Results of Malnutrition Correction in Children with Cystic Fibrosis with Hypercaloric Formulas for Enteral Nutrition for One Month: Cohort Study

Background. The use of hypercaloric formulas in cystic fibrosis patients has the risks of negative effects on carbohydrate and lipid metabolism. Thus, it is interesting to analyze the efficacy of malnutrition correction and the safety of hypercaloric enteral products with a low glycemic index and with medium-chain triglycerides content of 50%.Objective. The aim of the study is analyze the efficacy of malnutrition correction with therapeutic hypercaloric product for enteral nutrition in children with cystic fibrosis.Methods. The study included patients aged from 3 to 18 years with malnutrition (BMI < 50 percentile) who were prescribed therapeutic hypercaloric formula to correct the malnutrition. Anthropometric indicators (height, body weight), actual nutritional status, pancreatin doses, lung function, carbohydrate metabolism rates, and cholestasis marker (bile acid concentration) were measured initially and after 1 month of using formula nutrition.Results. The children’ body weight (Me) has increased from 24.5 (21.2; 38.7) to 25.3 kg (21.6; 39.7) (p = 0.001), growth (Me) — from 133.5 (120.2; 146.5) to 136.5 cm (123.0; 148.5) (p < 0.001) after 1 month of using hypercaloric formula. The growth percentile increased from 33 to 40, the z-criterion values — from –0.5 to –0.3 SD (p < 0.001). There was no increase in BMI in dynamics due to the fact that the growth of children was ahead of body weight increase. The daily energy intake increased by an average of 450 kcal that was 21.8% regarding physiological need.Conclusion. The inclusion of hypercaloric formula in the diet of children with cystic fibrosis for 1 month significantly increases the indicators of linear growth and positively affects the overall physical development. There were no negative effect of formula on carbohydrate and lipid metabolism.

IMBALANCED IMMUNOBIOLOGICAL REACTIVITY, INFECTION AND MUTAGENESIS FACTORS IN THE HEPATOBILIARY SYSTEM AFFECTED BY A NATURAL FOCAL HABITAT FACTOR – A TREMATODE INVASION BY OPISTHORCHIS FELINEUS

An interaction between decreasing host anti-infective defense due to long-term invasion with Opisthorchis felineus in the hepatobiliary system, duct bile colonization by microflora and revealing the endogenous mutagenesis (carcinogenesis) factor - secondary bile acids - in bile is considered in the article. The role of organism genotype in the pathogen-related immune response to Opisthorchis felineus trematode and helminth development in the hepatobiliary system has been shown. The role of dysregulated mechanisms of tissue homeostasis in induction of compensatory chronic homeostatic proliferation and somatic cell oncogenesis is discussed. The study results evidence that disturbed functioning of the regulatory T-cells, inhibition of the NK cell effector function and very high functional activity of the memory B-cells are of great importance in imbalanced host immunobiological reactivity, caused by chronic opistorchosis invasion. Decreased host anti-infective protection causes intrahepatic bile duct infection with different bacterial species. Presence of secondary bile acids in hepatobiliary system was associated with biliary bacterial strains inhabiting intestinal tract: Proteus vulgaris*, Proteus mirabilis*, Citrobacter freundii*, Bacteroides alcaligues faecalis*, Clostridium*, Streptococcus faecalis*, Еscherichia coli* (*gut microflora). Participation of microbiota in bile acid biotransformation immediately in the duct bile has been confirmed in in vitro experiments. Experimental methods on Drosophila melanogaster and Salmonella tiphimurium strains: TA 100, TA 98 allowed to find out that bile from chronic opistorchosis patients exerts higher mutagenic activity compared with control groups. Mutational events in somatic and bacterial cells depend on the presence of secondary bile acids (deoxycholic, lithocholic) in duct bile, as well as the level of total bile acid concentration. The study data confirm the concept by Professor A.A. Shain about presence of endogenous risk factor for developing primary cholangiocellular liver cancer such as secondary bile acids in the bile of chronic opistorchosis patients. A concept of cholangiocarcinogenesis, based on mutational events, is added up with disturbance of generative cycle in tissue cells and their differentiation due to decreased kylon factor activity, as well as sensitivity threshold to it. Level of investigation and understanding of mechanisms underlying cholangiocarcinogenesis during chronic opisthorchiasis invasion will allow to develop pathogenetic approaches to correct homeostasis regulation and prevention of cholangiocarcinomas.

