Search Results (2,691)

Background: Gut microbiota plays a critical role in host metabolism, immunity, and intestinal barrier integrity. Both chronic kidney disease (CKD) and kidney transplantation (KTR) are associated with gut dysbiosis, driven by uremic toxins, comorbidities, and immunosuppressive therapy. However, direct comparisons between hemodialysis (HD), KTR, and healthy controls (HC), while accounting for dietary factors, remain limited. Methods: We conducted a cross-sectional study including 48 HD patients, 75 KTR patients, and 13 HC. Stool patient samples were analyzed using 16S rRNA amplicon sequencing targeting the V4-V4 region to assess microbial composition and diversity. Data on clinical status, laboratory parameters, and dietary intake were collected and integrated with microbiome profiling. Results: Firmicutes and Bacteroidota dominated all groups, with Akkermansia enriched in HD and SCFA-producing genera (Faecalibacterium, Roseburia) more abundant in KTR. LEfSe and sPLS-DA analyses identified Akkermansia and Clostridia-related taxa as discriminants of HD, while Acidaminococcus and Megasphaera characterized KTR. HD patients exhibited higher alpha diversity (Faith’s PD and Chao1) than KTR (p < 0.05). Dietary intake differed across groups, but explained only a small proportion of microbial variance. Conclusions: Both HD and KTR patients display persistent gut dysbiosis with distinct microbial signatures. While transplantation partially restores SCFA producers, immunosuppression and diet shape new ecological shifts. These findings underscore the potential of microbiota as a biomarker and therapeutic target in renal replacement therapies. Full article

Background/Objectives: The aim of this study was to reveal the influence of the natural nanoparticles (Nnps) isolated from Gegen–Qinlian Decoction (GQD), i.e., GQD-Nnps, on the intestinal absorption and pharmacokinetic properties of several representative active GQD constituents. Methods: The morphology of GQD-Nnps was examined using scanning electron microscopy (SEM). Protein and polysaccharide contents were measured using the bicinchoninic acid (BCA) assay and phenol–sulfuric acid method, respectively. Major GQD constituents were quantified by liquid chromatography–tandem mass spectrometry (LC-MS/MS). Formation mechanisms were explored using dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), and high-resolution mass spectrometry (HRMS). Pharmacokinetic studies were conducted in mice with dextran sulfate sodium (DSS)-induced UC. Results: GQD-Nnps were spherical, with a size of 110.9 ± 8.1 nm and a zeta potential of −13.7 ± 1.5 mV. GQD-Nnps were primarily composed of proteins and polysaccharides. FTIR analysis revealed significant hydrogen bonding interactions between the small molecular and macromolecular constituents of GQD. HRMS analyses indicated complex formation among small molecules, particularly berberine, baicalin, and glycyrrhizic acid. DLS demonstrated good stability of GQD-Nnps in artificial gastric and intestinal fluids. Pharmacokinetic studies showed that, except for puerarin, blood and liver exposure levels of several constituents in the GQD-Nnps group were significantly higher than those in the GQD extract group, suggesting enhanced colonic absorption and hepatic distribution. Conclusions: GQD-Nnps create an oral drug delivery system through complex interactions, significantly enhancing the colonic absorption and hepatic distribution of several active GQD constituents. Full article

