Effects of Clostridium tyrobutyricum on Lipid Metabolism, Intestinal Barrier Function, and Gut Microbiota in Obese Mice Induced by High-Fat Diet.

Obesity and its complications constitute a main threat to global human health. The purpose of this investigation was to explore the influences of Clostridium tyrobutyricum (Ct) on lipid metabolism, intestinal barrier function, and intestinal microbiome in obese mice induced by a high-fat diet (HFD). After establishing the obesity model, 107 CFU/mL and 108 CFU/mL C. tyrobutyricum were used to intervene in HFD-fed mice by gavage for six weeks, and indexes related to obesity were measured. In the liver of HFD-fed mice, the results revealed that C. tyrobutyricum reduced liver weight and the levels of triglyceride (TG), total cholesterol (TC), and nonesterified fatty acid (NEFA), along with decreasing red lipid droplets and fat vacuoles. After C. tyrobutyricum intervention, the mRNA expression of peroxisome proliferator-activated receptor-γ (PPARγ) was downregulated, and AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor-α (PPARα), adipose triglyceride lipase (ATGL), and hormone-sensitive lipase (HSL) were upregulated in the liver. Additionally, C. tyrobutyricum alleviated intestinal morphology injury caused by HFD, decreased the expression of tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and IL-1ß in the colon, and upregulated tight junction protein expression. In addition, 16S rRNA sequencing revealed that C. tyrobutyricum increases the diversity of intestinal microbiota. Overall, C. tyrobutyricum improved HFD-induced lipid metabolism disorders, preserved the intestinal barrier's integrity, and modulated the structure of the intestinal microbiome. These findings provide a novel insight into the role of C. tyrobutyricum as a probiotic in regulating lipid metabolism.

Immunomodulatory biomaterials against bacterial infections: Progress, challenges, and future perspectives.

Bacterial infectious diseases are one of the leading causes of death worldwide. Even with the use of multiple antibiotic treatment strategies, 4.95 million people died from drug-resistant bacterial infections in 2019. By 2050, the number of deaths will reach 10 million annually. The increasing mortality may be partly due to bacterial heterogeneity in the infection microenvironment, such as drug-resistant bacteria, biofilms, persister cells, intracellular bacteria, and small colony variants. In addition, the complexity of the immune microenvironment at different stages of infection makes biomaterials with direct antimicrobial activity unsatisfactory for the long-term treatment of chronic bacterial infections. The increasing mortality may be partly attributed to the biomaterials failing to modulate the active antimicrobial action of immune cells. Therefore, there is an urgent need for effective alternatives to treat bacterial infections. Accordingly, the development of immunomodulatory antimicrobial biomaterials has recently received considerable interest; however, a comprehensive review of their research progress is lacking. In this review, we focus mainly on the research progress and future perspectives of immunomodulatory antimicrobial biomaterials used at different stages of infection. First, we describe the characteristics of the immune microenvironment in the acute and chronic phases of bacterial infections. Then, we highlight the immunomodulatory strategies for antimicrobial biomaterials at different stages of infection and their corresponding advantages and disadvantages. Moreover, we discuss biomaterial-mediated bacterial vaccines' potential applications and challenges for activating innate and adaptive immune memory. This review will serve as a reference for future studies to develop next-generation immunomodulatory biomaterials and accelerate their translation into clinical practice.

Influence of porosity on osteogenesis, bone growth and osteointegration in trabecular tantalum scaffolds fabricated by additive manufacturing.

Porous tantalum implants are a class of materials commonly used in clinical practice to repair bone defects. However, the cumbersome and problematic preparation procedure have limited their widespread application. Additive manufacturing has revolutionized the design and process of orthopedic implants, but the pore architecture feature of porous tantalum scaffolds prepared from additive materials for optimal osseointegration are unclear, particularly the influence of porosity. We prepared trabecular bone-mimicking tantalum scaffolds with three different porosities (60%, 70% and 80%) using the laser powder bed fusing technique to examine and compare the effects of adhesion, proliferation and osteogenic differentiation capacity of rat mesenchymal stem cells on the scaffolds in vitro. The in vivo bone ingrowth and osseointegration effects of each scaffold were analyzed in a rat femoral bone defect model. Three porous tantalum scaffolds were successfully prepared and characterized. In vitro studies showed that scaffolds with 70% and 80% porosity had a better ability to osteogenic proliferation and differentiation than scaffolds with 60% porosity. In vivo studies further confirmed that tantalum scaffolds with the 70% and 80% porosity had a better ability for bone ingrowh than the scaffold with 60% porosity. As for osseointegration, more bone was bound to the material in the scaffold with 70% porosity, suggesting that the 3D printed trabecular tantalum scaffold with 70% porosity could be the optimal choice for subsequent implant design, which we will further confirm in a large animal preclinical model for better clinical use.

