The Gut–Eye Axis: Lessons Learned from Murine Models

Floyd, Jason L.; Grant, Maria B.

doi:10.1007/s40123-020-00278-2

Cited by 82 publications

(76 citation statements)

References 106 publications

(146 reference statements)

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“…There are many studies depicting alterations in the GM that are associated with neurological disorders, multiple sclerosis, and the Parkinson's disease [126][127][128][129][130][131][132][133]. Similarly, unhealthy microbiome has been associated with the disruption of the ocular tissues, exacerbation of diabetic retinopathy, age-related macular degeneration, choroidal neovascularization, uveitis, glaucoma, and Sjogren's syndrome [134,135]. On the other hand, Treangen and colleagues in 2018 suggested the overall impact of TBI on bacterial dysbiosis, and they went on to show that microbial changes occur 24 h after TBI in mice, indicating that CCI causes a rapid shift in relative abundance of many species including Lactobacillus gasseri, Ruminococcus flavefaciens, and Eubacterium ventriosum that are commonly seen in the human GM [30].…”

Section: Gut Microbiome Brain (Gmb) Axismentioning

confidence: 99%

Rebuilding Microbiome for Mitigating Traumatic Brain Injury: Importance of Restructuring the Gut-Microbiome-Brain Axis

et al. 2021

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Traumatic brain injury (TBI) is a damage to the brain from an external force that results in temporary or permanent impairment in brain functions. Unfortunately, not many treatment options are available to TBI patients. Therefore, knowledge of the complex interplay between gut microbiome (GM) and brain health may shed novel insights as it is a rapidly expanding field of research around the world. Recent studies show that GM plays important roles in shaping neurogenerative processes such as blood-brain-barrier (BBB), myelination, neurogenesis, and microglial maturation. In addition, GM is also known to modulate many aspects of neurological behavior and cognition; however, not much is known about the role of GM in brain injuries. Since GM has been shown to improve cellular and molecular functions via mitigating TBI-induced pathologies such as BBB permeability, neuroinflammation, astroglia activation, and mitochondrial dysfunction, herein we discuss how a dysbiotic gut environment, which in fact, contributes to central nervous system (CNS) disorders during brain injury and how to potentially ward off these harmful effects. We further opine that a better understanding of GM-brain (GMB) axis could help assist in designing better treatment and management strategies in future for the patients who are faced with limited options.

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Section: Gut Microbiome Brain (Gmb) Axismentioning

confidence: 99%

Rebuilding Microbiome for Mitigating Traumatic Brain Injury: Importance of Restructuring the Gut-Microbiome-Brain Axis

et al. 2021

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“…While individual microbial species and phyla have been investigated for their association with AD and AMD, it is noteworthy that the hypothesis of infectious aetiology of neurodegenerative diseases may not require a specific disease-causing microbial strain or variant. The trigger for inflammation that causes damage may be attributable to interactions within the microbial population; for example, dysbiotic oral and gut microbiota have been proposed to play a role in the pathogenesis of AD/AMD (Pritchard et al, 2017 ; Sochocka et al, 2019 ; Arjunan, 2020 ; Floyd and Grant, 2020 ). It remains unknown whether a keystone pathogen exists, or an infection-initiated/mediated predisposing “immunological signature” contributes to cumulative pathological pathways that ultimately lead to disease development.…”

Section: Discussionmentioning

confidence: 99%

The Role of Inflammation and Infection in Age-Related Neurodegenerative Diseases: Lessons From Bacterial Meningitis Applied to Alzheimer Disease and Age-Related Macular Degeneration

Too

Hunt

Simunovic

2021

Front. Cell. Neurosci.

