Search Results (366)

Constipation is a prevalent gastrointestinal disorder that significantly impairs quality of life. While pharmacological agents such as loperamide are widely used to induce constipation in experimental models, there is increasing interest in natural alternatives for alleviating intestinal dysfunction. In this study, we investigated the laxative effects of soybean powder fermented by Bacillus subtilis DKU_09 in a loperamide-induced rat model of constipation. The probiotic strain was isolated from cheonggukjang, a traditional Korean fermented soybean paste, and its identity was confirmed through 16S rRNA sequencing. Fermented soybean powder was characterized morphologically via scanning electron microscopy and chemically via HPLC to assess its isoflavone content. Rats were administered loperamide (5 mg/kg) for four days to induce constipation and were then treated with fermented soybean powder at doses of 100, 200, or 300 mg/kg. No pharmacological laxatives (e.g., PEG) were used as a positive control; instead, values from the treatment groups were compared with those from the loperamide-only constipation group. Key outcomes of fecal output, water content, colonic fecal retention, and gastrointestinal transit ratio were measured. The fermented product significantly improved stool frequency and moisture content, reduced colonic fecal retention, and restored gastrointestinal transit in a dose-dependent manner. Notably, the 300 mg/kg group demonstrated nearly complete recovery of fecal parameters without affecting body weight. Statistical analysis was performed using one-way ANOVA followed by Tukey’s post hoc test. These findings suggest that Bacillus subtilis-fermented soybean powder exerts synergistic laxative effects through the combined action of probiotic viability and fermentation-enhanced bioactive compounds such as aglycone isoflavones. This study supports the potential use of fermented soybean-based nutraceuticals as a natural and safe intervention for constipation and gastrointestinal dysregulation. Full article

The growing interest in probiotic bacteria within the food industry is driven by their recognized health benefits for consumers. However, preserving their therapeutic viability and stability during gastrointestinal transit remains a formidable challenge. Hence, this research aimed to enhance the viability of Lactobacillus reuteri through microencapsulation using a binary polysaccharide mixture composed of low acyl gellan gum (LAG), high acyl gellan gum (HAG), and calcium for the microencapsulation of L. reuteri. To achieve this, the Box–Behnken design was applied, targeting the optimization of L. reuteri microencapsulated to withstand simulated gastrointestinal conditions. The microcapsules were crafted using the internal ionic gelation method, and optimization was performed using response surface methodology (RSM) based on the Box–Behnken design. The model demonstrated robust predictive power, with R² values exceeding 95% and a lack of fit greater than p > 0.05. Under optimized conditions—0.88% (w/v) LAG, 0.43% (w/v) HAG, and 24.44 mM Ca—L. reuteri reached a viability of 97.43% following the encapsulation process. After 4 h of exposure to simulated gastric fluid (SGF) and intestinal fluid (SIF), the encapsulated cells maintained a viable count of 8.02 log CFU/mL. These promising results underscore the potential of biopolymer-based microcapsules, such as those containing LAG and HAG, as an innovative approach for safeguarding probiotics during gastrointestinal passage, paving the way for new probiotic-enriched food products. Full article

Ulcerative colitis is a chronic intestinal disorder that belongs to the category of inflammatory bowel diseases, and is usually characterized by the presence of bloody diarrhea and abdominal pain, due to an accelerated transit and intestinal sensibilization following inflammation of the colonic mucosa. However, the literature reports that ulcerative colitis may sometimes feature fecal stasis with constipation. This apparent paradox may be partially explained by the motor abnormalities of the large bowel following inflammation, damage to the enteric innervation, and the onset of parietal fibrosis over time. Moreover, some anorectal abnormalities such pelvic floor dyssynergia may explain the symptoms of constipation reported in subsets of patients. Since these abnormalities may be responsible for diagnostic delays and non- or partial responses to therapy, it is important to recognize them as early as possible to avoid incorrect clinical and therapeutic approaches to these patients. Full article