The effect of spatial structure on binocular contrast perception.

To obtain a single percept of the world, the visual system must combine inputs from the two eyes. Understanding the principles that govern this binocular combination process has important real-world clinical and technological applications. However, most research examining binocular combination has relied on relatively simple visual stimuli and it is unclear how well the findings apply to real-world scenarios. For example, it is well-known that, when the two eyes view sine wave gratings with differing contrast (dichoptic stimuli), the binocular percept often matches the higher contrast grating. Does this winner-take-all property of binocular contrast combination apply to more naturalistic imagery, which include broadband structure and spatially varying contrast? To better understand binocular combination during naturalistic viewing, we conducted psychophysical experiments characterizing binocular contrast perception for a range of visual stimuli. In two experiments, we measured the binocular contrast perception of dichoptic sine wave gratings and naturalistic stimuli, and asked how the contrast of the surrounding context affected percepts. Binocular contrast percepts were close to winner-take-all across many of the stimuli when the surrounding context was the average contrast of the two eyes. However, we found that changing the surrounding context modulated the binocular percept of some patterns and not others. We show evidence that this contextual effect may be due to the spatial orientation structure of the stimuli. These findings provide a step toward understanding binocular combination in the natural world and highlight the importance of considering the effect of the spatial interactions in complex stimuli.

The use of social media inside and outside the classroom to enhance students' engagement in EFL contexts.

It could be claimed that without any doubt the Internet has revolutionized the educational system to a great extent. Even though some are still interested in traditional ways of teaching and learning and also face-to-face classes, technological advances, in particular, social media have changed the English as a foreign language (EFL) contexts in a way that they will not be compatible with any other methods that have long been utilized before. Despite the fact that some studies have been conducted in different learning contexts, to the researcher's best knowledge, attention has not been focused on the importance of social media inside and outside the classroom on EFL students' indulgence. Therefore, the aim of this review is to synthesize the findings of the previous studies to highlight the role of social media in EFL students' engagement throughout class and outside the class in both face-to-face and online classes. To reach this goal, this review first discusses the impact of social media on engagement, and then engagement and its classifications are dealt with. Next, the relationship between using social media and students' engagement is discussed. And finally, some implications are proposed.

Butyrate Glycerides Protect against Intestinal Inflammation and Barrier Dysfunction in Mice.

This study investigates the attenuating effects of butyrate glycerides (BG) on intestinal inflammatory responses and barrier dysfunction induced by LPS stimulation. An initial dose-response test was carried out to identify the optimal dose of BG for further testing. The mice were given intragastric administration of BG at different doses followed by lipopolysaccharide (LPS) intraperitoneal injection. The small intestinal morphology and cytokine mRNA expression were measured. With 1.5 g/kg BW BG administration, it was possible to alleviate the injury of duodenal morphology, attenuate ileum villus height reduction and promote IL-10 mRNA expression. Therefore, the optimal dosage of 1.5 g/kg BW BG was selected for the main experiment. The ultrastructure image of jejunum and ileum epithelial cells, mRNA expression, the level of cytokine and immunofluorescence in the ileum were analyzed. The results showed that BG maintain the ileac brush border, tight junction structures and protein expression. BG attenuated the increased inflammatory cytokines, TLR4 and JNK mRNA expression. Taken together, 1.5 g/kg BW BG administration maintained intestinal barrier function and reduced intestinal and body inflammation responses induced by LPS in mice. The mechanism by which BG alleviated intestinal inflammatory response and maintained intestinal barrier function may be related to the JNK signaling pathway.

The role of English as a foreign language learners' grit and foreign language anxiety in their willingness to communicate: Theoretical perspectives.

