Браузер не даёт сохранять данные (например, приватный режим): закладки пропадут после закрытия вкладки.
Поиск статей PubMed
Ключевые слова, автор, журнал, годы — результаты из PubMed, аннотации с переводом на русский, закладки в браузере.
Найдено: 3 210
Страница 232 из 321-
Huaganjian decoction ameliorates metabolic dysfunction-associated steatotic liver disease through liver-gut crosstalk.
ETHNOPHARMACOLOGICAL RELEVANCE: Huaganjian decoction (HGJD), a traditional Chinese medicine formula, has been widely acknowledged for its remarkable effects in soothing the liver, relieving depression, and alleviating hepatic inflammation. Clinically, it has been extensively applied in the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD). Nevertheless, the underlying mechanisms of its therapeutic actions remain incompletely understood, thus necessitating further in-depth investigations. AIM OF THE STUDY: This study aimed to comprehensively investigate the mechanisms through which HGJD modulates MASLD via liver-gut crosstalk. MATERIAL AND METHODS: In this research, a MASLD rat model was successfully established using a high-fat diet, and the therapeutic efficacy of HGJD was assessed through various indices. Subsequently, non-targeted liver metabolomics was employed to identify the relevant metabolic pathways in the liver. Concurrently, 16S rRNA sequencing and short-chain fatty acids (SCFAs) quantification analysis were used to explore differential gut microbiota. Finally, bile acid (BA) target metabolomics, immunohistochemical staining, Western blotting, qPCR, and ELISA were performed on liver and gut tissues to further validate the potential mechanisms of HGJD by which HGJD exerts its effects against MASLD. RESULTS: This study demonstrated that HGJD effectively mitigated the liver fat accumulation and improved liver function in MASLD models. Hepatic metabolomics analysis indicated that HGJD ameliorated MASLD primarily by modulating the biosynthesis of unsaturated fatty acids and primary BA. Results from 16S rRNA sequencing, SCFAs analysis and BA-targeted metabolomics revealed that HGJD regulated gut microbiota, increased intestinal SCFAs, and regulated BA homeostasis in both the gut and liver. Further investigations using immunohistochemical staining, Western blotting, qPCR, and ELISA elucidated that FXR/FGF15/SHP2/CYP7A1 pathway is implicated in the mechanism by which HGJD modulates liver-gut crosstalk. Additionally, HGJD inhibited the expression of lipogenic proteins (AMPK, SREBP-1c, FAS and P-ACC), activated lipid oxidation proteins (PPARα, CTP1B), strengthened the intestinal barrier, and alleviated liver inflammation. CONCLUSIONS: HGJD could ameliorate MASLD by regulating liver-gut crosstalk, primarily through modulating gut microbiota-dependent BA biosynthesis, FXR/FGF15/SHP2/CYP7A1 pathway, fatty acid biosynthesis and intestinal barrier protection.
-
Prebiotic Consumption Alters Microbiota but Not Biological Markers of Stress and Inflammation or Mental Health Symptoms in Healthy Adults: A Randomized, Controlled, Crossover Trial.