The cecal microbiota is essential for intestinal health and performance. This study describes the succession patterns of the cecal microbiota in Japanese quail (Coturnix japonica) until 42 days of age. Sixty quails were raised using standard conditions and fed corn–soybean meal diets. Cecal contents were sampled from five birds weekly from 7 to 42 days of age and submitted to Illumina 16S rRNA sequencing for metabarcoding analysis. Diversity and functional prediction were carried out with QIIME2, PICRUSt2, STAMP and MicrobiomeAnalyst 2.0. Firmicutes increased from 50% at 7 days to more than 80% at 42 days, whereas Bacteroidota decreased from 45% to 12% in the same period. Alpha diversity progressively increased with age, indicating a richer and more balanced microbiota at later ages. Genera such as Bacteroides were predominant in the beginning and later were replaced by Lachnospiraceae, Ruminococcus and Faecalibacterium. These developmental taxonomic features aligned with significant shifts in ten metabolic pathways identified by prediction, revealing a transition from biosynthetic functions to complex carbohydrate metabolism and cell wall biosynthesis. The first seven days are considered a critical window for probiotics intervention, which may favor the establishment of a microbiota that is more stable and beneficial to quail performance. Full article

This study developed phospholipid-based liposomes loaded with extract from wild thyme (Thymus serpyllum L.) tea processing residues to enhance polyphenol stability and delivery. Liposomes were prepared with phospholipids alone or combined with 10–30 mol% cholesterol or β-sitosterol. The effect of different lipid compositions on encapsulation efficiency (EE), particle size, polydispersity index (PDI), zeta potential, stability, thermal properties, diffusion coefficient, and diffusion resistance of the liposomes was investigated. Liposomes with 10 mol% sterols (either cholesterol or β-sitosterol) exhibited the highest EE of polyphenols, while increasing sterol content to 30 mol% resulted in decreased EE. Particle size and PDI increased with sterol content, while liposomes prepared without sterols showed the smallest vesicle size. Encapsulation of the extract led to smaller liposomal diameters and slight increases in PDI values. Zeta potential measurements revealed that sterol incorporation enhanced the surface charge and stability of liposomes, with β-sitosterol showing the most pronounced effect. Stability testing demonstrated minimal changes in size, PDI, and zeta potential during storage. UV irradiation and lyophilization processes did not cause significant polyphenol leakage, although lyophilization slightly increased particle size and PDI. Differential scanning calorimetry revealed that polyphenols and sterols modified the lipid membrane transitions, indicating interactions between extract components and the liposomal bilayer. FT-IR spectra confirmed successful integration of the extract into the liposomes, while UV exposure did not significantly alter the spectral features. Thiobarbituric acid reactive substances (TBARS) assay demonstrated the extract’s efficacy in mitigating lipid peroxidation under UV-induced oxidative stress. In contrast, liposomes enriched with sterols showed enhanced peroxidation. Polyphenol diffusion studies showed that encapsulation significantly delayed release, particularly in sterol-containing liposomes. Release assays in simulated gastric and intestinal fluids confirmed controlled, pH-dependent polyphenol delivery, with slightly better retention in β-sitosterol-enriched systems. These findings support the use of β-sitosterol- and cholesterol-enriched liposomes as stable carriers for polyphenolic compounds from wild thyme extract, as bioactive antioxidants, for food and nutraceutical applications. Full article

Background: Gastric cancer (GC) is a highly heterogeneous disease and remains one of the major causes of cancer-related mortality worldwide. The vast majority of GC cases are adenocarcinomas including diffuse and intestinal GC that may differ in their incidence between Asian and non-Asian cohorts. The intestinal-subtype GC has declined over the past 50 years. In contrast to the intestinal-subtype adenocarcinoma, the incidence of diffuse-subtype GC, often associated with poor overall survival, has constantly increased in the USA and Europe. The aim of this study was to analyze the expression and clinical significance of steroid hormone receptors, two membrane-bound receptors (ERRγ and GPER), and several genes involved in epigenetic alterations. The findings may contribute to revealing events driving tumorigenesis and may aid prognosis. Methods: Using mRNA from diffuse and intestinal GC tumor samples, the expression level of 11 genes, including those coding for sex hormone receptors (estrogen receptors ERα and ERβ), progesterone receptor (PR) and androgen receptor (AR), and the putative relevant ERRγ and GPER receptor were determined by RT-qPCR. Results: In diffuse GC, the expression of ERα, ERβ, PR and AR differed from their expression in the intestinal subtype. The expression of ERα and ERβ was strongly increased in the diffuse subtype compared to the intestinal subtype (×1.90, p = 0.001 and ×2.68, p = 0.002, respectively). Overexpression of ERα and ERβ was observed in diffuse GC (15 and 42%, respectively). The expression levels of PR and AR were strongly decreased in the intestinal subtype as compared to diffuse GC (×0.48, p = 0.005 and ×0.25, p = 0.003, respectively; 37.5% and 56% underexpression). ERα, ERβ, PR and AR showed notable differences for clinicopathological correlation in the diffuse and intestinal GC. A significant decrease of ERα, ERβ, PR and AR in intestinal GC correlated with the absence of lymphatic invasion and lower TNM (I-II). In diffuse GC, among the hormone receptors, increases of ERs and PR mainly correlated with expression of growth factors and receptors (IGF1, FGF7 and FGFR1), and with genes involved in epithelial-mesenchymal transition (VIM and ZEB2) or cell migration (MMP2). Our results also report the strong decreased expression of ERRγ and GPER (two receptors that bind estrogen or xenoestrogens) in diffuse and intestinal subtypes. Conclusions: Our study identified new target genes, namely hormone receptors and membrane receptors (ERRγ and GPER), whose expression is associated with an aggressive phenotype of diffuse GC, and revealed the importance of epigenetic factors (EZH2, HOTAIR, H19 and DNMT1) in gastric cancers. Full article

