Microbiota and the gut-brain-axis: Implications for new therapeutic design in the CNS

Liu, Longsha; Huh, Jun R.; Shah, Khalid

doi:10.1016/j.ebiom.2022.103908

Cited by 145 publications

(85 citation statements)

References 74 publications

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“…Moreover, preclinical studies in animal disease models have confirmed that the gut microbiome obtained from patients with neurological diseases can precipitate brain pathology and behavioral changes in mice [14]. Gut microorganisms can influence CNS functions by producing metabolites, neuroactive molecules, and hormones [15] (Figure 1). Amyloid + subjects: ↓ E. rectale and ↑ Escherichia/Shigella comapred to Amyloid − and HCs [16] Case control (25 AD and 25 HCs) 16S rRNA sequencing AD: ↓ Firmicutes and Actinobacteria and ↑ Bacteroides [17] Case control (24 AD, 33 other dementia, 51 HCs) Shotgun metagenomic sequencing AD: ↑ Bacteroides spp., Alistipes spp., Odoribacter spp., Barnesiella spp.…”

Section: The Gut Microbiome In Cns Homeostasismentioning

confidence: 99%

The Gut Microbiome–Brain Crosstalk in Neurodegenerative Diseases

et al. 2022

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The gut–brain axis (GBA) is a complex interactive network linking the gut to the brain. It involves the bidirectional communication between the gastrointestinal and the central nervous system, mediated by endocrinological, immunological, and neural signals. Perturbations of the GBA have been reported in many neurodegenerative diseases, suggesting a possible role in disease pathogenesis, making it a potential therapeutic target. The gut microbiome is a pivotal component of the GBA, and alterations in its composition have been linked to GBA dysfunction and CNS inflammation and degeneration. The gut microbiome might influence the homeostasis of the central nervous system homeostasis through the modulation of the immune system and, more directly, the production of molecules and metabolites. Small clinical and preclinical trials, in which microbial composition was manipulated using dietary changes, fecal microbiome transplantation, and probiotic supplements, have provided promising outcomes. However, results are not always consistent, and large-scale randomized control trials are lacking. Here, we give an overview of how the gut microbiome influences the GBA and could contribute to disease pathogenesis in neurodegenerative diseases.

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Section: The Gut Microbiome In Cns Homeostasismentioning

confidence: 99%

The Gut Microbiome–Brain Crosstalk in Neurodegenerative Diseases

et al. 2022

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“… Structure of the gut–microbiota–brain axis (The figure was adopted and reproduced from Liu et al with permission from the publisher) 116 …”

Section: Gut–microbiota–brain Axismentioning

confidence: 99%

“…These molecules can affect different metabolic pathways, i.e., glucose metabolism, catecholamine synthesis, and immunological pathways such as microglia maturation, thus giving rise to physiological and behavioral changes. [59][60][61] SCFAs also affect the hormonal secretion of EECs by the activation of some specific G protein-coupled receptors, direct induction of the F I G U R E 1 Structure of the gut-microbiota-brain axis (The figure was adopted and reproduced from Liu et al with permission from the publisher) 116 glucagon-like peptide 1 (GLP-1), release of peptide YY (PYY), and indirect release of ghrelin, which all are responsible for eating behaviors, including satiety, hunger, and appetite mechanisms. 14,62,63 The gut microbiota produces many neurotransmitters, such as catecholamines, GABA, and tryptophan, which can impact on the hypothalamus, thereby changing the neuroendocrine function.…”

Section: Endocrine System As a Link Between The Gut And The Brainmentioning

confidence: 99%

Obesity and gut–microbiota–brain axis: A narrative review

Asadi

Mehr

Mohamadi

et al. 2022

Clinical Laboratory Analysis

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Introduction Obesity is a major health problem that is associated with many physiological and mental disorders, such as diabetes, stroke, and depression. Gut microbiota has been affirmed to interact with various organs, including the brain. Intestinal microbiota and their metabolites might target the brain directly via vagal stimulation or indirectly through immune‐neuroendocrine mechanisms, and they can regulate metabolism, adiposity, homoeostasis and energy balance, and central appetite and food reward signaling, which together have crucial roles in obesity. Studies support the concept of bidirectional signaling within the gut–brain axis (GBA) in the pathophysiology of obesity, mediated by metabolic, endocrine, neural, and immune system mechanisms. Materials and methods Scopus, PubMed, Google Scholar, and Web of Science databases were searched to find relevant studies. Results The gut–brain axis (GBA), a bidirectional connection between the gut microbiota and brain, influences physiological function and behavior through three different pathways. Neural pathway mainly consists of the enteric nervous system (ENS) and vagus nerve. Endocrine pathway, however, affects the neuroendocrine system of the brain, particularly the hypothalamus–pituitary–adrenal (HPA) axis and immunological pathway. Several alterations in the gut microbiome can lead to obesity, by modulating metabolic pathways and eating behaviors of the host through GBA. Therefore, novel therapies targeting the gut microbiome, i.e., fecal microbiota transplantation and supplementation with probiotics and prebiotics, can be a potential treatment for obesity. Conclusion This study corroborates the effect of gut microbiome on physiological function and body weight. The results show that the gut microbiota is becoming a target for new antiobesity therapies.

