Search Results (491)

With the growing demand for sheep, the sheep farming industry has developed rapidly. However, lamb diarrhea, a disease with high mortality rates, significantly hampers the industry’s growth. Traditional antibiotic treatments often disrupt the Intestinal microbiota, induce antibiotic resistance, and cause adverse side effects, highlighting the urgent need to develop alternative therapies. Bacteroides fragilis, a candidate next-generation probiotic, has been closely associated with intestinal health. This study investigated the growth characteristics and probiotic effects of a sheep-derived Bacteroides fragilis isolate, focusing on its efficacy in alleviating lamb diarrhea and infectious intestinal diseases. The experiments demonstrated that the Bacteroides fragilis isolate grows well under mildly acidic conditions (pH 6–8), exhibits some tolerance to bile salts, and has survival rates of 38.89% and 92.22% in simulated gastric and intestinal fluids, respectively, indicating its potential as a probiotic. In a mouse model, Bacteroides fragilis intervention significantly alleviated colonic inflammation caused by Enterohemorrhagic Escherichia coli infection, enhanced tight junction protein expression, mitigated oxidative stress, and improved intestinal barrier function, with high-dose interventions showing superior effects. In lamb trials, Bacteroides fragilis intervention stopped diarrhea in four out of five lambs, partially restored intestinal microbiota diversity, and reduced the abundance of potential pathogens such as Aerococcus suis and Corynebacterium camporealensis. Therefore, Bacteroides fragilis exhibited remarkable effects in regulating intestinal homeostasis, alleviating inflammation, and promoting recovery from diarrhea. Full article

Aquaculture has grown significantly, contributing to global food security and sustainability; however, intensified fish farming has increased disease susceptibility and antibiotic resistance. This study assessed the probiotic potential of Lactobacillus plantarum PSCPL13 (hereafter, PSCPL13), isolated from the intestines of Japanese eels, for enhancing the health of olive flounder. After screening 16 Lactobacillus isolates, PSCPL13 was selected because of its potential broad-spectrum antibacterial activity against many pathogens, such as Vibrio and Edwardsiella. This strain exhibited high acid and bile salt tolerance, which is crucial for intestinal survival. Molecular characterisation confirmed PSCPL13 to be L. plantarum. It was resistant to all tested antibiotics and exhibited significant enzyme activity. In vivo assays in olive flounder revealed that the body weight and length of the fish were significantly higher, while the prevalence of pathogens was lower in their gut microbiota. Regarding haematological parameters, the treated groups exhibited lower eosinophil counts and higher IgM levels, suggesting enhancement of the immune system. These findings indicate that PSCPL13 is a potential probiotic that can be used in aquaculture for naturally improving fish health, growth and immunity, in addition to combating antibiotic resistance and reducing environmental impacts. These findings not only highlight the potential of PSCPL13 in sustainable aquaculture but also provide a foundation for the development of future probiotics. Full article

Cystic fibrosis (CF) is a rare genetic disorder commonly affecting multiple organs such as the lungs, pancreas, liver, kidney, and intestine. Our search focuses on the pathophysiological changes that affect the drugs’ absorption, distribution, metabolism, and excretion (ADME). This review aims to identify the ADME data that compares the pharmacokinetics (PK) of different drugs in CF and healthy subjects. The published data highlight multiple factors that affect absorption, such as the bile salt precipitation and the gastrointestinal pH. Changes in CF patients’ protein binding and body composition affected the drug distribution. The paper also discusses the factors affecting metabolism and renal elimination, such as drug–protein binding and metabolizing enzyme capacity. The majority of CF patients are on multidrug therapy, which increases the risk of drug–drug interactions (DDI). This is particularly true for those receiving the newly developed transmembrane conductance regulator (CFTR), as they are at a higher risk for CYP-related DDI. Our research highlights the importance of meticulously evaluating PK variations and DDIs in drug development and the therapeutic management of CF patients. Full article

