Search Results (831)

This review introduces a novel integrative framework linking gut dysbiosis, systemic inflammation, and cardiovascular risk in patients with inflammatory bowel disease (IBD). We highlight emerging biomarkers, including short-chain fatty acids (SCFAs), calprotectin, and zonulin, that reflect alterations in the gut microbiome and increased intestinal permeability, which contribute to cardiovascular pathology. Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality worldwide, and recent evidence identifies IBD, encompassing ulcerative colitis (UC) and Crohn’s disease (CD), as a significant non-traditional risk factor for CVD. This review synthesizes current knowledge on how dysbiosis-driven inflammation in IBD patients exacerbates endothelial dysfunction, hypercoagulability, and atherosclerosis, even in the absence of traditional risk factors. Additionally, we discuss how commonly used IBD therapies may modulate cardiovascular risk. Understanding these multifactorial mechanisms and validating reliable biomarkers are essential for improving cardiovascular risk stratification and guiding targeted prevention strategies in this vulnerable population. Full article

Suckling is crucial for piglet intestinal development and gut health, as it improves resilience during the challenging weaning phase and promotes subsequent growth. IPS, comprising Na⁺/K⁺ ions, whey protein, and glucose, has been shown to have positive effects on animal growth and intestinal health. The objectives of this study were to assess the impact of IPS consumption on the growth performance, immunity, intestinal growth and development, and microbiota structure of suckling piglets. A total of 160 newborn piglets were randomly divided into control and IPS groups, with IPS supplementation starting from 2 to 8 days after birth and continuing until 3 days before weaning. The findings revealed that IPS boosted the body weight at 24 days by 3.6% (p < 0.05) and improved the body weight gain from 16 to 24 days by 15.7% (p < 0.05). Additionally, the jejunal villus height and villus height to crypt depth ratio in the IPS group were notably increased to 1.08 and 1.31 times (p < 0.05), respectively, compared to the control group. Furthermore, IPS elevated the plasma levels of IgA and IgM, reduced the plasma levels of blood urea nitrogen (BUN), and enhanced the content of secretory immunoglobulin A (SIgA) in the jejunal mucosa of suckling piglets. Furthermore, IPS upregulated the mRNA expression of tight junction proteins GLP-2, ZO-1, and Claudin-1 in jejunal tissue, while downregulating the regulatory genes in the Toll-like pathway, including MyD88 and TLR-4 (p < 0.05). The analysis of gut microbiota indicated that IPS altered the relative abundance of gut microbes, with an increase in beneficial bacteria like Alloprevotella and Bacteroides. In conclusion, this study demonstrates that IPS supplementation enhances weaning weight, growth performance, immune function, and intestinal development in piglets, supporting the integration of IPS supplementation in the management of pre-weaning piglets. Full article

Background/Objectives: Autism spectrum disorder (ASD) encompasses several neurodevelopmental disorders, whose onset is correlated to genetic and environmental factors. Although the etiopathogenesis is not entirely clear, the involvement of inflammatory processes, the endocannabinoid system, and alterations in the permeability and composition of the intestinal microbiota are known to occur. Methods: This review systematically explores the literature available to date on the most widely used murine models for the study of ASD, the main biomarkers investigated for the diagnosis of ASD, and the therapeutic potential of probiotics, with a particular focus on the use of strains of Lactiplantibacillus (Lpb.) plantarum in in vivo models and clinical trials for ASD. Results: Several studies have demonstrated that targeting multifactorial biomarkers in animal models and patients contributes to a more comprehensive understanding of the complex mechanisms underlying ASD. Moreover, accumulating evidence supports the beneficial effect of probiotics, including Lpb. plantarum, as a promising alternative therapeutic strategy, capable of modulating gut–brain axis communication. Conclusions: Probiotic supplementation, particularly with selected Lpb. plantarum strains, is emerging as a potential complementary approach for ameliorating ASD-related gastrointestinal and behavioral symptoms. However, further large-scale clinical studies are essential to validate their efficacy and determine optimal treatment protocols and dietary strategies. Full article

