Gut-brain axis in the pathogenesis of sepsis-associated encephalopathy

Neurobiology of Disease, Journal Year: 2024, Volume and Issue: 195, P. 106499 - 106499

Published: April 7, 2024

The gut-brain axis is a bidirectional communication network linking the gut and brain, overseeing digestive functions, emotional responses, body immunity, brain development, overall health. Substantial research highlights connection between disruptions of various psychiatric neurological conditions, including depression Alzheimer's disease. Given impact on behavior, cognition, diseases, some studies have started to pay attention role in sepsis-associated encephalopathy (SAE), where cognitive impairment primary manifestation. SAE emerges as earliest form organ dysfunction following sepsis, potentially leading acute long-term decline patients. Notably, neuronal damage does not stem directly from central nervous system (CNS) infection but rather an occurring outside brain. posited pivotal factor this process. This review will delve into axis, exploring four crucial pathways through which inflammatory signals are transmitted elevate incidence SAE. These encompass vagus nerve pathway, neuroendocrine pathway involving hypothalamic-pituitary-adrenal (HPA) serotonin (5-HT) regulation, neuroimmune microbial regulation. can operate independently or collaboratively CNS modulate activity. Understanding how affects regulates could offer potential identify novel targets for preventing treating condition, ultimately enhancing prognosis individuals with

Language: Английский

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Metabolic shifts in tryptophan pathways during acute pancreatitis infections

JCI Insight, Journal Year: 2025, Volume and Issue: 10(5)

Published: March 9, 2025

Infectious complications (ICs) in acute pancreatitis (AP) are primarily driven by intestinal bacterial translocation, significantly increasing mortality and hospital stays. Despite this, the role of gut microenvironment, particularly its metabolic aspects, AP remains poorly understood. In this study, we investigated a cohort patients with AP, conducted supplemental murine studies, to explore relationship between metabolome development ICs. Metabolomic analysis revealed that disruptions tryptophan metabolism - especially reductions serotonin indole pathways key features associated IC occurrence. Additionally, elevated plasma levels metabolites within kynurenine pathway were identified as valuable predictive biomarkers for Mechanistic studies models demonstrated an impaired Th17 response, modulated these metabolites, plays critical development. Serotonin supplementation enhanced responses, reducing incidence, while administration kynurenic acid, metabolite, exacerbated pancreatic infections, potentially through immunosuppressive effects. These findings highlight pivotal pathogenesis, emphasizing their potential both markers therapeutic targets management.

Language: Английский

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Orm2 Deficiency Aggravates High‐Fat Diet‐Induced Obesity through Gut Microbial Dysbiosis and Intestinal Inflammation

Molecular Nutrition & Food Research, Journal Year: 2023, Volume and Issue: 68(1)

Published: Oct. 18, 2023

Scope Orosomucoid 2 (Orm2) is a hepatocyte‐secreted protein that plays crucial role in regulating obesity‐type metabolic disease and immunity. The imbalance of gut microbiota one the causes obesity, but mechanism relationship between Orm2 obesity remains unclear. Methods results Orm2‐/‐ (Orm2 knockout) mice on normal diet developed spontaneous disturbances at 20th week. Through 16S rRNA gene sequencing, study finds has different microbial composition compared to wild type (WT) mice. Furthermore, high‐fat (HFD) for 16 weeks exacerbates Lack promotes dysregulation under HFD, especially reduction Clostridium spp. Supplementation with butyricum alleviates alters WT mice, minimal effects In contrast, co‐housing rescues by reducing pathogenic bacteria mitigating intestinal inflammation. Conclusion These findings suggest deficiency HFD‐induced disturbance inflammation, providing novel insight into complex bacterial flora not single probiotic administration therapeutic strategy obesity.

