Activation of aryl hydrocarbon receptor (AhR) in Alzheimer’s disease: role of tryptophan metabolites generated by gut host-microbiota DOI Creative Commons
Antero Salminen

Journal of Molecular Medicine, Journal Year: 2023, Volume and Issue: 101(3), P. 201 - 222

Published: Feb. 9, 2023

Abstract Gut microbiota in interaction with intestinal host tissues influences many brain functions and microbial dysbiosis has been linked disorders, such as neuropsychiatric conditions Alzheimer’s disease (AD). l -tryptophan metabolites short-chained fatty acids (SCFA) are major messengers the microbiota-brain axis. Aryl hydrocarbon receptors (AhR) main targets of tryptophan microvessels which possess an enriched expression AhR protein. The Ah receptor is evolutionarily conserved, ligand-activated transcription factor not only a sensor xenobiotic toxins but also pleiotropic regulator both developmental processes age-related tissue degeneration. Major microbiota-produced involve indole derivatives, e.g., 3-pyruvic acid, 3-acetaldehyde, indoxyl sulfate, whereas indoleamine 2,3-dioxygenases (IDO/TDO) intestine cells activate kynurenine (KYN) pathway generating KYN metabolites, activators signaling. Chronic kidney (CKD) increases serum level sulfate promotes AD pathogenesis, it disrupts integrity blood–brain barrier (BBB) impairs cognitive functions. Activation signaling disturbs vascular homeostasis brain; (i) controls blood flow via renin-angiotensin system, (ii) inactivates endothelial nitric oxide synthase (eNOS), thus impairing NO production vasodilatation, (iii) induces oxidative stress, stimulates inflammation, cellular senescence, enhances calcification walls. All these alterations evident cerebral amyloid angiopathy (CAA) pathology. Moreover, can disturb circadian regulation probably affect glymphatic flow. It seems plausible that gut BBB activation aggravates Key messages Dysbiosis associated dementia disease. Tryptophan from host-microbiota to brain. aryl protein blood-brain barrier. inflammation pathology

Language: Английский

Microbiota in health and diseases DOI Creative Commons
Kejun Hou,

Zhuo‐Xun Wu,

Xuan-Yu Chen

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: April 23, 2022

Abstract The role of microbiota in health and diseases is being highlighted by numerous studies since its discovery. Depending on the localized regions, can be classified into gut, oral, respiratory, skin microbiota. microbial communities are symbiosis with host, contributing to homeostasis regulating immune function. However, dysbiosis lead dysregulation bodily functions including cardiovascular (CVDs), cancers, respiratory diseases, etc. In this review, we discuss current knowledge how links host or pathogenesis. We first summarize research healthy conditions, gut-brain axis, colonization resistance modulation. Then, highlight pathogenesis disease development progression, primarily associated community composition, modulation response, induction chronic inflammation. Finally, introduce clinical approaches that utilize for treatment, such as fecal transplantation.

Language: Английский

Citations

1603
Obesity, kidney dysfunction and hypertension: mechanistic links DOI
John E. Hall, Jussara M. do Carmo, Alexandre A. da Silva

et al.

Nature Reviews Nephrology, Journal Year: 2019, Volume and Issue: 15(6), P. 367 - 385

Published: April 23, 2019

Language: Английский

Citations

494
RETRACTED ARTICLE: Role of the gut microbiome in chronic diseases: a narrative review DOI Creative Commons
Amrita Vijay, Ana M. Valdes

European Journal of Clinical Nutrition, Journal Year: 2021, Volume and Issue: 76(4), P. 489 - 501

Published: Sept. 28, 2021

Language: Английский

Citations

329
Role of Hyperinsulinemia and Insulin Resistance in Hypertension: Metabolic Syndrome Revisited DOI Creative Commons
Alexandre A. da Silva, Jussara M. do Carmo, Xuan Li

et al.

Canadian Journal of Cardiology, Journal Year: 2020, Volume and Issue: 36(5), P. 671 - 682

Published: Feb. 12, 2020

Citations

263
Gut Microbial Metabolites of Aromatic Amino Acids as Signals in Host–Microbe Interplay DOI
Yali Liu,

Yuanlong Hou,

Guangji Wang

et al.

Trends in Endocrinology and Metabolism, Journal Year: 2020, Volume and Issue: 31(11), P. 818 - 834

Published: April 10, 2020

Language: Английский

Citations

258
Butyrate producers, “The Sentinel of Gut”: Their intestinal significance with and beyond butyrate, and prospective use as microbial therapeutics DOI Creative Commons
Vineet Singh, GyuDae Lee, HyunWoo Son

et al.

