-
1.
Impact of Teduglutide on Quality of Life Among Patients With Short Bowel Syndrome and Intestinal Failure.
Chen, K, Mu, F, Xie, J, Kelkar, SS, Olivier, C, Signorovitch, J, Jeppesen, PB
JPEN. Journal of parenteral and enteral nutrition. 2020;(1):119-128
-
-
Free full text
-
Abstract
BACKGROUND Teduglutide reduces or eliminates parenteral support (PS) dependency in patients with short bowel syndrome (SBS). Recent post hoc analyses demonstrated that effects are correlated with baseline PS volume. We assessed the SBS-related quality-of-life (QoL) impact of teduglutide, particularly whether improvements are greater among subgroups achieving more PS volume reduction. METHODS Using phase 3 trial data of teduglutide in patients with SBS (NCT00798967), change in Short Bowel Syndrome-Quality of Life (SBS-QoL) scores from baseline were compared between teduglutide vs placebo in the overall population and subgroups classified by baseline PS volume requirement, disease etiology, and bowel anatomy. Generalized estimating equation models were fitted to assess impact of teduglutide on SBS-related QoL using data from all visits, adjusted for baseline characteristics. RESULTS Of 86 patients, 43 each were randomized to teduglutide or placebo (mean age: 51 vs 50 years, respectively). In adjusted analyses, teduglutide had a nonsignificant reduction (improvement) of -8.6 points (95% CI: 2.6 to -19.8) in SBS-QoL sum score from baseline to Week-24 vs placebo. The impact of teduglutide varied by subgroup. Patients treated with teduglutide experienced significantly greater reductions in SBS-QoL sum score at Week-24 vs placebo in 2 subgroups, ie, the third (highest) tertile baseline PS volume (-27.3, 95% CI: -50.8 to -3.7) and inflammatory bowel disease (IBD; -29.6, 95% CI: -46.3 to -12.9). Results were similar for SBS-QoL subscale and item scores. CONCLUSIONS The impact of teduglutide treatment on SBS-related QoL vs placebo varied among subgroups and was significant and most pronounced among patients with highest baseline PS volume requirement or IBD.
-
2.
Dynamic Adjustments of Parenteral Support in Early Adult Intestinal Failure-Essential Role of Sodium.
Jacob, T, Glass, A, Witte, M, Reiner, J, Lamprecht, G
Nutrients. 2020;(11)
Abstract
Intestinal failure (IF) requires parenteral support (PS) substituting energy, water, and electrolytes to compensate intestinal losses and replenish deficits. Convalescence, adaptation, and reconstructive surgery facilitate PS reduction. We analyzed the effect of changes of PS on body mass index (BMI) in early adult IF. Energy, volume, and sodium content of PS and BMI were collected at the initial contact (FIRST), the time of maximal PS and BMI (MAX) and the last contact (LAST). Patients were categorized based on functional anatomy: small bowel enterostomy-group 1, jejuno-colic anastomosis-group 2. Analysis of variance was used to test the relative impact of changes in energy, volume, or sodium. Total of 50 patients were followed for 596 days. Although energy, volume, and sodium support were already high at FIRST, we increased PS to MAX, which was accompanied by a significant BMI increase. Thereafter PS could be reduced significantly, leading to a small BMI decrease in group 1, but not in group 2. Increased sodium support had a stronger impact on BMI than energy or volume. Total of 13 patients were weaned. Dynamic PS adjustments are required in the early phase of adult IF. Vigorous sodium support acts as an independent factor.
-
3.
Muscle and intestinal damage in triathletes.
