Therapeutics for neurodegenerative diseases by targeting the gut microbiome: from bench to bedside

Ma, Yuan-Yuan; Li, Xin; Yu, Jin-Tai; Wang, Yan-Jiang

doi:10.1186/s40035-024-00404-1

Cited by 8 publications

(6 citation statements)

References 195 publications

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“…Conversely, alterations in the EVs in gut microbiota can influence disease progression by modulating neuroinflammation, neurotransmitter production, and gut-brain axis signaling. This bidirectional communication underscores the potential of gut microbiome-targeted interventions as therapeutic avenues for managing neurodegenerative diseases in animals [92]. Similarly, in mitochondrial encephalopathies affecting dogs, characterized by mitochondrial dysfunction leading to neurological symptoms, the gut microbiome may contribute to the disease pathogenesis.…”

Section: Microbiota Evsmentioning

confidence: 85%

The Profound Influence of Gut Microbiome and Extracellular Vesicles on Animal Health and Disease

Barathan,

Ng,

Lokanathan

et al. 2024

IJMS

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The animal gut microbiota, comprising a diverse array of microorganisms, plays a pivotal role in shaping host health and physiology. This review explores the intricate dynamics of the gut microbiome in animals, focusing on its composition, function, and impact on host–microbe interactions. The composition of the intestinal microbiota in animals is influenced by the host ecology, including factors such as temperature, pH, oxygen levels, and nutrient availability, as well as genetic makeup, diet, habitat, stressors, and husbandry practices. Dysbiosis can lead to various gastrointestinal and immune-related issues in animals, impacting overall health and productivity. Extracellular vesicles (EVs), particularly exosomes derived from gut microbiota, play a crucial role in intercellular communication, influencing host health by transporting bioactive molecules across barriers like the intestinal and brain barriers. Dysregulation of the gut–brain axis has implications for various disorders in animals, highlighting the potential role of microbiota-derived EVs in disease progression. Therapeutic approaches to modulate gut microbiota, such as probiotics, prebiotics, microbial transplants, and phage therapy, offer promising strategies for enhancing animal health and performance. Studies investigating the effects of phage therapy on gut microbiota composition have shown promising results, with potential implications for improving animal health and food safety in poultry production systems. Understanding the complex interactions between host ecology, gut microbiota, and EVs provides valuable insights into the mechanisms underlying host–microbe interactions and their impact on animal health and productivity. Further research in this field is essential for developing effective therapeutic interventions and management strategies to promote gut health and overall well-being in animals.

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Section: Microbiota Evsmentioning

confidence: 85%

The Profound Influence of Gut Microbiome and Extracellular Vesicles on Animal Health and Disease

Barathan,

Ng,

Lokanathan

et al. 2024

IJMS

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“…High levels of heavy metals via their interaction with the GM and induction of dysbiosis, can also promote neuroinflammation and hence indirectly contribute to HD pathology (Figure 1). Understanding the intricate coordination of the GBA and specific effect of each heavy metal on this axis, may provide further therapeutic intervention in this devastating disease [149][150][151].…”

Section: Discussionmentioning

confidence: 99%

Heavy Metals Interactions with Neuroglia and Gut Microbiota: Implications for Huntington’s Disease

Tizabi,

Bennani,

El Kouhen

et al. 2024

Preprint

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Huntington’s disease (HD) is a rare but progressive and devastating neurodegenerative disease characterized by involuntary movements, cognitive decline, executive dysfunction, and neuropsychiatric conditions such as anxiety and depression. It follows an autosomal dominant inheritance pattern. Thus, a child who has a parent with the mutated huntingtin (mHTT) gene has a 50% chance of developing the disease. Since HTT protein is involved in many critical cellular processes including neurogenesis, brain development, energy metabolism, transcriptional regulation, synaptic activity, vesicle trafficking, cell signaling, and autophagy, its aberrant aggregates lead to disruption of numerous cellular pathways and neurodegeneration. Essential heavy metals are vital at low concentrations, however, at higher concentrations, can exacerbate HD by disrupting the glial-neuronal communication, and/or causing dysbiosis (disturbance in the gut microbiota, GM), both of which can lead to neuroinflammation and further neurodegeneration. Here, we discuss in detail the interactions of iron, manganese and copper with glial-neuron communication and GM and indicate how this knowledge may pave the way for development of a new generation of disease-modifying therapies in HD.

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“…Treg can enter the central nervous system via three routes, through: (i) the blood-brain barrier (BBB) (into the perivascular space); (ii) the subarachnoid space in the meninges, and (iii) the choroid plexus (into the cerebrospinal fluid). Treg accumulating in damaged areas infiltrate the brain and, being able to interact with microglia, exacerbate inflammation within the nervous system contributing to the development of neurodegenerative diseases ( Ma et al., 2024 ).…”

Section: Crohn’s Diseasementioning

confidence: 99%

Amyloid, Crohn’s disease, and Alzheimer’s disease - are they linked?

Duda-Madej,

Stecko,

Szymańska

et al. 2024

Front. Cell. Infect. Microbiol.

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Crohn’s disease (CD) is a chronic inflammatory disease that most frequently affects part of the distal ileum, but it may affect any part of the gastrointestinal tract. CD may also be related to systemic inflammation and extraintestinal manifestations. Alzheimer’s disease (AD) is the most common neurodegenerative disease, gradually worsening behavioral and cognitive functions. Despite the meaningful progress, both diseases are still incurable and have a not fully explained, heterogeneous pathomechanism that includes immunological, microbiological, genetic, and environmental factors. Recently, emerging evidence indicates that chronic inflammatory condition corresponds to an increased risk of neurodegenerative diseases, and intestinal inflammation, including CD, increases the risk of AD. Even though it is now known that CD increases the risk of AD, the exact pathways connecting these two seemingly unrelated diseases remain still unclear. One of the key postulates is the gut-brain axis. There is increasing evidence that the gut microbiota with its proteins, DNA, and metabolites influence several processes related to the etiology of AD, including β-amyloid abnormality, Tau phosphorylation, and neuroinflammation. Considering the role of microbiota in both CD and AD pathology, in this review, we want to shed light on bacterial amyloids and their potential to influence cerebral amyloid aggregation and neuroinflammation and provide an overview of the current literature on amyloids as a potential linker between AD and CD.

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Therapeutics for neurodegenerative diseases by targeting the gut microbiome: from bench to bedside

Cited by 8 publications

References 195 publications

The Profound Influence of Gut Microbiome and Extracellular Vesicles on Animal Health and Disease

The Profound Influence of Gut Microbiome and Extracellular Vesicles on Animal Health and Disease

Heavy Metals Interactions with Neuroglia and Gut Microbiota: Implications for Huntington’s Disease

Amyloid, Crohn’s disease, and Alzheimer’s disease - are they linked?

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