Search Results (51)

Aronia melanocarpa (black chokeberry) is a polyphenol-rich fruit recognized as a novel food ingredient; however, its efficacy against constipation and its underlying mechanisms remains poorly understood. In this study, we evaluated the therapeutic effects of the ethanol extract of A. melanocarpa fruit (AMFE) on loperamide-induced constipation in mice and investigated its mechanisms using serum pharmaco-chemistry, network pharmacology, and molecular docking analyses. AMFE treatment increased the intestinal transit rate and fecal water content in a dose-dependent manner, alleviated colonic histopathological damage, and restored the serum levels of gastrointestinal neurotransmitters (5-HT, MTL, SP, GAS, and VIP), inflammatory cytokines (IL-1β, IL-6, and TNF-α), and colonic oxidative stress markers (GSH and MDA). Using UHPLC-Q-TOF-MS, 31 compounds were identified in AMFE, of which 22 were detected in serum, including 14 prototype compounds and eight metabolites. Network pharmacology analysis revealed 472 common targets shared between AMFE and constipation, with AKT1, STAT3, JUN, GAPDH, IL-6, and TP53 as core targets. KEGG enrichment analysis highlighted the PI3K/AKT signaling pathway as a key regulatory axis. Molecular docking confirmed strong binding affinities between key active compounds (catechin, kaempferol, caffeic acid, naringenin, and isorhamnetin). Please see the core end of the document for further details on the references and targets, particularly isorhamnetin with GAPDH. Collectively, AMFE alleviated constipation through multi-component, multi-target, and multi-pathway mechanisms, providing a scientific basis for the development of A. melanocarpa as a functional food and therapeutic candidate for constipation. Full article

The present study examined for the first time the effect of native yeasts on the fermentation of artisanal Spondias purpurea L., wine produced in Santa Elena, Ecuador. To achieve this goal, three inoculation strategies were compared: a mixed culture containing Saccharomyces cerevisiae and Candida spp. (CLX), commercial S. cerevisiae (CL), and a spontaneous fermentation without added inoculum (SL). Five yeast isolates were identified from the fermentations, four belonging to Candida spp. and one to Kloeckera spp., using microbiological and biochemical methods. The CLX treatment showed the greatest yeast proliferation on PDA plates (2.7 × 10⁶ CFU/mL) and yielded the highest levels of higher alcohols, while the CL treatment produced the highest ethanol (3.72% ABV) and glycerol content (0.46%). All treatments were free of total and fecal coliforms, and their pH values (2.49–2.56) satisfied the requirements of the current Ecuadorian standard for wine production NTE INEN 374. Residual glucose content was specifically quantified using an enzymatic colorimetric (GOD-POD) assay, confirming the dry character of the wines. Molecular analysis of the final preparation obtained from the variant corresponding to the spontaneous fermentation without inoculum (SL) confirmed the presence of Hanseniaspora spp. (Kloeckera spp.), Diutina rugosa (C. rugosa), C. zeylanoides and Pichia kudriavzevii, after the obtained PCR amplicons using ITS1 and ITS4 were subjected to a blast analysis. Sensory evaluation by panelists (n = 15) favored the CLX wine, particularly for aroma and flavor attributes. The final glucose content reached a low value of 0.28 g/L, indicative of an extremely dry wine, with almost no fermentable sugar. Due to the lack of information related to wines produced from Spondias purpurea L., this study could contribute to a better understanding of the biological behavior and biodiversity of the microorganisms present in this fermentation process. These findings will help to improve wine regionality production, supporting the potential application of native regional yeasts in Spondias purpurea L. wine biotechnology. Full article