Accurate in vitro models of intestinal permeability are essential for predicting oral drug absorption. Standard models like Caco-2 cells have well-known limitations, including lack of segment-specific physiology, but are widely used. Emerging models such as organoid-derived monolayers and microphysiological systems (MPS) offer enhanced physiological relevance but require comparative validation. We performed a head-to-head evaluation of Caco-2 cells, human jejunal (J2) and duodenal (D109) enteroid-derived cells, and EpiIntestinal^TM tissues cultured on either static Transwell and flow-based MPS platforms. We assessed tissue morphology, barrier function (TEER, dextran leakage), and permeability of three model small molecules (caffeine, propranolol, and indomethacin), integrating the data into a physiologically based gut absorption model (PECAT) to predict human oral bioavailability. J2 and D109 cells demonstrated more physiologically relevant morphology and higher TEER than Caco-2 cells, while the EpiIntestinal^TM model exhibited thicker and more uneven tissue structures with lower TEER and higher passive permeability. MPS cultures offered modest improvements in epithelial architecture but introduced greater variability, especially with enteroid-derived cells. Predictions of human fraction absorbed (F_abs) were most accurate when using static Caco-2 data with segment-specific corrections based on enteroid-derived values, highlighting the utility of combining traditional and advanced in vitro gut models to optimize predictive performance for F_abs. While MPS and enteroid-based systems provide physiological advantages, standard static models remain robust and predictive when used with in silico modeling. Our findings support the need for further refinement of enteroid-MPS integration and advocate for standardized benchmarking across gut model systems to improve translational relevance in drug development and regulatory reviews. Full article

The balance between physiological, psychological, and environmental factors often shapes human experience. In recent years, research has drawn attention to the gut microbiota as a significant contributor to brain function and emotional regulation. This narrative review examines how changes in gut microbiota may relate to depression. We selected studies that explore the link between intestinal dysbiosis and mood, focusing on mechanisms such as inflammation, vagus nerve signaling, HPA axis activation, gut permeability, and neurotransmitter balance. Most of the available data come from animal models, but findings from human studies suggest similar patterns. Findings are somewhat difficult to compare due to differences in measurement procedures and patient groups. However, several microbial shifts have been observed in people with depressive symptoms, and trials with probiotics or fecal microbiota transplant show potential. These results remain limited. We argue that these interventions deserve more attention, especially in cases of treatment-resistant or inflammation-driven depression. Understanding how the gut and brain interact could help define clearer subtypes of depression and guide new treatment approaches. Full article

The intestinal barrier governs organismal health through nutrient absorption, microbial homeostasis, and immune surveillance. While calorie restriction (CR) enhances metabolic health, the molecular mechanisms underlying its beneficial effects on gut integrity remain unclear. Here, we demonstrate that the aryl hydrocarbon receptor (AHR), a conserved xenobiotic sensor and metabolic regulator, is essential for CR-mediated improvements in intestinal function. Using Caenorhabditis elegans (C. elegans), we subjected wild-type (N2) and AHR-deficient strains (CZ2485 and ZG24) to ad libitum feeding (AL), intermittent fasting (IF), or complete food deprivation (FD). In wild-type animals, intermittent fasting markedly reduced intestinal permeability and bacterial burden while enhancing mitochondrial function and reducing reactive oxygen species. Complete food deprivation conferred modest benefits. Remarkably, these protective effects were severely compromised in AHR mutants, which exhibited increased gut leakage, bacterial colonization, and mitochondrial oxidative stress under fasting conditions. These findings establish AHR as a critical mediator of fasting-induced intestinal resilience, revealing a previously unrecognized regulatory axis linking metabolic sensing to gut barrier homeostasis. Our work illuminates fundamental mechanisms through which calorie restriction promotes gastrointestinal health and identifies AHR-dependent pathways as promising therapeutic targets for metabolic and inflammatory distress affecting the gut–systemic interface. Full article