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“…The gastrointestinal (GI) tract of Homo sapiens contains a complex, dynamic, and highly interactive community of microorganisms collectively known as the GI-tract microbiome possessing a staggering complexity and diversity. Composed of about ∼10 15 microorganisms from many thousands of different microbial species, the vast majority of human GI-tract microbes are composed of anaerobic or facultative anaerobic bacteria with aerobic bacteria, fungi, protozoa, Archaebacteria (an ancient intermediate microbial group between the prokaryotes and eukaryotes), viruses, and other microorganisms making up the remainder (1)(2)(3). Increasing research evidence has demonstrated that the composition of the GI-tract microbiome can significantly affect normal physiological homeostasis and contribute to the pathogenesis of diseases ranging from various types of inflammatory bowel disease to cancer to neurodegenerative disorders such as Alzheimer's disease [AD; (3)(4)(5)(6)(7)].…”

Section: Introductionmentioning

confidence: 99%

“…Composed of about ∼10 15 microorganisms from many thousands of different microbial species, the vast majority of human GI-tract microbes are composed of anaerobic or facultative anaerobic bacteria with aerobic bacteria, fungi, protozoa, Archaebacteria (an ancient intermediate microbial group between the prokaryotes and eukaryotes), viruses, and other microorganisms making up the remainder (1)(2)(3). Increasing research evidence has demonstrated that the composition of the GI-tract microbiome can significantly affect normal physiological homeostasis and contribute to the pathogenesis of diseases ranging from various types of inflammatory bowel disease to cancer to neurodegenerative disorders such as Alzheimer's disease [AD; (3)(4)(5)(6)(7)]. Gut microbiota can interact with the central nervous system (CNS) through the microbiota-gut-brain axis and through interactions mediated by metabolic and hormonal signaling, neural stimulation, and microbial secretions that both enhance and disrupt neurophysiology and neurological health.…”

Section: Introductionmentioning

confidence: 99%

Downregulation of Neurofilament Light Chain Expression in Human Neuronal-Glial Cell Co-Cultures by a Microbiome-Derived Lipopolysaccharide-Induced miRNA-30b-5p

Pogue¹,

Jaber

Sharfman

et al. 2022

Front. Neurol.

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Microbiome-derived Gram-negative bacterial lipopolysaccharide (LPS) has been shown by multiple laboratories to reside within Alzheimer's disease (AD)-affected neocortical and hippocampal neurons. LPS and other pro-inflammatory stressors strongly induce a defined set of NF-kB (p50/p65)-sensitive human microRNAs, including a brain-enriched Homo sapien microRNA-30b-5p (hsa-miRNA-30b-5p; miRNA-30b). Here we provide evidence that this neuropathology-associated miRNA, known to be upregulated in AD brain and LPS-stressed human neuronal-glial (HNG) cells in primary culture targets the neurofilament light (NF-L) chain mRNA 3'-untranslated region (3'-UTR), which is conducive to the post-transcriptional downregulation of NF-L expression observed within both AD and LPS-treated HNG cells. A deficiency of NF-L is associated with consequent atrophy of the neuronal cytoskeleton and the disruption of synaptic organization. Interestingly, miRNA-30b has previously been shown to be highly expressed in amyloid-beta (Aβ) peptide-treated animal and cell models, and Aβ peptides promote LPS entry into neurons. Increased miRNA-30b expression induces neuronal injury, neuron loss, neuronal inflammation, impairment of synaptic transmission, and synaptic failure in neurodegenerative disease and transgenic murine models. This gut microbiota-derived LPS-NF-kB-miRNA-30b-NF-L pathological signaling network: (i) underscores a positive pathological link between the LPS of gastrointestinal (GI)-tract microbes and the inflammatory neuropathology, disordered cytoskeleton, and disrupted synaptic signaling of the AD brain and stressed brain cells; and (ii) is the first example of a microbiome-derived neurotoxic glycolipid having significant detrimental miRNA-30b-mediated actions on the expression of NF-L, an abundant neuron-specific filament protein known to be important in the maintenance of neuronal cell shape, axonal caliber, and synaptic homeostasis.

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Microbiota and the gut-brain-axis: Implications for new therapeutic design in the CNS

Cited by 145 publications

References 74 publications

The Gut Microbiome–Brain Crosstalk in Neurodegenerative Diseases

The Gut Microbiome–Brain Crosstalk in Neurodegenerative Diseases

Obesity and gut–microbiota–brain axis: A narrative review

Downregulation of Neurofilament Light Chain Expression in Human Neuronal-Glial Cell Co-Cultures by a Microbiome-Derived Lipopolysaccharide-Induced miRNA-30b-5p

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