Frontiers in Microbiology, Journal Year: 2023, Volume and Issue: 13

Published: Jan. 12, 2023

Gut-microbial butyrate is a short-chain fatty acid (SCFA) of significant physiological importance than the other major SCFAs (acetate and propionate). Most producers belong to Clostridium cluster phylum Firmicutes, such as Faecalibacterium , Roseburia Eubacterium Anaerostipes Coprococcus Subdoligranulum Anaerobutyricum . They metabolize carbohydrates via butyryl-CoA: acetate CoA-transferase pathway kinase terminal enzymes produce most butyrate. Although, in minor fractions, amino acids can also be utilized generate glutamate lysine pathways. Butyrogenic microbes play vital role various gut-associated metabolisms. Butyrate used by colonocytes energy, stabilizes hypoxia-inducible factor maintain anaerobic environment gut, maintains gut barrier integrity regulating Claudin-1 synaptopodin expression, limits pro-inflammatory cytokines (IL-6, IL-12), inhibits oncogenic pathways (Akt/ERK, Wnt, TGF-β signaling). Colonic shape microbial community secreting anti-microbial substances, cathelicidins, reuterin, β-defensin-1, homeostasis releasing anti-inflammatory molecules, IgA, vitamin B, molecules. Additionally, producers, anti-carcinogenic metabolites, shikimic precursor conjugated linoleic acid. In this review, we summarized significance butyrate, critically examined relevance contextualized their therapeutics.

Language: Английский

Citations

258
Dietary Fiber Protects against Diabetic Nephropathy through Short-Chain Fatty Acid–Mediated Activation of G Protein–Coupled Receptors GPR43 and GPR109A DOI Open Access
Yan Jun Li, Xiaochen Chen, Tony Kwan

et al.

Journal of the American Society of Nephrology, Journal Year: 2020, Volume and Issue: 31(6), P. 1267 - 1281

Published: May 1, 2020

Significance Statement The gut microbiota and its metabolites, in particular short-chain fatty acids derived from microbes’ fermentation of fiber, are emerging therapeutic targets for systemic inflammatory metabolic diseases, including diabetic nephropathy. authors report that high-fiber diets or supplementation with (acetate, butyrate, propionate) afforded protection against development kidney disease mice. Dietary fiber restored microbial ecology, corrected “dysbiotic” changes, increased production acids. Mice deficient the metabolite-sensing G protein–coupled receptors GPR43 GPR109A were not protected by acids, suggesting was mediated downstream binding to these receptors. Tapping into potential through diet may offer a novel approach address Background Studies have reported changes microbiota, such as depletion bacteria produce (SCFAs) CKD diabetes. is associated decreased inflammation mortality CKD, SCFAs been proposed mediate this effect. Methods To explore dietary fiber’s effect on experimental nephropathy, we used streptozotocin induce diabetes wild-type C57BL/6 knockout mice lacking genes encoding GPR109A. Diabetic randomized high-fiber, normal chow, zero-fiber diets, drinking water. We proton nuclear magnetic resonance spectroscopy profiling 16S ribosomal RNA sequencing assess microbiome. Results fed significantly less likely develop exhibiting albuminuria, glomerular hypertrophy, podocyte injury, interstitial fibrosis compared controls chow diet. Fiber beneficially reshaped ecology improved dysbiosis, promoting expansion SCFA-producing genera Prevotella Bifidobacterium , which fecal SCFA concentrations. reduced expression cytokines, chemokines, fibrosis-promoting proteins kidneys. SCFA-treated but absence In vitro modulated renal tubular cells podocytes under hyperglycemic conditions. Conclusions protects nephropathy modulation enrichment bacteria, production. critical SCFA-mediated condition. Interventions targeting warrant further investigation renoprotective therapy

Language: Английский

Citations

257
Short-chain fatty acids in diseases DOI Creative Commons
Dan Zhang,

Yong‐Ping Jian,

Yuning Zhang

et al.

Cell Communication and Signaling, Journal Year: 2023, Volume and Issue: 21(1)

Published: Aug. 18, 2023

Abstract Short-chain fatty acids (SCFAs) are the main metabolites produced by bacterial fermentation of dietary fibre in gastrointestinal tract. The absorption SCFAs is mediated substrate transporters, such as monocarboxylate transporter 1 and sodium-coupled 1, which promote cellular metabolism. An increasing number studies have implicated microorganisms crucial executors diet-based microbial influence on host. important fuels for intestinal epithelial cells (IECs) represent a major carbon flux from diet, that decomposed gut microbiota. play vital role multiple molecular biological processes, promoting secretion glucagon-like peptide-1 IECs to inhibit elevation blood glucose, expression G protein-coupled receptors GPR41 GPR43, inhibiting histone deacetylases, participate regulation proliferation, differentiation, function IECs. affect motility, barrier function, host Furthermore, regulatory roles local, intermediate, peripheral metabolisms. Acetate, propionate, butyrate SCFAs, they involved immunity, apoptosis, inflammation, lipid Herein, we review diverse functional this class reflect their ability intestine, metabolic, other diseases.

Language: Английский

Citations

208
Nitric oxide signalling in kidney regulation and cardiometabolic health DOI Open Access
Mattias Carlström

Nature Reviews Nephrology, Journal Year: 2021, Volume and Issue: 17(9), P. 575 - 590

Published: June 1, 2021

Language: Английский

Citations

185
Microbiome–metabolomics reveals gut microbiota associated with glycine-conjugated metabolites and polyamine metabolism in chronic kidney disease DOI
Ya‐Long Feng, Gang Cao, Dan‐Qian Chen

et al.

Cellular and Molecular Life Sciences, Journal Year: 2019, Volume and Issue: 76(24), P. 4961 - 4978

Published: May 30, 2019

Language: Английский

Citations

175