Background/Objectives: Probenecid (PBN) is a uricosuric agent that facilitates the excretion of uric acid and is used to treat gout. Here, a colon-targeted prodrug of PBN was designed to facilitate repositioning as a treatment for inflammatory bowel disease (IBD). Methods: The carboxylic group in PBN was amide-conjugated with the amine groups of acidic amino acids to yield aspartic acid-conjugated PBN (PBN-AA) and glutamic acid-conjugated PBN (PBN-GA). Conjugation with amino acids increased the hydrophilicity of PBN and decreased cell permeability across the Caco-2 cell monolayer. While remaining intact in buffers (pH 1.2, 6.8) and in the small intestinal contents of rats, the conjugates were cleaved to release PBN from the cecal contents of rats, with a significant difference in the maximal conversion percentage between PBN-AA (12%) and PBN-GA (74%). Results: Upon oral gavage, PBN-GA accumulated a much greater amount of PBN in the cecum than PBN alone, thus verifying the in vitro colon specificity of PBN-GA. Oral PBN-GA enhanced the anticolitis effectiveness in dinitrobenzene sulfonic acid-induced rat colitis and limited the systemic absorption of PBN, thus reducing the risk of systemic adverse effects ascribed to PBN. Moreover, PBN-GA therapeutically surpassed sulfasalazine, a currently used anti-IBD drug, in rat colitis. Conclusions: These results suggest that amide conjugation with GA can be used to design a colon-targeting prodrug for PBN. Colon-targeted PBN may not only enhance therapeutic effectiveness but also improve the safety of PBN repositioned for the treatment of IBD and may be a pharmacological alternative for current small-molecule anti-IBD drugs with low efficacy or serious adverse effects with long-term use. Full article

The operative management of complex abdominal wall hernias in nonagenarians entails significant risk, with emergent repair associated with mortality rates approaching 40%. We report the case of a functionally independent 90-year-old male presenting with a 48 h history of abdominal pain, obstipation, and emesis, consistent with an acute-on-chronic incarcerated ventral hernia. Despite advanced age and elevated perioperative risk, multidisciplinary evaluation supported surgical intervention. Laparotomy revealed a 22 × 18 cm hernia sac harboring an elongated sigmoid and approximately 150 cm of small intestine with signs of compromised perfusion secondary to an internal constriction band. Following adhesiolysis and decompression, bowel viability was restored, and a mesh repair was performed. The postoperative course was notable for transient respiratory failure necessitating reintubation and ICU management; however, full recovery was achieved by one-month follow-up. This case demonstrates that comprehensive assessment, rather than chronological age, should guide operative decision-making in nonagenarians and underscores the feasibility of complex abdominal wall reconstruction in this cohort when supported by multidisciplinary care and perioperative resources. Full article

The mechanisms of nutritional niche differentiation among sympatric Schizothoracinae fishes play an important role in their adaptive evolution and should be considered in conservation strategies. To date, there have been no reports about the role of different feeding strategies in nutritional niche differentiation among five Schizothoracinae species (Ptychobarbus leptosomus, PL; Gymnodiptychus pachycheilus, GP; Schizothorax kozlovi, SK; Schizopygopsis malacanthus, SM; and S. wangchiachii, SW). This study explored the role of feeding strategy differences in nutritional niche differentiation among sympatric Schizothoracinae fishes. We analyzed feeding/digestive organ morphology, diet composition, intestinal digestive enzyme activity, and microbial diversity in five species from the middle Yalong River. The results revealed dietary divergence: PL consumed small fish, invertebrates, and algae; GP/SK fed on invertebrates and algae; and SM/SW primarily ate algae. Additionally, α-amylase activity was lower in PL/GP/SK than in SM/SW (p < 0.05), while lipase activity was lower in SM/SW than in PL/GP/SK (p < 0.05), and PL exhibited the highest trypsin activity (p < 0.05). The intestinal microbial composition/diversity also varied: the PL group differed significantly from the GP + SK and SM + SW groups (p < 0.05), with Cetobacterium being dominant in the PL group and Clostridium being dominant in the other groups; the α diversity was highest in the SM + SW group and lowest in the PL group. PICRUSt2 predictions revealed significant differences in nutrient metabolism pathways between the PL group and the other groups (p < 0.05). Overall, the morphological differences in feeding/digestive organs and recent food intake may drive the dietary divergence, inducing adaptive changes in digestive enzymes and microbial diversity and ultimately promoting nutritional niche differentiation among sympatric Schizothoracinae species. Full article