Learners' willingness to communicate in a foreign language is regarded as a critical issue in educational contexts, so the role of emotional factors in learners' willingness to communicate has drawn the attention of investigators. This review investigated the studies on the relationship between English as a Foreign Language (EFL) learners' grit, foreign language anxiety, and willingness to communicate. This review showed a significant relationship between learners' grit and willingness to communicate. The earlier studies showed that gritty learners with incessant inspiring efforts are more likely to communicate in a foreign language. This review also indicated that lower anxious learners tend to have more willingness to communicate. Earlier studies also indicated that the theories, such as broaden-and-build, positive psychology, dynamic system, affective filter, and attentional control can justify the relationships between these constructs. Moreover, the study has some pedagogical implications and suggestions for teachers, learners, syllabus designers, material developers, teacher educators, policy-makers, and advisors. The ideas can improve their awareness of teachers' willingness to communicate, grit, and foreign language anxiety in educational environments.

Chitosan Oligosaccharide Attenuates Lipopolysaccharide-Induced Intestinal Barrier Dysfunction through Suppressing the Inflammatory Response and Oxidative Stress in Mice.

This study was conducted to investigate the protective effect of chitosan oligosaccharide (COS) against lipopolysaccharide (LPS)-induced intestinal injury. The results demonstrated that COS improved the mucosal morphology of the jejunum and colon in LPS-challenged mice. COS alleviated the LPS-induced down-regulation of tight junction protein expressions and reduction of goblet cells number and mucin expression. The mRNA expressions of anti-microbial peptides secreted by the intestinal cells were also up-regulated by COS. Additionally, COS decreased pro-inflammatory cytokine production and neutrophil recruitment in the jejunum and colon of LPS-treated mice. COS ameliorated intestinal oxidative stress through up-regulating the mRNA expressions of nuclear factor E2-related factor 2 and downstream antioxidant enzymes genes. Correlation analysis indicated that the beneficial effects of COS on intestinal barrier function were associated with its anti-inflammatory activities and antioxidant capacity. Our study provides evidence for the application of COS to the prevention of intestinal barrier dysfunction caused by the stress of a LPS challenge.

Early Emergent and Progressive Aberrant Subchondral Bone Remodeling Coupled with Aggravated Cartilage Degeneration in Developmental Dysplasia of the Hip.

OBJECTIVE: Developmental dysplasia of the hip (DDH) is the most common skeletal development in children and could result in secondary osteoarthritis. This study aims to clarify the alternations of subchondral trabecular bone remodeling and microstructural properties during the development of DDH, and the potential influence of these alternations on the overlying cartilage degeneration and DDH progression. DESIGN: Traditional straight-leg swaddling method was adopted to establish DDH model in newborn Sprague Dawley rats. Hip joint specimens from normal or DDH rats were used. Typical features of DDH in radiological examination were observed by x-ray analysis. Micro-computed tomography analysis was applied to evaluate the microstructural properties of subchondral bone at postnatal weeks 2, 4, and 6. Histological and immunohistochemical analyses were adopted to appraise subchondral bone remodeling activity and cartilage degeneration. The associations among subchondral bone, articular cartilage, and DDH severity were analyzed via multiple linear regression analysis. RESULTS: Compared with control group, the subchondral bone in DDH group displayed a gradual trend of deteriorated microstructure and worsening biomechanical properties along with aberrant bone remodeling, which might be responsible for the inhibition of stress transmission from the articular cartilage to the subchondral bone and thus leading to the cartilage degeneration and accelerated DDH progression. CONCLUSIONS: Our findings indicate that alternations of subchondral trabecular bone in a time-dependent manner could contribute to the DDH progression and the amelioration on subchondral bone might be a favorable therapeutic candidate for DDH.

Effect of ß-Mannanase Supplementation on Growth Performance, Ileal Digestibility, Carcass Traits, Intestinal Morphology, and Meat Quality in Broilers Fed Low-ME Diets.

Experiment was designed to analyze the effect of low caloric diets, supplemented with ß-mannanase on growth performance, carcass characteristics, nutrient digestibility, and other parameters in broilers. In this study, 400 broiler chicks were randomly divided into four treatments (Cont: without ß-mannanase; LM-30, MM-60, and HM-90: supplemented with 200, 400, and 600 mg/kg ß-mannanase, respectively). Dietary metabolizable energy (ME) in Cont was standard (starter diet 3100 kcal/kg; finisher diet 3200 kcal/kg) and reduced by 30, 60, and 90 kcal/kg, correspondingly in ß-mannanase-supplemented treatments. The results exhibited that growth performance was not affected by reducing dietary energy levels with supplementation of ß-mannanase. Ileal digestibility of DM and CF was improved (p < 0.01) by supplementation of ß-mannanase at low dietary ME levels. Concerning carcass traits, the relative weight of breast meat, drumstick, and abdominal fat increased (p < 0.05) with ß-mannanase supplementation in low-ME diets. Treatment HM-90 showed significantly (p < 0.05) better results regarding villus height and VH:CD. It could be concluded from the present results that supplementation of ß-mannanase could improve the nutrient digestibility so that it is possible to reduce the dietary energy level without compromising production performance, carcass trails, and meat quality in broilers.