Tota, Ł, Piotrowska, A, Pałka, T, Morawska, M, Mikuľáková, W, Mucha, D, Żmuda-Pałka, M, Pilch, W
PloS one. 2019;(1):e0210651
Abstract
The aim of the paper was to assess indicators of muscle and intestinal damage in triathletes. The study involved 15 triathletes whose objective for the season was to start in the XTERRA POLAND 2017 event (1,500-m swimming, 36-km cycling, and 10-km mountain running). Before the 14-week preparatory period, the competitors' body composition was measured, aerobic capacity was tested (graded treadmill test) and blood samples were collected to determine markers showing the level of muscle and intestinal damage. Subsequent tests for body composition were carried out before and after the competition. Blood samples for biochemical indicators were collected the day before the competition, after the completed race, and 24 and 48 hours later. A significant decrease in body mass was observed after completing the race (-3.1±1.5%). The mean maximal oxygen uptake level among the studied athletes equalled 4.9±0.4 L·min-1, 58.8±4.5 mL·kg-1·min-1. The significant increase in concentrations of cortisol, c-reactive protein and myoglobin after the competition, significantly correlated with the significant increase in zonulin concentration (post 1h: r = 0.88, p = 0.007, r = 0,79, p = 0.001, r = 0.78, p = 0.001, and post 12h: r = 0.75, p = 0.01, r = 0.71, p = 0.011, r = 0.83, p = 0.02). No significant changes in the concentration of tumour necrosis factor alpha among the examined competitors were noted at following stages of the study. The results of our research showed that in order to monitor overload in the training of triathletes, useful markers reflecting the degree of muscle and intestinal damage include cortisol, testosterone, testosterone to cortisol ratio, c-reactive protein, myoglobin and zonulin. Changes in muscle cell damage markers strongly correlated with changes in zonulin concentration at particular stages of the study. Thus, one can expect that the concentrations of markers depicting the level of muscle cell damage after an intense and long-lasting effort will significantly influence the level of the intestinal barrier.
-
4.
Intestinal phase-II metabolism of quercetin in HT29 cells, 3D human intestinal tissues and in healthy volunteers: a qualitative comparison using LC-IMS-MS and LC-HRMS.
Chalet, C, Hollebrands, B, Duchateau, GS, Augustijns, P
Xenobiotica; the fate of foreign compounds in biological systems. 2019;(8):945-952
Abstract
Flavonoids are a large class of dietary molecules, among which quercetin is the most ubiquitous, which undergo an extensive intestinal phase-II metabolism. We compared the in vivo metabolism of quercetin in healthy volunteers with two in vitro models, HT29 cells and 3 D human intestinal tissues. Supernatants of the in vitro experiments and the human intestinal fluids (HIF) were analyzed by LC-IMS-MS and LC-HRMS in a qualitative way. Quercetin glucuronides, sulfates and their methyl conjugates were detected in all three systems. The metabolic profiles were found to be different, both in terms of the metabolites produced and their relative proportions. In particular, quercetin sulfates were almost absent in supernatants from HT29 cells incubations while they were a major metabolite in HIF and also found in 3 D intestinal tissues incubations. IMS provided structural information as well as a third dimension of characterization, while HRMS brought increased sensitivity and MS/MS confirmation. HT29 cells are a useful tool to generate phase-II metabolites but do not represent the in vivo situation. 3 D intestinal tissues appear as a more relevant tool to study the intestinal phase-II metabolism of flavonoids.
-
5.
Aerobic Exercise Training with Brisk Walking Increases Intestinal Bacteroides in Healthy Elderly Women.
Morita, E, Yokoyama, H, Imai, D, Takeda, R, Ota, A, Kawai, E, Hisada, T, Emoto, M, Suzuki, Y, Okazaki, K
Nutrients. 2019;(4)
Abstract
This study examined the effect of an exercise intervention on the composition of the intestinal microbiota in healthy elderly women. Thirty-two sedentary women that were aged 65 years and older participated in a 12-week, non-randomized comparative trial. The subjects were allocated to two groups receiving different exercise interventions, trunk muscle training (TM), or aerobic exercise training (AE). AE included brisk walking, i.e., at an intensity of ≥ 3 metabolic equivalents (METs). The composition of the intestinal microbiota in fecal samples was determined before and after the training period. We also assessed the daily physical activity using an accelerometer, trunk muscle strength by the modified Kraus-Weber (K-W) test, and cardiorespiratory fitness by a 6-min. walk test (6MWT). K-W test scores and distance achieved during the 6MWT (6MWD) improved in both groups. The relative abundance of intestinal Bacteroides only significantly increased in the AE group, particularly in subjects showing increases in the time spent in brisk walking. Overall, the increases in intestinal Bacteroides following the exercise intervention were associated with increases in 6MWD. In conclusion, aerobic exercise training that targets an increase of the time spent in brisk walking may increase intestinal Bacteroides in association with improved cardiorespiratory fitness in healthy elderly women.
-
6.
In vivo evidence for transintestinal cholesterol efflux in patients with complete common bile duct obstruction.
