Search Results (2,619)

Background/Objectives: IBDs are chronic relapsing inflammatory intestinal disorders whose precise etiology is still only poorly defined: critical for their pathogenesis is the CCL20/CCR6 axis, whose modulation by small molecules may represent an innovative therapeutic approach. The aim of the present work is to test the potential efficacy of two molecules, MR120, a small selective CCR6 antagonist, active in TNBS- and chronic DSS-induced murine models of intestinal inflammation, and its derivative MR452, a well-tolerated agent endowed with improved anti-chemotactic in vitro properties, in the adoptive transfer colitis model. To the best of our knowledge, this is the first attempt to use adoptive transfer colitis to test modulators of the CCL20/CCR6 axis. Methods and Results: The induction of colitis in immunocompromised mice receiving CD4⁺CD25⁻ T cells i.p. resulted in a moderate inflammation and was met with limited protective responses following daily subcutaneous administration of MR120 or MR452 for 8 weeks. Both compounds significantly reduced colonic myeloperoxidase activity, and MR452 also lowered CCL20 levels in the gut, but they failed to prevent the increase in the Disease Activity Index, colon wall thickening, and macroscopic inflammation score. Conclusions: Our findings suggest that, despite the beneficial effects played by MR120 against subacute TNBS- and chronic DSS-induced colitis, the pharmacological targeting of the CCL20/CCR6 axis in the adoptive transfer model has a negligible effect in ameliorating the IBD-like phenotype driven by the altered intestinal immune homeostasis and by the disrupted function of immune-suppressive Treg cells. Full article

MPs are pervasive pollutants in marine ecosystems, posing risks to aquatic organisms due to their small size and bioaccumulation potential. This study investigated the intestinal toxicity of MP particles extracted from mangrove sediments in zebrafish, comparing the effects before and after microbial degradation. Zebrafish were exposed to either undegraded MPs or microbially degraded MP extracts at concentrations of 0 (control), 2, 10, and 50 mg/L for 21 days in 10 L tanks (stocking density: 10 fish/L), with three replicate tanks per concentration. MPs were dispersed ultrasonically before addition to the water. Intestinal samples were collected on 7, 14, and 21 days for the analysis of immune response (tumor necrosis factor-alpha, TNF-α; interleukin-1 beta, IL-1β; interleukin-6, IL-6; interleukin-8, IL-8) and antioxidant activity (superoxide dismutase, SOD; catalase, CAT). Histopathological analysis revealed intestinal wall thinning, villus damage, and epithelial cell detachment in zebrafish exposed to both undegraded and degraded MP extracts; however, undegraded MPs induced more severe intestinal damage. Results indicated dynamic changes in cytokine expression: TNF-α decreased initially before increasing, while IL-1β and IL-8 first rose then declined. IL-6 peaked on day 7, dropped by day 14, and increased again on day 21. CAT expression decreased, whereas SOD increased only in the pre-degradation group. Microbial degradation reduced intestinal damage severity, with effects intensifying at higher MP exposure levels. These findings demonstrate that MPs can impair zebrafish digestive systems, but microbial degradation mitigates their toxicity. This study underscores the importance of biodegradation as a potential environmental remediation strategy and provides experimental evidence on MPs’ impact on aquatic organisms. Full article

Small ruminant production is a significant sector of agricultural industry in Texas, USA. Heat stress has a negative effect on productivity and animal health. Cholecalciferol, a form of vitamin D₃, may enhance the function of immune cells and help ensure healthy immune function in farm animals exposed to heat stress. Practical applications of vitamin D₃ against infectious diseases can benefit from the protective effects of a delivery system comprised of soy protein isolate and stachyose in emulsion gel. The prebiotic oligosaccharide stachyose has shown to have a great potential as a substrate for beneficial intestinal bacteria, which are thought to modulate the immune system. Cellular and humoral immunity are both impaired in dairy animals under heat stress. The delivery of vitamin D₃ embedded within the soy protein isolate-stachyose emulsion gel resulted in a marked increase in 25-hydroxyvitamin D₃ [25-(OH)-D₃] concentration in blood serum. Chicken egg albumin (OVA)-immunized goats produced low anti-OVA immunoglobulin G (IgG) responses. In contrast, OVA-immunized goats fed vitamin D₃ within the soy protein isolate-stachyose emulsion gel diet strongly stimulated antibody production. These results show that anti-OVA IgG responses can be modulated in dairy goats using vitamin D₃, particularly if this vitamin is delivered in the form of emulsion gel. The results seem to depend on the highly hydrated gel matrix of soy protein isolate-stachyose at the low pH of the stomach as monitored by oxygen-17 (¹⁷O) and proton (¹H) nuclear magnetic resonance (NMR). In addition, the prebiotic nature of stachyose may boost beneficial gut bacteria, most notably for immune health and reducing the risk of infectious diseases. Full article