Escherichia coli (E. coli) is a common pathogen that causes diarrhea in newborns and animals. Antibiotics are typically used to treat bacterial diarrhea, a global intestinal health issue. Probiotics have gained interest as a potential substitute for antibiotics in the management of E. coli-induced diarrhea and present novel therapeutic options. In this study, the probiotic properties of Lactobacillus agilis SNF7 (L. agilis SNF7) isolated from feces were investigated, and whole genome sequencing was performed to evaluate the properties of the strain. Furthermore, we investigated the protective effects of L. agilis SNF7 in a mouse model of E. coli K99 infection. L. agilis SNF7 exhibits a high survival rate in artificial gastroenteric fluid and bile salt environments, along with an antagonistic effect against E. coli O₁₁₁:K₅₈ (B₄), Staphylococcus aureus (S. aureus), and E. coli K99. Multiple genes with probiotic properties, including bacteriostasis, anti-inflammation, antioxidant, CAZyme, and the utilization of carbohydrate compounds, were identified in genome. L. agilis SNF7 prevented the gut barrier from being damaged by E. coli K99, reducing the clinical manifestations of the infection. Furthermore, L. agilis SNF7 reduced the expression of inflammatory cytokines (IL-6, IL-1β, and TNF-α) by inhibiting the phosphorylation of proteins linked to the NF-κB and MAPK signaling pathways. L. agilis SNF7 improved the intestinal microbial barrier, controlled the balance of the intestinal microecology, and reduced the entry of harmful microbes into the intestine. By controlling gut flora and reducing the inflammatory response, L. agilis SNF7 may be able to prevent and treat E. coli K99 infections. The application of L. agilis SNF7 in the creation of probiotic formulations to stop intestinal illnesses brought on by E. coli infections is clarified by this work. Full article

Surfactants are very important compounds that are ubiquitous in biological systems and detergents. Among them, ferrocene surfactants are a very valuable class of stimuli-responsive materials since the presence of ferrocene moiety discloses the chance to control and even modify their amphiphilic properties via a redox-induced change in the surfactant charge. In this paper, we report a new ferrocene-based surfactant: a ferrocene C-3 derivative of cholic acid, a non-classical surfactant. The title compound of this work was meant to show the significant self-assembly behaviour typical of bile salts, improved by the presence of the aromatic ferrocene subunit. We intended to demonstrate that the presence of the redox mediator should provide the derivative with sensitivity to an oxidative stimulus and control over the aggregation properties. The title compound was prepared in two steps from easily accessible precursors, and its optical properties were investigated through UV-Vis absorption spectroscopy. The determination of its critical micellar concentration and redox potential confirmed this derivative’s amphiphilic nature and its tendency to be reversibly oxidized. Full article

This research sought to assess the anti-obesity potential of Enterococcus faecalis EF-1. An extensive and robust in vitro methodology confirmed EF-1’s significant potential in combating obesity, probably due to its excellent gastrointestinal tract adaptability, cholesterol-lowering property, bile salt hydrolase activity, α-glucosidase inhibition, and fatty acid absorption ability. Moreover, EF-1 exhibited antimicrobial activity against several pathogenic strains, lacked hemolytic activity, and was sensitive to all antibiotics tested. To further investigate EF-1’s anti-obesity properties in vivo, a high-fat diet (HFD) was used to induce obesity in C57BL/6J mice. Treatment with EF-1 (2 × 10⁹ CFU/day) mitigated HFD-induced body weight gain, reduced adipose tissue weight, and preserved liver function. EF-1 also ameliorated obesity-associated microbiota imbalances, such as decreasing the Firmicutes/Bacteroidetes ratio and boosting the levels of bacteria (Faecalibacterium, Mucispirillum, Desulfovibrio, Bacteroides, and Lachnospiraceae_NK4A136_group), which are responsible for the generation of short-chain fatty acids (SCFAs). Concurrently, the levels of total SCFAs were elevated. Thus, following comprehensive safety and efficacy assessments in vitro and in vivo, our results demonstrate that E. faecalis EF-1 inhibits HFD-induced obesity through the regulation of gut microbiota and enhancing SCFA production. This strain appears to be a highly promising candidate for anti-obesity therapeutics or functional foods. Full article