The transition from live bait (LF) feeding to compound feed (CF) feeding in aquaculture is of great production significance. In recent decades, cultivation with CF has become a focus for practitioners and researchers dealing with Siniperca chuatsi. This study focused on experimental subjects of S. chuatsi fed with CF and LF, using short-distance transportation as a stimulating factor. For the first time, the differences between S. chuatsi fed with CF and LF were analyzed from the perspective of stress response during transportation. This study found that after transportation stimulation, the activities of LZM and the contents of MDA, TGs, and glucose in the brain, liver, kidneys, muscles, stomach, pyloric caecum, intestines, and blood of S. chuatsi fed with CF were higher compared to S. chuatsi fed with LF (p < 0.05). Significant differences were observed in the impacts of various diets on the gastrointestinal tract, particularly in the intestine. In summary, this study found that S. chuatsi fed with CF could retain more energy after transport stimulation and exhibited stronger resistance to microbial stress, but they had a weaker antioxidant capacity. Therefore, in future research on CF for S. chuatsi, we need to focus on its ability to enhance antioxidant capacity. Full article

Crohn’s disease (CD), characterized by chronic gastrointestinal inflammation, is complicated by intestinal stenosis resulting from dysregulated fibrogenesis and is marked by excessive extracellular matrix (ECM) deposition, fibroblast activation, and luminal obstruction. While biologics control inflammation, their failure to halt fibrosis underscores a critical therapeutic void. Emerging evidence highlights the multifactorial nature of stenosis-associated fibrosis, driven by profibrotic mediators and dysregulated crosstalk among immune, epithelial, and mesenchymal cells. Key pathways, including transforming growth factor (TGF-β), drosophila mothers against decapentaplegic protein (Smad) signaling, Wnt/β-catenin activation, epithelial–mesenchymal transition (EMT), and matrix metalloproteinase (MMP) and tissue inhibitors of metalloproteinase (TIMP)-mediated ECM remodeling, orchestrate fibrotic progression. Despite the current pharmacological, endoscopic, and surgical interventions for fibrostenotic CD, their palliative nature and inability to reverse fibrosis highlight an unmet need for disease-modifying therapies. This review synthesizes mechanistic insights, critiques therapeutic limitations with original perspectives, and proposes a translational roadmap prioritizing biomarker-driven stratification, combinatorial biologics, and mechanistically targeted antifibrotics. Full article

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder associated with gut microbiota dysbiosis and impaired intestinal barrier function. Probiotic interventions have shown potential in alleviating intestinal inflammation and restoring microbial balance. This study explores the protective effects of Lacticaseibacillus paracasei (L. paracasei) E10 in mice. L. paracasei E10 demonstrated strong gastrointestinal transit tolerance, high mucosal adhesion, and probiotic properties such as hydrophobicity and aggregation ability (p < 0.05). The oral administration of L. paracasei E10 significantly alleviated colitis symptoms by reducing the disease activity index, preserving colonic architecture, increasing goblet cell density, and upregulating tight junction proteins, thereby enhancing intestinal barrier integrity. 16S rRNA sequencing revealed that L. paracasei E10 supplementation enriched microbial diversity, increased the abundance of Muribaculaceae, and modulated the Firmicutes/Bacteroidetes ratio, contributing to gut homeostasis. These findings indicate that L. paracasei E10 is a potential candidate for IBD management. Full article