Gut Microbiota-Derived Resveratrol Metabolites, Dihydroresveratrol and Lunularin, Significantly Contribute to the Biological Activities of Resveratrol.

Although resveratrol (RES) is barely detectable in the plasma and tissues upon oral consumption, collective evidence reveals that RES presents various bioactivities in vivo, including anti-inflammation and anti-cancer. This paradox necessitates further research on profiling and characterizing the biotransformation of RES, as its metabolites may contribute profound biological effects. After 4-week oral administration, 11 metabolites of RES were identified and quantified in mice by HPLC-MS/MS, including dihydro-resveratrol (DHR), lunularin (LUN), and conjugates (sulfates and glucuronides) of RES, DHR and LUN. Importantly, DHR, LUN, and their conjugates were much more abundantly distributed in tissues, gastrointestinal tract (GIT), and biological fluids compared to RES and its conjugates. Moreover, we established that DHR and LUN were gut bacteria-derived metabolites of RES, as indicated by their depletion in antibiotic-treated mice. Furthermore, the biological activities of RES, DHR, and LUN were determined at physiologically relevant levels. DHR and LUN exhibited stronger anti-inflammatory and anti-cancer effects than RES at the concentrations found in mouse tissues. In summary, our study profiled the tissue distribution of the metabolites of RES after its oral administration in mice and uncovered the important role of gut microbial metabolites of RES in the biological activities of RES in vivo.

Galactooligosaccharides as a protective agent for intestinal barrier and its regulatory functions for intestinal microbiota.

Present study was conducted to comprehensively investigate the protective effects of galactooligosaccharides (GOS, 100%) against LPS-induced intestinal barrier damages, and the regulatory effect for intestinal microbes. Results showed that GOS intervention restored villi (jejunum and ileum) integrity, which were atrophic and broken in LPS-challenged mice. Electron microscopy, western blotting and immunofluorescence analysis exhibited that mice administrated with GOS showed higher expression of tight junction, which was confirmed in IPEC-J2 cells model. Meanwhile, the GOS increased the secretion of mucin and SIgA, as well as it alleviated inflammatory response caused by LPS in NF-κB dependent way. Administration of GOS could also increase the relative abundances of several specific friendly bacteria, and enhance the adaptability of intestinal microbiota. Collectively, these results indicated the potential of GOS for protecting intestine from injuries caused by stress as LPS challenge.

Multi-Mode Antibacterial Strategies Enabled by Gene-Transfection and Immunomodulatory Nanoparticles in 3D-Printed Scaffolds for Synergistic Exogenous and Endogenous Treatment of Infections.

As research on refractory Staphylococcus aureus-related implant infection intensifies, certain challenges remain, including low antibiotic concentrations within infected areas, immune escape achieved by intracellular bacteria, myeloid-derived suppressor cells (MDSCs) inducing regional immunosuppression, and recurrence of residual pathogenic bacteria after drug suspension. Herein, a novel antimicrobial system to simultaneously address these issues is proposed. Specifically, an oxygen-species-responsive 3D-printed scaffold with shell-core nanoparticles is designed, which are loaded with an antimicrobial peptide plasmid (LL37 plasmid) and have LL37 grafted on their surface (LL37@ZIF8-LL37). The surface-grafted LL37 directly kills S. aureus and, following entry into cells, the nanoparticles kill intracellular bacteria. Moreover, in vitro and in vivo, following translation of the LL37 plasmid, cells function as factories of the antimicrobial peptide, thereby generating a continuous, prolonged antibacterial effect at the site of infection. This system significantly reduces the abnormal increase in MDSCs within the infected microenvironment, thus relieving the immunosuppressive state and restoring a protective antimicrobial immune response. Hence, this proposed antimicrobial system provides an antimicrobial immune response and a novel strategy for S. aureus-related infections by offering a combined active antimicrobial and immunotherapeutic strategy, thereby significantly reducing the recurrence rate following recovery from implant-associated infections.

Targeting ferroptosis suppresses osteocyte glucolipotoxicity and alleviates diabetic osteoporosis.