A novel diamine oxidase (DAO) was discovered in the bacterium Glutamicibacter halophytocola (DAO-GH). The gene of DAO-GH was integrated into the genome of the yeast Komagataella phaffii and recombinantly produced under control of the methanol-inducible AOX1 promoter in a bioreactor cultivation. A high DAO activity of 70.2 ± 5.2 µkat/L_culture (5.25 ± 0.22 µkat/g_protein) was yielded after 90 h of cultivation. The DAO-GH was partially purified by the polyethyleneimine precipitation of nucleic acids, fractionated ammonium sulfate precipitation and hydrophobic interaction chromatography, resulting in a specific DAO activity of 19.7 µkat/g_Protein. The DAO-GH was then biochemically investigated regarding its potential for histamine and tyramine degradation in fermented foods and the human small intestine. Interestingly, the DAO-GH showed activity even at a low pH of 5 and low temperature of 6 °C. Both histamine and tyramine were effectively degraded and DAO-GH showed especially very high affinity towards tyramine (K_m of 0.009 mM). The DAO-GH was shown to be capable of degrading around 20% of the initially applied histamine in tuna paste (pH 5.6) at 5 °C within 24 h and completely degraded the histamine in a simulated intestinal fluid within 1.5 h in bioconversion experiments. The DAO-GH was spray-dried for the production of a storable enzyme preparation. Only around 17% of activity were lost in this process and the DAO-GH remained stable at room temperature for at least 3 months. The discovery of this DAO with its very advantageous biochemical properties allows the preparation of histamine-reduced or -free fermented foods by a simple enzymatic treatment or the treatment of histamine intolerance symptoms as a dietary supplement or medicine. Full article

Cellulose nanofibers and pectin are promising candidates for polysaccharide-based gel carriers. However, their integration into a structurally modified hybrid gel system has not been extensively investigated. In this study, hybrid cryogels with a pH-responsive release profile favoring small intestinal delivery were prepared by freeze-drying various ratios of anionic nanofibrillar cellulose (aNFC) and amidated pectin (AP). Under acidic conditions, carboxylate protonation reduced intermolecular electrostatic repulsion, promoting the formation of the aNFC/AP hybrid gel network. Increasing the AP content enhanced the mechanical strength of the hydrogels and resulted in larger pore sizes after freeze-drying. The hybrid cryogels prolonged the release of a model drug for up to 20–30 min at pH 3.0, while exhibiting rapid release within 1–2 min when the pH exceeded 6.5, due to gel network collapse. The release behavior was governed by both the porous morphology and the crosslinking density of the cryogel scaffolds. These findings demonstrate that aNFC/AP hybrid cryogels possess a well-defined pH-responsive functional window (pH 6.5–7.0) and hold strong potential as oral drug delivery systems targeting the small intestine. Full article

Glutamine (Gln) supplementation during the weaning period can alleviate stress in piglets. However, free Gln has poor stability and low absorption in the small intestine. Glycyl-glutamine (Gly-Gln), a stable dipeptide form of Gln, has been evaluated as a potential alternative in pig nutrition. This study investigated the effects of Gly-Gln at 0, 0.125%, 0.25%, 0.375%, and 0.50%, as well as a Gly + Gln positive control, on growth performance, intestinal morphology, immunity, antioxidant status, and nutrient apparent digestibility in weaned piglets. The results showed that dietary supplementation with 0.25%, 0.375%, or 0.50% Gly-Gln significantly increased average daily gain, average daily feed intake, and final weight (p < 0.05). Linear and quadratic effects (p < 0.05) were observed for growth performance indicators, suggesting that moderate supplementation levels yielded optimal benefits. Dietary Gly-Gln supplementation with 0.25%, 0.375%, or 0.50% Gly-Gln significantly increased serum immunoglobulin (IgG, IgA, and IgM), insulin, insulin growth factor 1, growth hormone, and T4 and T3 contents, and decreased IFN-γ and IL-1β contents (p < 0.05). Diets supplemented with 0.25, 0.375, or 0.50% Gly-Gln increased total antioxidant capacity and superoxide dismutase content in serum and liver, and decreased MDA content (p < 0.05). Compared with the negative control group, dietary supplementation of 0.25%, 0.375%, or 0.50% Gly-Gln significantly increased the mRNA expression of ZO-1, Occludin, and Claudin-1 in the jejunum (p < 0.05). Furthermore, crude protein digestibility was significantly improved in piglets receiving 0.375% and 0.5% Gly-Gln (p < 0.05), with a significant linear relationship between Gly-Gln level and digestibility. In conclusion, 0.25% is the minimum effective dose of Gly-Gln for improving weaning outcomes. Gly-Gln is more effective than equivalent doses of free glycine and glutamine in enhancing growth performance, gut barrier integrity, and nutrient utilization in weaned piglets. Full article