Micelles formed by bile salts in aqueous solution are important for the solubilization of hydrophobic molecules in the gastrointestinal tract. The molecular level information about the mechanism and driving forces for primary-to-secondary micelle transition is still missing. In the current study, the micelle formation of 50 mM solutions of taurodeoxycholate (TDC) is studied by atomistic molecular dynamics simulations. It is shown that primary micelles with an aggregation number of 8–10 emerge and persist within the first 50 ns. Then, they coalesce to form secondary micelles with an aggregation number of 19 molecules. This transition is governed by hydrophobic interactions, which significantly decrease the solvent-accessible surface area per molecule in the secondary micelles. The addition of monomers of the sodium salt of fatty acids (FAs), as agents aiding hydrophobic drug delivery, to secondary TDC micelles results in the co-existence of mixed FA-TDC and pure FA micelles. The studied saturated FAs, with chain lengths of C14:0 and C18:0, are incorporated into the micelle core, whereas TDC molecules position themselves around the FAs, forming a shell on the micelle surface. In contrast, the tails of the C18:1 unsaturated fatty acid mix homogeneously with TDC molecules throughout the entire micelle volume. The latter creates a very suitable medium for hosting hydrophobic molecules in the micelles containing unsaturated fatty acids. Full article

Background: Patients with progressive familial intrahepatic cholestasis (PFIC) experience cholestasis-associated symptoms, including severe pruritus. Odevixibat is an ileal bile acid transporter inhibitor indicated for treatment of PFIC in the European Union and for the treatment of pruritus in PFIC in the United States. The aim of the current study was to characterize the real-world effectiveness and safety of odevixibat in patients with PFIC. Methods: This retrospective study included 9 patients with PFIC treated with odevixibat in a single center in Tübingen, Germany. Data were recorded using case report forms. Results: Of the 9 patients (PFIC1, n = 2; PFIC2, n = 7), 5 had improved serum bile acid levels, pruritus, liver function tests, and sleep with odevixibat treatment. Two siblings with periodic relapses of PFIC symptoms also had improved pruritus and sleep within 4 months of treatment. Two siblings with complete loss of bile salt export pump (BSEP) protein did not respond to treatment; both underwent liver transplantation (indications: hepatocellular carcinoma [HCC] manifestation [n = 1] and severe failure to thrive and refractory pruritus [n = 1]). Four patients reported abdominal complaints that were transient or responded to dose reduction; no other safety issues were reported. Conclusions: In this case series, clinical benefits were observed in most patients with PFIC1 and PFIC2 treated with odevixibat. In patients with periodic relapse of PFIC symptoms, ≥3 months of treatment with odevixibat may be required for symptom control. Patients with complete loss of BSEP did not have consistent symptom relief and require careful monitoring. Effectiveness and feasibility results from our cohort demonstrate potential for long-term benefits with odevixibat in real-world treatment of patients with PFIC. Full article

