Inflammatory pathways in Alzheimer’s disease mediated by gut microbiota

Qian, Xiaohang; Song, Xiaoxuan; Liu, Xiaoli; Chen, Shengdi; Tang, Huidong

doi:10.1016/j.arr.2021.101317

Cited by 89 publications

(61 citation statements)

References 188 publications

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“…GABAergic dysfunctions, including reduction of GABA receptors, loss of GABAergic neurons and synapses, aberrant GABA production in reactive astrocytes, and imbalance between excitatory and inhibitory signals of the CNS, are early events occurring in the brains of patients with AD and animal models (Govindpani et al, 2020;Zheng et al, 2021). Acetylcholine, produced by Bacillus subtilis and Lactobacillus plantarum, can reduce the production of IL-6, TNF-α, and IL-1β through the COX-2 pathway in astrocytes, inhibit pro-inflammatory cytokines by upregulating JAK2/STAT3 and PI3K/AKT signaling pathways in microglia and regulating immune homeostasis (Velazquez et al, 2019;Qian et al, 2021). Dopamine can be produced by Bacillus and Escherichia in humans.…”

Section: Metabolic Dysfunctionsmentioning

confidence: 99%

“…Dopamine can be produced by Bacillus and Escherichia in humans. Activation of the dopamine receptor D1 (DRD1) accelerates the degradation of the NLRP3 inflammasome via cyclic adenosine monophosphate, while DRD2 and DRD3 in astrocytes perform anti-inflammatory and pro-inflammatory functions, respectively (Montoya et al, 2019;Qian et al, 2021). 5-HT is an important neurotransmitter synthesized from tryptophan metabolism in enterochromaffin cells (Kennedy et al, 2017), which can be produced by Corynebacterium spp., Streptococcus spp., and E. coli.…”

Section: Metabolic Dysfunctionsmentioning

confidence: 99%

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Roles and Mechanisms of Gut Microbiota in Patients With Alzheimer’s Disease

Liu

Jiang

et al. 2021

Front. Aging Neurosci.

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Alzheimer’s disease (AD) is the most common age-related progressive neurodegenerative disease, characterized by a decline in cognitive function and neuronal loss, and is caused by several factors. Numerous clinical and experimental studies have suggested the involvement of gut microbiota dysbiosis in patients with AD. The altered gut microbiota can influence brain function and behavior through the microbiota–gut–brain axis via various pathways such as increased amyloid-β deposits and tau phosphorylation, neuroinflammation, metabolic dysfunctions, and chronic oxidative stress. With no current effective therapy to cure AD, gut microbiota modulation may be a promising therapeutic option to prevent or delay the onset of AD or counteract its progression. Our present review summarizes the alterations in the gut microbiota in patients with AD, the pathogenetic roles and mechanisms of gut microbiota in AD, and gut microbiota–targeted therapies for AD. Understanding the roles and mechanisms between gut microbiota and AD will help decipher the pathogenesis of AD from novel perspectives and shed light on novel therapeutic strategies for AD.

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Section: Metabolic Dysfunctionsmentioning

confidence: 99%

Section: Metabolic Dysfunctionsmentioning

confidence: 99%

Roles and Mechanisms of Gut Microbiota in Patients With Alzheimer’s Disease

Liu

Jiang

et al. 2021

Front. Aging Neurosci.

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“…Gram-negative bacteria are a significant source of Aβ and of LPS, and the increased levels of these molecules found in AD brain plaques were related to dysbiosis. Thus, Gram-negative bacteria are likely to be involved in the pathogenesis of neurodegeneration [ 12 , 50 ]. In the attempt to answer to the question whether the Aβ accumulated in the brain is of bacterial or cellular origin, several reports suggest the possibility that bacterial amyloid, which has prion-like properties, would induce molecular mimicry mechanisms and the accumulation of neuronal Aβ into the brain, promoting neuroinflammation and neurodegeneration [ 8 , 49 , 51 , 52 , 53 , 54 ].…”

Section: The Dysbiosis and The Alzheimer Diseasementioning

confidence: 99%

“…The observation that statin treatment for hypercholesterolemia was associated with a lower risk of developing AD, and the high frequency of elevated plasma level of this lipid in AD patients, has moved the attention to the implication of cholesterol and its metabolites in the pathogenesis of AD [ 62 ]. Altered cholesterol metabolism deeply affects the bile acids (BAs) production and metabolism [ 50 ]. BAs are synthesized in the liver from the cholesterol, and their blood levels as well the type of BA present depend on a combination of liver and microbiota co-metabolism [ 50 , 63 ].…”