The human gastrointestinal tract hosts a complex ecosystem known as the gut microbiota, which plays a crucial part in digestion and immune system function. Among the clinically recognized manifestations of dysbiosis in this system are Small Intestinal Bacterial Overgrowth (SIBO), Intestinal Methanogen Overgrowth (IMO), Small Intestinal Fungal Overgrowth (SIFO), and Large Intestinal Bacterial Overgrowth (LIBO). This study aims to investigate the complex pathophysiological mechanisms underlying these syndromes and their diagnostics and therapeutic options, focusing primarily on the roles of methane-producing archaea and fungal overgrowth. The methods employed in this study involve a comprehensive analysis and synthesis of peer-reviewed articles, systematic reviews, clinical trials, and meta-analyses. This review summarizes that methane production by Methanobrevibacter smithii was linked to altered fermentation, reduced microbial diversity, and slowed intestinal transit. Fungal species were associated with increased intestinal permeability, inflammation, and biofilm formation. Targeted interventions addressing microbial imbalances demonstrated potential therapeutic value. This review highlights the complex and multifactorial nature of gut dysbiosis, revealing its impact beyond the gastrointestinal tract. While emerging therapies targeting methanogens, fungi, and biofilms show promise, further research is essential to optimize their clinical application. The findings emphasize the need for interdisciplinary collaboration to refine diagnostic and therapeutic strategies. Full article

Background/Objectives: Medium- and long-chain triacylglycerol (MLCT) and 2′-fucosyllactose (2′-FL) are functional ingredients abundant in human milk; however, their effects on small intestinal development and health remain largely unknown, and no research has explored their potential combined effects. Methods: In this study, growing C57BL/6 mice (3 weeks old) were fed diets without or with 2.5 g/100 g of MLCT, 2′-FL, or the combination (MLCT + 2′-FL; 5:1) for 21 days. Body weight, major organ indices, small intestinal morphology-related indicators (small intestinal length, villus height, crypt depth, villus height/crypt depth (V/C) ratio, and epithelial cell proliferation), and intestinal barrier function markers (goblet cell and Paneth cell count, protein expression of ZO-1 and occludin, and levels of sIgA and LPS) were measured. Results: In addition to the shared promotion of epithelial cell proliferation, MLCT intervention raised villus height and crypt depth, while 2′-FL intervention elevated Paneth cell count and sIgA levels. Notably, MLCT + 2′-FL intervention offered additional advantages (increasing the V/C ratio, goblet cell count, and expression of ZO-1 and occludin) without affecting crypt depth. 16S rRNA sequencing analysis of cecal contents revealed that all three interventions mainly affected beta diversity rather than alpha diversity, and enriched differentially abundant bacterial taxa: Erysipelotrichaceae, Faecalibaculum, UBA1819, and Faecalitalea in the MLCT group; Enterobacteriaceae, Escherichia, and Allobaculum in the 2′-FL group; Bifidobacterium, Romboutsia, Clostridia, and several other bacterial taxa in the MLCT + 2′-FL group. Conclusions: These results indicate that MLCT and 2′-FL interventions alone appear to provide different benefits for small intestinal development, and their combination may confer more comprehensive advantages. Full article

