Intestinal Levels Research Articles

Cryptosporidium disease of small ruminants in the region of El Taref and Mostaghanem

In order to identify and quantify Cryptosporidium infection in small ruminants in northern Algeria, specifically in the regions of Tarf and Mostaganem, a three-year survey was conducted between 2019 and 2021. The epidemiological investigation covered several aspects of the prevalence and etiology of Cryptosporidium, including various factors suspected to contribute to the spread of the causative agent of this disease. In addition, a confirmatory study was initiated, with bacteriological and histopathological tests performed on samples collected during the survey period from the various farms examined. The results showed that the epidemic takes several aspects for its spread as well as its persistence, the bacteriological results showed a coincidence of the presence of the pathogen in a significant proportion, and the histopathological interpretation of the slides revealed the diversity of lesions at the intestinal level with the predominance and inversion of enterocytes by sporozoites, resulting in the recurrence of lesions in the different organs collected in all species studied, cattle, sheep and goats.

Multiomics analysis investigating the impact of a high-fat diet in female Sprague-Dawley rats: alterations in plasma, intestinal metabolism, and microbial composition.

With improvements in living conditions, modern individuals exhibit a pronounced inclination towards a high-fat diet, largely because of its distinctive gustatory appeal. However, the association between high-fat diets and metabolic complications has largely been ignored, and metabolic diseases such as obesity and non-alcoholic fatty liver disease now constitute a major public health concern. Because high-fat diets increase the risk of metabolic diseases, a thorough investigation into the impact of high-fat diets on gut microbiota and metabolism is required. We utilize 16S rRNA sequencing and untargeted metabolomics analysis to demonstrate that SD rats fed a high-fat diet exhibited marked alterations in gut microbiota and plasma, intestinal metabolism. Changes in gut microbiota included a decreased abundance at phylum level for Verrucomicrobiota, and a decreased abundance at genus level for Akkermansia, Ralstonia, Bacteroides, and Faecalibacterium. Additionally, significant changes were observed in both intestinal and plasma metabolite levels, including an upregulation of bile acid metabolism, an upregulation of glucose-lipid metabolism, and increased levels of metabolites such as norlithocholic acid, cholic acid, D-fructose, D-mannose, fructose lactate, and glycerophosphocholine. We also investigated the correlations between microbial communities and metabolites, revealing a significant negative correlation between Akkermansia bacteria and cholic acid. Overall, our findings shed light on the relationship between symbiotic bacteria associated with high-fat diets and metabolic biomarkers, and they provide insights for identifying novel therapeutic approaches to mitigate disease risks associated with a high-fat diet.

Neutrophil extracellular trap formation and its implications in nonsteroidal anti-inflammatory drug-induced small intestinal injury.

Nonsteroidal anti-inflammatory drugs (NSAIDs) damage the small intestine via neutrophil infiltration driven by the mucosal invasion of enterobacteria. The antimicrobial function of neutrophils is partially dependent on neutrophil extracellular traps (NETs). Excessive NET formation has been associated with several inflammatory diseases. Here, we aimed to investigate the role of NETs in NSAID-induced small intestinal damage using human samples and an experimental mouse model. Human small intestine specimens were obtained from NSAID users during double-balloon enteroscopy. Wild-type, protein arginine deiminase 4 (PAD4) knockout, and antibiotic-treated mice were administered indomethacin to induce small intestinal injury. The expression of NET-associated proteins, including PAD4, citrullinated histone H3 (CitH3), cell-free DNA, and myeloperoxidase (MPO), was evaluated. The double-positive stained area with CitH3 and MPO, which is specific for neutrophil-derived extracellular traps, was significantly high in the injured small intestinal mucosa of NSAID users. In a mouse model, small intestinal damage developed at 6h after indomethacin administration, accompanied by increased mRNA levels of interleukin-1β and keratinocyte chemoattractant and elevated NET-associated protein levels of PAD4, CitH3, and MPO in small intestine and serum levels of cell-free DNA. Both genetic deletion and pharmacological inhibition of PAD4 attenuated this damage by reducing the mRNA expression of inflammatory cytokines and NET-associated proteins. Furthermore, mice pretreated with antibiotics showed resistance to indomethacin-induced small intestinal damage, with less NET formation. These results suggest that NETs aggravate NSAID-induced small intestinal injury. Therefore, NET inhibition could be a potential treatment for NSAID-induced small intestinal injury.

