Gastrointestinal and brain barriers: unlocking gates of communication across the microbiota–gut–brain axis

Nature Reviews Gastroenterology & Hepatology, Год журнала: 2024, Номер 21(4), С. 222 - 247

Опубликована: Фев. 14, 2024

Crosstalk between gut and brain has long been appreciated in health disease, the microbiota is a key player communication these two distant organs. Yet, mechanisms through which influences development function of gut–brain axis remain largely unknown. Barriers present are specialized cellular interfaces that maintain strict homeostasis different compartments across this axis. These barriers include epithelial barrier, blood–brain barrier blood–cerebrospinal fluid barrier. ideally positioned to receive communicate microbial signals constituting gateway for gut–microbiota–brain communication. In Review, we focus on how modulation by can constitute an important channel Moreover, malfunction upon alterations composition could form basis various conditions, including often comorbid neurological gastrointestinal disorders. Thus, should unravelling molecular move from simplistic framing as 'leaky gut'. A mechanistic understanding barriers, especially during critical windows development, be aetiology The modulator This Review provides overview examines role disease.

Язык: Английский

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Feeding gut microbes to nourish the brain: unravelling the diet–microbiota–gut–brain axis

Nature Metabolism, Год журнала: 2024, Номер 6(8), С. 1454 - 1478

Опубликована: Авг. 22, 2024

Язык: Английский

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The gut microbiota-immune-brain axis: Therapeutic implications

Cell Reports Medicine, Год журнала: 2025, Номер unknown, С. 101982 - 101982

Опубликована: Март 1, 2025

Язык: Английский

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Melatonin Ameliorates Depressive‐Like Behaviors in Ovariectomized Mice by Improving Tryptophan Metabolism via Inhibition of Gut Microbe Alistipes Inops

Advanced Science, Год журнала: 2024, Номер unknown

Опубликована: Июль 8, 2024

Abstract Melatonin ( N ‐acetyl‐5‐methoxytryptamine) is reported to improve mood disorders in perimenopausal women and gut microbiome composition altered during menopausal period. The possible role of the treatment effect melatonin on depression remains unknown. Here, it shown that reverses microbiota dysbiosis depressive‐like behaviors ovariectomy (OVX) operated mice. This prevented by antibiotic cocktails (ABX) treatment. Transferring harvested from adolescent female mice OVX‐operated sufficient ameliorate behaviors. Conversely, transplantation or melatonin‐treated naïve recipient exhibits similar phenotypes donors. colonization Alistipes Inops , which abundant mice, confers with Further investigation indicates expansion induced OVX leads degradation intestinal tryptophan, destroys systemic tryptophan availability. supplementation restores metabolic suppressing growth ameliorates These results highlight previously unrecognized modulation OVX‐induced behavioral suggest application inhibit may serve as a potential strategy for preventing depressive symptoms.

Язык: Английский

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Lactobacillus reuteri or Lactobacillus rhamnosus GG intervention facilitates gut barrier function, decreases corticosterone and ameliorates social behavior in LPS-exposed offspring

Food Research International, Год журнала: 2024, Номер 197, С. 115212 - 115212

Опубликована: Окт. 20, 2024

Язык: Английский

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Fecal fermentation behaviors of Konjac glucomannan and its impacts on human gut microbiota

Food Chemistry X, Год журнала: 2024, Номер 23, С. 101610 - 101610

Опубликована: Июль 3, 2024

Dietary fiber targets the regulation of intestinal flora and thus affects host health, however, complex relationship between these factors lacks direct evidence. In this study, regulatory effects Konjac glucomannan (KGM) on key metabolites were examined by using

Язык: Английский

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Peripheral alcohol metabolism dictates ethanol consumption and drinking microstructure in mice

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 13, 2025

Abstract Background Ethanol metabolism is intimately linked with the physiological and behavioral aspects of ethanol consumption. mainly oxidized by alcohol dehydrogenase (ADH) to acetaldehyde further acetate via aldehyde dehydrogenases (ALDHs). Understanding how its metabolites work together initiate drive continued consumption crucial for identifying interventions use disorder (AUD). Therefore, goal our study was determine ADH1, which peripherally-expressed metabolizes >90% ingested ethanol, modulates metabolite distribution downstream behaviors. Methods in drinking-in-the-dark (DID) two-bottle choice (2BC) drinking paradigms, concentrations, lickometry were assessed after ADH1 inhibition and/or Adh1 -knockout ( KO) mice. Results We found that KO mice both sexes exhibited decreased preference compared wild-type (WT) DID 2BC. inhibitor fomepizole (4-MP) also significantly normal sweetened studies. Measurement revealed increased at 1h but not 15 min, peripheral slightly time points, ethanol-induced increases abolished administration controls. Similarly, accumulation as a function 2-fold higher or 4-MP treated then used this perturbation affects microstructure. consume most their first 30 min like WT display altered temporal shifts behaviors do form bout structures, resulting lower Conclusions Our demonstrates ADH1-mediated key determinant consumption, highlighting fundamental knowledge gap around

