Microbiome & Chronic Diseases

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Alzheimer's disease {40000139}

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Alzheimer's disease
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Shared Notes

  • [1.10
    - Fungi in gut linked to higher Alzheimers risk can be reduced through ketogenic diet.
  • [1.11
    - Amyloid SUVR uptake is positively associated with
    - blood LPS
    - acetate and valerate
    - pro-inflammatory cytokines
    - biomarkers of endothelial dysfunction
    - Amyloid SUVR uptake is is negatively correlated with
    - butyrate
    - anti-inflammatory cytokine IL10
    -Endothelial dysfunction is positively associated with
    - pro-inflammatory cytokines, acetate and valerate
    -Endothelial dysfunction is negatively associated with
    - butyrate and IL10 levels.
  • [1.12
    - The gut microbiome of AD participants has decreased microbial diversity.
    - Bacteroidetes are increased and Bifidobacterium and Firmicutes are decreased in the microbiome of AD participants.
    - Porphyromonas gingivalis, the keystone pathogen in chronic periodontitis, identified in the brain of Alzheimers disease patients. Toxic proteases from the bacterium called gingipains were also identified in the brain of Alzheimes patients, and levels correlated with tau and ubiquitin pathology.
    - Oral infections with Porphyromonas gingivalis, or introduction of its lipopolysaccharide (LPS), in various mouse models has demonstrated the development of key neuropathological hallmark lesions defining AD.
  • [1.13
    - Curli are cell surface amyloid proteins abundantly expressed by E. coli to exacerbate αSyn-induced behavioral deficits, including intestinal and motor impairments.
  • [1.14
    - Porphyromonas gingivalis, the keystone pathogen in chronic periodontitis, was identified in the brain of Alzheimer’s disease patients. Toxic proteases from the bacterium called gingipains were also identified in the brain of Alzheimer’s patients, and levels correlated with tau and ubiquitin pathology.
  • [1.15
    - Resveratrol has been proposed as a beneficial compound to delay ageing and cellular senescence.
  • [1.16
    - The gut microbiota-derived metabolite TMAO is elevated in the CSF of individuals with MCI and AD dementia, and that levels of CSF TMAO are associated with CSF biomarkers of AD pathology and neuronal degeneration.
  • [1.3
    - Bifidobacterium breve, improves cognition.
    - The improvement of cognitive function reveal an inverse correlation of HbA1c with total RBANS score amelioration after the study only in the probiotic group.
  • [1.17
    - Increasing evidence points to several mitochondrial functions that are affected in AD.
    - Deficit in this mitochondrial may be at the heart of the progression of AD itself.
  • [1.18
    - Various gut microbes such as Actinobacteria, Bacteroidetes, E. coli, Firmicutes, Proteobacteria, Tenericutes, and Verrucomicrobia are known to play a crucial role in the pathogenesis of AD.
    - These microbes and their metabolites modulate various physiological processes that contribute to AD pathogenesis, such as neuroinflammation and other inflammatory processes, amyloid deposition, cytokine storm syndrome, altered BDNF and NMDA signaling, impairing neurodevelopmental processes.
    - Epigenetic markers associated with AD mainly include histone modifications and DNA methylation, which are under the direct control of a variety of enzymes, such as acetylases and methylases which activity is dependent upon the metabolites generated by the host’s gut microbiome.
  • [1.8
    - At genera and species levels, higher subgingival periodontal dysbiosis was associated with reduced CSF amyloid beta (Aβ)42 but not with P‐tau.
  • [1.19
    - Colonization of the C. elegans gut with enteric bacterial pathogens disrupted proteostasis in the intestine, muscle, neurons, and the gonad.
    - The presence of bacteria that conditionally synthesize butyrate, a molecule previously shown to be beneficial in neurodegenerative disease models, suppressed aggregation and the associated proteotoxicity.
  • [1.20
    - The effects of gut microbiota in AD are mediated by microbial metabolites that either act on local neurons in the gut and surrounding tissues and send signals to the brain, and/or get absorbed from the gut and reach to brain through circulation. Such examples are monoamines, short-chain fatty acids (SCFAs), gamma-aminobutyric acid (GABA), beta-methylamino-L-alanine, brain-derived neurotrophic factor, serotonin, and dopamine
  • - Patients with MCI and AD also show higher levels of gut microbiota-derived trimethylamine N-oxide (TMAO) in the cerebrospinal fluid.
    - TMAO correlate with AD biomarkers including pTau, total Tau, and Aβ42.
    - TMAO treatment reduces cognitive function and aging signs in mice, by ameliorating neuronal senescence and mitochondrial dysfunction.