Changes in the composition of the gut microbiota and content of microbial-derived uremic toxins in patients undergoing hemodialysis

Recent data highlight a significant role of the gut microbiota in the pathogenesis of chronic kidney disease, particularly in its terminal stage. However, little is known about the features of intestinal dysbiosis in people undergoing programed hemodialysis. Changes in the intestinal microbiota and blood levels of uremic toxins of microbial origin in patients with terminal renal insufficiency receiving hemodialysis were analyzed. This cross-sectional study included 80 patients receiving hemodialysis and 20 individuals with normal kidney function. The state of the microbiocenosis of the colon was studied using a polymerase chain reaction with a commercial set Colonoflor 16 (premium) manufactured by Alfalab (Russia). Serum levels of trimethylamine and its metabolite trimethylamine-N-oxide were determined by liquid chromatography/mass spectrometry. The concentrations of indoxyl sulfate and p-cresyl sulfate were evaluated by enzyme immunoassay according to the instructions of a commercial kit. In patients undergoing programed hemodialysis, increased colonization of enterococci was combined with the reduction of lacto and bifidophlora, E. coli, ruminococci, bacteria producing short-chain fatty acids (Faecalibacterium prausnitzii, Eubacterium rectale, Roseburia inulinivorans, and Blautia spp.) and microorganisms involved in maintaining the integrity of the intestinal barrier (Bacteroides thetaomicron and Akkermansia muciniphila). In addition, high titer levels of representatives of opportunistic and even pathogenic flora were often found in this group. Intestinal dysbiosis in patients undergoing programed hemodialysis was accompanied by a significant increase in the concentration of uremic toxins in the blood. Compared with individuals with normal renal function, the trimethylamine level in patients undergoing programed hemodialysis was increased 22 times; trimethylamine-N-oxide, 23 times; indoxyl sulfate, 21 times; and p-cresyl sulfate, 5 times. Thus, patients receiving hemodialysis exhibited pronounced pathological changes in intestinal microbiocenosis, accompanied by a significant increase in serum levels of uremic toxins of microbial origin.

Lactobacillus rhamnosus alters intestinal IgA levels and IgA–microbiota interactions in healthy mice in a strain-specific manner

Immunoglobulin A (IgA), a mucosal immune antibody, exhibits different degrees of affinity to intestinal bacteria and performs a diverse range of immune functions. IgA secretion is closely related to microbial stimulation. The stimulation pathways and effects of pathogenic intestinal bacteria and probiotics are reported to be different. However, it is unclear whether the mode of action between probiotics, gut microbiota, and IgA in healthy hosts varies depending on strain differences. In this study, six different strains of Lactobacillus rhamnosus from humans were used to investigate the differences in their effects on IgA levels and the gut microbiota affinitive to IgA in the intestines of healthy mice. It was found that six strains of L. rhamnosus exerted different effects on IgA levels and IgA-coated bacteria in the intestines of healthy mice. Short-term administration of L. rhamnosus CCFM1228, 28L2 and W6L1 improved the secretion of intestinal IgA and the IgA index values for Escherichia–Shigella, Pseudomonas, and other potential pathogens. However, for other species in the intestinal, L. rhamnosus strains showed different trends in their regulatory effects. L. rhamnosus CCFM1228 decreased the affinity of IgA for Enterococcus and increased the IgA index values for Alistipes and Alloprevotella. But L. rhamnosus 66L1 and W6L1 significantly increased the affinity of IgA for Pseudomona. However, this change was not significantly correlated with caecal SCFA levels or colonic inflammatory factors. Finally, only L. rhamnosus 66L1, CCFM1228, and W6L1, which enhanced 1 week faecal IgA concentration, promoted the transcription level of ACIDA. This study helps to provide new insights into the effect of L. rhamnosus on the intestinal IgA level and IgA–microbiota interactions in the gut of healthy hosts, thus supporting the individualized selection of probiotics for immune intervention.

Probiotics may alleviate intestinal damage induced by cardiopulmonary bypass in children.