BACKGROUND: Chronic stress contributes to systemic inflammation and diminished mental health. Although animal work suggests strong links with the microbiota-gut-brain axis, clinical trials investigating the effectiveness of prebiotics in improving mental health and reducing inflammation are lacking. OBJECTIVES: We aimed to determine fructooligosaccharide (FOS) and galactooligosaccharide (GOS) effects on biological markers of stress and inflammation and mental health symptoms in adults. Secondary outcomes included fecal microbiota and metabolites, digestive function, emotion, and sleep. METHODS: Twenty-four healthy adults (25-45 y; 14 females, 10 males; BMI, 29.3 ± 1.8 kg/m2) from central Illinois participated in a 2-period, randomized, controlled, single-blinded crossover trial. Interventions included the prebiotic (PRE) treatment (237 mL/d Lactaid low-fat 1% milk, 5 g/d FOS, 5 g/d GOS) and control (CON) (237 mL/d Lactaid), which were consumed in counterbalanced order for 4 wk each, separated by ≥4-wk washout. Inflammatory markers were measured in blood plasma (>10-h fast) and cortisol in urine. The Depression Anxiety Stress Scales-42 assessed mental health symptoms. Fecal samples were collected for 16S rRNA gene (V4 region) sequencing and analysis. Emotion was measured by rating images from a computer task. Sleep was assessed using 7-d records and accelerometers. Change scores were analyzed using linear mixed models with treatment and baseline covariate as fixed effects and participant ID as the random effect. RESULTS: There were no differences in change scores between PRE and CON treatments on biological markers of stress and inflammation or mental health. PRE increased change in percent sequences (q = 0.01) of Actinobacteriota (CON: 0.46 ± 0.70%; PRE: 5.40 ± 1.67%) and Bifidobacterium (CON: -1.72 ± 0.43%; PRE: 4.92 ± 1.53%). There were also no differences in change scores between treatments for microbial metabolites, digestive function, emotion, or sleep quality. CONCLUSIONS: FOS+GOS did not affect biological markers of stress and inflammation or mental health symptoms in healthy adults; however, it increased Bifidobacterium. CLINICAL TRIAL REGISTRY: NCT04551937, www. CLINICALTRIALS: gov.
-
Traditional Chinese medicine formulation Chang-Kang-Fang restores gut-brain homeostasis in IBS-D via the Lactobacillus johnsonii-indole-3-lactic acid-aryl hydrocarbon receptor/interleukin-22 axis.
BACKGROUND: Gut dysbiosis contributes to irritable bowel syndrome (IBS) by disrupting intestinal barrier functions and promoting inflammation. Chang‑kang‑fang (CKF), a Chinese herbal formula proven effective for diarrhea‑predominant IBS (IBS‑D) in a phase III trial, is thought to modulate the gut microbiota, yet the underlying mechanism remains unclear. PURPOSE: To elucidate how CKF ameliorates IBS‑D by modulating the gut microbiota. METHODS: IBS‑D was induced by restraint stress, tail pinch, and senna gavage. Intestinal function, inflammation, and behavior were evaluated. Gut microbiota and metabolites were profiled via 16S rRNA sequencing and metabolomics. FMT confirmed the causal involvement of the microbiota. The key microbe and metabolite were validated in vivo. Mechanistic analyses evaluated intestinal barrier integrity, systemic inflammation, hippocampal blood‑brain barrier (BBB) function, neuroinflammation, and synaptic plasticity. RESULTS: CKF alleviated diarrhea, visceral hypersensitivity, inflammation, barrier dysfunction, and anxiety‑ and depression‑like behaviors. These benefits were associated with gut microbiota remodeling, featuring enrichment of Lactobacillus johnsonii and enhanced tryptophan metabolism. FMT confirmed that this microbial remodeling mediates the therapeutic effects of CKF. Supplementation with L. johnsonii or its metabolite indole‑3‑lactic acid (ILA) largely recapitulated these gut-brain benefits via AhR/IL‑22 activation. Mechanistically, CKF‑induced L. johnsonii enrichment activated the ILA-AhR-IL‑22 pathway, which enhanced intestinal and BBB integrity, thereby attenuating systemic and neuroinflammation, and restoring hippocampal synaptic plasticity. CONCLUSION: This study positions CKF as a microbiota‑modulating therapy for IBS‑D that restores gut‑brain homeostasis via the L. johnsonii-ILA-AhR-IL‑22 axis, highlighting L. johnsonii and ILA as potential therapeutics for IBS and its comorbidities.
-
Beneficial effects of GABA-producing potential probiotic Limosilactobacillus fermentum L18 of human origin on intestinal permeability and human gut microbiota.