Language: Английский

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Gut microbiota dysbiosis and neurological function recovery after intracerebral hemorrhage: an analysis of clinical samples

Microbiology Spectrum, Journal Year: 2024, Volume and Issue: 12(11)

Published: Sept. 24, 2024

ABSTRACT We aimed to investigate the microbial community composition in patients with intracerebral hemorrhage (ICH) and its effect on prognosis. designed two clinical cohort studies explore gut dysbiosis after ICH their relationship neurological function First, fecal samples from at three time points: T1 (within 24 h of admission), T2 (3 days surgery), T3 (7 healthy volunteers were subjected 16S rRNA sequencing using Illumina high-throughput technology. When differential microbiota was identified, correlation between indicators microbiotas analyzed. Subsequently, categorized into GOOD POOR groups based Glasgow Outcome Scale Extended (GOS-E) score, disparities assessed. Univariate multivariate logistic regression analyses performed identify independent risk factors. The diversity different those control group changed dynamically extension course cerebral hemorrhage. abundances Enterococcaceae , Clostridiales incertae sedis XI Peptoniphilaceae significantly increased ICH, whereas Bacteroidaceae Ruminococcaceae Lachnospiraceae Veillonellaceae reduced. relative abundance Enterococcus gradually duration surgery, Bacteroides decreased. before surgery found be negatively associated patient original score status factors for predicting prognosis ( P < 0.05). Changes related may have a protective IMPORTANCE Acute central nervous system injuries like hemorrhagic stroke are major global health issues. While surgical hematoma removal can alleviate brain damage, severe cases still high 1-month mortality rate up 40%. Gut impacts health, treatments transplantation (FMT) probiotics improve damage by correcting imbalances caused ischemic stroke. However, few explored this This study investigated impact microbiota, we that poor (ICH). findings offer potential insights application FMT it patients.

Language: Английский

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Gut Microbiota and Respiratory Infections: Insights from Mendelian Randomization

Microorganisms, Journal Year: 2023, Volume and Issue: 11(8), P. 2108 - 2108

Published: Aug. 18, 2023

The role of the gut microbiota in modulating risk respiratory infections has garnered increasing attention. However, conventional clinical trials have faced challenges establishing precise relationship between two. In this study, we conducted a Mendelian randomization analysis with single nucleotide polymorphisms employed as instrumental variables to assess causal links and infections. Two categories bacteria, family Lactobacillaceae genus Family XIII AD3011, were causally associated occurrence upper tract (URTIs). Four existed that lower (LRTIs), order Bacillales Paraprevotella showing positive association Alistipes Ruminococcaceae UCG009 negative association. metabolites metabolic pathways only played development LRTIs, metabolite deoxycholine acting negatively menaquinol 8 biosynthesis positively. identification specific bacterial populations, metabolites, may provide new clues for mechanism research concerning therapeutic interventions Future should focus on elucidating potential mechanisms regulating developing effective strategies reduce incidence These findings significantly improve global health.

Language: Английский

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Association between gut microbiota and endometriosis: a two-sample Mendelian randomization study

Frontiers in Microbiology, Journal Year: 2023, Volume and Issue: 14

Published: Sept. 27, 2023

Background Recent studies have shown that an imbalance in gut microbiota (GM) may not always be associated with endometriosis (EMS). To investigate this further, we conducted a two-sample Mendelian randomization study. Methods MR analysis was performed on genome-wide association study (GWAS) summary statistics of GM and EMS. Specifically, the MiBioGen GWAS ( N = 18,340) used as exposure. The FinnGen (8,288 EMS cases 68,969 controls) outcome. We primarily inverse variance weighted (IVW) method to analyze correlation sensitivity verify its reliability. Results (1) analysis: results IVW confirmed total 8 taxa were related risk Class- Melainabacteria p 0.036), family- Ruminococcaceae 0.037), genus- Eubacteriumruminantium 0.015) had protective effect EMS, whereas order -Bacillales 0.046), family -Prevotellaceae 0.027), genus -Anaerotruncus 0.025), -Olsenella 0.036) RuminococcaceaeUCG002 0.035) could increase (2) Sensitivity Cochrane’s Q test &gt; 0.05), MR-Egger intercept leave-one-out robustness results. Conclusion This two large national databases identified between These potentially utilized for indirectly diagnosing lead novel perspectives research regarding pathogenesis, diagnosis, treatment

Language: Английский

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The microbiota and renal cell carcinoma

Cellular Oncology, Journal Year: 2023, Volume and Issue: 47(2), P. 397 - 413

Published: Oct. 25, 2023

Language: Английский

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Beyond faecal microbiota transplantation, the non-negligible role of faecal virome or bacteriophage transplantation