Intestinal ischaemia-reperfusion injury induced by cardiopulmonary bypass causes intestinal epithelial barrier dysfunction, leading to dysbiosis and bacterial translocation. We conducted a randomized prospective study with 2 objectives: (i) to investigate epithelial barrier dysfunction and bacterial translocation induced by cardiopulmonary bypass and changes in the gut microbiota and (ii) to verify whether probiotics can improve these conditions. Between 2019 and 2020, patients 0-15 years old scheduled to undergo cardiac surgery using cardiopulmonary bypass were enrolled and randomly allocated to 2 groups: the intervention group received probiotics and the control group did not receive probiotics. We analysed the microbiota in faeces and blood, organic acid concentrations in faeces, plasma intestinal fatty acid-binding protein and immunological responses. Eighty-two patients were enrolled in this study. The characteristics of the patients were similar in both groups. The total number of obligate anaerobes was higher in the intervention group than in the control group after postoperative day 7. We identified 4 clusters within the perioperative gut microbiota, and cluster changes showed a corrective effect of probiotics on dysbiosis after postoperative day 7. Organic acid concentrations in faeces, incidence of bacterial translocation, intestinal fatty acid-binding protein levels and immunological responses, except for interleukin -17A, were not markedly different between the 2 groups. Administration of probiotics was able to correct dysbiosis but did not sufficiently alleviate the intestinal damage induced by cardiopulmonary bypass. More effective methods should be examined to prevent disturbances induced by cardiac surgery using cardiopulmonary bypass. https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000037174 UMIN000035556.

Intestinal melatonin levels and gut microbiota homeostasis are independent of the pineal gland in pigs.

Melatonin (MEL) is a crucial neuroendocrine hormone primarily produced by the pineal gland. Pinealectomy (PINX) has been performed on an endogenous MEL deficiency model to investigate the functions of pineal MEL and its relationship with various diseases. However, the effect of PINX on the gastrointestinal tract (GIT) MEL levels and gut microbiome in pigs has not been previously reported. By using a newly established pig PINX model, we detected the levels of MEL in the GIT by liquid chromatography-tandem mass spectrometry. In addition, we examined the effects of PINX on the expression of MEL synthesis enzymes, intestinal histomorphology, and the intestinal barrier. Furthermore, 16S rRNA sequencing was performed to analyze the colonic microbiome. PINX reduced serum MEL levels but did not affect GIT MEL levels. Conversely, MEL supplementation increased MEL levels in the GIT and intestinal contents. Neither PINX nor MEL supplementation had any effect on weight gain, organ coefficient, serum biochemical indexes, or MEL synthetase arylalkylamine N-acetyltransferase (AANAT) expression in the duodenum, ileum, and colon. Furthermore, no significant differences were observed in the intestinal morphology or intestinal mucosal barrier function due to the treatments. Additionally, 16S rRNA sequencing revealed that PINX had no significant impact on the composition of the intestinal microbiota. Nevertheless, MEL supplementation decreased the abundance of Fibrobacterota and increased the abundance of Actinobacteriota, Desulfobacterota, and Chloroflexi. We demonstrated that synthesis of MEL in the GIT is independent of the pineal gland. PINX had no influence on intestinal MEL level and microbiota composition in pigs, while exogenous MEL alters the structure of the gut microbiota.

Selenium bioaccesibility after in vitro digestion/fermentation of foods differs in adults and children