BACKGROUND: Gamma-aminobutyric acid (GABA) is a non-protein amino acid with neuroinhibitory, antidiabetic, and antihypertensive properties and is used as a drug for treating anxiety and depression. Some strains of lactobacilli are known to produce GABA and strengthen the gut barrier function which play an important role in ameliorating the effects caused by the pathogen on the gut barrier. The probiotic bacteria are also known to modulate the human fecal microbiota, however, the role of GABA-producing strains on the gut epithelium permeability and gut microbiota is not known. RESULTS: In this study, we report the production of high levels of GABA by potential probiotic bacterium Limosilactobacillus fermentum L18 for the first time. The kinetics of the production of GABA by L18 showed that the maximum production of GABA in the culture supernatant (CS) occurred at 24 h, whereas in fermented milk it took 48 h of fermentation. The effect of L18 on the restoration of lipopolysaccharide (LPS)-disrupted intestinal cell membrane permeability in Caco-2 monolayers showed that it significantly restored the transepithelial electrical resistance (TEER) values, by significantly increasing the levels of junction proteins, occludin and E-cadherin in L18 and LPS-treated Caco-2 cells as compared to only LPS-treated cells. The effect of GABA-secreting L18 on the metataxonome of human stool samples from healthy individuals was investigated by a batch fermentor that mimics the conditions of the human colon. Although, no differences were observed in the α and β diversities of the L18-treated and untreated samples at 24 h, the relative abundances of bacterial families Lactobacillaceae and Bifidobacteriaceae increased in the L18-treated group, but both decreased in the untreated groups. On the other hand, the relative abundance of Enterobacteriaceae decreased in the L18 samples but it increased in the untreated samples. CONCLUSION: These results indicate that Li. fermentum L18 is a promising GABA-secreting strain that strengthens the gut epithelial barrier by increasing junction protein concentrations and positively modulating the gut microbiota. It has the potential to be used as a psychobiotic or for the production of functional foods for the management of anxiety-related illnesses.
-
The dentate gyrus in depression.
Extensive preclinical research has been conducted in recent years to reveal the cell types, neuronal circuits and molecular and morphological changes implicated in the function of the dentate gyrus in depression. This was profoundly facilitated by the emergence of methods such as gene targeting, neuronal cell activity manipulation, including optogenetics and chemogenetics, and the development of novel RNA sequencing technology and powerful MRI imagers that were used in clinical studies. These advancements provided researchers with the precise skills needed to evaluate the changes in the dentate gyrus structure and cell function in rodent models as well as in brains of depressed and medicated patients. Here, we review these latest findings and discuss the existing gaps in our knowledge of the role of the dentate gyrus in depression and in mediating the response to antidepressant therapies.
-
Determination and Application of Nineteen Monoamines in the Gut Microbiota Targeting Phenylalanine, Tryptophan, and Glutamic Acid Metabolic Pathways.
It has been reported that monoamine neurotransmitters can be produced by gut microbiota, and that several related metabolites of amino acids in these pathways are associated with nervous system (NVS) diseases. Herein, we focused on three pathways, namely, phenylalanine (Phe), tryptophan (Trp), and glutamic acid (Glu), and established an underivatized liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of nineteen monoamine neurotransmitters and related metabolites in the gut microbiota. The neurotransmitters and related metabolites included Phe, tyrosine (Tyr), l-dopa (Dopa), dopamine (DA), 3-methoxytyramine, Trp, hydroxytryptophan, 5-hydroxytryptamine (5-HT), 5-hydroxyindole-3-acetic acid (5-HIAA), kynurenine (KN), kynurenic acid (KYNA), melatonin, tryptamine (TA), indole-3-lactic acid (ILA), indole-3-acetic acid (IAA), indolyl-3-propionic acid (IPA), Glu, gamma-aminobutyric acid (GABA), and acetylcholine (Ach). A fluoro-phenyl bonded column was used for separation, and the mobile phase consisted of methanol:acetonitrile (1:1) and water, with 0.2% formic acid in both phases. The compounds exhibited symmetric peak shapes and sufficient sensitivity under a total analysis time of 8.5 min. The method was fully validated with acceptable linearity, accuracy, precision, matrix effect, extraction recovery, and stability. The results showed that neurotransmitters, such as Dopa, DA, 5-HT, GABA, and Ach, were present in the gut microbiota. The metabolic pathway of Trp was disordered under depression, with lower levels of 5-HT, 5-HIAA, KN, KYNA, TA, ILA, IAA, IPA, and Glu, and a higher ratio of KYNA/KN. In addition, some first-line NVS drugs, such as sertraline, imipramine, and chlorpromazine, showed regulatory potential on these pathways in the gut microbiota.