Journal of Microbiology Immunology and Infection, Journal Year: 2023, Volume and Issue: 56(5), P. 893 - 908

Published: Feb. 26, 2023

Intestinal microbiota, which contains bacteria, archaea, fungi, protists, and viruses including bacteriophages, is symbiotic evolves together with humans. The balanced intestinal microbiota plays indispensable roles in maintaining regulating host metabolism health. Dysbiosis has been associated not only diseases but other such as neurology disorders cancers. Faecal transplantation (FMT) or faecal virome bacteriophage (FVT FBT), transfers bacteria viruses, a focus on bacteriophage, from one healthy individual to another (normally unhealthy condition), aims restore the gut assist subduing diseases. In this review, we summarized applications of FMT FVT clinical settings, discussed advantages challenges currently proposed several considerations prospectively. We further provided our understanding why have their limitations raised possible future development strategy FVT.

Language: Английский

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Alterations in the gut microbiome and metabolome profiles of septic mice treated with Shen FuHuang formula

Frontiers in Microbiology, Journal Year: 2023, Volume and Issue: 14

Published: March 8, 2023

Sepsis has a high mortality rate, and treating sepsis remains significant challenge worldwide. In former studies, our group found that traditional Chinese medicine, Shen FuHuang formula (SFH), is promising medicine in coronavirus disease 2019 (COVID-19) patients with the septic syndrome. However, underlying mechanisms remain elusive. present study, we first investigated therapeutic effects of SFH on mice. To investigate SFH-treated sepsis, identified gut microbiome profile exploited untargeted metabolomics analyses. The results demonstrated significantly enhanced mice's 7-day survival rate hindered release inflammatory mediators, i.e., TNF-α, IL-6, IL-1β. 16S rDNA sequencing further deciphered decreased proportion Campylobacterota Proteobacteria at phylum level. LEfSe analysis revealed treatment enriched Blautia while Escherichia_Shigella. Furthermore, serum indicated could regulate glucagon signaling pathway, PPAR galactose metabolism, pyrimidine metabolism. Finally, relative abundance Bacteroides, Lachnospiraceae_NK4A136_group, Escherichia_Shigella, Blautia, Ruminococcus, Prevotella were closely related to enrichment metabolic pathways, including L-tryptophan, uracil, glucuronic acid, protocatechuic gamma-Glutamylcysteine. conclusion, study alleviated by suppressing response hence reduced mortality. mechanism for may be ascribed beneficial flora modulation sum up, these findings provide new scientific perspective clinical application sepsis.

Language: Английский

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Metabolomic interplay between gut microbiome and plasma metabolome in cardiac surgery‐associated acute kidney injury

Rapid Communications in Mass Spectrometry, Journal Year: 2023, Volume and Issue: 37(11)

Published: March 15, 2023

Cardiac surgery-associated acute kidney injury (CSA-AKI) is a prevalent complication of cardiac surgery, which may be associated with great risk developing chronic disease and mortality. This study aimed to investigate the possible links between gut microbiota metabolism CSA-AKI.A prospective cohort patients who underwent surgery was continuously recruited, were further divided into CSA-AKI group Non-AKI based on clinical outcomes. Their faecal plasma samples collected before separately analysed by nontargeted targeted metabolomics. The differential metabolites related screened out using statistical methods, altered metabolic pathways determined examining Kyoto Encyclopedia Genes Genomes database.Nearly 1000 detected through high-resolution mass spectrometry (MS) bioinformatics at high mid confidence levels, 49 level perform essential biological functions provide potential diagnostic indicators. Compared group, in displayed dramatic changes metabolism, including amino acid nicotinate nicotinamide purine ATP-binding cassette (ABC) transporters. Meanwhile, 188 identified quantified tandem MS, 34 two groups univariate analysis. These primarily enriched following pathways: sulphur biosynthesis, tryptophan ABC Furthermore, content indole higher than that group.Patients have dysbiosis their intestinal abnormalities system surgery. Thus, some biomarkers new therapeutic targets for disease.

Language: Английский

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