Selenium (Se) as essential element regulates the immune, endocrine, reproductive and neurological systems through selenoproteins. More important than its content, is the fraction available to be absorbed (bioaccesibility) to exert its important metabolic functions. The objective of this study was to determine the bioaccessibility of Se (Se-BA) in multiple foods by an in vitro digestion/fermentation method. Samples were subjected to homemade culinary techniques and fermented with feces from healthy adults (HE-AD), and healthy (HE-CH) and unhealthy children (with gluten related disorders, GRD-CH; obesity, OB-CH; or allergy/intolerance to cow's milk proteins, AICM-CH). Se-BA varied largely among samples depending on their vegetal/animal origin, category and type of food. Animal-vs. plant-based foods have higher mean Se concentration and total Se-BA (82.5(±97.5) and 93.6(±8.58) vs. 44.3(±55.6) μg/kg and 77.7(±20.4)%, respectively). In plant-based foods, higher Se-BA values were found in the large intestine (41.0(±25.7) vs. 30.1(±26.7%) in animal-base foods). In comparison to raw foods, the cooking techniques of vegetal- and animal-based foods grouped by heating in liquid media (frying-boiling) or hot air (roasting-grilling) decrease Se-BA in the small intestine (42.5(±27.0) vs. 34.8(±25.1) and 34.0(±24.3), and 75.9(±38.0) vs. 52.4(±28.9) and 71.3(±24.8)%, respectively), while it is increased in the large intestine (36.6(±28.5) vs. 41.3(±24.9) and 44.2(±23.6), and 19.9(±30.4) vs. 39.9(±26.0) and 23.4(±22.7)%, respectively). The higher Se-BA levels in the large intestine found in HE-CH (42.1 (±26.5) vs. HE-AD (35.2(±27.1) and unhealthy children (GRD-CH and OB-CH; 38.0(±24.6) and 35.8(±28.1)%, respectively) could be related to greater demands on growth and specific fermentative microbiota.

Dietary Protein Levels in the Small Intestine and Carcass Traits of Cross-Breed Chickens

Protein is a source of nutrients that plays a significant role in biological processes. The current study aimed to evaluate the effects of feed with different protein levels on the pH and viscosity of the small intestine, ileum characteristics, and carcass traits of cross-breed chickens. A total of 160 cross-breed unsexed chicks aged 2 days were divided into three treatments (T1-T3), each consisting of 6 replications with 9 chicks per replication, consisting of a diet with protein level (T1; starter 18% and finisher 16%;), a diet with protein level (T2; starter 20% and finisher 18%), and a diet with protein level (T3; starter 22% and finisher 20%). Cross-breed chickens were crossed between Bangkok males and Lohmann laying hens. The variables were analyzed, including pH and viscosity of digesta, ileum characteristics consisting of total villous, height of villous, and depth of crypt. The carcass percentages consisting of the carcass, breast, thicks, wings, and back were measured. The research was analyzed using a completely randomized design. The results indicated that different protein levels in treatments were significantly different in total villous, height of villous, and depth of crypt but did not indicate a significant difference in pH and viscosity. Furthermore, the treatments have a significant difference in the carcass percentage and thick percentage but did not significantly affect the breast, wings, and back. It can be concluded that 22% crude protein in the starter and 20% crude protein in the finisher produced the greatest results in the intestinal characteristics and also in the carcass percentage of cross-breed chickens. Keywords: Carcass, Cross-breed chicken, Feed, Intestinal characteristic, Protein

Pasteurized Akkermansia muciniphila improves immunity and relieves other toxic effects in 5-fluorouracil treated BALB/c mice

This study explored how pasteurized Akkermansia muciniphila mitigates the immunosuppressive and toxic effects of the chemotherapy drug 5-FU in mice. Pasteurized A. muciniphila raised the index of immune organs, helped restore hematopoietic functions, and greatly increased the ability of both T and B lymphocytes to multiply. This process also resulted in an increase in the percentages of CD3+ T lymphocytes as well as in the ratios of CD4+ to CD8+ T cells. Pasteurized A. muciniphila enhances serum immunoglobulin secretion. Additionally, it increased the liver's antioxidant capacity, decreased ALT and AST levels, and mitigated chemotherapy-related liver damage. Pasteurized A. muciniphila regulates intestinal mucosal immunity by influencing the gut microbiota structure. It restored small intestinal villi and crypt structures, increased intestinal sIgA levels, and increased the number of CD3+ and CD4+ T lymphocytes, thus effectively rectifying intestinal mucosal immune dysfunctions. In conclusion, pasteurized A. muciniphila significantly improved the immunosuppressive and other toxic effects induced by 5-FU in mice. These findings indicate that pasteurized A. muciniphila has the potential to be developed as a dietary strategy to reduce chemotherapy-induced toxicity.

Impact of In Vitro Gastrointestinal Digestion on the Phenolic Bioaccessibility and Bioactive Properties of Insect-Containing Beef Burgers.

