Front Cell Neurosci. 2013; 7: 153.Emerging studies indicate that the HM may contribute to the regulation of multiple neuro-chemical and neuro-metabolic pathways through a complex series of highly interactive and symbiotic host-microbiome signaling systems that mechanistically
Published online 2013 Sep 17. doi: 10.3389/fncel.2013.00153
PMCID: PMC3775450
Alzheimer's disease and the microbiome
Surjyadipta Bhattacharjee and Walter J. Lukiw*
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This article has been cited by other articles in PMC.
“Microbial colonization of mammals is an evolution-driven process that modulates host physiology, many of which are associated with immunity and nutrient intake”—Heijtz et al.(2011)
The recognition of the human microbiome (HM) as a substantial contributor to nutrition, health and disease is a relatively recent one, and currently, peer-reviewed studies linking alterations in microbiota to the etiopathology of human disease are few.
Firstly, the microbiome of the human GI tract is the largest reservoir of microbes in the body, containing about 1014 microorganisms; over 99% of microbiota in the gut are anaerobic bacteria, with fungi, protozoa, archaebacteria and othermicroorganisms making up the remainder. There is currently an expanding interest in the ability of intestinal bacteria to influence neuro-immune functions well beyond the GI tract. Since mitochondria are believed to originate from bacteria via
Equally interesting are microbiome interactions with the N-methyl-D-aspartate (NMDA) glutamate receptor, a prominent CNS device that regulates synaptic plasticity and cognition (Lakhan et al., 2013). For example, the NMDA-, glutamate-targeting,glutathione-depleting and oxidative-stress-inducing neurotoxin β-N-methylamino-L-alanine (BMAA), found elevated in the brains of patients with amyotrophic-lateral sclerosis (ALS), Parkinson-dementia (PD) complex of Guam and AD, has been hypothesized to
Regarding potentially pathogenic micobiota stationed outside of the GI tract, about 95% of all humans harbor the highly neurotrophic herpes simplex-1 (HSV-1) in their trigeminal ganglia, but whether this is a neutral or symbiotic relationship, ordetrimental to the host, remains open to speculation. Induction of HSV-1, and other forms of endogenous viral reactivation are certainly stress-related, but whether GI tract HM-derived metabolites are involved in these kinds of pathogenic activation
Further studies of symbiotic HM-CNS communication intrinsically suggests the potential for microbial-based therapeutic strategies that may aid in the augmentation of the HM, for the treatment of human disease, including neurological disorders (Forsytheet al., 2012; Collins et al., 2013). The original observation of the health-promoting benefits of GI tract bacteria and the HM was first introduced in 1907 by the Russian biologist Ilya Metchnikoff (Nobel Prize in Medicine 1908, shared with Paul Erlich;
Lastly, the US NIH “Roadmap” program has recently initiated the HM project (HMP; http://commonfund.nih.gov/Hmp/), using recently discovered genomic technologies with the specific aims (i) to characterize the microbial communities at severaldifferent sites on the human body, including nasal, oral and otic cavities, the skin, GI and urogenital tracts; (ii) to analyze the role of these microbes in homeostatic human physiology; (iii) to catalog specific microbiome speciation, composition and
Go to:was supported through a COBRE Project, a Translational Research Initiative Grant (LSUHSC), the Louisiana Biotechnology Research Network, Alzheimer Association Investigator-Initiated Research Grant IIRG-09-131729, and NIA Grants AG18031 and AG038834.
Acknowledgments
This work was presented in part at the 42nd Society for Neuroscience Meeting, New Orleans LA, October 2012. Research in the Lukiw laboratory involving miRNA, the innate-immune response, amyloidogenesis and neuro-inflammation in AD and prion disease,
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Links
PubMed
NMDA Receptor Activity in Neuropsychiatric Disorders.
[Front Psychiatry. 2013]
Blue-green algae or cyanobacteria in the intestinal micro-flora may produce neurotoxins such as Beta-N-Methylamino-L-Alanine (BMAA) which may be related to development of amyotrophic lateral sclerosis, Alzheimer's disease and Parkinson-Dementia-Complex
[Med Hypotheses. 2013]
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[Wiley Interdiscip Rev Syst Biol Med. 2013]
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[Curr Opin Rheumatol. 2013]
Review Protein misfolding in the late-onset neurodegenerative diseases: common themes and the unique case of amyotrophic lateral sclerosis.
[Proteins. 2013]
Review Microbial amyloids--functions and interactions within the host.
[Curr Opin Microbiol. 2013]
Review Intracerebral propagation of Alzheimer's disease: strengthening evidence of a herpes simplex virus etiology.
[Alzheimers Dement. 2013]
Review Effect of intestinal microbial ecology on the developing brain.
[JAMA Pediatr. 2013]
HSV-1 infection of human brain cells induces miRNA-146a and Alzheimer-type inflammatory signaling.
[Neuroreport. 2009]
Review Exposure to herpes simplex virus type 1 and cognitive impairments in individuals with schizophrenia.
[Schizophr Bull. 2012]
Review Intracerebral propagation of Alzheimer's disease: strengthening evidence of a herpes simplex virus etiology.
[Alzheimers Dement. 2013]
Review Infectious particles, stress, and induced prion amyloids: a unifying perspective.
[Virulence. 2013]
Review Metabolomics approaches for characterizing metabolic interactions between host and its commensal microbes.
[Electrophoresis. 2013]
Review On communication between gut microbes and the brain.
[Curr Opin Gastroenterol. 2012]
Review The adoptive transfer of behavioral phenotype via the intestinal microbiota: experimental evidence and clinical implications.
[Curr Opin Microbiol. 2013]
Historical overview of studies on inflammation in Russia.
[Inflamm Res. 2013]
Review The intestinal microbiome, probiotics and prebiotics in neurogastroenterology.
[Gut Microbes. 2013]
Review Role of probiotics in health and disease: a review.
[J Pak Med Assoc. 2013]
Review Probiotics and prebiotics and health in ageing populations. [Maturitas. 2013]
Review The role of regulatory T cells in neurodegenerative diseases.
[Wiley Interdiscip Rev Syst Biol Med. 2013]
Review The influence of nutritional factors on the prognosis of multiple sclerosis.
[Nat Rev Neurol. 2012]
Review Dairy constituents and neurocognitive health in ageing.
[Br J Nutr. 2011]
Review Communication between gastrointestinal bacteria and the nervous system.
[Curr Opin Pharmacol. 2012]
Review Exposure to herpes simplex virus type 1 and cognitive impairments in individuals with schizophrenia.
[Schizophr Bull. 2012]
Review Effect of intestinal microbial ecology on the developing brain.
[JAMA Pediatr. 2013]
"Snake-oil," "quack medicine," and "industrially cultured organisms:" biovalue and the commercialization of human microbiome research.
[BMC Med Ethics. 2012]
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