Moreau, F, Blanchard, C, Perret, C, Flet, L, Douane, F, Frampas, E, Mirallie, E, Croyal, M, Aguesse, A, Krempf, M, et al
Journal of clinical lipidology. 2019;(1):213-217.e1
Abstract
BACKGROUND Beyond the hepatobiliary pathway, studies have demonstrated that direct transintestinal cholesterol efflux (TICE) of plasma-derived cholesterol may contribute to reverse cholesterol transport. The clinical evidence of TICE in human remains challenged because of the difficulty to discriminate the hepatobiliary and transintestinal routes in vivo. OBJECTIVE To provide the first proof of concept that TICE exists in vivo in humans by demonstrating that plasma labeled cholesterol can be excreted in the feces of patients with complete bile duct obstruction. METHODS Plasma, bile, and fecal cholesterol excretion was measured by mass spectrometry 24, 48, and 72 hours after intravenous injection of D7-cholesterol in two patients presenting cholangiocarcinomas with a total obstruction of their primary bile duct. RESULTS No trace of bile acids was detected in the feces of the two patients. Despite this, a significant amount of plasma D7-cholesterol was quantified in the feces of the two patients 48 hours and 72 hours after the intravenous injection. CONCLUSION Our data bring a direct proof that TICE is an active pathway in humans.
-
7.
Association between sn-2 fatty acid profiles of breast milk and development of the infant intestinal microbiome.
Jiang, T, Liu, B, Li, J, Dong, X, Lin, M, Zhang, M, Zhao, J, Dai, Y, Chen, L
Food & function. 2018;(2):1028-1037
Abstract
Increasing evidence shows that host diet and gut microbes are related. Previous studies have shown the effects of specific dietary fatty acids (FAs) on intestinal microbiota, but little is known about the effect of the stereospecifically numbered sn-2 position in triglycerides (TG) of human milk on the gut microbiome of infants. This study aimed at examining possible effects of sn-2 FAs of human milk on the gut microbial development of breastfeeding babies. Sn-2 FAs and intestinal microbiota were assessed by GC-MS and high-throughput 16S rRNA sequencing, respectively. The results showed that breast milk from mothers in China contained ten major sn-2 FAs dominated by palmitic acid (C16:0, 54.42%), oleic acid (C18:1 n-9, 14.95%), linoleic acid (LA, C18:2 n-6, 12.81%), myristic acid (C14:0, 4.50%) and C12:0 (3.17%). Total long chain unsaturated fatty acids (LCUFA) decreased from colostrum to mature milk, while total saturated fatty acids (SFA) showed no significant difference during lactation. A significant association between sn-2 FAs in milk and infant gut microbiota was found between decanoic acid (C10:0), myristic acid (C14:0), stearic acid (C18:0), C16:0, arachidonic acid (AA, C20:4 n-6), docosahexaenoic acid (DHA, C22:6 n-3) with Bacteroides, Enterobacteriaceae, Veillonella, Streptococcus, and Clostridium. These microbes were involved in short-chain fatty acid (SCFA) production and other functions, and significantly increased at 13-15 d after breastfeeding was initiated. C16:0 and DHA were relevant to most of the microbes. This study demonstrated the relatively steady profiles of sn-2 FAs in breast milk and gut microbiota of infants, together with their correlation during the breastfeeding period. The above results provided important information for designing the configuration of FAs in next-generation formulas for Chinese infants.
-
8.
Evidence of dysbiosis in the intestinal microbial ecosystem of children and adolescents with primary hyperlipidemia and the potential role of regular hazelnut intake.
Gargari, G, Deon, V, Taverniti, V, Gardana, C, Denina, M, Riso, P, Guardamagna, O, Guglielmetti, S
FEMS microbiology ecology. 2018;(5)
-
-
Free full text
-
Abstract
Hyperlipidemia starts at a pediatric age and represents an unquestionable risk factor for cardiovascular disease. Modulation of the intestinal microbial ecosystem (IME), in principle, can ameliorate lipid profiles. In this study, we characterized the IME of children and adolescents with primary hyperlipidemia by analyzing fecal samples through 16S rRNA gene profiling (n = 15) and short chain fatty acid (SCFA) quantification (n = 32). The same analyses were also carried out on age-matched normolipidemic controls (n = 15). Moreover, we evaluated the modulatory effect of regular hazelnut intake (approximately 0.43 g of hazelnuts with skin per kg of body weight) on the IME of 15 children and adolescents with hyperlipidemia for eight weeks. We found alterations of numerous operational taxonomic units potentially associated with SCFA-producing bacteria and reductions in the fecal levels of acetate, butyrate and propionate in hyperlipidemic subjects. Furthermore, we observed that an eight-week hazelnut intervention may induce limited changes in fecal microbiota composition but can significantly modulate the fecal levels of predominant intestinal SCFAs, such as acetate. Finally, correlation analyses indicated that changes in lipidemic parameters are linked to modifications of the abundance of specific bacterial taxa, such as the families Lachnospiraceae and Ruminococcaceae and the genera Akkermansia, Bacteroides, Roseburia, and Faecalibacterium. This study suggests that children and adolescents with primary hyperlipidemia possess an altered IME. The promising results presented here support the need for future dietary interventions aimed at positively modulating the IME of hyperlipidemic subjects.