Mealworm, migratory locust, and house cricket have recently been recognized by the European Commission as novel foods, thus being suitable in different food applications. In this work, we tested their powders as meat extenders at 5% (w/w) inclusion in beef burgers, considering their ability to vehicle phenolic compounds during simulated in vitro static gastrointestinal digestion (INFOGEST). Insect powders were abundant in different phenolic classes, recording the highest values in locust (LP; 314.69 mg/kg), followed by cricket (CP; 113.3 mg/kg) and mealworm (MWP; 51.9 mg/kg). Following a pan-cooking process, LP burgers were confirmed as the best source of phenolics, with a marked abundance of flavonoids and phenolic acids. Interestingly, the insect powders were found to affect the in vitro gastrointestinal bioaccessibility of phenolic compounds when compared with the CTR burger, likely promoted by the interactions between the phenolic compounds and proteins characterizing the tested insect powders. Among the most discriminant phenolic metabolites at the gastrointestinal level, we found several phenolic acids (mainly hydroxycinnamics), recording the highest content for the digested CP-containing burgers. Finally, stilbenes showed significant correlation values at the intestinal level with both antioxidant and enzymatic activities, while total flavonoids were the most correlated with the inhibition of acetylcholinesterase. Taken together, our preliminary findings demonstrated that insect powders added to beef burgers can promote the bioaccessibility and potential bioavailability of phenolics in the distal tracts of the intestine.

Sishen Wan enhances intestinal barrier function via regulating endoplasmic reticulum stress to improve mice with diarrheal irritable bowel syndrome

BackgroundDiarrheal irritable bowel syndrome (IBS-D), characterized primarily by the presence of diarrhea and abdominal pain, is a clinical manifestation resulting from a multitude of causative factors. Furthermore, Sishen Wan (SSW) has demonstrated efficacy in treating IBS-D. Nevertheless, its mechanism of action remains unclear. MethodsA model of IBS-D was induced by a diet containing 45 % lactose and chronic unpredictable mild stress. Additionally, the impact of SSW was assessed by measuring body weight, visceral sensitivity, defecation parameters, intestinal transport velocity, intestinal neurotransmitter levels, immunohistochemistry, and transmission electron microscopy analysis. Immunofluorescent staining was used to detect the expression of Mucin 2 (MUC2) and Occludin in the colon. Western blotting was used to detect changes in proteins related to tight junction (TJ), autophagy, and endoplasmic reticulum (ER) stress in the colon. Finally, 16S rRNA amplicon sequencing was used to monitor the alteration of gut microbiota after SSW treatment. ResultsOur study revealed that SSW administration resulted in reduced visceral sensitivity, improved defecation parameters, decreased intestinal transport velocity, and reduced intestinal permeability in IBS-D mice. Furthermore, SSW promotes the secretion of colonic mucus by enhancing autophagy and inhibiting ER stress. SSW treatment caused remodeling of the gut microbiome by increasing the abundance of Blautia, Muribaculum and Ruminococcus torques group. ConclusionSSW can improve intestinal barrier function by promoting autophagy and inhibiting ER stress, thus exerting a therapeutic effect on IBS-D.

Intestinal Epithelial Cell-specific Knockout of METTL3 Aggravates Intestinal Inflammation in CLP Mice by Weakening the Intestinal Barrier.

Many studies have demonstrated that the expression of methyltransferase- like 3 (METTL3) is altered in various inflammatory diseases. Its specific mechanistic role in the intestinal inflammatory response during sepsis remains limited and requires further investigation. Explore the potential mechanism of METTL3 in the intestinal inflammatory response during sepsis. Immunohistochemical analysis was utilized to detect the expression of METTL3 in the necrotic intestine of patients with intestinal necrosis and the small intestine of cecal ligation and puncture (CLP) mice. Mice were subjected to the CLP and Sham surgeries, intestine tissue was harvested and performed HE staining, and ELISA to examine intestinal inflammatory responses, while TUNEL staining was applied to detect intestinal cell apoptosis. Additionally, ELISA was used to detect diamine oxidase (DAO) and intestinal fatty acid binding protein (I-FABP) levels in intestinal tissue. Immunohistochemistry and RT-qPCR were also employed to examine the mRNA and protein expression levels of Zona Occludens 1 (ZO-1) and Claudin-1. Finally, transcriptomic sequencing was performed on the small intestine tissues of METTL3 Knock-out (KO) and Wild-type (WT) mice in response to sepsis. METTL3 exhibited lower expression level in the necrotic intestine of patients and the small intestine of CLP mice. Loss of METTL3 in CLP mice triggered significantly higher expression of TNF-α and IL-18, down-regulated expression of ZO-1 and claudin-1, and decreased expression of DAO and I-FABP in the intestinal tissue. KEGG enrichment analysis showed that the differential genes were significantly enriched in immune-related pathways. This study reveals a novel mechanism responsible for exacerbated intestinal inflammation orchestrated by METTL3. Particularly, METTL3 null mice displayed decreased ZO- 1 and Claudin-1 expression, which largely hampered intestinal epithelial barrier function, resulting in bacterial and toxin translocation and intestinal immune activation and inflammation against sepsis.