Thymol gastro-resistant self-emulsifying pellets were used to achieve thymol targeted release on the side of the intestine with the most intensive absorption to enhance its oral bioavailability. Forty-eight rabbits (35 d of age) were divided into two groups fed with a standard diet containing gastro-resistant enteric pellets (control, CG; without thymol, initial live weight 1350.0 ± 18.0, and experimental, EG; with thymol 250 mg/kg, initial live weight 1352.0 ± 19.9 g). The experiment lasted 28 days: thymol was administered for 21 days and then withdrawn for 7 days. Thymol was significantly higher in duodenal wall (DW) than in plasma during both periods (p = 0.0053, p < 0.0001). Significant correlation was established between thymol concentration in plasma and DW during its application (r_s = 0.9333, p < 0.001). Thymol was below the limit of quantitation in plasma, spleen and muscle only after its withdrawal, and its significantly higher concentration in kidney and fat than in plasma (p = 0.0182, p = 0.0003) and muscle (p = 0.0236, p = 0.0004) indicates its efficient accumulation. Thymol in gastro-resistant form prevented its degradation due to adverse conditions in the stomach and ensured its release at the site of greatest absorption in the small intestine. Full article

The gut microbiota plays a vital role in regulating the host’s physiological functions, including metabolism and immunity. The microbial composition and metabolism are modulated by multiple factors; host sex is an important yet under-explored determinant. To investigate the sex-dependent differences in the gut microbiota within the small and large intestine, sixteen somatic mature Jiangshan black pigs (eight males and eight females) were analyzed. The ileal and colonic microbial community and metabolites were profiled using 16S rRNA gene high-throughput sequencing and gas chromatography. Distinct sex-related discrepancies were observed in both the microbial composition and metabolism of the ileum and colon. In the ileum, compared with the male group, the female group exhibited higher abundances of Unclassified Chloroplast and Pseudomonas but a lower abundance of Romboutsia (adjusted p < 0.05). Functional prediction indicated enrichment in amino acid metabolism pathway in females, with more copy numbers of genes encoding key enzymes for propionate (mmdA) generation and elevated valerate levels (p < 0.05). In the colon, compared with the male group, the female group showed higher abundances of Streptococcus, Phascolarctobacterium, and Prevotella spp. and lower abundances of Eubacterium coprostano-ligenes group, Blautia, Christensenellaceae R-7 group, and Ruminococcus (adjusted p < 0.05). Additionally, the female group had more copies of genes mmdA and LcdA (associated with lactate production), along with higher concentrations of propionate and lactate (p < 0.05). Correlation analysis between microbial metabolites and sex-biased bacteria further revealed that the SCFA concentration positively correlated with Prevotella spp. and negatively correlated with Romboutsia, Christensenellaceae R-7 group, and Blautia. Collectively, these findings highlight the pronounced sex-dependent discrepancies in the microbial composition and metabolism within the small and large intestines of Jiangshan black pigs, providing new insights for precisely modulating the microbiota community and metabolism in pigs according to sex. Full article

Improving nitrogen efficiency in dairy cattle requires a better understanding of the dietary and ruminal factors that regulate nitrogen partitioning. This meta-analysis evaluated the effects of ruminal pH and dietary characteristics on microbial nitrogen (MN), non-microbial non-ammonia nitrogen (NANMN), and NAN flows to the small intestine in lactating cows. A dataset was assembled from 44 peer-reviewed in vivo studies (163 data points), with dietary intake and ruminal variables standardized across trials. Mixed linear models were developed for each N fraction, and the relative contribution of each predictor to the explained variance was assessed using semipartial coefficients of determination (pR²). Efficiency of microbial protein synthesis (EMPS), rumen undegraded protein intake (RUPI), and organic matter truly digested in the rumen (OMTDR) were the most relevant predictors of NANMN and NAN. Although the ruminal pH itself was not statistically significant in the models, the dietary components that influenced pH, starch concentration, physically effective fiber, and RUP supply were strongly associated with nitrogen flow profiles. Nitrogen utilization was not affected by ruminal pH, but rather by the combination of fermentable substrates and the supply of rumen-degradable and undegraded protein. Full article

