Gut Microbiota and Their Neuroinflammatory Implications in Alzheimer’s Disease

Giau, Vo Van; Wu, Si Ying; Jamerlan, Angelo; An, Seong Soo A.; Kim, SangYun; Hulme, John

doi:10.3390/nu10111765

Cited by 172 publications

(138 citation statements)

References 139 publications

(180 reference statements)

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“…The gastrointestinal (GI) tract of Homo sapiens contains a complex microbiome consisting primarily of bacteria, with archaea, fungi, microbial eukaryotes, protozoa, viruses, and other microorganisms making up the balance [3][4][5]7,8,16,19,25,26,89,90]. Together with human host cells this microbiome comprises the entire meta-organism whose host interactions and symbiotic associations are critical to human health and disease [4,16,18,35,72,[88][89][90].…”

Section: Overview: Human Gi-tract Microbiome and Bacteroides Fragilismentioning

confidence: 99%

Lipopolysaccharide-stimulated, NF-kB-, miRNA-146a- and miRNA-155-mediated molecular-genetic communication between the human gastrointestinal tract microbiome and the brain

Alexandrov¹,

Zhai²,

Li³

et al. 2019

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Through the use of RNA sequencing, microRNA (miRNA) and messenger RNA (mRNA) microfluidic array analysis, LED Northern, Western and ELISA analysis and multiple bioinformatics algorithms we have discovered a novel route for pathogenic communication between the human gastrointestinal (GI)-tract microbiome and the brain. The evidence suggests that this pathogenic gut-brain circuit involves: (i) lipopolysaccharide (LPS) from the GI-tract resident enterotoxigenic Gram-negative bacteria Bacteroides fragilis (BF-LPS); (ii) LPS transit across the GI-tract barrier into the systemic circulation; (iii) transport of a highly pro-inflammatory systemic BF-LPS across the blood-brain barrier (BBB) into the brain-parenchyma and neuronal-cytoplasm; (iv) activation and signaling via the pro-inflammatory NF-kB (p50/p65) transcription-factor complex; (v) NF-kB-coupling and significant up-regulation of the inducible pro-inflammatory microRNA-146a (miRNA-146a) and microRNA-155 (miRNA-155); each containing multiple NF-kB DNA-binding and activation sites in their immediate promoters; and (vi) subsequent down-regulation of miRNA-146a-miRNA-155 regulated mRNA targets such as that encoding complement factor H (CFH), a soluble complement control glycoprotein and key repressor of the innate-immune response. Down-regulated CFH expression activates the complement-system, the major non-cellular component of the innate-immune system while propagating neuro-inflammation. Other GI-tract microbes and their highly complex pro-inflammatory exudates may contribute to this pathogenic GI-tract-brain pathway. We speculate that it may be significant that the first Gram-negative anaerobic bacterial species intensively studied as a potential contributor to the onset of Alzheimer's disease (AD), that being the bacillus Bacteroides fragilis appears to utilize damaged or leaky physiological barriers and an activated NF-kB (p50-p65)-pro-inflammatory miRNA-146a-miRNA-155 signaling circuit to convey microbiome-derived pathogenic signals into the brain.

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Section: Overview: Human Gi-tract Microbiome and Bacteroides Fragilismentioning

confidence: 99%

Lipopolysaccharide-stimulated, NF-kB-, miRNA-146a- and miRNA-155-mediated molecular-genetic communication between the human gastrointestinal tract microbiome and the brain

Alexandrov¹,

Zhai²,

Li³

et al. 2019

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“…Gut physiology (8,9) Nutrient production and absorption (10) Host development and physiology (11) Energy balancing (12) Metabolic functions (13,14) Immune system functions (15)(16)(17) Inflammatory processes (18) Neurons-brain-behavior system (19)(20)(21)(22) The majority of those studies cited here have demonstrated improvement in the clinical status of patients after targeted intervention influencing the gut microbiota. Similar studies relatively recently have led to definition of the so-called microbiome-gut-brain axis.…”

Section: Kubelkova Macela: Microbiota-gut-brain Axis 42 Box 2: Biolomentioning

confidence: 98%

Microbiota-Gut-Brain Signaling: A Minireview

Kubelková¹,

Macela²

2020

Mil. Med. Sci. Lett.

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The gut microbiota of vertebrates, including humans, constitutes an integral genomic part that, together with the genome of the host, may be included under the umbrella concept of hologenome, which itself can be seen as one of the possible tools for evolution. Present-day lifestyles, technologically processed nutrients, and various diseases impact significantly upon composition of the intestinal microbiota. Knowledge recently brought to light has shown the gut microbiota to be a component of the microbiota-gut-brain axis having feedback effects on physiological and psychological processes of the host organism and its health. This minireview summarizes current knowledge and opinions on the importance of the microbiota-gut-brain axis and discusses possibilities for beneficially modulating one of the organism's most vital axes.

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“…However, the effect of probiotics supplementation on anti-inflammation or cognitive function in AD patients has not been very promising to date [201,202]. Future studies should focus on fields including proneurogenic and anti-inflammatory effects of dietary intervention and the modulation of gut microbiota and their therapeutic impact in AD models [198,203].…”

Section: Potential Therapeutic Approaches Targeting Adult Neurogenesimentioning

confidence: 99%

Neuroinflammation and Neurogenesis in Alzheimer’s Disease and Potential Therapeutic Approaches

Sung

Lin

Liu

et al. 2020

IJMS

134

108

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In adult brain, new neurons are generated throughout adulthood in the subventricular zone and the dentate gyrus; this process is commonly known as adult neurogenesis. The regulation or modulation of adult neurogenesis includes various intrinsic pathways (signal transduction pathway and epigenetic or genetic modulation pathways) or extrinsic pathways (metabolic growth factor modulation, vascular, and immune system pathways). Altered neurogenesis has been identified in Alzheimer’s disease (AD), in both human AD brains and AD rodent models. The exact mechanism of the dysregulation of adult neurogenesis in AD has not been completely elucidated. However, neuroinflammation has been demonstrated to alter adult neurogenesis. The presence of various inflammatory components, such as immune cells, cytokines, or chemokines, plays a role in regulating the survival, proliferation, and maturation of neural stem cells. Neuroinflammation has also been considered as a hallmark neuropathological feature of AD. In this review, we summarize current, state-of-the art perspectives on adult neurogenesis, neuroinflammation, and the relationship between these two phenomena in AD. Furthermore, we discuss the potential therapeutic approaches, focusing on the anti-inflammatory and proneurogenic interventions that have been reported in this field.

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Gut Microbiota and Their Neuroinflammatory Implications in Alzheimer’s Disease

Cited by 172 publications

References 139 publications

Lipopolysaccharide-stimulated, NF-kB-, miRNA-146a- and miRNA-155-mediated molecular-genetic communication between the human gastrointestinal tract microbiome and the brain

Lipopolysaccharide-stimulated, NF-kB-, miRNA-146a- and miRNA-155-mediated molecular-genetic communication between the human gastrointestinal tract microbiome and the brain

Microbiota-Gut-Brain Signaling: A Minireview

Neuroinflammation and Neurogenesis in Alzheimer’s Disease and Potential Therapeutic Approaches

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