Polystyrene microplastics promote intestinal colonization of Aeromonas veronii through inducing intestinal microbiota dysbiosis

The premise that pathogen colonized microplastics (MPs) can promote the spread of pathogens has been widely recognized, however, their role in the colonization of pathogens in a host intestine has not been fully elucidated. Here, we investigated the effect of polystyrene MPs (PS-MPs) on the colonization levels of Aeromonas veronii, a typical aquatic pathogen, in the loach (Misgurnus anguillicaudatus) intestine. Multiple types of MPs were observed to promote the intestinal colonization of A. veronii, among which PS-MPs exhibited the most significant stimulating effect (67.18% increase in A. veronii colonization). PS-MPs inflicted serious damage to the intestinal tracts of loaches and induced intestinal microbiota dysbiosis. The abundance of certain intestinal bacteria with resistance against A. veronii colonization decreased, with Lactococcus sp. showing the strongest colonization resistance (73.64% decline in A. veronii colonization). Fecal microbiota transplantation was performed, which revealed that PS-MPs induced intestinal microbiota dysbiosis was responsible for the increased colonization of A. veronii in the intestine. It was determined that PS-MPs reshaped the intestinal microbiota community to attenuate the colonization resistance against A. veronii colonization, resulting in an elevated intestinal colonization levels of A. veronii.

Co-release of paclitaxel and encequidar from amorphous solid dispersions increase oral paclitaxel bioavailability in rats

The oral bioavailability of paclitaxel is limited due to low solubility and high affinity for the P-glycoprotein (P-gp) efflux transporter. Here we hypothesized that maximizing the intestinal paclitaxel levels through apparent solubility enhancement and controlling thesimultaneous release of both paclitaxel and the P-gp inhibitor encequidar from amorphous solid dispersions (ASDs) would increase the oral bioavailability of paclitaxel. ASDs of paclitaxel and encequidar in polyvinylpyrrolidone K30 (PVP-K30), hydroxypropylmethylcellulose 5 (HPMC-5), and hydroxypropylmethylcellulose 4 K (HPMC-4K) were hence prepared by freeze-drying. In vitro dissolution studies showed that both compounds were released fastest from PVP-K30, then from HPMC-5, and slowest from HPMC-4K ASDs. The dissolution of paclitaxel from all polymers resulted in stable concentration levels above the apparent solubility. The pharmacokinetics of paclitaxel after oral administration to male Sprague-Dawley rats was investigated with or without 1 mg/kg encequidar, as amorphous solids or polymer-based ASDs. The bioavailability of paclitaxel increased 3- to 4-fold when administered as polymer-based ASDs relative to solid amorphous paclitaxel. However, when amorphous paclitaxel was co-administered with encequidar, either as an amorphous powder or as a polymer-based ASD, the bioavailability increased 2- to 4-fold, respectively. Interestingly, a noticeable increase in paclitaxel bioavailability of 24-fold was observed when paclitaxel and encequidar were co-administered as HPMC-5-based ASDs. We, therefore, suggest that controlling the dissolution rate of paclitaxel and encequidar in order to obtain simultaneous and timed release from polymer-based ASDs is a strategy to increase oral paclitaxel bioavailability.