Emerging evidence suggests a bidirectional relationship between gut microbiota, melatonin synthesis, and breast cancer (BC) development in hormone receptor-positive patients (HR+HER2+ and HR+HER2-). This study investigated alterations in gut microbiota composition, the serum serotonin–N-acetylserotonin (NAS)–melatonin axis, fecal short-chain fatty acids (SCFAs) and beta-glucuronidase (βGD) activity, and serum zonulin in HR+ BC patients compared to healthy controls. Blood and fecal samples were analyzed using mass spectrometry for serotonin, NAS, melatonin, and SCFAs; ELISA for AANAT, ASMT, 14-3-3 protein, and zonulin; fluorometric assay for βGD activity; and 16S rRNA sequencing for gut microbiota composition. HR+ BC patients exhibited gut dysbiosis with reduced Bifidobacterium longum and increased Bacteroides eggerthii, alongside elevated fecal βGD activity, SCFA levels (e.g., isovaleric acid), and serum zonulin, indicating increased intestinal permeability. Serum serotonin and N-acetylserotonin (NAS) levels were elevated, while melatonin levels were reduced, with a higher NAS/melatonin ratio in BC patients. AANAT levels were increased, and ASMT levels were decreased, suggesting disrupted melatonin synthesis. Bifidobacterium longum positively correlated with melatonin and negatively with βGD activity, while Bacteroides eggerthii showed a positive correlation with βGD activity. These findings suggested that gut microbiota alterations, disrupted melatonin synthesis, microbial metabolism, and intestinal permeability may contribute to BC pathophysiology. The NAS/melatonin ratio could represent a potential biomarker, necessitating further mechanistic studies to confirm causality and explore therapeutic interventions. Full article

Background/Objectives: Colitis is a chronic condition affecting millions worldwide. Purple muscadine wine polyphenols have a unique composition and possible disease-preventive properties. This study aims to determine how dealcoholized muscadine wine (DMW) affects the development of colitis and gut microbiome in IL-10^−/− mice, compared to wild types (WT). Methods: Six-week-old male IL-10^−/− and WT C57BL/6 mice were fed either a DMW-supplemented diet (4.8% v/w) or a control diet based on AIN-93M for 154 days. Colitis severity was evaluated by disease activity, intestinal permeability, gene expression of cytokines and tight junction proteins in the colon, and inflammatory cytokines in the serum. Fecal samples were collected for gut microbiome profiling via 16S rRNA gene sequencing. Results: DMW contained predominantly anthocyanins and a significant amount of ellagic acid. IL-10^−/− mice developed mild colitis as indicated by the disease activity index. DMW × gene interactions decreased intestinal permeability, colonic mRNA levels of IL-1β, and serum TNF-α in the IL-10^−/− mice. DMW suppressed the colonic mRNA levels of IL-6, enhanced the gene expression of ZO-1, but did not influence the mRNA level of TNF-α or occludin. While DMW did not alter α-diversity of the gut microbiome, it significantly influenced β-diversity in the WT mice. DMW significantly reduced the relative abundances of Akkermansia in the IL-10^−/− and WT mice. DMW and DMW×gene interaction decreased the relative abundance of Parasutterella only in IL-10^−/− mice. Conclusions: These results suggested that polyphenols from DMW interacted with genes to moderately alleviate the development of colitis in IL-10^−/− mice and could be a useful dietary strategy for IBD prevention. Full article

Emerging evidence highlights the critical role of the gut microbiota in the development and progression of eating disorders (EDs), particularly in women, who are more frequently affected by these conditions. Women with anorexia nervosa, bulimia nervosa, and binge eating disorder exhibit distinct alterations in gut microbiota composition compared to healthy controls. These alterations, collectively termed dysbiosis, involve reduced microbial diversity and shifts in key bacterial populations responsible for regulating metabolism, inflammation, and gut–brain signaling. The gut microbiota is known to influence appetite regulation, mood, and stress responses—factors closely implicated in the pathogenesis of EDs. In women, hormonal fluctuations related to menstruation, pregnancy, and menopause may further modulate gut microbial profiles, potentially compounding vulnerabilities to disordered eating. Moreover, the restrictive eating patterns, purging behaviors, and altered dietary intake often observed in women with EDs exacerbate microbial imbalances, contributing to intestinal permeability, low-grade inflammation, and disturbances in neurotransmitter production. This evolving understanding suggests that microbiota-targeted therapies, such as probiotics, prebiotics, dietary modulation, and fecal microbiota transplantation (FMT), could complement conventional psychological and pharmacological treatments in women with EDs. Furthermore, precision nutrition and personalized microbiome-based interventions tailored to an individual’s microbial and metabolic profile offer promising avenues for improving treatment efficacy, even though these approaches remain exploratory and their clinical applicability has yet to be fully validated. Future research should focus on sex-specific microbial signatures, causal mechanisms, and microbiota-based interventions to enhance personalized treatment for women struggling with eating disorders. Full article