In humans, the bioactivity of polyphenols is highly dependent on dose intake and their interactions with the gastrointestinal tract and gut microbiota, which metabolize polyphenols into bioactive or inactive derivatives. Polyphenols are only partially absorbed in the small intestine, where enzymatic hydrolysis releases aglycone forms that may cross the gut barrier. A significant proportion of polyphenols escapes absorption and reaches the colon, where resident microbes convert them into simpler phenolic metabolites. Such molecules are often more bioavailable than the parent compounds and can enter systemic circulation, leading to distant effects. Although higher polyphenol consumption has been associated with preventive and therapeutic outcomes, even low intake or poor intestinal absorption may still confer benefits, as polyphenols in the colon can positively modulate gut microbiota composition and function, contributing to favorable shifts in the microbial metabolome. These interactions can influence host metabolic, immune, and neurological pathways, particularly through the gut–liver–brain axis. To provide a comprehensive understanding of these relationships, this review examines the dose-related activity of polyphenols, their microbiota-mediated biotransformation, their bioavailability, and the health effects of their metabolites, while also presenting a comparative overview of key studies in the field. We underscore the importance of integrating microbiome and polyphenol research to recapitulate and contextualize the health benefits of dietary polyphenols. 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/Objectives: Fluoroquinolones (FQs) are broad-spectrum antibiotics associated with a constellation of severe, long-lasting adverse effects termed Fluoroquinolone-Associated Disability (FQAD), which often includes neuropsychiatric and gastrointestinal (GI) symptoms. Despite patient reports, GI dysfunction is not formally recognized within FQAD. This study aimed to establish a rodent model to investigate whether ciprofloxacin (CPX), the most commonly prescribed FQ, exposure induced long-lasting anxiety-like behavior and/or GI motility alterations. Methods: To test our hypothesis, Sprague Dawley rats were orally administered 20 mg/kg CPX, amoxicillin (AMX, antibiotic control), or saline (CTL) daily for 14 days. Anxiety-like behaviors were assessed weekly for 4 weeks post-treatment using the Elevated Plus-Maze, Marble Burying, and Open Field tests. GI transit was measured 2 weeks post-treatment via phenol red dye recovery analysis from the stomach and portions of the small intestine. Results: Our results demonstrated that CPX induced a transient, mild anxiety-like phenotype in rats, with behavioral changes largely resolving by week 4, becoming statistically indistinguishable from the CTL group. In contrast, CPX significantly accelerated GI transit, similar to the known prokinetic AMX, as evidenced by increased fractional dye recovery in the stomach and distal small intestine. This accelerated GI motility persisted weeks after CPX discontinuation. Conclusions: These findings establish a putative rodent model for FQAD, providing evidence that even small doses of CPX can induce acute, transient neuropsychiatric effects and, critically, persistent GI dysmotility. This supports the inclusion of GI dysfunction in FQAD symptomatology and highlights the need for judicious FQs prescription and comprehensive patient monitoring. Full article

Ducks exhibit substantial ecological and dietary diversity, which drives morphological and functional adaptations in their digestive systems. This study analyzed the small intestine and cecum of three wild duck species: Mallard (Anas platyrhynchos), Tufted Duck (Aythya fuligula), and Green-Winged Teal (Anas crecca) collected post-mortem. Histomorphometric analysis and immunohistochemistry (IHC) with the pan-neuronal marker HuC/D were performed. The Tufted Duck showed the thickest intestinal muscle layers, particularly in the duodenum and ileum, and the largest enteric ganglia, indicating adaptation to a fibrous and protein-rich diet. The Mallard displayed the longest villi and deepest crypts, consistent with its omnivorous diet rich in plant material. The Green-Winged Teal, which consumes highly digestible insect-rich food, had the shortest villi and thinnest muscle layers. Differences in enteric ganglion size and organization among species suggest varying neuroregulatory demands in different gut segments. These findings confirm that intestinal morphology and enteric nervous system (ENS) structure are tightly linked to dietary specialization and ecological strategies. The results highlight the high adaptive plasticity of the avian digestive system in response to feeding behavior. Full article