Section: The Dysbiosis and The Alzheimer Diseasementioning

confidence: 99%

“…Altered cholesterol metabolism deeply affects the bile acids (BAs) production and metabolism [ 50 ]. BAs are synthesized in the liver from the cholesterol, and their blood levels as well the type of BA present depend on a combination of liver and microbiota co-metabolism [ 50 , 63 ]. Studies in AD patients have demonstrated a significant association between an altered BA profile in the blood and cognitive impairment [ 63 ].…”

Section: The Dysbiosis and The Alzheimer Diseasementioning

confidence: 99%

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The Microbiota–Gut–Brain Axis and Alzheimer Disease. From Dysbiosis to Neurodegeneration: Focus on the Central Nervous System Glial Cells

Giovannini

Lana

Traini

et al. 2021

JCM

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The microbiota–gut system can be thought of as a single unit that interacts with the brain via the “two-way” microbiota–gut–brain axis. Through this axis, a constant interplay mediated by the several products originating from the microbiota guarantees the physiological development and shaping of the gut and the brain. In the present review will be described the modalities through which the microbiota and gut control each other, and the main microbiota products conditioning both local and brain homeostasis. Much evidence has accumulated over the past decade in favor of a significant association between dysbiosis, neuroinflammation and neurodegeneration. Presently, the pathogenetic mechanisms triggered by molecules produced by the altered microbiota, also responsible for the onset and evolution of Alzheimer disease, will be described. Our attention will be focused on the role of astrocytes and microglia. Numerous studies have progressively demonstrated how these glial cells are important to ensure an adequate environment for neuronal activity in healthy conditions. Furthermore, it is becoming evident how both cell types can mediate the onset of neuroinflammation and lead to neurodegeneration when subjected to pathological stimuli. Based on this information, the role of the major microbiota products in shifting the activation profiles of astrocytes and microglia from a healthy to a diseased state will be discussed, focusing on Alzheimer disease pathogenesis.

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Gastric Acid‐Responsive ROS Nanogenerators for Effective Treatment of Helicobacter pylori Infection without Disrupting Homeostasis of Intestinal Flora

Guo

Yan

et al. 2023

Advanced Science

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Helicobacter pylori (H. pylori) has infected more than half of the world's population, and is the major cause of gastric cancer. The efficacy of standard antibiotic-based triple therapy is declining due to drug resistance development. Herein, a pH-responsive reactive oxygen species (ROS) nanogenerator (Fe-HMME@DHA@MPN) composed of acid-responsive metal polyphenol network (MPN) shell and mesoporous metal-organic nanostructure core [Fe-HMME (hematoporphyrin monomethyl ether, sonosensitizer)] loaded with dihydroartemisinin (DHA) is reported. These nanoparticles generate more ROS singlet oxygen than sonosensitizer HMME under ultrasonication, and this sonodynamic process is fueled by oxygen generated through Fenton/Fenton-like reactions of the degraded product in gastric acid Fe (II) and hydrogen peroxide (H 2 O 2 ) in the infection microenvironment. The encapsulated DHA, as a hydroperoxide source, is found to enhance the peroxidase-like activity of the Fe-HMME@DHA@MPN to generate ROS hydroxyl radical, beneficial for the microenvironment without sufficient H 2 O 2 . In vitro experiments demonstrate that the ROS nanogenerators are capable of killing multidrug-resistant H. pylori and removing biofilm, and ROS nanogenerators show high therapeutic efficacy in a H. pylori infection mouse model. Unlike the triple therapy, the nanogenerators display negligible side effects toward the normal gut microbiota. Taken together, these self-enhanced ROS nanogenerators have a great potential for treatment of H. pylori infection.

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Inflammatory pathways in Alzheimer’s disease mediated by gut microbiota

Cited by 89 publications

References 188 publications

Roles and Mechanisms of Gut Microbiota in Patients With Alzheimer’s Disease

Roles and Mechanisms of Gut Microbiota in Patients With Alzheimer’s Disease

The Microbiota–Gut–Brain Axis and Alzheimer Disease. From Dysbiosis to Neurodegeneration: Focus on the Central Nervous System Glial Cells

Gastric Acid‐Responsive ROS Nanogenerators for Effective Treatment of Helicobacter pylori Infection without Disrupting Homeostasis of Intestinal Flora

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