Effects of water quality on growth performance and health of nursery pigs

An experiment was conducted to determine effects of providing drinking water of differing qualities on growth performance and health of nursery pigs. Weanling pigs (n = 450; 150 pigs/group; 10 pigs/pen) were assigned randomly to one of three experimental groups consisting of three water sources of varying quality: 1) Water source A containing 1,410 ppm hardness (CaCO3 equivalent), 1,120 ppm sulfates, and 1,500 ppm total dissolved solids (TDS); 2) Water source B containing 909 ppm hardness (CaCO3 equivalent), 617 ppm sulfates, and 1,050 ppm TDS; and 3) Water source C containing 235 ppm hardness (CaCO3 equivalent), 2 ppm sulfates, and 348 ppm TDS. Pigs were provided ad libitum access to their respective water sources for the duration of the study which began at weaning (21 d of age) and ended 40 d later (61 d of age). Individual pig weights were recorded weekly along with feed intake on a pen basis. Occurrences of morbidity and mortality were recorded daily. Subjective fecal scores were assigned on a pen basis and blood samples were used to evaluate blood chemistry, cytokine concentrations, and phagocytic activity. A differential sugar absorption test was used to assess intestinal permeability. Fecal grab samples were used to establish diet digestibility, and drinking behavior was video-recorded to assess pigs’ acceptance of water sources provided. The statistical model considered fixed effects of water source, room, and their interaction with the random effect of pen. A repeated measures analysis was conducted to determine effects of water quality over time. There were no differences (P > 0.440) among water sources in average daily gain (A, 0.46 kg/d; B, 0.46 kg/d; C, 0.47 kg/d) or average daily feed intake (A, 0.68 kg/d; B, 0.69 kg/d; C, 0.71 kg/d). Overall mortality of pigs was 0.44% and did not differ across the three water sources. There were no differences in apparent total tract digestibility of the diet, intestinal permeability, immune parameters, or blood chemistry attributable to quality of water consumed by pigs. Pigs did not show an aversion to the water sources provided, because total time pigs spent at the drinker did not differ (P > 0.750) among water sources on d 1 through 3 of the experiment. These data indicate that the water sources of differing quality studied did not affect growth performance or health of nursery pigs.

Integration of In Silico, In Vitro and In Situ Tools for the Preformulation and Characterization of a Novel Cardio-Neuroprotective Compound during the Early Stages of Drug Development

The main aim of this work is the biopharmaceutical characterization of a new hybrid benzodiazepine-dihydropyridine derivative, JM-20, derived with potent anti-ischemic and neuroprotective effects. In this study, the pKa and the pH-solubility profile were experimentally determined. Additionally, effective intestinal permeability was measured using three in vitro epithelial cell lines (MDCK, MDCK-MDR1 and Caco-2) and an in situ closed-loop intestinal perfusion technique. The results indicate that JM-20 is more soluble at acidic pH (9.18 ± 0.16); however, the Dose number (Do) was greater than 1, suggesting that it is a low-solubility compound. The permeability values obtained with in vitro cell lines as well as with the in situ perfusion method show that JM-20 is a highly permeable compound (Caco-2 value 3.8 × 10−5). The presence of an absorption carrier-mediated transport mechanism was also demonstrated, as well as the efflux effect of P-glycoprotein on the permeability values. Finally, JM-20 was provisionally classified as class 2 according to the biopharmaceutical classification system (BCS) due to its high intestinal permeability and low solubility. The potential good oral absorption of this compound could be limited by its solubility.

GPR120 prevents colorectal adenocarcinoma progression by sustaining the mucosal barrier integrity

GPR120 (encoded by FFAR4 gene) is a receptor for long chain fatty acids, activated by ω-3 Polyunsaturated Fatty Acids (PUFAs), and expressed in many cell types. Its role in the context of colorectal cancer (CRC) is still puzzling with many controversial evidences. Here, we explored the involvement of epithelial GPR120 in the CRC development. Both in vitro and in vivo experiments were conducted to mimic the conditional deletion of the receptor from gut epithelium. Intestinal permeability and integrity of mucus layer were assessed by using Evans blue dye and immunofluorescence for MUC-2 protein, respectively. Microbiota composition, presence of lipid mediators and short chain fatty acids were analyzed in the stools of conditional GPR120 and wild type (WT) mice. Incidence and grade of tumors were evaluated in all groups of mice before and after colitis-associated cancer. Finally, GPR120 expression was analyzed in 9 human normal tissues, 9 adenomas, and 17 primary adenocarcinomas. Our work for the first time highlights the role of the receptor in the progression of colorectal cancer. We observed that the loss of epithelial GPR120 in the gut results into increased intestinal permeability, microbiota translocation and dysbiosis, which turns into hyperproliferation of epithelial cells, likely through the activation of β -catenin signaling. Therefore, the loss of GPR120 represents an early event of CRC, but avoid its progression as invasive cancer. these results demonstrate that the epithelial GPR120 receptor is essential to maintain the mucosal barrier integrity and to prevent CRC developing. Therefore, our data pave the way to GPR120 as an useful marker for the phenotypic characterization of CRC lesions and as new potential target for CRC prevention.