Background/Objectives: This study evaluated whether yoghurt containing Apilactobacillus kunkeei DSM 12361 protects rats against non-alcoholic fatty liver disease (NAFLD). We hypothesized that this fructophilic probiotic, with anti-inflammatory properties, may affect NAFLD progression by improving the gut microbiome, lowering intestinal ethanol production, and modulating inflammatory and metabolic pathways linked to hepatic fat accumulation. Methods: Wister rats were randomized into three groups; rats in the control group (HFrD) were fed a high-fructose (70%) diet while rats in experimental groups were fed the same diet mixed with 10% of yoghurt containing YC-180 starter culture (HFrD-Y) or yoghurt containing YC-180 and Apilactobacillus kunkeei DSM 12361 (HFrD-Y-A). Results: After six weeks of intervention, levels of plasma triglycerides, cholesterol, glucose, liver enzymes (ALT and AST), interleukin (IL)-6, fecal ethanol, Enterobacteriaceae, and hepatic index were significantly increased (p < 0.05) in the HFrD group as compared to rats in both experimental groups. Moreover, plasma levels of liver enzymes, lipid profile, glucose, and IL-6 were significantly lower (p < 0.05) in rats of the HFrD-Y-A group than those in the HFrD-Y group. Furthermore, plasma levels of IL-10 and fecal Lactobacilli and Bifidobacteria were significantly increased (p < 0.05) in the experimental groups when compared to rats in the control group. Conclusions: In sum, the obtained results indicated that yoghurt containing Apilactobacillus kunkeei could decrease the risk of non-alcoholic fatty liver disease (NAFLD) through (a) blocking the inflammation process associated with NAFLD, (b) enhancing the lipid profile, (c) lowering fecal ethanol, and (III) decreasing the levels of fecal Enterobacteriaceae in comparison with levels of fecal Lactobacilli and Bifidobacteria in rats. More research on molecular mechanisms of the potential effects of the Apilactobacillus kunkeei strain against NAFLD is still required. Full article

Background: Micro-RNAs (miRNAs) are emerging as pivotal regulators of pathophysiological processes, reflecting systemic responses to stress, inflammation and metabolic imbalance. Their role in advanced liver disease and in modulating responses to therapeutic interventions, such as fecal microbiota transfer (FMT), remains insufficiently characterized. Methods: We conducted a prospective study including six male patients with toxic ethanolic liver cirrhosis undergoing FMT and six healthy controls. Stool and blood samples were collected pre- and post-FMT. Fecal micro-RNA expression (miR-21, miR-122, miR-125, miR-146 and miR-155) was quantified using RT-qPCR and normalized to miR-26c. Associations with noninvasive fibrosis markers (FIB-4, APRI, elastography, CAP) and biological parameters were analyzed through multivariable regression and Pearson correlation, with internal validation by bootstrapping. Results: One week after fecal microbiota transfer, miR-21 and miR-146 exhibited significant expression changes, while miR-122, miR-125, and miR-155 showed non-significant trends toward increased expression. Post-FMT increases in miR-21, miR-122, miR-146 and miR-155 were consistently associated with reductions in hepatic fibrosis markers (FIB-4, APRI and liver stiffness), whereas no significant associations were observed with CAP. Conclusions: Fecal micro-RNAs reflect interconnected molecular networks that capture systemic adaptations to FMT. Despite a limited cohort, these findings highlight their potential as integrative biomarkers and as therapeutic targets in advanced liver disease. Larger-scale studies are warranted to validate clinical utility. Full article

Recombinant Bacillus subtilis endospores are promising bacterial expression platforms for oral protein delivery, such as oral vaccines. A simple and effective spore inactivation method that preserves protein functionality, however, is needed to prevent potential shedding into the environment. This study evaluated iron or copper combined with EDTA and ethanol as sporicidal solutions for the inactivation of recombinant spores expressing the 1PR82 gene. Immunoblot and immunofluorescence (IF) assay confirmed the presence of antigenic proteins post-treatment, while electron microscopy (SEM/TEM) assessed spore morphology. Mice immunization tested immunogenicity, and fecal analysis monitored gastrointestinal persistence. Iron ethanol treatment completely inactivated the spores while maintaining recombinant protein detection using antibody-based assays. SEM/TEM revealed morphological damage, yet antigenicity was preserved, as evidenced by robust IgG responses in immunized mice. Fecal analysis showed no prolonged spore shedding, confirming effective inactivation. These findings demonstrate that iron ethanol efficiently inactivates recombinant B. subtilis spores without compromising protein antigenicity. Despite structural damage, the recombinant protein remained immunogenic, and inactivated spores posed no environmental persistence risk. This inactivation method supports the safe use of Bacillus subtilis recombinant spores for oral delivery applications, balancing inactivation efficacy with functional protein preservation. Further research could optimize this approach for clinical or industrial applications. Full article