    - TMAO and its precursors have inflammatory biomarkers, possibly contributing to AD-related leaky gut.
  • - The Western diet consists of low-fiber, high-fat, and high-protein foods, where it is common to eat fatty red meats and eggs that are rich in TMA and choline, thus increase TMAO production.
  • - Oxidative stress can be modulated by diet, for example, high-fruit-and-vegetable diets improve cognition, which is linked with decreased oxidative stress in elderly;
  • - MD-ketogenic diet improved the AD biomarkers viz. amyloid and tau proteins in the cerebrospinal fluids of MCI patients, wherein these changes linked with increased gut butyrate.
    - There is a significant reduction in Aβ levels and increase in behavioral responses after 12-weeks of sodium butyrate supplementation in mouse
  • - Lipopolysaccharide (LPS), an outer cell wall component of Gram-negative bacteria that can be highly pro-inflammatory, can enhance Aβ accumulation in brain and induce cognitive dysfunction.
    - AD patients show higher LPS levels in blood plasma, and neocortex and hippocampus.
    - LPS can also cause chronic neuroinflammation, nerve cell death in entorhinal cortex, and impairment of synaptic plasticity of neurons in hippocampus.
  • - Specific bacteria, for example, Escherichia coli, Bacillus subtilis, Salmonella typhimurium, and Salmonella enterica can also produce amyloids.
  • [1.7
    - The ApoE4 allele is the most well-studied genetic risk factor for Alzheimer’s disease, a condition that is increasing in prevalence and remains without a cure.
    - Precision nutrition targeting metabolic pathways altered by ApoE4 provides a tool for the potential prevention of disease.
  • [1.21
    - AD elders had increased proportions of specific bacterial species that have associations with neurological disorders (including AD). These include Odoribacter splanchnicus, a bacterial species with genes that have been associated with the Alzheimers pathway (5)
    - Blautia were more abundant in AD patients.
    - Elevated GABA was potentially associated with a lower risk of AD.
    - Gut microbial neurotransmitter GABA, a downstream product of Blautia-dependent arginine metabolism, was related to a reduced risk of AD.
    - Lower levels of gut product of GABA were observed in patients with AD.
    - The biological mechanisms of GABA production include degradation of putrescine, decarboxylation of glutamate, or from arginine or ornithine. In
    - Blautia has a strong correlation with arginine metabolism, which may be involved in AD pathogenesis by regulating its downstream products such as GABA, supporting the potential pathway.
    - Elevated Enterobacteriales was also associated with a higher risk of ASD.
    - Gut microbiome may excrete large quantities of lipopolysaccharides and amyloids, resulting in the pathogenesis of AD during aging when the permeability of gastrointestinal tract epithelium or blood-brain barrier increases.
  • [1.24
    - AD elders were also depleted in Adlercreutzia equolifaciens, an equol-producing bacterium, which has beneficial effects in reducing experimental cutaneous inflammation in mice and the loss of which has been associated with the neurodegenerative disorder multiple sclerosis.
    - Bacteroides vulgatushe is a predictor of AD dementia which cause inflammatory states.
    - Increased proportions of Bacteroides, Alistipes, Odoribacter, and Barnesiella and decreased proportions of Lachnoclostridium were present in AD elders.
    - Increased proportions of Odoribacter and Barnesiella and decreased proportions of Eubacterium , Roseburia , Lachnoclostridium and Collinsella were seen in elders with other dementia types.
  • [1.25
    - At the follow-up visit 2 months post-FMT, the patient’s wife reported improvements in the patient’s mental acuity and affect. The MMSE was re-administered by the gastroenterologist (and subsequently by the neurologist) and the patient scored 26, indicating normal cognition. Four months post-FMT, the patient reported continued improvement in memory, with no progression in symptoms. The patient now remembered his daughter’s birthday, which he had not been able to recall previously, and was able to correct the physician’s recollections of his symptoms. Six months post-FMT, the patient reported a marked improvement in mood, was more interactive, and showed more expressive affect.
  • [1.9
    - Reduction of glutamine > causally associated with occurrence of AD.
  • [1.28
    - Treatment with Rifamixin > significant reduction in serum neurofilament-light levels >significant increase in fecal phylum Firmicutes microbiota.
    Treatment with Rifamixin > reduces Serum pTau181 and GFAP levels and non-significant downward trend in serum cytokine IL-6 and IL-13 levels.
    Increases in stool Erysipelatoclostridium > correlated significantly with reductions in serum pTau 181 and serum GFAP.

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