The enteric nervous system

Physiological Reviews, Journal Year: 2022, Volume and Issue: 103(2), P. 1487 - 1564

Published: Dec. 15, 2022

Of all the organ systems in body, gastrointestinal tract is most complicated terms of numbers structures involved, each with different functions, and types signaling molecules utilized. The digestion food absorption nutrients, electrolytes, water occurs a hostile luminal environment that contains large diverse microbiota. At core regulatory control digestive defensive functions enteric nervous system (ENS), complex neurons glia gut wall. In this review, we discuss 1) intrinsic neural involved 2) how ENS interacts immune system, microbiota, epithelium to maintain mucosal defense barrier function. We highlight developments have revolutionized our understanding physiology pathophysiology control. These include new molecular architecture ENS, organization function motor circuits, roles glia. explore transduction stimuli by enteroendocrine cells, regulation intestinal glia, local role microbiota regulating structure ENS. Multifunctional work together glial macrophages, interstitial cells integrating an array signals initiate outputs are precisely regulated space time homeostasis.

Language: Английский

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Mechanisms of Blood–Brain Barrier Protection by Microbiota-Derived Short-Chain Fatty Acids

Cells, Journal Year: 2023, Volume and Issue: 12(4), P. 657 - 657

Published: Feb. 18, 2023

Impairment of the blood-brain barrier (BBB) integrity is implicated in numerous neurological disorders associated with neuroinflammation, neurodegeneration and aging. It now evident that short-chain fatty acids (SCFAs), mainly acetate, butyrate propionate, produced by anaerobic bacterial fermentation dietary fiber intestine, have a key role communication between gastrointestinal tract nervous system are critically important for preservation BBB under different pathological conditions. The effect SCFAs on improvement compromised based decrease paracellular permeability via restoration junctional complex proteins affecting their transcription, intercellular localization or proteolytic degradation. This review focused revealed putative underlying mechanisms direct indirect effects function brain endothelial cells. We consider G-protein-coupled receptor-mediated SCFAs, SCFAs-stimulated acetylation histone non-histone inhibition deacetylases, crosstalk these signaling pathways transcriptional factors NF-κB Nrf2 as mainstream SCFA's integrity.

Language: Английский

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Role of the Gut Microbiota and Its Metabolites in Tumorigenesis or Development of Colorectal Cancer

Advanced Science, Journal Year: 2023, Volume and Issue: 10(23)

Published: June 1, 2023

Colorectal cancer (CRC) is the most common of digestive system with high mortality and morbidity rates. Gut microbiota found in intestines, especially colorectum, has structured crosstalk interactions host that affect several physiological processes. The gut include CRC-promoting bacterial species, such as Fusobacterium nucleatum, Escherichia coli, Bacteroides fragilis, CRC-protecting Clostridium butyricum, Streptococcus thermophilus, Lacticaseibacillus paracasei, which along other microorganisms, viruses fungi, play critical roles development CRC. Different features are identified patients early-onset CRC, combined different patterns between fecal intratumoral microbiota. may be beneficial diagnosis treatment CRC; some bacteria serve biomarkers while others regulators chemotherapy immunotherapy. Furthermore, metabolites produced by essential CRC cells. Harmful primary bile acids short-chain fatty acids, whereas others, including ursodeoxycholic acid butyrate, impede tumor progression. This review focuses on its metabolites, their potential development, diagnosis,

Language: Английский

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Gut-derived β-amyloid: Likely a centerpiece of the gut–brain axis contributing to Alzheimer’s pathogenesis

Gut Microbes, Journal Year: 2023, Volume and Issue: 15(1)

Published: Jan. 22, 2023

Peripheral β-amyloid (Aβ), including those contained in the gut, may contribute to formation of Aβ plaques brain, and gut microbiota appears exert an impact on Alzheimer's disease (AD) via gut-brain axis, although detailed mechanisms are not clearly defined. The current study focused uncovering potential interactions among gut-derived aging, microbiota, AD pathogenesis. To achieve this goal, expression levels several key proteins involved metabolism were initially assessed mouse with results confirmed human tissue. demonstrated that a high level was detected throughout both mice human, Aβ42 increased age wild type mutant amyloid precursor protein/presenilin 1 (APP/PS1) mice. Next, microbiome characterized by 16S rRNA sequencing, we found altered significantly aged APP/PS1 fecal transplantation (FMT) BACE1 levels. Intra-intestinal injection isotope or fluorescence labeled combined vagotomy also performed investigate transmission from brain. data showed that, mice, transported brain mainly blood rather than vagal nerve. Furthermore, FMT induced neuroinflammation, phenotype mimics early pathology. Taken together, suggests is likely critical source can further upregulate production, thereby potentially contributing

Language: Английский

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The microbiome stabilizes circadian rhythms in the gut

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(5)

Published: Jan. 23, 2023

The gut microbiome is well known to impact host physiology and health. Given widespread control of by circadian clocks, we asked how the interacts with rhythms in Drosophila gut. did not cycle flies fed ad libitum, timed feeding (TF) drove limited cycling only clockless per01 flies. However, TF loss influenced composition transcriptome, independently together. Moreover, both interventions increased amplitude rhythmic gene expression, effects at least partly due changes histone acetylation. Contrary expectations, rendered animals more sensitive stress. Analysis function revealed that germ-free reset rapidly shifts light:dark cycle. We propose stabilizes prevent rapid fluctuations changing environmental conditions.