Background/Objectives: The interplay between host metabolism and gut microbiota is central to the pathophysiology of metabolic diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD). In this study, we investigated the underexplored fecal host–microbiota co-metabolism profile of male and female Wistar rats after 21 weeks of high-fat diet (HFD), a model previously validated for early MASLD. Methods: Using ¹H-NMR spectroscopy, we detected and quantified metabolites in fecal samples associated with hepatic metabolism beyond short-chain fatty acids (SCFAs), such as energy-related metabolites, amino acid turnover, branched-chain amino acid (BCAA) catabolism, and microbial fermentation. Results: Distinct metabolic signatures were identified according to diet and sex, and statistical analysis was performed. Notably, alterations were observed in bile acids (BAs) such as cholate and glycocholate, suggesting disruptions in enterohepatic circulation. The presence of fucose, a sugar linked to liver pathology, was also elevated. Energy-related metabolites indicated a shift from lactate production to increased acetoacetate and malonate levels, implying redirection of pyruvate metabolism and inhibition of the TCA cycle. BCAA derivatives such as 3-methyl-2-oxovalerate and 3-aminoisobutyrate were altered, supporting earlier findings on disrupted amino acid metabolism under HFD conditions. Furthermore, microbial metabolites including methanol and ethanol showed group-specific differences, suggesting shifts in microbial activity. Conclusions: These findings complement previous longitudinal data and provide a functional interpretation of newly identified metabolites. These metabolites, previously unreported, are now functionally contextualized and linked to hepatic and microbial dysregulation, offering novel biological insights into early MASLD mechanisms. Full article

Inflammatory bowel diseases (IBD), such as Crohn’s disease (CD) and ulcerative colitis (UC), are chronic, progressive conditions with increasing prevalence worldwide. The aim of this study was to evaluate the usefulness of a porcine model of colitis induced by 2,4-dinitrobenzenesulfonic acid (DNBS) as a translational model of IBD. Sixteen Polish White pigs were divided into a control group and colitis group. Colitis was induced by rectal administration of DNBS (80 mg/kg in 50% ethanol). Clinical status, hematological and biochemical parameters, fecal calprotectin levels, cytokine plasma concentrations, and histopathological changes in the gastrointestinal tract were evaluated. DNBS administration resulted in persistent diarrhea and mild abdominal pain without general deterioration of health. Significant increases in fecal calprotectin levels and aspartate aminotransferase (AST) activity were observed. Histopathological changes in the colon were limited to the mucosa, which is similar to human UC, while the mild changes observed in the ileum indicate similarity to CD. This model is characterized by moderate inflammation, high reproducibility, and low mortality, making it valuable model in translational research on IBD. Full article

