Questo è quello che abbiamo trovato per te
This study compares the efficacy of 2% perioperative intravenous lidocaine infusion vs 0.9% saline placebo on return of gut function after elective minimally invasive colon resection.
Mood disorders and DGBI are highly prevalent, commonly co-morbid and lack fully effective therapies. Although SSRIs are first line pharmacological treatments for these disorders, they may impart adverse effects including anxiety, anhedonia, dysmotility and, in children exposed in utero, an increased risk of cognitive, mood and gastrointestinal disorders. SSRIs act systemically to block SERT and enhance serotonergic signaling in the brain, intestinal epithelium and enteric neurons. Yet, the compartments that mediate the therapeutic and adverse effects of SSRIs are unknown, as is whether gestational SSRI exposure directly contributes to human DGBI development.
The colonisation and assembly of the neonatal microbiota is essential for the development and maturation of the immune system, and the early life from birth to 2 years of age is regarded as a crucial window period. Abnormal microbial colonisation and reduced gut microbiota diversity during this period are linked to the subsequent development of immune-mediated diseases. Dysbiosis of intestinal microbiota in early life can promote dysfunction of the CD4+ T-cell population,1 impacting the development of the child’s immune system and increasing the risk of atopic diseases. Atopic diseases are excessive IgE-mediated immune responses that commonly affect the nose, eyes, skin and lungs. Of these, atopic dermatitis (AD), a chronic and recurring inflammatory skin disease, affects at least 10%–20% of children, often starting in infancy and continuing into adulthood.2 The factors influencing AD are complex. Researchers have conducted meta-analyses of the various factors correlating to…
Objective
The specific breast milk-derived metabolites that mediate host–microbiota interactions and contribute to the onset of atopic dermatitis (AD) remain unknown and require further investigation.
Design
We enrolled 250 mother–infant pairs and collected 978 longitudinal faecal samples from infants from birth to 6 months of age, along with 243 maternal faecal samples for metagenomics. Concurrently, 239 corresponding breast milk samples were analysed for metabolomics. Animal and cellular experiments were conducted to validate the bioinformatics findings.
Results
The clinical findings suggested that a decrease in daily breastfeeding duration was associated with a reduced incidence of AD. This observation inspired us to investigate the effects of breast milk-derived fatty acids. We found that high concentrations of arachidonic acid (AA), but not eicosapentaenoic acid (EPA) or docosahexaenoic acid, induced gut dysbiosis in infants. Further investigation revealed that four specific bacteria degraded mannan into mannose, consequently enhancing the mannan-dependent biosynthesis of O-antigen and lipopolysaccharide. Correlation analysis confirmed that in infants with AD, the abundance of Escherichia coli under high AA concentrations was positively correlated with some microbial pathways (eg, ‘GDP-mannose-derived O-antigen and lipopolysaccharide biosynthesis’). These findings are consistent with those of the animal studies. Additionally, AA, but not EPA, disrupted the ratio of CD4/CD8 cells, increased skin lesion area and enhanced the proportion of peripheral Th2 cells. It also promoted IgE secretion and the biosynthesis of prostaglandins and leukotrienes in BALB/c mice fed AA following ovalbumin immunostimulation. Moreover, AA significantly increased IL-4 secretion in HaCaT cells costimulated with TNF-α and INF-.
Conclusions
This study demonstrates that AA is intimately linked to the onset of AD via gut dysbiosis.
Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a wide spectrum of liver injuries, ranging from hepatic steatosis, metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, cirrhosis to MASLD-associated hepatocellular carcinoma (MASLD-HCC). Recent studies have highlighted the bidirectional impacts between host genetics/epigenetics and the gut microbial community. Host genetics influence the composition of gut microbiome, while the gut microbiota and their derived metabolites can induce host epigenetic modifications to affect the development of MASLD. The exploration of the intricate relationship between the gut microbiome and the genetic/epigenetic makeup of the host is anticipated to yield promising avenues for therapeutic interventions targeting MASLD and its associated conditions. In this review, we summarise the effects of gut microbiome, host genetics and epigenetic alterations in MASLD and MASLD-HCC. We further discuss research findings demonstrating the bidirectional impacts between gut microbiome and host genetics/epigenetics, emphasising the significance of this interconnection in MASLD prevention and treatment.
Introduction
The gut microbiome plays an important role in maintaining both cognitive and physical functions in older adults, and gut dysbiosis is an important pathophysiological mechanism of mild cognitive impairment (MCI) in older adults. As a typical traditional Chinese mind-body exercise, regular Baduanjin training has been shown to improve cognitive function and modulate the gut microbiome in community-dwelling older adults. However, the potential role of the gut microbiome in the benefits of Baduanjin on cognitive function remains unclear. The aim of this study is to investigate the mediating effect of gut microbiome between regular Baduanjin training and improvement in cognitive function in community-dwelling older adults with MCI.