Bile acid salts are steroid biosurfactants that build relatively small micelles compared to surfactants with an alkyl chain due to the rigid conformation of the steroid skeleton. In order to increase the capacity of micellar solubilization of the hydrophobic molecular guest, certain C7 alkyl derivatives were synthesized. Namely, introducing an alkyl group in the C7 position of the steroid skeleton results in a more effective increase in the micelle’s hydrophobic domain (core) than the introduction in the C3 position. In comparison, fewer synthetic steps are required than if alkyl groups are introduced into the C12 position of cholic acid in the Grignard reaction. Here, the thermodynamic parameters of micellization (demicellization) of C7 alkyl (number of C atoms in the alkyl group: 2, 3, 4, and 8) derivatives of cholic acid anion in an aqueous solution without additives are examined (which have not yet been determined) in the temperature interval T (10–40) °C. The critical micellar concentration and the change in the standard molar enthalpy of demicellization ($∆h_{\mathrm{d}\mathrm{e}\mathrm{m}\mathrm{i}\mathrm{c}}^0$) are determined by isothermal calorimetric titration (ICT). From the temperature dependence of $∆h_{\mathrm{d}\mathrm{e}\mathrm{m}\mathrm{i}\mathrm{c}}^0$, the change in the standard molar heat capacity of demicellization is obtained ($∆C_{\mathrm{d}\mathrm{e}\mathrm{m}\mathrm{i}\mathrm{c}}^0$), the value of which is proportional to the hydrophobic surface of the monomer, which in the micellar state is protected from hydrophobic hydration. The values of $∆C_{\mathrm{d}\mathrm{e}\mathrm{m}\mathrm{i}\mathrm{c}}^0$ indicate that in the case of C7-alkyl derivatives of cholic acid anion with butyl and octyl chains, parts of the steroid skeleton and alkyl chain remain shielded from hydration after disintegration of the micelle. Conformational analysis can show that starting from the C7 butyl chain in the alkyl chain, sequences with gauche conformation are also possible without the formation of steric repulsive strain between the alkyl chain and the steroid skeleton so that the C7 alkyl chain takes an orientation above the convex surface of the steroid skeleton instead of an elongated conformation toward the aqueous solution. This is a significant observation, namely, if the micelle is used as a carrier of a hydrophobic drug and after the breakdown of the micelle in the biological system, the released drug has a lower tendency to associate with the monomer if its hydrophobic surface is smaller, i.e., the alkyl chain is oriented towards the angular methyl groups of the steroid skeleton (the ideal monomer increases the hydrophobic domain of the micelle, but in aqueous solution, it adopts a conformation with the as small hydrophobic surface as possible oriented towards the aqueous solution)—which then does not disturb the passage of the drug through the cell membrane. Full article

Background/Objectives: Clonorchiasis is a foodborne parasitic disease that can lead to severe biliary fibrosis and cholangiocarcinoma. While praziquantel (PZQ) is available for clonorchiasis treatment, it cannot revert the histopathological damage incurred through parasite-induced fibrosis. Curcumin (CUR) is an emerging experimental drug possessing anti-inflammatory and fibrosis-alleviating effects, thus signifying its potential as an anthelmintic drug. Here, we evaluated the effect of CUR+PZQ combinatorial drug treatment on C. sinensis infection as well as its effect on ameliorating fibrotic tissue damage in rats. Methods: Worm viabilities following CUR and PZQ treatments were confirmed through microscopy and tetrazolium salt absorption. Anthelminthic effect and hepatobiliary damage mitigation in rats were determined by quantifying worm recovery, histopathological staining, and enzyme-linked immunosorbent assay. Results: CUR+PZQ at LD₅₀ doses demonstrated a time- and dose-dependent antiparasitic effect in vitro, which was markedly greater than either drug alone. Rats were infected with C. sinensis, and drugs were administered at 1 and 4 weeks post-infection (wpi) to assess drug-induced changes in worm burden. Significant reductions in worm burden recoveries were observed following CUR+PZQ treatment at both time points, accompanied by markedly reduced serum and mucosal IgG responses. ALT and AST levels were also substantially lower in combinatorial drug treatment groups than controls. Histopathological examinations confirmed that parasite-induced bile duct lumen widening and liver fibrosis were suppressed at 1 wpi, implying that CUR+PZQ co-treatment can alleviate clonorchiasis-associated pathologies. Conclusions: Our findings indicate that CUR+PZQ co-treatment improved parasite clearance and promoted the resolution of hepatobiliary tissue damage resulting from chronic clonorchiasis. Full article