-
9.
Postoperative Enteral Nutrition Guidelines Reduce the Risk of Intestinal Failure-Associated Liver Disease in Surgical Infants.
Shores, DR, Alaish, SM, Aucott, SW, Bullard, JE, Haney, C, Tymann, H, Nonyane, BAS, Schwarz, KB
The Journal of pediatrics. 2018;:140-147.e1
-
-
Free full text
-
Abstract
OBJECTIVE To assess the effectiveness of postoperative feeding guidelines in reducing the incidence and severity of intestinal failure-associated liver disease (IFALD) among infants. STUDY DESIGN Two cohorts of infants <6 months old undergoing intestinal surgery were compared: preguideline (retrospective data from 2007 to 2013; n = 83) and postguideline (prospective data from 2013 to 2016; n = 81). The guidelines included greater initial enteral nutrition volumes of 20 mL/kg/d and daily feeding advancement if tolerated. The primary outcomes were incidence of IFALD (peak direct bilirubin [DB] >2 mg/dL) and severity (DB >5 mg/dL for moderate-severe). Multiple logistic regression was used to determine the odds of developing IFALD. Other outcomes were time to reach 50% and 100% goal calories from enteral nutrition and the incidence of necrotizing enterocolitis after feeding. RESULTS The incidence of IFALD decreased from 71% to 51% (P = .031), and median peak DB decreased from 5.7 to 2.4 mg/dL (P = .001). After adjusting for diagnosis and prematurity, the odds of developing IFALD of any severity were reduced by 60% (OR 0.40, 95% CI 0.20-0.85), and the odds of developing moderate-to-severe IFALD were reduced by 72% (OR 0.28, 95% CI 0.13-0.58) with guideline use. Time to reach 50% enteral nutrition decreased from a median of 10 to 6 days (P = .020) and time to reach 100% enteral nutrition decreased from 35 to 21 days (P = .035) with guideline use. The incidence of necrotizing enterocolitis after initiating enteral nutrition did not change (5% vs 9%, P = .346). CONCLUSIONS Implementation of feeding guidelines reduced time to reach feeding goals, significantly reducing IFALD incidence and severity.
-
10.
Pharmacokinetics of Mycophenolic Acid and Dose Optimization in Children After Intestinal Transplantation.
Barau, C, Mellos, A, Chhun, S, Lacaille, F, Furlan, V
Therapeutic drug monitoring. 2017;(1):37-42
Abstract
BACKGROUND Mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (MPS) is now commonly used in pediatric intestinal transplantation (Tx), but to date, no clear recommendations regarding the dosing regimen have been made in this population. The aim of this study was to determine the MMF/MPS dosage required to achieve an area under the plasma concentration-time curve from 0 to 12 hours (AUC0-12) for mycophenolic acid (MPA) greater than 30 mg·h·L in children after intestinal transplantation. METHODS A pharmacokinetic study was conducted in 8 children (median, 9.4 years; range, 0.75-15.8 years) at a median time of 113 months (range, 1.5-160 months) after intestinal transplantation. RESULTS MMF was initially introduced at a low median starting dose of 687 mg·m·d (range, 310-1414 mg·m·d). One of the 3 patients who received MPS and 2 of the 6 patients who received MMF had an MPA AUC0-12 value below 30 mg.h.L. The median MMF dosage had to be increased by 91% (1319 mg·m·d versus 687 mg·m·d) to reach AUC0-12 values above the defined target level of 30 mg·h·L. CONCLUSIONS When used in combination with tacrolimus and steroids, an initial MMF dose of 600 mg/m twice a day would be recommended to children after intestinal transplantation to achieve MPA exposure similar to those observed in adults and children after the transplantation of other organs. Further studies are required to recommend a suitable dosage for pediatric intestinal transplant recipients who receive MPA.