-
Involvement of mucosal flora and enterochromaffin cells of the caecum and descending colon in diarrhoea-predominant irritable bowel syndrome.
BACKGROUND: Accumulating evidence supports the pivotal role of intestinal flora in irritable bowel syndrome (IBS). Serotonin synthesis by enterochromaffin (EC) cells is influenced by the gut microbiota and has been reported to have an interaction with IBS. The comparison between the microbiota of the caecal and colonic mucosa in IBS has rarely been studied. The aim of this study was to investigate the relationship between the gut microbiota, EC cells in caecum and descending colon, and diarrhoea-predominant IBS (IBS-D) symptoms. RESULTS: A total of 22 IBS-D patients and 22 healthy controls (HCs) were enrolled in our study. Hamilton anxiety (HAM-A) and Hamilton depression (HAM-D) grades increased significantly in IBS-D patients. In addition, the frequency of defecation in IBS-D patients was higher than that in HCs. Among the preponderant bacterial genera, the relative abundance of the Ruminococcus_torques_ group increased in IBS-D patients in caecum samples while Raoultella and Fusobacterium were less abundant. In the descending colon, the abundance of the Ruminococcus_torques_group and Dorea increased in IBS-D patients and Fusobacterium decreased. No difference was observed between the descending colon and caecum in regards to the mucosal-associated microbiota. The number of EC cells in the caecum of IBS-D patients was higher than in HCs and the expression of TPH1 was higher in IBS-D patients both in the caecum and in the descending colon both at the mRNA and protein level. Correlation analysis showed that the Ruminococcus_torques_group was positively associated with HAM-A, HAM-D, EC cell number, IBS-SSS, degree of abdominal pain, frequency of abdominal pain and frequency of defecation. The abundance of Dorea was positively associated with EC cell number, IBS-SSS, HAM-A, HAM-D and frequency of abdominal pain. CONCLUSIONS: EC cell numbers increased in IBS-D patients and the expression of TPH1 was higher than in HCs. The Ruminococcus torques group and Dorea furthermore seem like promising targets for future research into the treatment of IBS-D patients.
-
Effects of dietary raw or Enterococcus faecium fermented soybean meal on growth, antioxidant status, intestinal microbiota, morphology, and inflammatory responses in turbot (Scophthalmus maximus L.).
Fermentation has been reported to improve the utilization of plant ingredients including soybean meal (SBM) by fish, but the detailed mechanism is still poorly understood. This study compared the effects of partial replacement of fish meal (FM) protein with SBM or Enterococcus faecium fermented SBM (EFSM) on the growth, antioxidant status, intestinal microbiota, morphology, and inflammatory responses in turbot (Scophthalmus maximus L.). The FM-based diet was used as the control (CONT). Two experimental diets were formulated in which 45% of the FM protein was replaced with SBM or EFSM. Each diet was fed to triplicate groups of fish (7.57 ± 0.01 g) twice daily for 79 d. Inferior growth performance was observed in SBM group, however, no significant depression was observed in EFSM group compared to the CONT group. The CONT group had the highest values of lysozyme, complement component 3, total antioxidant capacity, superoxide dismutase and catalase, followed by the EFSM group, and the lowest in SBM group. The malondialdehyde content was lowest in the CONT group, followed by the EFSM group, and was highest in the SBM group. Gut morphology showed that SBM diet induced alterations typical for intestinal inflammation including decreased villus and microvillus height, and increased width and inflammatory cell infiltration of the lamina propria. However, the EFSM group alleviated such SBM-induced intestinal pathological disruption. Paralleled with the morphological symptoms, the inflammatory gene expression levels of tumor necrosis factor alpha, interleukin-1 beta and interleukin-8 were highest in the SBM group, followed by the EFSM group, and were lowest in the CONT group. Furthermore, the intestinal microbiota analysis revealed that EFSM group had an overall more similar microbiota with CONT group than SBM group. Specifically, compared with the SBM group, EFSM group significantly enhanced the probiotics Lactobacillus and anti-inflammatory bacterium Faecalibaculum, and inhibited the Vibrio. Collectively, this study indicated that Enterococcus faecium fermentation effectively counteracted the negative effects of SBM by enhancing antioxidant capacity, suppressing inflammatory responses, and modulating gut microbiota in turbot.