Effect of dietary folic acid and energy density on immune response, gut morphology, and oxidative status in blood and breast muscle of broiler chickens

Folic acid (FA) plays an essential role in the functioning of the gut and serves as an antioxidant. Therefore, dietary supplementation with high levels of FA may improve gut health and prevent oxidative stress caused by feeding a high energy density diet to broiler chickens. Broiler chickens were assigned into eight treatments, consisting of either a normal energy (NE) or high energy (HE) density diet, and four FA levels (2.2, 5, 10, and 15 ppm). Data were analyzed by SAS 16 GLM procedure. Birds fed HE diets had increased (P<0.05) plasma concentrations of calcium and albumin but reduced (P<0.005) weights of ceca and bursa compared to those fed NE diets. Dietary supplementation with 10ppm FA significantly increased (P<0.05) birds’ heart weight and bile acid concentration. FA and energy density interactions were significant for jejunal villus height (VH; P=0.0226), villus width (VW; P<0.0001), and crypt depth (CD; P=0.0332). Among the NE group, birds fed 5-15ppm FA had reduced (P<.0001) VW, while in the HE groups, 15ppm FA supplementation resulted in an increased jejunal VH (P=0.0317) compared to other treatments. In conclusion, dietary supplementation with increased levels of FA in HE diets could be beneficial for the intestinal health of broiler chickens.

Changes in Serum Lipid Profiles among Canine Patients Suffering from Chronic Hepatitis

Hyperlipidemia is a risk factor for nonalcoholic fatty liver disease (NAFLD) in humans. However, the association between serum lipids and canine chronic hepatitis remains unknown. In this study, serum lipids, hepatic profiles, and hepatic ultrasound scores of healthy dogs and dogs with chronic hepatitis were evaluated. Serum triglyceride and cholesterol concentrations were significantly higher (p < 0.01) in dogs with chronic hepatitis. There were 62.2% of dogs with chronic hepatitis accompanied by hypertriglyceridemia, hypercholesterolemia, or both. Positive correlations were observed between serum ALT and cholesterol (r = 0.8287, p < 0.01), serum ALP and cholesterol (r = 0.8436, p < 0.01), serum GGT and cholesterol (r = 0.5640, p < 0.01), serum bile acid and cholesterol (r = 0.3310, p < 0.01) and serum ALP and triglycerides (r = 0.2582, p < 0.05). No significant differences were found between ultrasound scores of diseased dogs with and without hypertriglyceridemia and diseased dogs with and without hypercholesterolemia. Canine chronic hepatitis is associated with hyperlipidemia. A significant positive association was identified between hyperlipidemia, especially hypercholesterolemia, liver enzymes, and bile acid concentration in dogs suffering from chronic hepatitis. The underlying mechanisms connecting hyperlipidemia and canine chronic hepatitis remain elusive.

Intrahepatic Cholestasis of Pregnancy

Intrahepatic cholestasis of pregnancy (ICP) is a rare but potentially serious complication of pregnancy, the main symptom of which is intense pruritus with elevated serum levels of bile acids. The elevated serum bile acid concentration is regarded as a predictor for poor perinatal outcome including intrauterine death. Ursodeoxycholic acid (UDCA) has become established as the treatment of choice in clinical management to achieve a significant improvement in symptoms and reduce the cholestasis. Pregnant women with severe intrahepatic cholestasis should always be managed in a perinatal centre with close interdisciplinary monitoring and treatment involving perinatologists and hepatologists to minimise the markedly increased perinatal morbidity and mortality as well as maternal symptoms.

Analysis on Microbial Profiles & Components of Bile in Patients with Recurrent CBD Stones after Endoscopic CBD Stone Removal: A Preliminary Study

Background/Aim: Common bile duct (CBD) stone recurrence after endoscopic treatment is a major concern as a late complication. Biliary bacterial factors and biochemical factors determine the path of gallstone formation. The aim of this preliminary study was to investigate the microbial profile and components of bile in patients with and without recurrent CBD stones after endoscopic CBD stone removal. Methods: Among patients who had undergone an initial endoscopic procedure for the removal of CBD stones and were followed up for >2 years, 11 patients who experienced at least two CBD stone recurrences, six months after endoscopic retrograde cholangiopancreatography (ERCP), were categorized into the recurrence group. Nine patients without CBD recurrence events were matched. Results: Polymicrobial infections are generally seen in all patients who have biliary sphincteroplasty. Microbial richness, measured by the numbers of operational taxonomic units (OTUs), was reduced in the recurrence group. The microbial evenness was also significantly lower than in the non-recurrence group. The overall microbial communities in the recurrence group deviated from the non-recurrence group. Infection with bacteria exhibiting β-glucuronidase activity was more frequent in the recurrence group, but there was no statistical significance. In an analysis of the bile components, the bile acid concentration was higher in the non-recurrence group than in the recurrence group. However, the other metabolites were not significantly different. Conclusions: Microbiota dysbiosis and altered bacterial community assembly in bile duct and decreased bile acid in bile juice were associated with recurrence of bile duct stone.