Methods and analysis
This is a two-arm, randomised, parallel-controlled, single-blinded trial. Four residential communities (clusters) with a total of 64 eligible participants (16 participants in each residential community) will be randomised 1:1 to either the 24-week Baduanjin exercise intervention group (60 min per session, four sessions per week) or the no specific exercise intervention control group. Global cognitive function and the subdimensions of cognition including executive function, visuospatial function, language function and memory function will be assessed using the Montreal Cognitive Assessment Scale, Trail Making Test, Auditory Verbal Learning Test, Boston Naming Test-30 and Clock-Drawing Test, while the gut microbiome and its metabolomics will be detected using 16S rRNA and ultra-high-performance liquid chromatography–tandem mass spectrometry at baseline and at the end of 24-week intervention. The intervention effect of Baduanjin exercise and mediating role of gut microbiota will be analysed using linear mixed models and the bootstrapping method in the Hayes process.
Ethics and dissemination
This study conforms to Declaration of Helsinki principles and relevant ethical guidelines. Ethical approval has been obtained from the Ethics Committee of the Shanghai University of Medicine and Health Sciences (approval number: 2023-GZR-011). Written informed consent will be obtained from all participants. Results will be disseminated to relevant groups in peer-reviewed journal(s), and at relevant international or national scientific conferences. Key findings will also be shared with social media, healthcare providers, participants or community-dwelling older adults to support access for non-research audiences.
Trial registration number
ChiCTR2300078147.
The effect of the gut microbiome on the bioavailability and efficacy of orally administered drugs is of considerable importance for personalised medicine.1 We, therefore, read with great interest the ‘GI highlights from the literature’ focussing on gut microbial metabolism of 5-aminosalicylic acid (5-ASA) in inflammatory bowel disease (IBD), originally published in the journal Nature Medicine.2 3 Mehta et al. used metagenomics, metatranscriptomics and metabolomics from the IBD-Integrative Human Microbiome Project (HMP2) to identify 12 microbial acetyltransferase gene families that encode 5-ASA inactivating enzymes and confirmed the results using in vitro analyses. They confirmed that four of these genes—profiled in metagenomic data from stool samples—are associated with 5-ASA treatment failure in two cohorts of patients with IBD, implying that it might be possible to predict 5-ASA treatment outcome by profiling gut microbiota of patients. However, to generalise these findings, they need to be confirmed…
Circulation, Volume 150, Issue Suppl_1, Page A4141474-A4141474, November 12, 2024. Background:5-Hydroxytryptophan (5-HTP) has shown positive clinical effects on various neuropsychiatric and metabolic disorders, particularly depression. While it is known to increase serotonin levels in the brain and gastrointestinal tract, its pharmacology remains largely unexplored. Additionally, 5-HTP influences the mouse gut microbiome, which is closely linked to depression through the “microbiota-gut-brain axis.” However, the role of 5-HTP in vascular disease is not well understood. This study aimed to investigate the potential correlation between serum 5-HTP levels and the severity of coronary artery calcification (CAC) in patients with acute coronary syndrome (ACS).Methods and Results:This study included 183 ACS patients who underwent coronary angiography. The severity of coronary calcification was recorded, and serum 5-HTP levels were measured after the coronary event. The study period was from February 4, 2009, to August 9, 2020. The primary exposure variable was 5-HTP levels, and the primary outcome was the severity of coronary calcification assessed through fluoroscopy. Logistic regression was used to determine the association between 5-HTP levels and calcification severity, adjusting for age, gender, smoking status, chronic kidney disease, hyperlipidemia, and diabetes. Odds ratios (OR) and 95% confidence intervals (CI) measured the strength of associations, with statistical significance set at p < 0.05.High 5-HTP levels were significantly associated with more severe calcification (p = 0.04, OR = 3.3, 95% CI = 2.6 to 40686.5). For other factors, the OR for smokers was 0.97 (0.53 to 1.77); dyslipidemia 0.91 (0.5 to 1.63); hypertension 1.57 (0.87 to 2.82); male gender 1.35 (0.45 to 4.01); age 1.07 (1.03 to 1.10); diabetes 1.24 (0.67 to 2.31); chronic kidney disease 1.07 (0.33 to 3.50). After adjusting for conventional risk factors, the association between 5-HTP and calcification remained significant (p < 0.05).Conclusion:Higher 5-HTP levels are positively associated with greater severity of coronary artery calcification. This correlation persists even after adjusting for conventional risk factors.