Language: Английский

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Psychological stress-induced microbial metabolite indole-3-acetate disrupts intestinal cell lineage commitment

Cell Metabolism, Journal Year: 2024, Volume and Issue: 36(3), P. 466 - 483.e7

Published: Jan. 23, 2024

Language: Английский

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Gut dysbiosis induces the development of depression-like behavior through abnormal synapse pruning in microglia-mediated by complement C3

Microbiome, Journal Year: 2024, Volume and Issue: 12(1)

Published: Feb. 20, 2024

Abstract Background Remodeling eubiosis of the gut microenvironment may contribute to preventing occurrence and development depression. Mounting experimental evidence has shown that complement C3 signaling is associated with pathogenesis depression, disruption microbiota be an underlying cause system activation. However, mechanism by which participates in gut-brain crosstalk depression remains unknown. Results In present study, we found chronic unpredictable mild stress (CUMS)-induced mice exhibited obvious depression-like behavior as well cognitive impairment, was significant dysbiosis, especially enrichment Proteobacteria elevation microbiota-derived lipopolysaccharides (LPS). addition, peripheral central activation C3/CR3-mediated aberrant synaptic pruning microglia have also been observed. Transplantation from CUMS-induced model into specific pathogen-free germ-free induced concomitant impairment recipient mice, accompanied increased C3/CR3 pathway prefrontal cortex abnormalities microglia-mediated pruning. Conversely, antidepressants fecal transplantation antidepressant-treated donors improved behaviors restored microbiome disturbances depressed mice. Concurrently, inhibition pathway, amelioration abnormal pruning, expression synapsin postsynaptic density protein 95 were Collectively, our results revealed dysbiosis induces through synapse C3, key targeting microbes treat Conclusions Our findings provide novel insights involvement chemotactic

Language: Английский

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A chemogenetic screen reveals that Trpv1-expressing neurons control regulatory T cells in the gut

Science, Journal Year: 2024, Volume and Issue: 385(6708)

Published: Aug. 1, 2024

Neuroimmune cross-talk participates in intestinal tissue homeostasis and host defense. However, the matrix of interactions between arrays molecularly defined neuron subsets immunocyte lineages remains unclear. We used a chemogenetic approach to activate eight distinct neuronal subsets, assessing effects by deep immunophenotyping, microbiome profiling, transcriptomics organs. Distinct immune perturbations followed activation: Nitrergic neurons regulated T helper 17 (T

Language: Английский

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Neuroimmune Interactions in the Intestine

Annual Review of Immunology, Journal Year: 2024, Volume and Issue: 42(1), P. 489 - 519

Published: June 28, 2024

Recent advances have contributed to a mechanistic understanding of neuroimmune interactions in the intestine and revealed an essential role this cross talk for gut homeostasis modulation inflammatory infectious intestinal diseases. In review, we describe innervation by intrinsic extrinsic neurons then focus on bidirectional communication between immune cells. First, highlight contribution neuronal subtypes development colitis discuss different epithelial cell types that are regulated via release neuropeptides neurotransmitters. Next, review inflammation visceral hypersensitivity summarize how mediators induce peripheral central sensitization gut-innervating sensory neurons. Finally, outline importance cells microbiota survival function populations at during bacterial helminth infection.

Language: Английский

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Oxidative and Excitatory Neurotoxic Stresses in CRISPR/Cas9-Induced Kynurenine Aminotransferase Knockout Mice: A Novel Model for Despair-Based Depression and Post-Traumatic Stress Disorder

Frontiers in Bioscience-Landmark, Journal Year: 2025, Volume and Issue: 30(1)

Published: Jan. 20, 2025

Backgrounds: Memory and emotion are especially vulnerable to psychiatric disorders such as post-traumatic stress disorder (PTSD), which is linked disruptions in serotonin (5-HT) metabolism. Over 90% of the 5-HT precursor tryptophan (Trp) metabolized via Trp-kynurenine (KYN) metabolic pathway, generates a variety bioactive molecules. Dysregulation KYN metabolism, particularly low levels kynurenic acid (KYNA), appears be neuropsychiatric disorders. The majority KYNA produced by aadat (kat2) gene-encoded mitochondrial kynurenine aminotransferase (KAT) isotype 2. Little known about consequences deleting enzyme gene. Methods: In CRISPR/Cas9-induced knockout (kat2-/-) mice, we examined effects on emotion, memory, motor function, Trp its metabolite levels, activities plasma urine 8-week-old males compared wild-type mice. Results: Transgenic mice showed more depressive-like behaviors forced swim test, but not tail suspension, anxiety, or memory tests. They also had fewer center field corner entries, shorter walking distances, jumping counts open test. Plasma generally consistent with those urine: antioxidant KYNs, 5-hydroxyindoleacetic acid, indole-3-acetic were lower; KATs, kynureninase, monoamine oxidase/aldehyde dehydrogenase lower, 3-monooxygenase was higher; oxidative excitotoxicity indices higher. displayed depression-like behavior learned helplessness model, emotional indifference, deficits, coupled decrease KYNA, shift metabolism toward KYN-3-hydroxykynurenine partial gut microbial Trp-indole pathway metabolite. Conclusions: This first evidence that gene induces uniquely experiences despair, appear associated excitatory neurotoxic stresses. may lead development double-hit preclinical model despair-based depression, better understanding these complex conditions, effective therapeutic strategies elucidating relationship between PTSD pathogenesis.

Language: Английский

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