The role of microbiome-host interactions in the development of Alzheimer´s disease

Abstract

Alzheimer`s disease (AD) is the most prevalent cause of dementia. It is often assumed that AD is caused by an aggregation of extracellular beta-amyloid and intracellular tau-protein, supported by a recent study showing reduced brain amyloid levels and reduced cognitive decline under treatment with a beta-amyloid-binding antibody. Confirmation of the importance of amyloid as a therapeutic target notwithstanding, the underlying causes of beta-amyloid aggregation in the human brain, however, remain to be elucidated. Multiple lines of evidence point towards an important role of infectious agents and/or inflammatory conditions in the etiology of AD. Various microorganisms have been detected in the cerebrospinal fluid and brains of AD-patients and have thus been hypothesized to be linked to the development of AD, including Porphyromonas gingivalis (PG) and Spirochaetes. Intriguingly, these microorganisms are also found in the oral cavity under normal physiological conditions, which is often affected by multiple pathologies like caries or tooth loss in AD patients. Oral cavity pathologies are mostly accompanied by a compositional shift in the community of oral microbiota, mainly affecting commensal microorganisms and referred to as ‘dysbiosis’. Oral dysbiosis seems to be at least partly mediated by key pathogens such as PG, and it is associated with a pro-inflammatory state that promotes the destruction of connective tissue in the mouth, possibly enabling the translocation of pathogenic microbiota from the oral cavity to the nervous system. It has therefore been hypothesized that dysbiosis of the oral microbiome may contribute to the development of AD. In this review, we discuss the infectious hypothesis of AD in the light of the oral microbiome and microbiome-host interactions, which may contribute to or even cause the development of AD. We discuss technical challenges relating to the detection of microorganisms in relevant body fluids and approaches for avoiding false-positives, and introduce the antibacterial protein lactoferrin as a potential link between the dysbiotic microbiome and the host inflammatory reaction.

Oral Microbiome Stamp in Alzheimer’s Disease

“…However, the recent animal study of Liu et al demonstrated the protective feature of Lactobacillus; an increase of this taxon led to the attenuation of AD symptoms [46]. Interestingly, we did not observe the increase in Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans in AD patients despite several existing studies proving these taxa's relation to AD disease, according to a recent review by Weber et al [47] and Wan et al [48]. However, our regionbased analysis results revealed the increase of Porphyromonas and Actynobaccillus in the Astana-AD subgroup.…”

Mouse maternal odontogenic infection with Porphyromonas gingivalis induces cognitive decline in offspring

“…P. gingivalis -LPS increased serum IL-1β and decreased tight junction protein, induce depression-like behavior by initiating the neuroinflammation through damaging the permeability of BBB ( 72 ). In addition, it has also been reported that IL-6 in serum induces neuroinflammation in the hippocampus and destruction of the BBB in a mouse model with experimental periodontitis ( 73 ). Since in the present study, P. gingivalis has been detected in the brains of offspring, it has possibility that the virulence factor of P. gingivalis is also transferred.…”

“…Thus, it is gradually evident that the oral microbiome-host interactions plays an important role in development of various behavior abnormalities AD ( 73 ).…”

Physiological Correlates of Hypnotizability: Hypnotic Behaviour and Prognostic Role in Medicine

“…In cancer patients and geriatric patients' positive immune effects of hypnotic relaxation have also been reported [69]. Finally, the highs' ability to modulate their autonomic activity [83,90,91], challenged by only one study [92] could positively influence their microbiota, whose alteration is involved in cognitive decline owing to the cerebral effects of locally produced cytokines and the activation of afferent vagal fibers [93]. The negative effects of microbiota alteration of have been described, in fact, in case of degenerative physical and cognitive decline [94][95][96][97][98][99][100].…”