The idea that gut microbes or a “bacillus of crime” might promote criminal behavior was popularized in the early 20th century. Today, advances in neuromicrobiology and related omics technologies are lending credibility to the idea. In recent cases of dismissal of driving while intoxicated charges, courts in the United States and Europe have acknowledged that gut microbes can manufacture significant amounts of systemically available ethanol, without a defendant’s awareness. Indeed, emergent research is raising difficult questions for criminal justice systems that depend on prescientific notions of free moral agency. Evidence demonstrates that gut microbes play a role in neurophysiology, influencing cognition and behaviors. This may lead to justice involvement via involuntary intoxication, aggression, anger, irritability, and antisocial behavior. Herein, we discuss these ‘auto-brewery syndrome’ court decisions, arguing that they portend a much larger incorporation of neuromicrobiology and multi-omics science within the criminal justice system. The legalome, which refers to the application of gut microbiome and omics sciences in the context of forensic psychiatry/psychology, will likely play an increasing role in 21st century criminal justice. The legalome concept is bolstered by epidemiology, mechanistic bench science, fecal transplant studies, multi-omics and polygenic research, Mendelian randomization work, microbiome signature research, and human intervention trials. However, a more robust body of microbiota–gut–brain axis research is needed, especially through the lens of prevention, intervention, and rehabilitation. With ethical guardrails in place, greater inclusion of at-risk or justice-involved persons in brain science and microbiome research has the potential to transform justice systems for the better. Full article

Background/Objectives: Alcoholic liver disease (ALD) is intricately linked to gut microbiota dysbiosis and metabolic disturbances along the gut–liver axis. Octenyl succinic anhydride (OSA) starch escapes digestion in the small intestine and ferments in the colon, modulating gut microbiota and metabolism. This study explored the protective effects of OSA starch against ALD and elucidated the underlying gut microbiota–metabolite interactions. Methods: A chronic ethanol-fed mouse model was conducted to evaluate the protective effects of OSA starch against ALD, and multi-omics analyses integrating 16S rRNA sequencing, PICRUSt2 functional predictions, and metabolomics were used to reveal potential mechanism. Results: OSA starch supplementation in ALD mice significantly reduced liver fat accumulation, lowered the liver index to 4.11%, and restored serum transaminase levels closer to normal. Multi-omics analyses revealed that OSA starch enriched beneficial gut bacteria such as Faecalibaculum rodentium and Bifidobacterium adolescentis. OSA starch also enhanced microbial metabolic functions, including pyruvate, butanoate, and propanoate metabolism. These shifts were accompanied by regulation of fecal and serum metabolites, including pyruvate, 2-hydroxybutanoic acid, and lactic acid. Structural equation modeling further confirmed that OSA starch ameliorates ALD via coordinated modulation of gut microbiota, microbial functions, metabolites, and serum markers. Conclusions: OSA starch protects against alcoholic liver injury by remodeling the gut–liver metabolic network, presenting a promising dietary strategy for ALD. Full article

Background: Chronic ethanol consumption is a major global health concern traditionally associated with liver disease. Ethanol disrupts gut microbial communities, compromises intestinal barrier function, and contributes to hepatic, metabolic, and neurocognitive disorders. Methods: We conducted a systematic PubMed search and meta-analysis of 11 human and 19 animal studies evaluating ethanol-induced gut microbiota alterations. Studies were assessed for microbial diversity, taxonomic shifts, barrier integrity, and systemic effects. Effect sizes were calculated where possible, and interventional outcomes were examined. Results: Across species, ethanol exposure was consistently associated with reduced microbial diversity and depletion of beneficial commensals such as Faecalibacterium, Lactobacillus, Akkermansia, and Bifidobacterium, alongside an expansion of proinflammatory taxa (Proteobacteria, Enterococcus, Veillonella). Our analysis uniquely highlights discrepancies between human and animal studies, including opposite trends in specific genera (e.g., Akkermansia and Bifidobacterium) and the impact of confounders such as antibiotic exposure in human cohorts. We also demonstrate that microbiota-targeted interventions can partially restore diversity and improve clinical or behavioral outcomes. Conclusions: This meta-analysis highlights reproducible patterns of ethanol-induced gut dysbiosis across both human and animal studies. Full article