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Age-related neurodegenerative diseases, such as Alzheimer disease (AD) and age-related macular degeneration (AMD), are multifactorial and have diverse genetic and environmental risk factors. Despite the complex nature of the diseases, there is long-standing, and growing, evidence linking microbial infection to the development of AD dementia, which we summarize in this article. Also, we highlight emerging research findings that support a role for parainfection in the pathophysiology of AMD, a disease of the neurosensory retina that has been shown to share risk factors and pathological features with AD. Acute neurological infections, such as Bacterial Meningitis (BM), trigger inflammatory events that permanently change how the brain functions, leading to lasting cognitive impairment. Neuroinflammation likewise is a known pathological event that occurs in the early stages of chronic age-related neurodegenerative diseases AD and AMD and might be triggered as a parainfectious event. To date, at least 16 microbial pathogens have been linked to the development of AD; on the other hand, investigation of a microbe-AMD relationship is in its infancy. This mini-review article provides a synthesis of existing evidence indicating a contribution of parainfection in the aetiology of AD and of emerging findings that support a similar process in AMD. Subsequently, it describes the major immunopathological mechanisms that are common to BM and AD/AMD. Together, this evidence leads to our proposal that both AD and AMD may have an infectious aetiology that operates through a dysregulated inflammatory response, leading to deleterious outcomes. Last, it draws fresh insights from the existing literature about potential therapeutic options for BM that might alleviate neurological disruption associated with infections, and which could, by extension, be explored in the context of AD and AMD.

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“…Gut-retina axis has been proposed according to the mice experiments [4] and the hypothesize that diabetic-associated microbiome could lead to increased in ammation and vascular permeability, which in uence the development and progression of DR [8]. However, alterations of gut microbiota have not been directly linked to DR in human studies.…”

Section: Discussionmentioning

confidence: 99%

“…Gut microbiota is the most densely populated microbial ecosystem in human body and is integral to the maintenance of human health. Alterations in the gut microbiota have been implicated in the onset and development of various human diseases including diabetes [3] and ocular disorders [4]. Previous studies in murine models have demonstrated that type 2 diabetes-altered gut microbiota is associated with the exacerbation of DR, indicating a possible role of gut-retina axis [4].…”

Section: Introductionmentioning

confidence: 99%

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Alterations of the Gut Microbiome and Metabolome in Patients with Proliferative Diabetic Retinopathy

Yao

Ye²,

Zhang³

et al. 2020

Preprint

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Background: Diabetic retinopathy (DR) has been reported to associate with gut microbiota alterations in murine models and thus “gut-retina-axis” has been proposed. However, the role of gut microbiome and the associated metabolism in DR patients still need to be elucidated. Results: Fecal samples from 45 patients with proliferative DR (PDR) and 90 matched diabetic patients (1:2 according to age, sex and duration of diabetes) without DR (NDR) were subjected to 16S rRNA gene sequencing and untargeted metabolomics. Significantly lower bacterial diversity was observed in PDR group than that in NDR group. Differential gut bacterial composition was found, with significant depletion of 22 families (e.g., Coriobacteriaceae, Veillonellaceae and Streptococcaceae) and enrichment of 2 families (Burkholderiaceae and Burkholderiales_unclassified) in PDR group as compared to NDR group. There were significantly different fecal metabolic features, which were enriched in metabolic pathways such as arachidonic acid and microbial metabolism, between the two groups. Among 36 co-abundance metabolite clusters, 11 were positively/negatively contributed to PDR using logistic regression analysis. Fifteen gut microbial families were significantly correlated with the 11 metabolite clusters. Furthermore, a fecal metabolites-based classifier was constructed to distinguish PDR patients from NDR patients accurately.Conclusions: PDR is associated with reduced diversity and altered composition of gut microbiota and specific microbe-metabolite interplay. Our findings help to better understand the disease pathogenesis and provide novel diagnostic biomarkers and therapeutic targets for PDR.

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The Gut–Eye Axis: Lessons Learned from Murine Models

Cited by 82 publications

References 106 publications

Rebuilding Microbiome for Mitigating Traumatic Brain Injury: Importance of Restructuring the Gut-Microbiome-Brain Axis

Rebuilding Microbiome for Mitigating Traumatic Brain Injury: Importance of Restructuring the Gut-Microbiome-Brain Axis

The Role of Inflammation and Infection in Age-Related Neurodegenerative Diseases: Lessons From Bacterial Meningitis Applied to Alzheimer Disease and Age-Related Macular Degeneration

Alterations of the Gut Microbiome and Metabolome in Patients with Proliferative Diabetic Retinopathy

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