Diabetic osteoporosis (DOP) is the leading complication continuously threatening the bone health of patients with diabetes. A key pathogenic factor in DOP is loss of osteocyte viability. However, the mechanism of osteocyte death remains unclear. Here, we identified ferroptosis, which is iron-dependent programmed cell death, as a critical mechanism of osteocyte death in murine models of DOP. The diabetic microenvironment significantly enhanced osteocyte ferroptosis in vitro, as shown by the substantial lipid peroxidation, iron overload, and aberrant activation of the ferroptosis pathway. RNA sequencing showed that heme oxygenase-1 (HO-1) expression was notably upregulated in ferroptotic osteocytes. Further findings revealed that HO-1 was essential for osteocyte ferroptosis in DOP and that its promoter activity was controlled by the interaction between the upstream NRF2 and c-JUN transcription factors. Targeting ferroptosis or HO-1 efficiently rescued osteocyte death in DOP by disrupting the vicious cycle between lipid peroxidation and HO-1 activation, eventually ameliorating trabecular deterioration. Our study provides insight into DOP pathogenesis, and our results provide a mechanism-based strategy for clinical DOP treatment.

Felodipine enhances aminoglycosides efficacy against implant infections caused by methicillin-resistant Staphylococcus aureus, persisters and biofilms.

Methicillin-resistant Staphylococcus aureus (MRSA), biofilms, and persisters are three major factors leading to recurrent and recalcitrant implant infections. Although antibiotics are still the primary treatment for chronic implant infections in clinical, only few drugs are effective in clearing persisters and formed biofilms. Here, felodipine, a dihydropyridine calcium channel blocker, was reported for the first time to have antibacterial effects against MRSA, biofilm, and persisters. Even after continuous exposure to sub-lethal concentrations of felodipine, bacteria are less likely to develop resistance. Besides, low doses of felodipine enhances the antibacterial activity of gentamicin by inhibiting the expression of protein associated with aminoglycoside resistance (aacA-aphD). Next, biofilm eradication test and persisters killing assay suggested felodipine has an excellent bactericidal effect against formed biofilms and persisters. Furthermore, the result of protein profiling, and quantitative metabonomics analysis indicated felodipine reduce MRSA virulence (agrABC), biofilm formation and TCA cycle. Then, molecular docking showed felodipine inhibit the growth of persisters by binding to the H pocket of ClpP protease, which could lead to substantial protein degradation. Furthermore, murine infection models suggested felodipine in combination with gentamicin alleviate bacterial burden and inflammatory response. In conclusion, low dose of felodipine might be a promising agent for biomaterial delivery to enhance aminoglycosides efficacy against implant infections caused by MRSA, biofilm, and persisters.

Effect of partially replacing soybean meal with sunflower meal with supplementation of multienzymes on growth performance, carcass characteristics, meat quality, ileal digestibility, digestive enzyme activity and caecal microbiota in broilers.

OBJECTIVE: An experiment was conducted to evaluate the effects of partially replacing soybean meal (SBM) with sunflower meal (SFM) with added exogenous multienzymes (MEs) on various biological parameters in broilers. METHODS: One week-old, 400 broiler chicks were randomly divided into four treatments (control, 3SFM, 6SFM, and 9SFM) with 5 replicates/treatment (20 chicks/replicate). Control diet was without SFM and MEs, while diets of 3SFM, 6SFM, and 9SFM treatments were prepared by replacing SBM with SFM at levels of 3%, 6%, and 9%, respectively, and were supplemented with MEs (100 mg/kg). Feeding trial was divided into grower (8 to 21 day) and finisher phases (22 to 35 day). External marker method was used to measure the nutrient digestibility. At the end of trial, twenty birds (one birds per replicate) with similar body weight were slaughtered for samples collection. RESULTS: No significant effect of dietary treatments was found on all parameters of growth performance and carcass characteristics, except relative weight of bursa. Weight (25.0 g) and length (15.80 cm) of duodenum were significantly (p<0.05) higher in 3SFM than control. Lowest (p<0.05) villus height/crypt depth ratio was found in 3SFM and 9SFM than control. Most of meat quality parameters remained unaffected, however, highest pH of breast meat (6.16) and thigh meat (6.44) were observed in 9SFM and 3SFM, respectively. Lowest (p<0.05) cook loss of thigh meat was found in 6SFM (31.76%). Ileal digestibility of crude protein was significantly (p<0.05) higher in 3SFM (72.35%) than control (69.46%). In addition, amylase (16.87 U/mg) and protease (85.18 U/mg) activities were significantly (p<0.05) higher in 3SFM than control. However, cecal microbial count remained unaffected. CONCLUSION: Partial replacement (up to 9%) of SBM with SFM, with added MEs can help to improve the nutrient digestibility, intestinal morphology, and digestive enzyme activities without affecting cecal microbial count and growth performance in broilers.