Background/Objective: Alcohol consumption has been linked to alterations in gut microbiota and insulin resistance. The alcohol dehydrogenase 1B (ADH1B) gene plays a crucial role in alcohol catabolism, where rs1229984 variant carriers (CT/TT) catabolize ethanol at an 80-fold faster rate than non-carriers (CC). This study investigates the relationships between ADH1B gene rs1229984 mutation, alcohol consumption, gut microbiota, and insulin resistance. Methods: We performed cross-sectional analysis on fecal metagenomic sequencing data from diabetes-free participants in a longitudinal cohort of the Hispanic Community Health Study/Study of Latinos. We used Analysis of Composition of Microbiomes to identify gut microbial species associated with alcohol consumption in non-carriers (n = 1399) and carriers (n = 193). We constructed genotype-specific gut microbiome scores (GMSs) based on the identified species associated with alcohol consumption to examine how gut microbiota may influence the relationship between alcohol consumption and insulin resistance across ADH1B genotypes. Insulin resistance was defined as Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) > 2.5. Results: Distinct microbial species associated with alcohol consumption were identified in non-carriers (54 species) and carriers (16 species). In non-carriers, the genotype-specific GMS modified the relationship between alcohol consumption and insulin resistance (P_interaction = 0.011). The odds ratios (OR) for insulin resistance with increasing alcohol consumption levels across low, moderate, and high tertiles of GMS were 0.75 (95%CI 0.58–0.96), 0.82 (0.67–1), and 1.13 (0.93–1.39), respectively. We identified that individual alcohol-related species, such as Prevotella copri, Ruminococcus callidus, and Erysipelatoclostridium ramosum, modified the relationship between alcohol consumption and insulin resistance in non-carriers. Conclusions: This study suggests that the ADH1B gene rs1229984 mutation is associated with gut microbiota profiles altered by alcohol consumption. Our findings also suggest a potential role of gut microbiota in the protective association between alcohol consumption and insulin resistance in the ADH1B variant non-carriers. Full article

The discovery that human beings may endogenously produce ethanol is not new and dates back at the end of the 19th century; recently, however, it has become clear that through the proliferation of gut microorganisms that produce ethanol from sugars or other substrates, blood alcohol level may be greater than 0, despite Homo sapiens sapiens lacking the enzymatic pathways to produce it. Very rarely this can lead to symptoms and/or to a disease, named gut fermentation syndrome or auto-brewery syndrome (ABS). The list of microorganisms (mostly bacteria and fungi) is very long and contains almost 100 different strains, and many metabolic pathways are involved. Endogenous ethanol production is a neglected entity, but it may be suspected in patients in whom ethanol consumption may be firmly excluded. Nevertheless, due to the growing prevalence of NAFLD (now renamed as MAFLD) worldwide, an ethanol-producing microorganism responsible for endogenous ethanol production such as Klebsiella pneumoniae or Saccharomices cerevisiae is increasingly sought in NAFLD patients, or in patients with metabolic diseases such as diabetes mellitus, obesity, or metabolic syndrome, at least in selected instances. In the absence of standard diagnostic and therapeutic guidelines, ABS requires a detailed patient history, including dietary habits, alcohol consumption, and gastrointestinal symptoms, and a comprehensive physical examination to detect unexplained ethanol intoxication. It has been proposed to start the diagnostic protocol with a standardized carbohydrate challenge test, followed, if positive, by the use of antifungal agents or antibiotics; indeed, fecal microbiota transplantation might be the only way to cure a patient with refractory ABS. Scientific societies should produce internationally agreed recommendations for ABS and other conditions linked to excessive endogenous ethanol production. Full article

Chronic alcohol consumption induces oxidative stress not only in the liver but also in the gastrointestinal tract, where prolonged intestinal ethanol absorption plays a pivotal and underrecognized role. This review reframes ethanol pharmacokinetics to emphasize sustained jejunal and ileal uptake, which maintains elevated blood alcohol levels and perpetuates redox imbalance across the gut–liver axis. We integrate recent findings on ethanol-induced barrier dysfunction, CYP2E1-mediated ROS production, microbial dysbiosis, and mitochondrial disruption, proposing that the intestine is an active site of injury and a driver of systemic inflammation. Key mechanistic insights reveal that gut-derived endotoxins, compromised epithelial integrity, and microbiome–mitochondria interactions converge to exacerbate hepatic and extrahepatic damage. We further explore emerging therapeutic strategies—ranging from NAD⁺ repletion and probiotics to fecal microbiota transplantation—that target this upstream pathology. Recognizing prolonged intestinal ethanol absorption as a clinically meaningful phase offers new directions for early intervention and redox-based treatment in alcohol-associated disease. Full article