Effects of High-Dose Whey Protein Concentrate Intake on Hepatorenal and Intestinal Tissues

Introduction: This study aims to compare the antioxidant effects of high doses of whey protein (WP) concentrate intake on liver, kidney, and intestinal tissues. Methods: 18 rats were divided into three groups control (n=6), control+ 8 g/kg WP (n=6), and control + 2 g/kg WP (n=6). 8 g/kg WP group was fed with whey protein added rat chow. 2 g/kg WP group, addition to their standard ad libitum feed, received the whey protein concentrate by oral gavage. On day 10, liver, kidney and intestinal tissues were removed. Lipid peroxidation, glutathione levels and superoxide dismutase and glutathione-S- transferase activities were determined in liver, kidney and intestine tissues. Results: While lipid peroxidation did not change in all groups, glutathione level, superoxide dismutase, and glutathione-S-transferase activities increased in whey protein-administered groups. Liver glutathione level was higher in the 2 g/kg WP compared to the 8 g/kg WP group. There were no significant differences in intestinal glutathione levels between the groups. Kidney GST activity decreased in the kidney and intestine tissues of the 8 g/kg WP group compared to the 2 g/kg WP group. SOD activity was higher in all tissues in the 2 g/kg WP group compared to the other groups. Conclusion: As a result, both whey protein treatments showed different antioxidant effects in the tissues examined. High-dose whey protein application showed lower antioxidant capacity compared to the optimal whey protein dose.

Neuroprotective Effects of Bifidobacterium animalis subsp. lactis NJ241 in a Mouse Model of Parkinson’s Disease: Implications for Gut Microbiota and PGC-1α

Intestinal dysbiosis plays a critical role in the pathogenesis of Parkinson’s disease (PD), and probiotics have emerged as potential modulators of central nervous system function through the microbiota-gut-brain axis. This study aimed to elucidate the anti-inflammatory effects and underlying mechanisms of the probiotic strain Bifidobacterium animalis subsp. lactis NJ241 (NJ241) in a mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The impact of NJ241 was comprehensively assessed in PD mice through behavioral tests, immunofluorescence, Western blotting, enzyme-linked immunosorbent assay (ELISA), 16S rRNA sequencing, and short-chain fatty acid (SCFA) detection. NJ241 exhibited notable efficacy in mitigating MPTP-induced weight loss, gastrointestinal dysfunction, and behavioral deficits in mice. Furthermore, it demonstrated protected against MPTP-induced dopaminergic neuron death and inhibited the activation of glial cells in the substantia nigra (SN). NJ241 demonstrated the ability to normalized dysbiosis in the intestinal microbiota and elevate SCFA levels in PD mice. Additionally, NJ241 reversed MPTP-induced reductions in colonic GLP-1 levels and the expression of GLP-1R and PGC-1α in the SN. Notably, GLP-1R antagonists partially reversed the inhibitory effects of NJ241 on the activation of glial cells in the SN. In summary, NJ241 exerts a neuroprotective effect against MPTP-induced neuroinflammation by enhancing intestinal GLP-1 levels and activating nigral PGC-1α signaling. These findings provide a rationale for the exploration and development of probiotic-based therapeutic strategies for PD.

The differential effect of two cereal foods on gut environment: a randomized, controlled, double-blind, parallel-group study.

Cereal-based foods such as fruit granola (FG) and corn flakes (CF) form part of a fiber-rich diet. Dietary fiber has a good effect on human health. However, changes in gut microbiota and intestinal immunity have not been investigated. We conducted a randomized, double-blind, placebo-controlled trial to investigate the effects of FG and CF intake on gut microbiota, metabolome, and the immune system. Subjects continuously consume CF or FG for 4 weeks. Stool samples, and questionnaires on defecation were collected before, 2 weeks after, and 4 weeks after intake. Gut microbiota was analyzed using 16S rRNA gene amplicon sequencing. Fecal metabolomes were analyzed using GC/MS and CE-TOF/MS. Fecal IgA was analyzed using ELISA. The defecation frequency after cereal based food intake was improved. The different cereal-based foods had different effects on gut microbiome. The increase in intestinal IgA levels was positively correlated with the relative abundance of Dialister and the Lachnospiraceae ND3007 group in CF and FG group, respectively. SCFAs showed a positive correlation with Prevotella 9 in the FG group. This study showed that the supplement in dietary fiber contained in CF and FG improves bowel movements. CF and FG each had different effects on gut microbes, metabolites and different relationships between fecal IgA or SCFAs and gut microbiota.