Oxidative stress is the key contributor to the onset of numerous diseases. Herein, we develop tea polyphenol–zinc (Tp-Zn) using a metal–polyphenol coordination strategy through a simple hybrid approach. The product is characterized by methods such as dynamic light scattering (DLS), ultraviolet–visible spectroscopy (UV–vis) and transmission electron microscopy (TEM) to evaluate the particle size and potential of Tp-Zn. Oxidative stress was induced in mice by administering diquat (25 mg/kg body weight) followed by pre-treatment with 210 mg/kg body weight tea polyphenols (TPs), 280 mg/kg body weight Tp-Zn, and 70 mg/kg body weight ZnSO₄ for 7 days. Results showed that Tp-Zn treatment significantly improved intestinal barrier function by preventing the diquat-induced down-regulation of tight junction proteins Zonula Occludens protein 1 (ZO-1) and occludin. It also mitigated liver inflammation and damage, as evidenced by reduced serum levels of Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), and Alkaline phosphatase (AKP). Furthermore, Tp-Zn enhanced the antioxidant response in both the intestine and liver by up-regulating the mRNA expression of antioxidant enzymes and reducing the levels of Malondialdehyde (MDA) and reactive oxygen species (ROS) compared to the diquat group (DIQ group). Also, the detection of ROS in the small intestine confirmed Tp-Zn markedly increased intestinal Nuclear factor erythroid 2-related factor 2 (Nrf2) expression compared to the control group. This study aims to clarify that metal–polyphenol coordination with multifaceted regulation of the inflammatory microenvironment could be a novel approach for preventing or treating oxidative stress-related diseases. Full article

Background/Objectives: Fecal peritonitis following penetrating abdominal trauma is a serious condition that often results in sepsis and organ failure. The aim of our study was to develop a novel conscious porcine model of sepsis and organ dysfunction caused by multiple penetrating injuries to the small and large intestines. Methods: Twelve female Yorkshire pigs (average weight 50.6 ± 6.5 kg) were divided into two groups: Penetrating Abdominal Trauma (PAT) (n = 8) and Control (n = 4). All surgical procedures were performed under anesthesia with adequate analgesia. In the PAT group, the small and large intestines were punctured, and feces mixed with saline were introduced into the abdominal cavity to induce peritonitis. The Control group received sham surgery with only saline solution. The animals were observed in a conscious state over a period of 72 h, vital parameters were recorded, and blood samples were taken regularly. We adapted a pig-specific SOFA score and developed pig-specific SIRS criteria and NEWS2 score to assess organ function. The model was validated by independent investigators. Results: The survival rate in the PAT group was 75%, with an average survival time of 58.5 h, while all animals in the Control group survived to euthanasia. Monitoring showed pathophysiological changes, such as tachycardia, leucopenia, and thrombocytopenia, indicative of sepsis and organ dysfunction. Blinded investigators independently confirmed the model’s validity. Conclusions: A new swine model of penetrating abdominal trauma and sepsis has been successfully developed that demonstrates significant physiological and immunologic changes comparable to human sepsis. This new model provides a realistic platform for future research into sepsis, its diagnostics, and the evaluation of therapeutic strategies. Full article

Background/Objectives: Coronavirus disease 2019 (COVID-19) is associated with gastrointestinal (GI) symptoms. Small intestinal bacterial overgrowth (SIBO) is emerging as a significant GI sequela post-COVID-19 infection. This study aimed to evaluate the prevalence and incidence of SIBO post-COVID-19 infection across different age groups and to identify associated risk factors in a global cohort. Methods: A retrospective study utilized the TriNetX database and included adult patients (≥18 years) diagnosed with SIBO following COVID-19 infection (1 January 2022–30 May 2024). A propensity score matching (1:1) was used to adjust for demographics and SIBO risk factors. Kaplan–Meier survival analysis assessed the SIBO incidence within 12 months. Results: Among 1,660,092 COVID-19 patients and 42,322,017 controls, SIBO was diagnosed in 353 COVID-19 patients without hydrogen breath tests (BT) and 78 with BT, compared to 3368 controls without BT and 871 with BT. Age-specific analysis demonstrated a clear, progressive increase in the SIBO incidence, becoming distinctly significant by 6 months and highest at 12 months post-infection. The highest risks were noted in ages 60–69 (0.011% vs. 0.004%, OR 2.6, p = 0.0003) and 70–79 (0.011% vs. 0.005%, OR 2.0, p = 0.0004), with younger age groups (30–49 years) also showing significantly increased risks. The medication analysis revealed strong associations with chronic opioid, proton pump inhibitor, and antidiarrheal medication. Conclusions: COVID-19 significantly increased the risk of SIBO, particularly within the first 12 months post-infection, across various age groups and, notably, in association with certain chronic medications. Clinical vigilance and targeted management strategies are recommended to mitigate long-term GI consequences. Full article