Bile salts possess innate antibacterial properties and can cause significant damage to bacteria. To survive in the mammalian gut, Klebsiella pneumoniae has developed mechanisms to tolerate bile salts; however, the specific mechanisms remain unclear. Transposon library screening revealed that the efflux pump AcrAB is involved in bile salt resistance. acrA and acrB mutants exhibited high sensitivity not only to bile salts but also to SDS and various antibiotics, with a switch-loop, comprising residues G615, F616, A617, and G618, proving to be crucial in this process. A colonization defect of acrA and acrB mutants was demonstrated to be located in the mouse small intestine, where the bile salt concentration is higher compared to the large intestine. Additionally, both acrA and acrB mutants displayed reduced virulence in the Galleria mellonella model. In conclusion, our results suggest that the Resistance-Nodulation-Cell Division efflux pump serves as a critical determinant in the pathogenesis of K. pneumoniae through various aspects. Full article

Goat milk butter, locally known as “Dhan”, from the Sfisfa region of Algeria, holds significant cultural and economic value. This study investigates the probiotic properties of lactic acid bacteria (LAB) present in Dhan, focusing particularly on Lactobacillus strains. Molecular identification using 16S rRNA revealed a dominance of Levilactobacillus brevis and Lactiplantibacillus plantarum, forming a substantial part of the bacterial profile. Three LAB isolates (DC01-A, DC04, and DC06) were selected from fresh samples, and rigorous analyses were performed to evaluate their probiotic properties. Safety assessments confirmed the absence of gelatinase, DNase, and haemolytic activities in all isolates. The isolates demonstrated high tolerance to bile salts and acidic conditions, along with the ability to survive simulated gastrointestinal digestion. Notably, strain DC06 exhibited exceptional survival at low pH (1.5) and high bile salt concentrations (0.15–0.3%). All isolates showed substantial growth in MRS medium with 2% phenol, although growth was significantly decreased at 5% phenol. Furthermore, our strains exhibited high adhesion rates to various solvents, demonstrating their potential for strong interaction with cell membranes. Specifically, adhesion to chloroform was observed at 98.26% for DC01-A, 99.30% for DC04, and 99.20% for DC06. With xylene, the adhesion rates were 75.94% for DC01-A, 61.13% for DC04, and 76.52% for DC06. The LAB strains demonstrated impressive growth in ethanol concentrations up to 12%, but their tolerance did not exceed this concentration. They also exhibited robust growth across temperatures from 10 °C to 37 °C, with strains DC04 and DC06 able to proliferate at 45 °C, though none survived at 50 °C. Additionally, the isolates showed significant resistance to oxidative stress induced by hydrogen peroxide (H₂O₂) and displayed medium to high autolytic activity, with rates of 50.86%, 37.53%, and 33.42% for DC01-A, DC04, and DC06, respectively. The cell-free supernatant derived from strain DC04 exhibited significant antimicrobial activity against the tested pathogens, while strain DC06 demonstrated moderate antioxidant activity with the highest DPPH scavenging rate at 68.56%, compared to the probiotic reference strain LGG at 61.28%. These collective findings not only suggest the probiotic viability of LAB strains found in Dhan but also highlight the importance of traditional food practises in contributing to health and nutrition. Consequently, this study supports the potential of traditional Dhan butter as a functional food and encourages further exploration of its health benefits. Full article