Gallic Acid-Based Hydrogels for Phloretin Intestinal Release: A Promising Strategy to Reduce Oxidative Stress in Chronic Diabetes.

Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia caused by abnormalities in insulin secretion and/or action. In patients with diabetes, complications such as blindness, delayed wound healing, erectile dysfunction, renal failure, heart disease, etc., are generally related to an increase in ROS levels which, when activated, trigger hyperglycemia-induced lesions, inflammation and insulin resistance. In fact, extensive cell damage and death occurs mainly due to the effect that ROS exerts at the level of cellular constituents, causing the deterioration of DNA and peroxidation of proteins and lipids. Furthermore, elevated levels of reactive oxygen species (ROS) and an imbalance of redox levels in diabetic patients produce insulin resistance. These destructive effects can be controlled by the defense network of antioxidants of natural origin such as phloretin and gallic acid. For this reason, the objective of this work was to create a nanocarrier (hydrogel) based on gallic acid containing phloretin to increase the antioxidant effect of the two substances which function as fundamental for reducing the mechanisms linked to oxidative stress in patients suffering from chronic diabetes. Furthermore, since the bioavailability problems of phloretin at the intestinal level are known, this carrier could facilitate its release and absorption. The obtained hydrogel was characterized using Fourier transform infrared spectroscopy (FT-IR). Its degree of swelling (a%) and phloretin release were tested under pH conditions simulating the gastric and intestinal environment (1.2, 6.8 and 7.4). The antioxidant activity, inhibiting lipid peroxidation in rat liver microsomal membranes induced in vitro by a free radical source, was evaluated for four hours. All results showed that gallate hydrogel could be applied for releasing intestinal phloretin and reducing the ROS levels.

A251 GUT-SPECIFIC DOWNREGULATION OF INTERFERON-LAMBDA RESPONSES OCCURS IN INFLAMMATORY BOWEL DISEASES

Abstract Background Inflammatory bowel diseases (IBD) affect 1:140 Canadians, resulting in significant inflammation and gut damage. Unlike type I and II interferons (IFNs), the most recently discovered IFNs, interferon-lambdas (IFN-λs), uniquely downregulate gut inflammation and promote gut healing in mouse models. However, it remains unknown if the important anti-inflammatory IFN-λ signaling pathways induced downstream of the IFN-λR1/IL-10RB heterodimeric receptor are altered in IBD. Aims To compare intestinal and peripheral IFN-λR levels and responses in people with active or remission IBD and those without IBD. We hypothesized that intestinal IFN-λR1 levels and downstream activities are decreased in people living with IBD, which could contribute to IBD pathology (gut inflammation and mucosal damage). Methods During routine colonoscopy, uninflamed biopsy samples were obtained from the terminal ileum and sigmoid colon. IFN-λR1 levels were quantified in intestinal biopsy and blood samples from persons with or without IBD (n=12 adults and n=12 pediatric) by immunohistochemistry and flow cytometry. Fresh intestinal biopsies were also cultured ex vivo for 24 hr in media +/- IFN-λ3 and gene expression was quantified by RT-qPCR. Results In IBD gut tissues, a significant decrease in IFN-λR1+ cells was more prominent in IBD patients with active disease (pampersand:003C0.01, 30-50% reduction). The decrease was more prominent in IBD patients with active disease. Consequently, there was a significantly lower IFN-λ-driven upregulation of genes such as IFIT1 and MX1 in IBD as compared to non-IBD tissues (pampersand:003C0.05, 4-7-fold reduction). Interestingly, IFN-λR1 levels were not decreased in peripheral blood immune cells, indicating the dysregulation of IFN-λR responses is likely gut-specific. Conclusions Our findings demonstrate that people living with IBD have dysregulated IFN-λ responses in the gut which could lead to the lower induction of key anti-inflammatory pathways. This work supports the further study of mechanisms regulating the IFN-λ system to develop strategies to restore and promote IFN-λ responses as a novel potential future IBD therapy. Funding Agencies University of Manitoba, Weston Family Foundation, The Children's Hospital Research Institute of Manitoba.