An updated review on probiotics as an alternative of antibiotics in poultry - A review.

Antibiotics used to be supplemented to animal feeds as growth promoter and as an effective strategy to reduce the burden of pathogenic bacteria present in the gastro-intestinal tract. However, in-feed antibiotics also kill bacteria that may be beneficial to the animal. Secondly, unrestricted use of antibiotics enhanced the antibiotic resistance in pathogenic bacteria. To overcome above problems, scientists are taking a great deal of measures to develop alternatives of antibiotics. There is convincing evidence that probiotics could replace in-feed antibiotics in poultry production. Because they have beneficial effects on growth performance, meat quality, bone health and eggshell quality in poultry. Better immune responses, healthier intestinal microflora and morphology which help the birds to resist against disease attack were also identified with the supplementation of probiotics. Probiotics establish cross-feeding between different bacterial strains of gut ecosystem and reduce the blood cholesterol level via bile salt hydrolase activity. The action mode of probiotics was also updated according to recently published literatures, i.e antimicrobial substances generation or toxin reduction. This comprehensive review of probiotics is aimed to highlight the beneficial effects of probiotics as a potential alternative strategy to replace the antibiotics in poultry.

Effect of multi-enzymes supplementation on growth performance, meat quality, ileal digestibility, digestive enzyme activity and caecal microbiota in broilers fed low-metabolizable energy diet.

OBJECTIVE: This study was conducted to evaluate the effect of using low energy diet with multi-enzymes supplementation on different biological parameters in broilers. METHODS: Three hundred Arbor Acres broiler chicks were randomly divided into three groups (Cont, standard metabolizable energy(ME); L-ME, ME reduced by 50 kcal/kg without enzyme; and L-ME-MES, L-ME diet was supplemented with multi-enzymes) with five replicates per group (20 chicks per replicate) at the start of second week. Grower and finisher diets were formulated according to breed specific guide and offered with free access in respective phase (two weeks for grower [8 to 21 d]; two weeks for finisher [22 to 35 d]). External marker method was used to measure the nutrient digestibility. After feeding trial, fifteen birds (one bird per replicate) were selected randomly and slaughtered for samples collection. RESULTS: The results exhibited no effect (p>0.05) of dietary treatments on all parameters of growth performance, carcass traits, relative weight of internal organs except bursa and overall parameters of thigh meat quality. Relative weight of bursa was significantly (p<0.05) higher in L-ME than control. Multi-enzymes supplementation in low-ME diet significantly (p<0.05) improved the breast meat pH 24 h, digestibility of crude protein, duodenum weight and length, jejunal morphology, counts of Lactobacillus spp. and Bifidobacterium spp., lipase and protease activities than control. Jejunum length was increased in both L-ME and L-ME-MES treatments than that of the control (p<0.05). Breast meat cooking loss and color lightness was lower in L-ME (p<0.05) than control. CONCLUSION: It can therefore be concluded that broilers could be reared on low energy diet with supplementation of multi-enzymes without compromising the growth performance. In addition, it is beneficial for other biological parameters of broilers.

Gastrointestinal biotransformation and tissue distribution of pterostilbene after long-term dietary administration in mice.

The metabolic fate of dietary compounds is closely related to their biological functions. Pterostilbene (PT) is a methylated stilbene found in many plant foods. Herein, we investigated gastrointestinal biotransformation and tissue distribution of PT in mice fed with 0.05% PT (w/w) for 5 weeks. PT and its major metabolites i.e. PT sulfate (PT-S), pinostilbene, pinostilbene sulfate, hydroxylated PT and hydroxylated PT sulfate were identified and quantified in the mucosa and content of the digestive tissues, blood, urine and vital organs. The results showed PT underwent demethylation, hydroxylation and conjugation in the small intestine, while the conjugated metabolites were largely deconjugated in the colon. Anaerobic fermentation with mouse cecal bacteria demonstrated the microbiota mediated deconjugation and demethylation of PT-S and PT, respectively. In conclusion, oral consumption of PT led to extensive biotransformation in mouse gastrointestinal tract and the metabolites of PT might play important roles in the bioactivity of PT.