The gut microbiota plays an important role in maintaining the body’s homeostasis, and its disruption has been linked to the pathogenesis of coronary atherosclerosis and cognitive decline. This review attempted to assess whether the composition of the gut microbiota differs significantly according to the severity of coronary atherosclerosis and whether the presence of specific cytokines and inflammatory markers in the microbiota of patients with atherosclerosis may correlate with cognitive impairment. In addition, it considered whether increased dietary fiber intake may contribute to lower levels of inflammatory markers compared to a low-fiber diet. This review included publications from 2015 to 2024, searched in the PubMed and Scopus databases. Only studies meeting the quality criteria were included. The pooled data indicate that intestinal dysbiosis can lead to increased intestinal barrier permeability and lipopolysaccharide (LPS) translocation, which promotes chronic inflammation. This process plays an important role in both atherosclerosis and neurodegeneration. In addition, some studies indicate a beneficial effect of dietary fiber in reducing inflammatory markers. The conclusions of this review highlight the need for further, well-designed studies to identify the causal relationship between the microbiota, its metabolites, atherosclerosis, and cognitive deficits, which may provide the basis for new therapeutic strategies. Full article

Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease linked to fibrosis and hepatocellular carcinoma (HCC). Gut-derived lipopolysaccharide (LPS) promotes hepatic inflammation, fibrosis, and angiogenesis through toll-like receptor 4 (TLR4) signaling. This study examined the effects of rifaximin, a non-absorbable, gut-targeted antibiotic, on MASH-related liver fibrosis and early hepatocarcinogenesis, with a focus on the LPS–epiregulin–IL-8–angiogenesis axis.MASH was induced in Fischer 344 rats using a choline-deficient, L-amino acid-defined high-fat diet (CDAHFD). Rifaximin (30 mg/kg/day) was orally administered for 12 weeks. Liver histology, gene expression, intestinal permeability, LPS levels, and angiogenic markers were evaluated. Rifaximin reduced hepatic inflammation, fibrosis, hydroxyproline content, and fibrogenic gene expression. The number and size of GST-P-positive preneoplastic lesions and proliferation-related genes were decreased. Portal LPS levels and Kupffer cell activation declined, with downregulation of Lbp, Cd14, Tlr4, and inflammatory cytokines. Rifaximin decreased hepatic epiregulin and IL-8 expression, attenuated CD34-positive neovascularization, and suppressed proangiogenic gene expression, accompanied by improved intestinal barrier function and reduced gut permeability. Rifaximin mitigates MASH progression by restoring gut barrier integrity, limiting LPS translocation, and inhibiting fibrogenic and angiogenic pathways. These results suggest its potential as a chemopreventive agent in MASH-related hepatocarcinogenesis. Full article

Early-life brain injuries are major causes of long-term neurodevelopmental disorders such as cerebral palsy. Emerging evidence suggests these injuries can alter the gut microbiota composition, intestinal integrity, and neuroinflammatory responses. This systematic review evaluated the impact of early-life brain injuries on the gut microbiota in rodent models. A scientific literature search was conducted across Medline/PubMed, Web of Science, Scopus, and Embase. Initially, 7419 records were identified, and 21 eligible studies were included. Eligible studies focused on evaluating the microbiota alterations and related gut–brain axis markers at the neonatal or post-weaning stages. The data extraction and synthesis followed PRISMA guidelines. Most studies reported gut dysbiosis characterized by a decreased abundance of Bacteroidetes, and Lactobacillus. Alterations were associated with an increased gut permeability, reduced tight junction proteins, and elevated pro-inflammatory cytokines. Several studies showed reduced levels of short-chain fatty acids and metabolic pathway disruptions. Brain outcomes included neuroinflammation, white matter injury, altered gene expression, and impaired structural integrity. These results suggest that early-life brain injury induces complex alterations in the gut microbiota and its metabolic products, which may contribute to systemic and neuroinflammatory processes. Understanding these interactions offers insights into the pathophysiology of neurodevelopmental disorders and highlights the gut–brain axis as a potential target for early interventions. Full article