The gut microbiota plays a central role in host energy metabolism and the development of metabolic disorders, partly through its influence on mitochondrial function. Probiotic supplementation, particularly with Lactobacillus rhamnosus GG, has been proposed as a strategy to modulate the microbiota and improve host metabolic health. Adolescent binge-like alcohol consumption is a critical public health issue known to induce neuroinflammation, oxidative stress, mitochondrial dysfunction, and intestinal dysbiosis, contributing to disorders such as alcoholic liver disease (ALD). This study aimed to evaluate the effects of L. rhamnosus GG supplementation on mitochondrial physiology in Sprague Dawley rats exposed to binge-like ethanol (BEP group) or saline (SP group) during adolescence (postnatal days 30–43). Starting on postnatal day 44, L. rhamnosus GG was administered orally for 28 days. Fecal colonization was confirmed by qPCR, and mitochondrial function was assessed in the liver, heart, and bone marrow through quantification of NADH, ATP, ADP/ATP ratio, total antioxidant capacity, and the expression of mitochondrial genes Higd2a, MnSOD1, and AMPKα1. L. rhamnosus GG supplementation induced tissue-specific mitochondrial adaptations. In the liver, it increased Higd2a expression and restored antioxidant and energy balance in ethanol-exposed rats. In the bone marrow, it reversed ethanol-induced metabolic stress and enhanced AMPKα1 expression. In contrast, in the heart, L. rhamnosus GG had minimal impact on mitochondrial energy markers but increased antioxidant capacity, indicating a more limited, redox-focused effect. These findings suggest that L. rhamnosus GG exerts context-dependent, tissue-specific benefits on mitochondrial physiology, primarily through the modulation of antioxidant defenses, activation of AMPKα1, and remodeling of respiratory complexes. This probiotic may represent a promising therapeutic strategy to mitigate mitochondrial dysfunction associated with early-life alcohol exposure. Full article

A promising strategy to improve the gut microbiome in hypertension is to target the gut microbiota. This study evaluated the effects of a potential nutraceutical product composed of three strains of Limosilactobacillus (L.) fermentum, quercetin, and resveratrol on the intestinal microbiome of healthy and hypertensive subjects. The nutraceutical product consisting of strains of L. fermentum 139, 263 and 296, fructooligosaccharides (200 mg), quercetin (160 mg), and resveratrol (150 mg) (LfQR) was added to the in vitro fecal fermentation process occurring for 48 h. Fecal samples of healthy and hypertensive subjects were allocated into four groups: (i) healthy controls (CTL); (ii) healthy controls with the addition of LfQR (CTL + LfQR); (iii) hypertensive (HTN) subjects; and (iv) hypertensive subjects with the addition of LfQR (HTN + LfQR). The diversity and composition of the fecal microbiota and the production of microbial metabolites were evaluated. CTL and HTN groups exhibited a distinct gut microbiota composition, as shown by the β-diversity assessment. The addition of the potentially nutraceutical-modulated β-diversity was similar between CTL and HTN groups, suggesting a similar gut microbiome composition after nutraceutical addition. The addition of the nutraceutical product increased the relative abundance of Enterobacteriaceae in the CTL group and that of Lachnospiraceae in the HTN group. The nutraceutical media showed higher levels of sugars (maltose, fructose, and glucose), lactic acid, ethanol, succinic acid, and acetic acid compared to the CTL and HTN media. Although the results are heterogeneous between healthy and hypertensive fermentation media, it was demonstrated that the nutraceutical formulation can modulate the intestinal microbiota and its metabolic activity. Full article