Study of the dissolution kinetics of drugs in solid dosage form with lisinopril and atorvastatin and intestinal permeability to assess their equivalence in vitro

Atorvastatin and lisinopril are a successful combination for the treatment of patients with chronic heart failure and hypertension. Study of the dissolution kinetics of drugs in solid dosage form with lisinopril and atorvastatin and intestinal permeability to assess their equivalence in vitro were described. In medium with hydrochloric acid pH 1.2, in the medium of acetate buffer solution with a pH of 4.5 and in the medium phosphate buffer solution with a pH of 6.8 for 15 min more than 85% of the active substance passes into solution, hence the dissolution profiles these drugs in these environments are similar, and the drugs in them are “very quickly soluble”. Among the in vitro models that make it possible to assess the degree of absorption of API, the most widely used culture of adenocarcinoma cells of the colon – Caco-2. The development of the analytical methodology and its validation is the final stage of both the dissolution study and the Caco-2 test, as well as the biowaver procedure. It plays the most important role in the reliability of the results for all the above procedures and tests. To study permeability, method LC-MS/MS was developed. According to the obtained results, atorvastatin and lisinopril showed low permeability. The values ​​of recovery of transport of test and control substances through the monolayer of cells of the Caco-2 line indicate that the results of the experiment can be considered reliable. The equivalence of the drugs “Lisinopril”, tablets of 10 mg and “Atorvastatin”, tablets of 10 mg, belongs to class III BCS proven by in vitro studies.

Bifidobacterium bifidum Shows More Diversified Ways of Relieving Non-Alcoholic Fatty Liver Compared with Bifidobacterium adolescentis

The occurrence of non-alcoholic fatty liver disease (NAFLD) is closely related to intestinal microbiota disturbance, and probiotics has become a new strategy to assist in alleviating NAFLD. In order to investigate the effect of Bifidobacterium on NAFLD and the possible pathway, a NAFLD model was established by using a high-fat diet (HFD) for 18 weeks. Fourteen strains of Bifidobacterium were selected (seven Bifidobacterium adolescentis and seven Bifidobacterium bifidum) for intervention. The effects of different bifidobacteria on NAFLD were evaluated from liver cell injury, liver fat deposition, liver inflammatory state and liver histopathology, and were taken as entry points to explore the mitigation approaches of bifidobacteria through energy intake, lipid metabolism, glucose metabolism and intestinal permeability. The results showed that Bifidobacterium exerts species-specific effects on NAFLD. B. bifidum exerted these effects mainly through regulating the intestinal microbiota, increasing the relative abundance of Faecalibaculum and Lactobacillus, decreasing the relative abundance of Tyzzerella, Escherichia-Shigella, Intestinimonas, Osillibacter and Ruminiclostridium, and further increasing the contents of propionic acid and butyric acid, regulating lipid metabolism and intestinal permeability, and ultimately inhibiting liver inflammation and fat accumulation to alleviate NAFLD. B. adolescentis exerted its effects mainly through changing the intestinal microbiota, increasing the content of propionic acid, regulating lipid metabolism and ultimately inhibiting liver inflammation to alleviate NAFLD.

Glucose but Not Fructose Alters the Intestinal Paracellular Permeability in Association With Gut Inflammation and Dysbiosis in Mice