Circulation, Volume 150, Issue Suppl_1, Page A4146466-A4146466, November 12, 2024. Background:Without timely intervention, pressure-overloading left ventricular (poLV) remodeling may become progressive and readily degenerate into heart failure. The relative risk is especially high in children with congenital heart disease who are awaiting surgical correction.Aims:The aims of this study were to identify a plasma metabolite that is clinically and mechanically linked to poLV remodeling and heart failure in children and investigate a safe, efficacious treatment that blocks its action.Methods:We used multi-omics including untargeted metabolomics on the plasma of poLV children and neonatal ascending aorta constriction (nAAC) mice, whole-transcriptome resequencing and single-nucleus RNA sequencing of mouse and human LV samples, and metagenomics analysis of mouse gut microbiota to disclose the gut microbiota-kynurenine (Kyn)-remodeling axis. Aryl hydrocarbon receptor (AHR) knockout mice and germ-free (GF) mice as well as fecal microbiota transplantation were used to clarify its mechanism.Results:Abnormally elevated plasma kynurenine (Kyn) was detected in both the patient cohort and the mouse model. Plasma Kyn levels were clinically associated with the cardiac functions and the degree of remodeling. Excessive Kyn induced the hypertrophy and fibrosis phenotypes both in vitro and in vivo, which was blocked by AHR inhibitors and by AHR knockout, respectively. It was demonstrated that Kyn affected both cardiomyocytes and cardiac fibroblasts by promoting AHR nuclear translocation, initiating ADAMTS2 transcription which accelerates hypertrophy, and inducing FN1 and COL1A1 which exacerbate fibrosis. There were significant alterations in the gut microbiota of nAAC mice.Transplantation of nAAC mouse feces to GF mice augmented their Kyn level, indicating the existence of a gut microbiota-Kyn relationship. Oral probiotic supplementation reconstructed the gut microbiota in the nAAC mice, modulated the Kyn-AHR axis, and alleviated poLV remodeling.Conclusions:Plasma Kyn levels were strongly correlated with cardiac remodeling and function in pediatric patients and mice with poLV. Kyn is a pathological signal from an altered gut microbiota to activates AHR and its gene targets in poLV remodeling heart, promoting hypertrophy and fibrosis in respective cells. Oral probiotics reshaped the gut microbiota, lowered Kyn levels, and showed great potential at delaying cardiac remodeling and preventing heart failure.
Circulation, Volume 150, Issue Suppl_1, Page A4113494-A4113494, November 12, 2024. End-stage ischemic heart disease necessitates heart transplantation, and emerging cell therapy presents a promising solution to address donor scarcity. Disruption of gut microbiota significantly influences various diseases and treatments, including transplantation. However, the impact of immunosuppression and cardiac cell therapy on gut microbiota remains largely unexplored. To elucidate this relationship, we investigated gut microbiota dynamics in response to immunosuppression and cell therapy in a nonhuman primate (NHP) cardiac ischemia/reperfusion (IR) model, with controlled genetic, dietary, and environmental factors. Immunosuppression enriched anaerobes (Faecalibacterium, Streptococcus, Anaerovibrio, Dialister), increasing gut microbiota diversity. These changes correlated with metabolic shifts towards amino acid metabolism and nucleosides/nucleotides biosynthesis. Combined treatment of human induced pluripotent stem cell (iPSC)-derived endothelial cells (EC) and cardiomyocytes (CM) also increased gut microbiota diversity, with specific genera alterations. The EC/CM co-treatment group displayed gut microbiota resembling the pre-injury group, with host metabolism shifting towards amino acid and fatty acid/lipid biosynthesis post-cell therapy. These observed microbiota changes and metabolic shifts could serve as biomarkers for monitoring cell therapy and immunosuppression outcomes, offering potential therapeutic targets to enhance efficacy.
Circulation, Volume 150, Issue Suppl_1, Page A4141398-A4141398, November 12, 2024. Background:Hypertension is the most common cardiovascular disease risk factor of which African Americans have a greater burden. Gut microbial production of short chain fatty acids (SCFA) has been associated with blood pressure status in animals, with limited evidence in humans. The complex and diverse gut microbial ecosystem contributes to synthesizing the SCFA butyrate. Aim: The goal of the study is to determine if butyrate production in the gut is associated with hypertension and how the microbial composition differs in normal and hypertensive participants.Methods:Fecal samples from 20 participants diagnosed with normal (n = 10) or high (n = 10) blood pressure were sequenced via the 16S rRNA gene. Inference-based modeling generated functional (PICRUSt2) and metabolic (MICOM) models of microbial communities focusing on carbohydrate fermentation pathways. Supervised learning was conducted to identify significant (p < 0.05) differences in predicted functional genes and microbial communities.Results:Microbial dominance was inversely correlated with increasing systolic blood pressure (Pearson, p < 0.05, R = -0.44); however, no significant correlation was measured for beta diversity between the two groups. More importantly, inference modeling showed differences in microbial function and metabolism between groups. Functional pathways associated with carbohydrate fermentation were significantly (ANOVA, p < 0.05) lower for hypertensive compared to normal participants. Carbohydrate fermentation accounted for only 8.05% of the predicted functions of the identified pathways. Within this subset, pyruvate fermentation to isobutanol was the most abundant pathway (12.6%), followed by starch degradation (9.6%) and glycolysis III (9.34%). Additionally, metabolic flux models revealedCatenibacterium, Subdoligranulum, andRoseburiawere predicted as butyrate producers.CatenibacteriumandSubdoligranulumproduced 51% and 44% butyrate, respectively, in the normal group. In contrast, a different distribution was observed in the hypertensive group, withCatenibacteriumaccounting for 97% andRoseburiacontributing 3% of the butyrate production.Conclusion:Our preliminary investigation elucidates the potential relationship between SCFA producers (as well as butyrate producers) and blood pressure status among minority participants, providing insights into how gut microbiota may influence or be influenced by blood pressure.