Background/Objectives: Colorectal cancer (CRC) is one of the most prevalent cancers worldwide. Even though the screening programs have decreased the incidence rates, the prognosis for CRC varies depending on the stage at diagnosis. Thus, early diagnosis is still a big challenge due to screening methods, and subsequent diagnosis is not very sensitive. Methods: In this work, LC-MS-based metabolomics, a powerful and sensitive tool to study complex dynamic changes, was used to analyze 211 human fecal samples from control individuals (CTRL), adenoma (AA), and CRC patients. Results: Multivariate and univariate statistical analysis highlighted cholesteryl esters (CEs) and fecal haemoglobin, quantified by fecal immunochemical test (FIT), as relevant biomarkers that clearly differentiate CRC from AA and CTRL. Predictive models based on random forest and the area under the curve (AUC) of the receiver operating characteristic curve (ROC) demonstrate that CEs, together with FIT measurement, improved the CRC and CTRL classification, but not AA. This study revealed that the AA group is a transitional stage with high heterogeneity. The increased tendency observed in CEs from CTRL to CRC might be related to the imbalance of cholesterol homeostasis due to cancer cells requiring a high cholesterol level for cell development and proliferation. The free cholesterol is probably obtained from CEs, as it is the most cost/effective way to obtain the needed cholesterol. Conclusions: The accumulation of CEs is produced by two possible approaches: (1) dysfunction of cholesterol absorption in the small intestine and/or (2) transported inside exosomes from cell to cell to promote proliferation. Full article

Pelagic nudibranchs exemplify evolutionary convergences towards streamlined, transparent body forms adapted for life in the planktonic environment. Here, we describe a new genera and species, designated as Pleuropyge melaquensis gen. et sp. nov. This species belongs to the family Phylliroidae and is distinguished by key diagnostic characters, including a laterally positioned anus approximately one-third of the body length from the head, the absence of a cephalic disc, and an anterior hepatic caecum that is longer than the intestine. The description of P. melaquensis contributes to the classification of a third genus and a fourth species within the Phylliroidae family. This study offers novel insights into the functional and structural traits that have enabled nudibranchs to transition from benthic to pelagic environments. Full article

Bariatric surgery involves major changes in the anatomy and physiology of the gastrointestinal tract, which may alter oral drug bioavailability and efficacy. Phosphodiesterase-5 inhibitor (PDE5i) drugs are the first-line treatment of erectile dysfunction, a condition associated with a higher BMI. In this paper, we examine the PDE5i vardenafil for possible post-bariatric changes in solubility/dissolution and absorption. Vardenafil solubility was determined in vitro, as well as ex vivo using aspirated gastric contents from patients prior to vs. following bariatric procedures. Dissolution was tested in vitro under unoperated stomach vs. post-gastric sleeve/bypass conditions. Lastly, the gathered solubility/dissolution data were used to produce an in silico physiologically based pharmacokinetic (PBPK) model (GastroPlus^®), where gastric volume, pH, and transit time, as well as proximal GI bypass (when relevant) were all adjusted for, evaluating vardenafil dissolution, gastrointestinal compartmental absorption, and pharmacokinetics before vs. after different bariatric procedures. pH-dependent solubility was demonstrated for vardenafil with low (pH 7) vs. high solubility (pH 1–5), which was confirmed ex vivo. The impaired dissolution of all vardenafil doses under post-gastric bypass conditions was demonstrated, contrary to complete (100%) dissolution under pre-surgery and post-sleeve gastrectomy conditions. Compared to unoperated individuals, PBPK simulations revealed altered pharmacokinetics post-gastric bypass (but not after sleeve gastrectomy), with 30% lower peak plasma concentration (C_max) and 40% longer time to C_max (T_max). Complete absorption after gastric bypass is predicted for vardenafil, which is attributable to significant absorption from the large intestine. The biopharmaceutics and PBPK analysis indicate that vardenafil may be similarly effective after sleeve gastrectomy as before the procedure. However, results after gastric bypass question the effectiveness of this PDE5i. Specifically, vardenafil’s onset of action might be delayed and unpredictable, negatively affecting the practicality of the intended use. Full article