Background: Metabolic syndrome (MetS) is characterized by chronic inflammation, oxidative stress, and mitochondrial dysfunction. MetS is associated with increased intestinal permeability and dysbiosis. The objective of this study was to investigate the effects of peanut shell extract (PSE) and luteolin (LUT) on the kidneys, colon, and ileum in a MetS-like murine model. Methods: Thirty-six male Slc6a14^y/− mice were divided into four groups: low-fat diet (LFD), high-fat diet (HFD), HFD + 200 mg PSE/kg BW (PSE, p.o.), and HFD + 100 mg LUT/kg BW (LUT, p.o.) for 4 months. Outcome measures included glucose homeostasis, intestinal permeability, gut microbiome composition, and mRNA gene expression of mitochondrial homeostasis and inflammation/oxidative stress in the kidneys, colon, and ileum. Results: HFD resulted in glucose dysregulation with hyperglycemia and insulin resistance. PSE and LUT improved insulin tolerance and beta-cell function. PSE and LUT mitigated HFD-increased serum lipopolysaccharide-binding protein concentration. Perturbations in the gut microbiome were associated with HFD, and PSE or LUT reversed some of these changes. Specifically, Phocaeicola vulgatus was depleted by HFD and reverted by PSE or LUT. Relative to the LFD group, the HFD group (1) upregulated mitochondrial fusion (MFN1, MFN2, OPA1), mitophagy (TLR4, PINK1, LC3B), and inflammation (NFκB, TNFα, IL6), and (2) downregulated mitochondrial fission (FIS1, DRP1), biosynthesis (PGC1α, NRF1, NRF2, TFAM), electron transport chain (complex I), and antioxidant enzyme (SOD1) in the kidneys, colon, and ileum. Conclusions: PSE and LUT reversed such HFD-induced changes in the aforementioned gene expression levels. Full article

Autism spectrum disorder (ASD) is a neurodevelopmental condition frequently associated with gastrointestinal symptoms, gut dysbiosis, and metabolic dysfunctions such as insulin resistance (IR). Recent evidence suggests that the gut microbiota may influence both metabolic and neurological processes through the gut–brain–metabolic axis. This review explores the molecular mechanisms linking dysbiosis, IR, and ASD, focusing on pathways such as TLR/NF-κB activation, PI3K/Akt/mTOR disruption, and the action of microbial metabolites, like short-chain fatty acids (SCFAs), lipopolysaccharide (LPS), and γ-aminobutyric acid (GABA). We discuss how dysbiosis may contribute to increased intestinal permeability, systemic inflammation, and neuroimmune activation, ultimately affecting brain development and behavior. Common microbial alterations in ASD and IR—including increased Clostridium, Desulfovibrio, and Alistipes, and reduced Bifidobacterium and butyrate-producing genera—suggest a shared pathophysiology. We also highlight potential therapeutic strategies, such as microbiota modulation, insulin-like growth factor 1 (IGF-1) treatment, and dietary interventions. Understanding these interconnected mechanisms may support the development of microbiota-targeted approaches for individuals with ASD metabolic comorbidities. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the most prevalent chronic liver condition. Its prevalence is estimated to further increase. The gut–liver axis, which represents both anatomical and functional connections, contributes significantly to the development of MASLD. Dysbiosis, characterized by an imbalance in gut microbiota, can exacerbate the disease by increasing intestinal permeability, which permits harmful bacteria and their components to enter the bloodstream. This review sought to explore the impact of probiotics, prebiotics, and synbiotics on the treatment of MASLD. Method: The methodology for scoping reviews in accordance with Prisma-ScR guidelines was followed. A comprehensive search was conducted in databases such as PubMed, Scopus, and Medline. Out of 1390 studies screened, 25 were selected for the final analysis. Results: The findings of this scoping review highlight the therapeutic potential of probiotics, prebiotics, and synbiotics in the management and treatment of MASLD, as showcased by the existing literature. Conclusions: This scoping review offers important insights into the advantages of probiotics, prebiotics, and synbiotics in the treatment of MASLD. The limitations identified in this study emphasize the necessity for larger, long-term, and geographically diverse studies in order to obtain more solid scientific results. Full article