-
Blocking coprophagy increases the levels of inflammation and depression in healthy mice as well as mice receiving fecal microbiota transplantation from disease model mice donors.
Rodents have been extensively used as animal models in microbiome studies. However, all rodents have a habitual nature called coprophagy, a phenomenon that they self-reinoculate feces into their gastrointestinal tract. Recent studies have shown that blocking coprophagy can alter rodents' diversity of gut microbiota, metabolism, neurochemistry, and cognitive behavior. However, whether rodents' coprophagy behavior affects the levels of inflammation and depression is unclear. In order to address this problem, we first blocked coprophagy in healthy mice. It displayed an increase in the levels of depression, verified by depressive-like behaviors and mood-related indicators, and inflammation, verified by the increased levels of the pro-inflammatory cytokine, in coprophagy-blocked mice. Furthermore, we transplanted fecal microbiota from chronic restraint stress (CRS) depression model mice and lipopolysaccharide (LPS) inflammation model mice to healthy recipient mice, respectively. It showed that the disease-like phenotypes in the coprophagy-blocked group were worse than those in the coprophagy-unblocked group, including severer depressive symptoms and higher levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α and IFN-γ) in serum, prefrontal cortex (PFC), and hippocampus (HIP). These findings showed that blocking coprophagy in mice not only increased the levels of inflammation and depression in healthy mice but also aggravated inflammation and depression induced by fecal microbiota from disease donors. The discovery may provide a vital reference for future research involving FMT in rodents.
-
Modulation of Glucose Homeostasis, Metabolic Endotoxemia and Circulating Short-Chain Fatty Acids Following Multi-Species Probiotic Supplementation: Findings from a 12-Week Randomised Placebo-Controlled Trial.
Background: Altered gut microbiota and gut-derived inflammation impair glucose regulation and promote metabolic endotoxemia, yet evidence on probiotic effects across combined glycaemic, inflammatory and short-chain fatty acid (SCFA) outcomes remains limited. This study investigated the effects of a 12-week multi-species probiotic on glucose homeostasis, incretin hormones, inflammatory biomarkers and circulating SCFAs in adults with subthreshold depression. Methods: In a 12-week double-blind, randomised, placebo-controlled trial, 39 adults with subthreshold depression were allocated to either a probiotic supplement containing Limosilactobacillus fermentum LF16, Lacticaseibacillus rhamnosus LR06, Lactiplantibacillus plantarum LP01 and Bifidobacterium longum 04 (n = 19) or placebo (n = 20). Fasting glucose, insulin, HOMA-IR, glucose-dependent insulinotropic peptide (GIP), high-sensitivity C-reactive protein (hs-CRP), lipopolysaccharide-binding protein (LBP), soluble CD14 (sCD14) and SCFAs were evaluated at three time points: baseline, week 6 and week 12. Between-group and treatment × time effects were analysed using general linear models. Results: Probiotic supplementation significantly reduced fasting glucose at 12 weeks compared with placebo (-1.8 vs. 0.1 mmol/L; p = 0.036). In the probiotic group, greater reductions in GIP (p = 0.012; p = 0.037), LBP (p < 0.001), sCD14 (p = 0.002; p = 0.001) and hs-CRP (p = 0.047) were also observed compared with placebo. Plasma SCFA concentrations remained largely unchanged, with no significant treatment × time interactions, except for higher valerate levels at 12 weeks in the probiotic group (p = 0.019). Conclusions: Twelve weeks of multi-species probiotic supplementation improved fasting glucose, reduced incretin and inflammatory biomarkers and attenuated metabolic endotoxemia, without alterations in circulating SCFAs. These findings support beneficial modulation of metabolic-immune pathways and highlight the promising role of probiotics to enhance glucose regulation and systemic inflammatory tone in adults with subthreshold depression.