Impact of Acute and Chronic Amyloid-β Peptide Exposure on Gut Microbial Commensals in the Mouse

Guilherme, Malena dos Santos; Todorov, Hristo; Osterhof, Carina; Möllerke, Anton; Cub, Kristina; Hankeln, Thomas; Gerber, Susanne

doi:10.3389/fmicb.2020.01008

Cited by 19 publications

(14 citation statements)

References 65 publications

(99 reference statements)

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“…65 These SCFA have multiple effects and are able to modulate enteric neuron properties (eg, butyrate interacts with the cholinergic system of the gut) which results, for example, in gut motility enhancement. 66,67 It has been shown, that the gut microbiome composition of 5xFAD mice differs from that of wild-type littermates, 35,68 and therefore might play an important role in modifying gut motility. It should be noted that an altered gut transit time is of major importance for further investigations of fecal microbiota in 5xFAD animals, since faster transit time itself has an impact on microbiota composition of the feces.…”

Section: F I G U R Ementioning

confidence: 99%

Alzheimer's disease in the gut—Major changes in the gut of 5xFAD model mice with ApoA1 as potential key player

Stoye

Guilherme

2020

FASEB j.

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Alzheimer's disease (AD) affects around 33 million people worldwide, which makes it the most prominent form of dementia. The main focus of AD research has been on the central nervous system (CNS) for long, but in recent years, the gut gained more attention. The intestinal tract is innervated by the enteric nervous system (ENS), built of numerous different types of neurons showing great similarity to neurons of the CNS. It already has been demonstrated that the amyloid precursor protein, which plays a major role in AD pathology, is also expressed in these cells. We analyzed gut tissue of AD model mice (5xFAD) and the respective wild‐type littermates at different pathological stages: pre‐pathological, early pathological and late pathological. Our results show significant difference in function of the intestine of 5xFAD mice as compared to wild‐type mice. Using a pathway array detecting 84 AD‐related gene products, we found ApoA1 expression significantly altered in colon tissue of 5xFAD mice. Furthermore, we unveil ApoA1's beneficial impact on cell viability and calcium homeostasis of cultured enteric neurons of 5xFAD animals. With this study, we demonstrate that the intestine is altered in AD‐like pathology and that ApoA1 might be one key player within the gut.

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Section: F I G U R Ementioning

confidence: 99%

Alzheimer's disease in the gut—Major changes in the gut of 5xFAD model mice with ApoA1 as potential key player

Stoye

Guilherme

2020

FASEB j.

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“…Previous studies have reported lower bacterial diversity and more similar bacteria composition when young AD mice are compared with wildtype counterparts [ 90 , 107 , 132 ], while further differences are shown as the age of the animals increase [ 90 ]. Following this idea, gut microbiota from young APP/PS1 mice [ 107 ] and 5xFAD mice [ 131 , 133 ] are similar to that observed in wildtype animals. No significant differences in either α- or β-diversity have been observed in 5xFAD mice at 9–10 weeks old [ 133 ], although α-diversity is lower in these mice by 6 and 12 months of age [ 134 ].…”

Section: Diet Inflammation and Gut Microbiota In Ad Modelsmentioning

confidence: 98%

Alzheimer’s Disease and Diabetes: Role of Diet, Microbiota and Inflammation in Preclinical Models

et al. 2021

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Alzheimer’s disease (AD) is the most common cause of dementia. Epidemiological studies show the association between AD and type 2 diabetes (T2DM), although the mechanisms are not fully understood. Dietary habits and lifestyle, that are risk factors in both diseases, strongly modulate gut microbiota composition. Also, the brain-gut axis plays a relevant role in AD, diabetes and inflammation, through products of bacterial metabolism, like short-chain fatty acids. We provide a comprehensive review of current literature on the relation between dysbiosis, altered inflammatory cytokines profile and microglia in preclinical models of AD, T2DM and models that reproduce both diseases as commonly observed in the clinic. Increased proinflammatory cytokines, such as IL-1β and TNF-α, are widely detected. Microbiome analysis shows alterations in Actinobacteria, Bacteroidetes or Firmicutes phyla, among others. Altered α- and β-diversity is observed in mice depending on genotype, gender and age; therefore, alterations in bacteria taxa highly depend on the models and approaches. We also review the use of pre- and probiotic supplements, that by favoring a healthy microbiome ameliorate AD and T2DM pathologies. Whereas extensive studies have been carried out, further research would be necessary to fully understand the relation between diet, microbiome and inflammation in AD and T2DM.

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“…The presence of certain metal ions, such as aluminum (Al 3+ ), iron (Fe 2+ ), copper (Cu 2+ ), zinc (Zn 2+ ), and mercury (Hg 2+ ), and mitochondrial dysfunction, also contribute to the pathogenesis of AD [ 7 ]. Recently, studies in mice investigating the possibility that Aβ peptide from the intestinal microbiome might be a trigger leading to AD opened a new avenue of research in this area [ 8 , 9 ]. Therefore, AD can be caused by several mechanisms, leading to the possibility of being treated by different pathways, which are outlined in Figure 2 [ 10 ].…”

Section: Alzheimer’s Diseasementioning

confidence: 99%

Marine Natural Products, Multitarget Therapy and Repurposed Agents in Alzheimer’s Disease

et al. 2020

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Alzheimer’s disease (AD) is a multifactorial disease characterized by the presence of amyloid plaques, neurofibrillary tangles, and nerve cell death that affects, mainly, older people. After decades of investigation, the search for an efficacious treatment for AD remains and several strategies can be and are being employed in this journey. In this review, four of the most promising strategies, alongside with its most promising agents under investigation or development are highlighted. Marine natural products (MNP) are a source of unique chemical structures with useful biological activities for AD treatment. One of the most promising compounds, a marine-derived acidic oligosaccharide (GV-971) just passed phase III clinical trials with a unique mechanism of action. Combination therapy and multitargeted-directed ligand therapy (MTDL) are also two important strategies, with several examples in clinical trials, based on the belief that the best approach for AD is a therapy capable of modulating multiple target pathways. Drug repurposing, a strategy that requires a smaller investment and is less time consuming, is emerging as a strong contender with a variety of pharmacological agents resurfacing in an attempt to identify a therapeutic candidate capable of modifying the course of this disease.

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Impact of Acute and Chronic Amyloid-β Peptide Exposure on Gut Microbial Commensals in the Mouse

Cited by 19 publications

References 65 publications

Alzheimer's disease in the gut—Major changes in the gut of 5xFAD model mice with ApoA1 as potential key player

Alzheimer's disease in the gut—Major changes in the gut of 5xFAD model mice with ApoA1 as potential key player

Alzheimer’s Disease and Diabetes: Role of Diet, Microbiota and Inflammation in Preclinical Models

Marine Natural Products, Multitarget Therapy and Repurposed Agents in Alzheimer’s Disease

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