Protective roles of intestinal microbiota derived short chain fatty acids in Alzheimer’s disease-type beta-amyloid neuropathological mechanisms

Ho, Lap; Ono, Kenjiro; Tsuji, Mayumi; Mazzola, Paolo; Singh, Risham; Pasinetti, Giulio Maria

doi:10.1080/14737175.2018.1400909

Cited by 258 publications

(191 citation statements)

References 34 publications

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“…SCFAs' effects on Ab peptide aggregation were examined both in vitro and in vivo studies. The in vitro study carried out by Ho et al (2018) with photoinduced crosslinking of unmodified proteins protocol found that butyric acid, propionic acid and valeric acid inhibited Ab 40 oligomerization in a dose-dependent manner (the most effective dose is 4 : 1 = SCFAs: Ab). GABA homologue, valeric acid was reported to show the strongest inhibitory effect.…”

Section: Gut Metabolites and Ab Clearancementioning

confidence: 99%

“…In another human study, Cattaneo et al (2017) indicated that the numbers of Eubacterium rectale and Bacteroides fragilis organisms in patients with amyloidosis (Amy +) were significantly reduced as compared to the control group, while the number of Escherichia/Shigella organisms significantly increased, which supports the notion that AD affects the gut bacterial flora. Aside from the studies outlined above, a large number of studies have shown that gut microbes interact with the host in many respects (Bonfili et al 2017;Wu et al 2017;Ho et al 2018).…”

Section: Introductionmentioning

confidence: 99%

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The role of gut microbiota in pathogenesis of Alzheimer's disease

Bostancıklıoğlu

2019

Journal of Applied Microbiology

133

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This paper describes the effects of the gut microbiota on the pathogenesis of Alzheimer's pathology by evaluating the current original key findings and identifying gaps in the knowledge required for validation. The diversity of the gut microbiota declines in the elderly and in patients with Alzheimer's disease (AD). Restoring the diversity with probiotic treatment alleviates the psychiatric and histopathological findings. This presents a problem: How does gut microbiota interact with the pathogenesis of AD? The starting point of this comprehensive review is addressing the role of bacterial metabolites and neurotransmitters in the brain under various conditions, ranging from a healthy state to ageing and disease. In the light of current literature, we describe three different linkages between the present gut microbiome hypothesis and the other major theories for the pathogenesis of AD as follows: bacterial metabolites and amyloids can trigger central nervous system inflammation and cerebrovascular degeneration; impaired gut microbiome flora inhibits the autophagy‐mediated protein clearance process; and gut microbiomes can change the neurotransmitter levels in the brain through the vagal afferent fibres.

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Section: Gut Metabolites and Ab Clearancementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The role of gut microbiota in pathogenesis of Alzheimer's disease

Bostancıklıoğlu

2019

Journal of Applied Microbiology

133

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“…Second, both quercetin (Porras et al, ) and dAGEs (Qu et al, ) could affect the structure and relative abundance of gut microbiota. In addition, short chain fatty acids (SCFAs) produced via fermentation of nondigestible compounds by the gut microbiota not only function as a signaling molecule between microbes, but also may be protective against AD (Ho et al, ; Stilling et al, ). Consequently, it could be of interest to explore how a short‐term dAGEs intervention and/or quercetin would affect the gut microbiota profiles and SCFAs level.…”

Section: Introductionmentioning

confidence: 99%

Quercetin is protective against short‐term dietary advanced glycation end products intake induced cognitive dysfunction in aged ICR mice

et al. 2020

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Dietary advanced glycation end products (dAGEs) might be potential toxins involved in the pathogenesis of Alzheimer’s disease (AD). Quercetin is a flavonoid possessing neuroprotective effects. We aimed to explore whether a 21 days of dAGEs intake would result in cognitive dysfunction in aged ICR mice, and the protective effects of quercetin, with potential mechanisms explored. Fourteen‐month old ICR mice were randomly assigned into four groups, that is, Control, AGEs, quercetin, and AGE diet supplemented with quercetin. Key markers involved in Aβ, tau, and neuroinflammation from hippocampus and cortex were measured via western blot. Gut microbiota and short chain fatty acids profiles from intestinal contents were measured via 16S rRNA gene sequencing and gas chromatography (GC), respectively. Quercetin alleviated cognitive impairment induced by dAGEs in aged mice. This might be associated with that quercetin reduced cathepsin B, tau phosphorylation, and neuroinflammation, and elevated α‐diversity index (ACE, Chao1, and Shannon index), and reduced phylum Verrucomicrobia of gut microbiota. Practical applications Alzheimer’s disease (AD) has been regarded as the commonest cause of progressive dementia for the elderly. This study is the very first to demonstrate that even a short‐term dietary advanced glycation end product (dAGEs) intake induced impaired cognitive function in aged ICR mice, and querectin is capable of reversing dAGEs‐induced cognitive dysfunction. Reduced tau phosphorylation, neuroinflammation, and altered gut microbiota profiles may be involved in querectin’s protective effects against dAGEs‐induced cognitive impairment. Our study suggested that quercetin supplementation might be beneficial for improving cognitive function in elderly subjects with high consumption of dAGEs such as grilling, frying, and broiling of food.

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“…We detected a higher level of SCFAs including acetate, lactate, propionate, and pyruvate in APOE3 mice which might be the result of a high abundance of butyrate-producing bacteria. Several SCFAs have been shown to inhibit the formation of toxic soluble Aβ aggregates in vitro (Ho et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Association between Apolipoprotein E genotype and the gut microbiome composition in humans and mice

Tran

Corsini

Kellingray

et al. 2018

Preprint

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Apolipoprotein E (APOE) genotype is the strongest prevalent genetic risk factor for Alzheimer's disease.Numerous studies have provided insights into the pathological mechanisms. However, a comprehensive understanding of the impact of APOE genotype on microflora speciation and metabolism is completely lacking. The aim of this study was to investigate the association between APOE genotype and the gut microbiome composition in human and APOE-targeted replacement (TR, APOE3 and APOE4) transgenic mice. Faecal microbiota amplicon sequencing from matched individuals with different APOE genotypes revealed no significant differences in overall microbiota diversity (alpha or beta diversity) in groupaggregated human APOE genotypes. However, several bacterial taxa showed significantly different relative abundance between APOE genotypes. Notably, we detected an association of Prevotellaceae and Ruminococcaceae and several butyrate-producing genera abundances with APOE genotypes. These findings were confirmed by comparing the gut microbiota of APOE-TR mice. Furthermore, metabolomic analysis of faecal water from murine samples detected significant differences in microbe-associated amino acids and short-chain fatty acids between APOE genotypes. Together, the findings indicate that APOE genotype associated with specific gut microbiome profiles in both humans and in APOE-TR mice. This suggests that the gut microbiome is worth further investigation as a potential therapeutic target to mitigate the deleterious impact of the APOE4 allele on cognitive decline and the prevention and treatment of AD.

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Protective roles of intestinal microbiota derived short chain fatty acids in Alzheimer’s disease-type beta-amyloid neuropathological mechanisms

Cited by 258 publications

References 34 publications

The role of gut microbiota in pathogenesis of Alzheimer's disease

The role of gut microbiota in pathogenesis of Alzheimer's disease

Quercetin is protective against short‐term dietary advanced glycation end products intake induced cognitive dysfunction in aged ICR mice

Association between Apolipoprotein E genotype and the gut microbiome composition in humans and mice

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