The Comparison of Total Bile Acid Concentration and Alcohol Dehydrogenase Activity as Markers of Intrahepatic Cholestasis of Pregnancy

Background: Intrahepatic cholestasis of pregnancy (ICP) is the liver disorder in the second or early third trimester of pregnancy. It is characterized by pruritus with increased serum total bile acids concentration (TBA) and increased liver enzymes. It is important to recognize the disease in its early stage. We aimed to investigate the serum alcohol dehydrogenase (ADH) activity and compare it with the concentration of total bile acid (TBA) in women with ICP..Methods: Serum samples were taken from 80 pregnancies with ICP in the second or third trimester of pregnancy and from 80 healthy pregnant women. For measurement of ADH we used the spectrofluorometric and photometric methods. Results: The results shows a statistically significant increase in the activity of ADH I and ADH total (about 60% and 41%, respectively). Activity of ADH I well correlated with aminotransferases (alanine ALT and aspartate AST) and TBA concentration. The total ADH activity was also positively correlated with ALT, AST and TBA. Conclusion: We can state that the activity of class I ADH isoenzyme in the sera of patients with ICP is increased and seems to be a good indicator of liver cell destruction during ICP and is comparable with the value of other markers.

Investigating the Role Intestinal-Specific FXR and SHP in Regulating Lipid Metabolism in Mice

Dysregulation of lipid metabolism is a causal factor that can lead to a variety of disorders, such as obesity and metabolic syndrome. Dietary fats are digested in the small intestine by the physiological detergents known as bile acids. They emulsify the fats and break them down into smaller molecules in order for the enterocytes to absorb the nutrients through simple diffusion or through the utilization of specific lipid transporters. Interestingly, the nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) not only regulates bile acid synthesis and circulation, but also lipid metabolism. Although many studies have examined the role of FXR in hepatic and intestinal lipid metabolism, studies investigating the role of SHP in the intestine are still lacking. Although FXR and SHP cooperate to regulate many metabolic pathways, FXR or SHP knockout models exhibit different lipid phenotypes. These data indicate there are FXR-dependent and -independent pathways of SHP that controls lipid metabolism. To delineate these two interconnecting yet separate pathways, we will utilize intestine-specific Shp knockout (IShpKO) and intestine-specific Fxr knockout (IFxrKO) mice model and place them on high fat diet to investigate their intestinal intestinal absorption and transportation of lipids. We will also monitor the bile acid pool in the intestine, serum, and liver in these knockouts to evaluate the consequence of intestinal deletion of Fxr as well as Shp on bile acid homeostasis and how this may affect lipid absorption. These experiments will identify how FXR and/or SHP regulates intestinal fat digestion and absorption and if this is secondary to the alterations in bile acid concentration and lipid transporters. In addition, we will also investigate the intestinal Fxr-Shp double knockout (IDKO) mice model to determine their combined contribution in intestinal lipid metabolism. Overall, the results obtained from this research will elucidate if intestinal FXR and SHP cooperate or can independently regulate lipid metabolism and homeostasis.

Metabolic Regulations by lncRNA, miRNA, and ceRNA Under Grass-Fed and Grain-Fed Regimens in Angus Beef Cattle

Beef cattle raised under grass-fed and grain-fed have many differences, including metabolic efficiency and meat quality. To investigate these two regimens' intrinsic influence on beef cattle, we used high-throughput sequencing and metabolomics analyses to explore differentially expressed genes (DEGs) and metabolimic networks in the liver. A total of 200 DEGs, 76 differentially expressed miRNAs (DEmiRNAs), and two differentially expressed lncRNAs (DElncRNAs) were detected between regimen groups. Metabolic processes and pathways enriched functional genes including target genes of miRNAs and lncRNAs. We found that many genes were involved in energy, retinol and cholesterol metabolism, and bile acid synthesis. Combined with metabolites such as low glucose concentration, high cholesterol concentration, and increased primary bile acid concentration, these genes were mainly responsible for lowering intramuscular fat, low cholesterol, and yellow meat in grass-fed cattle. Additionally, we identified two lncRNAs and eight DEGs as potential competing endogenous RNAs (ceRNAs) to bind miRNAs by the interaction network analysis. These results revealed that the effects of two feeding regimens on beef cattle were mainly induced by gene expression changes in metabolic pathways mediated via lncRNAs, miRNAs, and ceRNAs, and contents of metabolites in the liver. It may provide a clue on feeding regimens inducing the metabolic regulations.