Язык: Английский

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The 16p11.2 microdeletion influences how early-life microbiota perturbations affect hippocampal development and behavior throughout the lifespan

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 25, 2025

Neurodevelopmental disorders result from interactions between genetic predisposition and environmental risk factors, with infancy being the most vulnerable period. We designed a longitudinal study to determine how short-term antibiotic exposure during early postnatal life impacts gut microbiome, neurodevelopment, behavior, whether these alterations were exacerbated by neurodevelopmental disorder-associated 16p11.2 microdeletion (16pDel) mutation. The cephalosporin antibiotic, cefdinir, broadly altered microbiome acutely, persistent reductions in several Lachnospiraceae genera despite overall recovery. These preceded long-term behavioral changes, including reduced juvenile sociability, compromised assessment, deficits associative learning. Remarkably, only cefdinir-exposed 16pDel mice had changes hippocampal stem cell proliferation, subsequent adolescent numbers, gene expression compared other groups, demonstrating that can modulate effects of early-life on neurodevelopment. may be mediated gastrointestinal disturbances, as males increased intestinal permeability shifted metabolite profiles arginine biosynthesis glycerophospholipid metabolism. Taken together, this highlights microbial affect behavior reveals influences antibiotic-induced development. Further, insights identify metabolic mechanisms potential targets for intervention raise concerns regarding use infancy.

Язык: Английский

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Exploring the Association Between Human Blood Metabolites and Autism Spectrum Disorder Risk: A Bidirectional Mendelian Randomization Study

Health Science Reports, Год журнала: 2025, Номер 8(3)

Опубликована: Март 1, 2025

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with poorly understood etiology. Recent studies have suggested that metabolic dysregulation might be linked to the development of ASD; however, causal relationships remain unclear. This study aimed investigate association between these factors using two-sample Mendelian randomization (TSMR). We conducted TSMR analysis assess relationship blood metabolites and ASD summarized GWAS data. The metabolite dataset from Canadian Longitudinal Study Aging included 1091 309 ratios 7824 European individuals. data Psychiatric Genomics Consortium comprised 18,381 cases 27,969 controls. Blood were set as exposures outcome. primarily used inverse-variance weighted method, supplemented by MR-Egger, median, simple mode, mode methods. also sensitivity analyses confirm robustness. Replication, confounding, reserve performed verify causation. Additionally, pathway network pharmacology explore potential mechanisms. identified 55 known including 13 10 unknown associated ASD. our pathways, among which tryptophan metabolism was most notable (p = 0.0388). Gene Ontology functional Kyoto Encyclopedia Genes Genomes highlighted crucial such cellular glucuronidation, glucuronosyltransferase activity, bile secretion, significance apical part cell. Our findings indicate dodecenedioate, methionine sulfone, cysteine alanine ratio proline glutamate an impact on These results enhance understanding pathways involved in could lead new avenues for intervention prevention. Further research needed mechanisms underlying associations different populations.

Язык: Английский

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Peripheral alcohol metabolism dictates ethanol consumption and drinking microstructure in mice

Alcohol Clinical and Experimental Research, Год журнала: 2025, Номер unknown

Опубликована: Март 21, 2025

Ethanol metabolism is intimately linked with the physiological and behavioral aspects of ethanol consumption. mainly oxidized by alcohol dehydrogenase (ADH) to acetaldehyde further acetate via aldehyde dehydrogenases (ALDHs). Understanding how its metabolites work together initiate drive continued consumption crucial for identifying interventions use disorder (AUD). Therefore, goal our study was determine ADH1, which peripherally expressed metabolizes >90% ingested ethanol, modulates metabolite distribution downstream behaviors. in drinking-in-the-dark (DID) two-bottle choice (2BC) drinking paradigms, concentrations, lickometry were assessed after ADH1 inhibition and/or Adh1-knockout (Adh1 KO) mice. We found that Adh1 KO mice both sexes exhibited decreased preference compared wild-type (WT) DID 2BC. inhibitor fomepizole (4-MP) also significantly normal sweetened studies. Measurement revealed increased at 1 h but not 15 min, peripheral slightly timepoints, ethanol-induced increases abolished administration controls. Similarly, accumulation as a function 2-fold higher or 4-MP-treated then used this perturbation affects microstructure. consume most their first 30 like WT mice, display altered temporal shifts behaviors do form bout structures, resulting lower Our demonstrates ADH1-mediated key determinant consumption, highlighting fundamental knowledge gap regarding

Язык: Английский

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