neurodevelopmental disorders, including ASD, rare neurological diseases, and epilepsy 8,16,27,28 . Among these disorders, CDD stands out due to its intricate and diverse clinical presentation, encompassing global developmental delay, intellectual disability, speech impairments, visual and motor skill deficits, sleep disturbances, and GI issues 29 .…”

Section: Discussionmentioning

confidence: 99%

“…This recent research suggests that changes in the gut could be linked to neurological issues. For example, multiple studies in rodents have shown a connection between the gut microbiota and the central nervous system 8,9 . Microbiota signals and byproducts have been found to play a role in regulating various aspects of brain-related processes and behavior, including stress responses, anxiety and emotional behaviors, cognitive function, myelination, neurogenesis, microglia maturation, and blood-brain barrier integrity 10,11 .…”

Section: Introductionmentioning

confidence: 99%

Gut microbiota profile in CDKL5 deficiency disorder patients as a potential marker of clinical severity

Borghi,

Xynomilakis,

Ottaviano

et al. 2023

Preprint

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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.

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“…As the composition analysis revealed differences in the CDKL5 fecal microbiota, we hypothesize the presence of a dysbiosis condition. Dysbiosis has been observed in several neuropsychiatric disorders (32), and in mouse models has been linked to behavioral and neurofunctional impairments (11,33). Therefore, we treated mice with an antibiotic cocktail (ABX) in drinking water to target intestinal microbes, particularly bacteria taxa, and tested the potential improvement in functional and behavioral outcomes.…”

Section: Antibiotic Treatment Improves Functional and Behavioral Outc...mentioning

confidence: 99%

“…At least part of this association could be due to abnormal composition of the gut microbiome, i.e. the assemblage of microorganisms residing in the GI tract that engage symbiotic interactions with their host (11,12). Indeed, ASD patients display alterations in the composition of the gut microbiota (13) as well as RTT patients (14,15).…”

Section: Introductionmentioning

confidence: 99%

Multi-Site Investigation of Gut Microbiota in CDKL5 Deficiency Disorder Mouse Models: Targeting Dysbiosis to Improve Neurological Outcomes

Damiani,

Giuliano,

Cornuti

et al. 2024

Preprint

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BackgroundCyclin-Dependent Kinase-Like 5 (CDKL5) deficiency disorder (CDD) is a rare X-linked developmental encephalopathy caused by pathogenic variants of the CDKL5 gene. In addition to a diverse range of neurological symptoms, CDD patients frequently manifest gastrointestinal (GI) issues and subclinical immune dysregulation. This comorbidity suggests a potential association with the intestinal microbiota, prompting an investigation into whether gut dysbiosis contributes to the severity of both GI and neurological symptoms.MethodsWe examined the gut microbiota composition in two CDKL5 null (KO) mouse models in males at three different developmental stages: postnatal day (P) 25 and P32 during youth, and P70 during adulthood.ResultsChanges in diversity and composition were observed, particularly during juvenile ages, suggesting a potential gut microbiota dysbiosis in the CDD mouse models. To further understand the role of the gut microbiota in CDD, we administered an antibiotic cocktail to the mice and conducted functional and behavioral assessments. Remarkably, significant improvement in visual cortical responses and reductions in hyperactive behavior were observed. To shed light on the cellular mechanisms we focused on microglia. Alterations in specific aspects of microglia morphology, indicative of activation state and surveillance of the microenvironment, were observed in the CDKL5 KO mice and ameliorated by antibiotic administration.ConclusionsOur findings highlight the potential impact of modifications in the intestinal microbiota on the severity of CDD symptoms, expanding our understanding beyond GI disturbances to encompass influences on neurological outcomes. This cross-border study provides valuable insights into the intricate interplay between gut microbiota and neurodevelopmental disorders.

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The gut-brain connection: Exploring the influence of the gut microbiota on neuroplasticity and neurodevelopmental disorders

Cited by 19 publications

References 337 publications

Association between hippocampal microglia, AD and LATE‐NC, and cognitive decline in older adults

Association between hippocampal microglia, AD and LATE‐NC, and cognitive decline in older adults

Gut microbiota profile in CDKL5 deficiency disorder patients as a potential marker of clinical severity

Multi-Site Investigation of Gut Microbiota in CDKL5 Deficiency Disorder Mouse Models: Targeting Dysbiosis to Improve Neurological Outcomes

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