Cytarabine (CTR) is a hydrophilic anticancer drug used to treat leukemia. It suffers from poor permeability and intestinal metabolism, diminishing its oral bioavailability. Background/Objectives: The objective was to develop and evaluate niosomes and bilosomes for enhanced intestinal absorption; hence, oral bioavailability. Results: CTR-loaded niosomes and bilosomes with vesicle sizes of 152 and 204.3 nm were successfully prepared with acceptable properties. The presence of bile salts increased the zeta potential of bilosomes. The recorded entrapment efficiency of cytarabine was acceptable for such a hydrophilic drug. CTR-bilosomes showed a pH-dependent drug release pattern with preferred release in pH 6.8. Intestinal absorption behavior indicated a site-dependent CTR absorption pattern with unfavorable absorption in the distal intestine. Niosomal and bilosomal formulations enhanced intestinal absorption parameters with evidence for a predominant paracellular absorption mechanism that bypasses intestinal barriers. The investigation of the anti-leukemic effect of niosomal and bilosomal formulations indicated that both formulations ameliorated the blood parameters, reflecting significant improvement in leukemia treatment compared with the drug solution. Pathological examination of blood films revealed decreased blast cells in peripheral blood in groups treated with tested formulations. Methods: Tested formulations were prepared according to the pro-concentrate method and characterized for particle size, zeta potential, entrapment efficiency, and in vitro release. CTR-loaded niosomes and bilosomes were evaluated for enhanced intestinal absorption utilizing the single-pass in situ intestinal perfusion method in rabbits, and the anti-leukemic effect was assessed using the benzene-induced leukemia model in rats. Conclusions: This study introduced surfactant vesicles for enhanced oral bioavailability of CTR. Full article

The digestion and absorption properties of 1,3-dipalmitoyl-2-oleoyl glycerol (POP)-rich lipids was evaluated using in vitro gastrointestinal digestion and a Caco-2 cell-mediated coupled model. Caco-2 cell viability and monolayer integrity were assessed by an MTT assay and transepithelial electrical resistance. The IC50 for bile salts, pancreatin, and free fatty acid (FFA) were 0.22 mM, 0.22 mg/mL, and 1.47 mM, respectively, and no cytotoxicity was observed for bovine serum albumin (0.01–0.20 mM) or triacylglycerol (1.00–10.00 mM). The in vitro-digested POP-rich lipid containing FFA > 2.95 mM caused the disruption of monolayer tight junctions in Caco-2 cells. The major triacylglycerols (TAG) of POP-rich lipids were POP (50.8%), POO (17.8%), POL/OPL/PLO (7.6%), PPO (7.1%), and PLP (6.8%). Following digestion and uptake into Caco-2 cells, the resynthesized TAGs included PPO (20.6%), PPP (15.9%), POO (14.0%), POL/OPL/PLO (12.2%), POP (10.9%), OOO (7.5%), OPO (7.0%), OOL/OLO (6.7%), PLP (3.1%), and PPL (2.2%). The secreted major TAGs were POL/OPL/PLO (50.8%), PPP (11.1%), and OOL/OLO (8.4%), indicating a diverse TAG profile in newly synthesized lipids. This study provides a coupled model for lowering cytotoxicity and maintaining the monolayer in Caco-2 cells, and for evaluating the digestion and absorption properties of functional lipids containing specific fatty acids incorporated into TAG. Full article

Mycotoxin contamination is a major food safety issue worldwide, posing a serious threat to animal production performance and human health. Lactic acid bacteria are generally regarded as safe fermentation potential probiotics. They have the advantages of low toxicity, small pollution, strong specificity and high safety, and can reduce the contamination of microorganisms and mycotoxins. In this study, we compared the mycotoxin degradation capacity of 15 lactic acid bacteria strains from the rumen of Qinghai yak, through comprehensive analysis, we finally identified the strains as potential probiotics because they have a fast growth speed, strong acid production capacity (pH < 4.5), and they can grow normally in an environment with a pH of 3.5, bile salt concentration of 0.1%, and good self-agglutination and hydrophobicity. It was found that the fermentation group (Pediococcus acidilactici C2, Pediococcus acidilactici E28, Pediococcus pentosaceus A16 and Enterococcus lactis C16) could significantly reduce mycotoxin content, and both the nutritional and fermentation quality of the feed improved after 7 days of fermentation, meaning that the fermentation group can be used as a functional feed additive. Full article