Fructose malabsorption is characterized as the incomplete absorption of fructose in the small intestine. Fructose is one of the most common monosaccharides in the human diet. The purpose of this review is to provide an updated overview of insights into the relationship between high-fructose diet, fructose malabsorption, gut microbiota and clinical consequences. Incomplete absorption of fructose causes accumulation in the colon, which leads to fermentation by gut microbiota and abdominal symptoms such as bloating and excessive gas production. Malabsorption may result from exceeding the absorptive capacity of GLUT5 or insufficient upregulation, with incidence increasing with age and higher dietary fructose concentrations. High-fructose diets generally promote an increase in inflammatory bacterial groups such as Desulfovibrio and Deferribacteraceae, while reducing beneficial Bacteroidetes. These microbial alterations may impair intestinal barrier function, modify short-chain fatty acid profiles, and contribute to systemic inflammation, metabolic disorders, and potentially mental health issues. Animal studies using fructose malabsorption models present inconclusive results regarding the impact of fructose on the composition of gut microbiota. Additional research is essential to fully comprehend the complex relationship between diet, fructose malabsorption and gut microbiota, to develop personalized, effective dietary approaches for managing symptoms of fructose malabsorption. Full article

Sinomenine (SIN) is a promising candidate for the treatment of rheumatoid arthritis (RA). Although it possesses the advantage of being non-addictive, its poor aqueous solubility and low oral bioavailability have limited its clinical application. To address these issues, SIN was encapsulated into lipid cubic liquid crystal nanoparticles (LCNPs) and systematically characterized. Molecular dynamics (MD) simulations were first employed to screen suitable excipients for formulation development. Combined with single-factor optimization and Box–Behnken response surface design, the optimal composition and preparation process were determined. The resulting SIN-LCNPs exhibited a particle size of 149.7 ± 0.9 nm, a polydispersity index (PDI) of 0.223 ± 0.01, a zeta potential of −18.9 mV, and an encapsulation efficiency (EE%) of 92.2%. Spectroscopic analyses confirmed successful incorporation of SIN into the lipid matrix. Pharmacodynamic studies revealed that SIN-LCNPs enhanced targeted drug delivery to inflamed joints, significantly alleviating inflammation and suppressing disease progression in rats. In vivo single-pass intestinal perfusion (SPIP) experiments further demonstrated that SIN was primarily absorbed through the small intestine and that the LCNP carrier effectively improved its intestinal permeability. Collectively, this study provides a novel strategy and theoretical foundation for developing efficient formulations of poorly water-soluble drugs, highlighting the potential clinical application of SIN-LCNPs in RA therapy. Full article

Obesity is associated with enteric dysfunctions, including gut dysmotility and neurodegeneration, which may involve Toll-like receptor 4 (TLR4) signaling. To investigate this relationship, we examined the impact of TLR4 deficiency on the enteric nervous system (ENS) of the small intestine in a mouse model of high-fat diet (HFD)-induced obesity. Male TLR4^−/− and wild-type (WT) C57BL/6J mice were fed either a standard diet (SD; 18% kcal fat) or an HFD (60% kcal fat) for 8 weeks. ENS alterations were evaluated using real-time qPCR and confocal immunofluorescence microscopy on longitudinal muscle–myenteric plexus (LMMP) whole-mount preparations. Alterations in gut motility were evaluated by assessing stool frequency, transit of a fluorescent-labeled marker, and isometric motor responses of ileal preparations to receptor- and non-receptor-mediated stimuli. In WT mice, HFD induced delayed gastrointestinal transit, impaired cholinergic and nitrergic responses, and altered 5-HT-mediated concentration–response curves. These functional deficits were accompanied by neuroglial network disruption, myenteric neurodegeneration, loss of ChAT⁺ and nNOS⁺ neurons, and increased 5-HT ileal tissue levels. In contrast, TLR4 deficiency mitigated body weight gain and largely prevented HFD-induced structural and functional alterations. Overall, our findings highlight a key role for TLR4 signaling in modulating small intestine inflammation and ENS remodeling associated with obesity. Full article