A causal correlation between the metabolic disorders associated with sugar intake and disruption of the gastrointestinal (GI) homeostasis has been suggested, but the underlying mechanisms remain unclear. To unravel these mechanisms, we investigated the effect of physiological amounts of fructose and glucose on barrier functions and inflammatory status in various regions of the GI tract and on the cecal microbiota composition. C57BL/6 mice were fed chow diet and given 15% glucose or 15% fructose in drinking water for 9 weeks. We monitored caloric intake, body weight, glucose intolerance, and adiposity. The intestinal paracellular permeability, cytokine, and tight junction protein expression were assessed in the jejunum, cecum, and colon. In the cecum, the microbiota composition was determined. Glucose-fed mice developed a marked increase in total adiposity, glucose intolerance, and paracellular permeability in the jejunum and cecum while fructose absorption did not affect any of these parameters. Fructose-fed mice displayed increased circulation levels of IL6. In the cecum, both glucose and fructose intake were associated with an increase in Il13, Ifnγ, and Tnfα mRNA and MLCK protein levels. To clarify the relationships between monosaccharides and barrier function, we measured the permeability of Caco-2 cell monolayers in response to IFNγ+TNFα in the presence of glucose or fructose. In vitro, IFNγ+TNFα-induced intestinal permeability increase was less pronounced in response to fructose than glucose. Mice treated with glucose showed an enrichment of Lachnospiracae and Desulfovibrionaceae while the fructose increased relative abundance of Lactobacillaceae. Correlations between pro-inflammatory cytokine gene expression and bacterial abundance highlighted the potential role of members of Desulfovibrio and Lachnospiraceae NK4A136 group genera in the inflammation observed in response to glucose intake. The increase in intestinal inflammation and circulating levels of IL6 in response to fructose was observed in the absence of intestinal permeability modification, suggesting that the intestinal permeability alteration does not precede the onset of metabolic outcome (low-grade inflammation, hyperglycemia) associated with chronic fructose consumption. The data also highlight the deleterious effects of glucose on gut barrier function along the GI tract and suggest that Desulfovibrionaceae and Lachnospiraceae play a key role in the onset of GI inflammation in response to glucose.

Microbiota and intestinal permeability as drivers of gastroenterological manifestations of new coronavirus infection (COVID-19)

An important area of effective control of the COVID-19 pandemic is the study of the pathogenetic features of SARSCoV-2 infection, including those based on the assessment of the state of the microbiota and intestinal permeability.Purpose: To study the clinical features of the new coronavirus infection (COVID-19) in patients of mild and moderate severity at the stage of hospitalization, to determine the role of intestinal permeability disorders, changes in the qualitative and quantitative composition of the microbiota in the formation of systemic inflammation in COVID-19 patients.Material and methods: The study was performed in 80 patients with COVID-19, whose average age was 45 years, 19 of them had mild and 61 had moderate severity of the disease. The scope of the examination included traditional clinical, clinical and laboratory, biochemical, instrumental and radiation studies, as well as original methods for studying microbiota and intestinal permeability.Results and conclusions: Clinical features of the course of COVID-19 were studied, clinical and biochemical features, manifestations of systemic inflammation, changes in the intestinal microbiome of patients with mild and moderate severity were identified, concentration levels of proinflammatory cytokines, insulin, fecal calprotectin and zonulin were determined, reflecting the features of intestinal permeability against the background of COVID-19. The role of intestinal permeability and microbiota as the main drivers of the development of gastroenterological manifestations of COVID-19, accompanied by a more severe course of the disease, is emphasized.

Mediterranean Diet Adherence in People With Parkinson's Disease Reduces Constipation Symptoms and Changes Fecal Microbiota After a 5-Week Single-Arm Pilot Study

Introduction: Non-motor symptoms of Parkinson's disease (PD) such as gastrointestinal (GI) dysfunction are common, yet little is known about how modifying dietary intake impacts PD symptoms. The aim of this study in individuals with PD was to determine whether a Mediterranean diet intervention is feasible and affects GI function, intestinal permeability and fecal microbial communities.Methods: A single-arm, 5-week Mediterranean diet intervention study was conducted in eight people with PD. Daily and weekly questionnaires were administered to determine changes in GI symptoms. Urine and stool samples were collected at baseline and after 5 weeks to assess intestinal permeability and fecal microbial communities. Additionally, live-in partners of the participants with PD were matched as controls (n = 8) for baseline urine and stool samples.Results: Participants with PD increased intake of Mediterranean diet based on adherence scores from baseline to week 5 (4.4 ± 0.6 vs. 11.9 ± 0.7; P < 0.01 with >10 representing good adherence), which was linked with weight loss (77.4 kg vs. 74.9 kg, P = 0.01). Constipation syndrome scores decreased after 5 weeks (2.3 ± 0.5 vs. 1.5 ± 0.3; P = 0.04). Bilophila, was higher at baseline in PD (0.6 ± 0.1% vs. 0.2 ± 0.1% P = 0.02) and slightly decreased after the diet intervention (0.5 ± 0.1%; P = 0.01). Interestingly, the proportion of Roseburia was significantly lower in PD compared to controls (0.6 ± 0.2% vs. 1.6 ± 0.3%; P = 0.02) and increased at week 5 (0.9 ± 0.2%; P < 0.01). No differences were observed for markers of intestinal permeability between the control and PD groups or post-intervention.Conclusions: Short-term Mediterranean diet adherence is feasible in participants with PD; correlated with weight loss, improved constipation, and modified gut microbiota.Clinical Trial Registration:ClinicalTrials.gov, identifier: NCT03851861.