Neuropeptide FF (NPFF) receptor antagonists prevent morphine-mediated antinociceptive tolerance, and compounds with dual mu opioid receptor (MOR) agonist and NPFF antagonist activity produce antinociception without tolerance. Compounds synthesized showed affinities in radioligand competition binding assays in the nM and µM range at the opioid and NPFF receptors, respectively, and displayed substitution-dependent functional profiles in the [³⁵S]GTPγS functional assay. From six compounds screened in vivo for antinociception and ability to prevent NPFF-induced hyperalgesia in mouse warm water tail withdrawal tests, compound 22b produced dose-dependent MOR-mediated antinociception with an ED₅₀ value (and 95% confidence interval) of 6.88 (4.71–9.47) nmol, i.c.v., and also prevented NPFF-induced hyperalgesia. Meanwhile, 22b did not demonstrate the respiratory depression, hyperlocomotion, or impaired intestinal transit of morphine. Moreover, repeated treatment with 22b produced a 1.6-fold rightward shift in antinociceptive dose response, significantly less acute antinociceptive tolerance than morphine. Evaluated for microsomal stability in vitro and in vivo pharmacokinetic profile, 22b showed suitable microsomal stability paired in vivo with a large apparent volume of distribution and a clearance smaller than the hepatic flow in rats, suggesting no extra-hepatic metabolism. In conclusion, the present study confirms that dual-action opioid–NPFF ligands may offer therapeutic promise as analgesics with fewer liabilities of use. Full article

Endometriosis (EMS) is a long-term inflammatory disease. It represents one of the most prevalent gynecological conditions, impacting an estimated 5% of reproductive women. Therefore, endometriosis contributes to substantial worldwide health challenges and healthcare costs. In EMS disease, endometrial glandular and stromal tissues are abnormally located outside the uterus. Similarly to the natural endometrium, these tissues grow and proliferate in response to estrogen-dependent signals. The pain and limited effectiveness of treatments are often linked to the inflammatory reaction triggered by EMS-associated ectopic tissue. This is especially amplified during the peaks of estrogen release that occur as the menstrual cycle transitions from the proliferative phase to ovulation. Maintaining the integrity of the mucosal lining, defending against pathogenic insults, and controlling physiological processes are all made possible by a healthy, balanced state of gut biomass. Additionally, numerous intestinal bacteria have been discovered to possess estrogen-metabolizing enzymes, which affect the estrobolome and, consequently, influence estrogen-related disorders. Therefore, there is increasing interest in understanding the role of microbiota and the estrobolome in endometriosis pathogenesis. This review will focus on the role of microbiota and the impact of estrobolome alterations in endometriosis pathogenesis. Full article

This randomized, double-blind, placebo-controlled, three-arm clinical trial evaluated the effects of a proprietary bioactive fucoidan-rich extract derived from Saccharina latissima (SLE-F) on gut microbial composition and function in healthy adults. The objective of the study was to assess the potential of SLE-F to beneficially modulate the gut microbiome, with this paper specifically reporting on microbial diversity, taxonomic shifts, and functional pathway outcomes. Ninety-one participants received either a low dose (125 mg), high dose (500 mg), or placebo twice daily for four weeks. The primary endpoint was the microbiome composition assessed via 16S rRNA sequencing (V3–V4 region), with secondary outcomes including surveys, adverse event monitoring, and clinical evaluations. High-dose supplementation resulted in dose-dependent improvements in the microbial diversity; increased abundance of beneficial taxa, including Bifidobacterium, Faecalibacterium, and Lachnospiraceae; and reductions in inflammation-associated taxa, such as Enterobacteriaceae and Pseudomonadota. A functional pathway analysis showed enhancement in short-chain fatty acid biosynthesis and carbohydrate metabolism. The low-dose group showed modest benefits, primarily increasing Bifidobacterium, with limited functional changes. In vitro colonic simulations further demonstrated a dose-dependent increase in short-chain fatty acids and postbiotic metabolite production following SLE-F exposure. SLE-F was well tolerated, with only mild, nonspecific adverse events reported. These findings support the potential of SLE-F as a safe and effective microbiome-modulating agent, warranting further study of the long-term use and synergy with dietary interventions. Full article