Bile acids, the primary components of bile, are cholesterol-derived molecules synthesized in the liver and secreted to the small intestine. Besides their primary digestive roles, bile acids have antimicrobial properties and serve as an environmental cue for intestinal pathogens, modulating the expression of virulence factors, e.g., toxins and effector proteins. Whereas timely recognition and neutralization of pathogenic toxin effectors by the host is critical, our understanding of the effects of bile on their structure and function is limited. In this work, we found that bile effectively protected cultured IEC-18 enterocytes from the mixture of Aeromonas hydrophila secreted toxins, containing hemolysin, aerolysin, and RtxA (MARTX). To explore whether these effects have broad specificity, we employed biochemical and biophysical techniques to test the in vitro effects of bile and bile acids on several effector domains of MARTX and VgrG toxins from Vibrio cholerae and Aeromonas hydrophila, and catalytic domains of TcdA and TcdB toxins from Clostridioides difficile. Bile compromised the structural integrity of the tested effectors to various degrees in a protein charge-dependent manner. Bile and bile acids promoted exposure of hydrophobic residues and the unfolding of most, but not all, of the tested effectors, facilitating their precipitation and cleavage by chymotrypsin. Bile also inhibited specific activities of the tested effector enzymes, partially due to imposed oxidation of their catalytic residues. To summarize, this work validated bile as a non-proteinaceous factor of innate immunity, capable of compromising the structural integrity and function of the effector domains of various bacterial toxins. Full article

Small pelagic fish, such as sardines and sprats, are an affordable and nutritionally rich source of omega-3 fatty acids and bioactive peptides. While their nutritional value is well established, the impact of standard household cooking methods on their immunomodulatory potential and effects on intestinal integrity remains poorly understood. Fish were prepared using five culinary techniques (raw, boiled, steamed, baked, and fried), digested via the INFOGEST protocol, and applied at 1% concentration in a Caco-2 co-culture model combined with lipopolysaccharide-stimulated RAW264.7 macrophages. NO and TNF-α production, and epithelial permeability were assessed. Steamed sardines induced the highest NO levels (122%) in activated macrophages, while raw sardines inhibited NO production (73%). Baked sardines and raw sprats triggered higher TNF-α production (>400 pg/mL). Boiled sardines and baked sprats caused the strongest disruption of epithelial permeability (>13%), whereas steamed sardines and raw sprats preserved barrier integrity (<11%). Notably, digested baked and fried fish preserved suppressive effects on NO and TNF-α even after translocation across the epithelial layer. Culinary processing significantly modulates the bioactivity of fish. In general comparison, steaming is gentler than dry heat cooking methods, as it better preserves anti-inflammatory effects and barrier-promoting properties. These findings highlight the relevance of cooking practices in modulating the functional benefits of fish consumption. Full article

Small intestine tumors are rare. The four main groups include adenocarcinomas, neuroendocrine neoplasms (NEN), lymphomas, and mesenchymal tumors. The jejunum and ileum can only be examined endoscopically with device-assisted enteroscopy techniques (DAET), which are indicated only when specific clinical or imaging findings are present. The initial diagnosis of tumors of the small intestine is mostly made using computed tomography (CT). Video capsule endoscopy (VCE), computed tomography (CT) enterography, and magnetic resonance (MR) enterography are also time-consuming and costly modalities. Modern transabdominal gastrointestinal ultrasound (US) with high-resolution transducers is a dynamic examination method that is underrepresented in the diagnosis of small intestine tumors. US can visualize wall thickening, loss of wall stratification, luminal stenosis, and dilatation of proximal small-intestinal segments, as well as associated lymphadenopathy. This review aims to highlight the role and imaging features of ultrasound in the diagnosis of small-intestinal tumors. Full article

Background and Clinical Significance: Adult small intestinal intussusception is rare and, in this population, is usually secondary to a pathological lead point, such as benign or malignant masses. The symptoms are non-specific, and patients frequently present with intermittent abdominal pain, diarrhea, nausea, vomiting, and, in rare cases, bleeding. There are currently no specific guidelines. Surgery remains the gold standard treatment. Case Presentation: We report the case of a 55-year-old female affected by Shone’s syndrome, presenting to the emergency department with melena, severe anemia, diffuse abdominal pain, weakness, and palpitations. Diagnostic tests showed active bleeding in the small intestine and a subocclusive condition. Urgent surgery was performed, revealing an intussusception. Conclusions: A multidisciplinary approach is essential for its management. Surgical resection is the only option in these cases, as it allows histological examination to rule out malignancy. Full article