Odile Corriol

Some new insights in intestinal failure-associated liver disease.

Purpose of reviewTo point new insights in the cholestasis that is a complication of both intestinal failure and parenteral nutrition. View on liver disease has recently evolved with the onset of fish oil-based intravenous lipid emulsions (ILE). Recent findingsFocused on the role of ILE in causing liver disease. Reversal of cholestasis was recently achieved in infants with short bowel syndrome, by replacing the ‘reference’ soybean oil-based ILE by fish oil-based ILE. SummaryIt is likely that this reversal involves several factors such as the change in n-6: n-3 ratio, the reduction in phytosterol load, the increased provision of α-tocopherol as antioxidant agent. Alternative issue might be based on the use of a new generation of ILE aiming to provide n-3 and to reduce n-6 fatty acids load while enhancing α-tocopherol intake. New data are based on the use of an ILE containing a balanced proportion of four types of oil as a physical mixture of 30% soybean oil, 30% medium-chain triglycerides, 25% olive oil and 15% fish oil with amounts of α-tocopherol calculated according to the number of double bonds. This new emulsion was reported to be beneficial in reversing or preventing liver disease.

Aluminum contamination of parenteral nutrition and aluminum loading in children on long-term parenteral nutrition.

BackgroundChildren who are receiving parenteral nutrition are at risk of aluminum overload, which may contribute to such side effects as osteopenic bone disease. The aim of the present study is to determine the aluminum contamination of parenteral nutrition solutions and their components, and to assess the aluminum status of children on long-term parenteral nutrition. MethodsAluminum concentrations were determined by graphite furnace absorption spectroscopy in components and in final parenteral nutrition solutions. The urinary aluminum excretion and plasma aluminum concentration were determined in 10 children on long-term parenteral nutrition. ResultsThe mean aluminum concentration in the administered parenteral nutrition solutions was 1.6 ± 0.9 &mgr;mol × l−1(mean ± standard deviation (SD)). The resulting mean aluminum daily intake of the 10 patients was 0.08 ± 0.03 &mgr;mol × kg−1 × day−1. ConclusionsCompared to two previous studies performed in 1990 and in 1995 in our hospital, the aluminum contamination of parenteral nutrition solutions and the daily aluminum intake of the children seemed to decrease. However, the plasma aluminum concentration and daily urinary aluminum excretion of the children still remain above normal standards. The children had no clinical symptoms of bone disease but aluminum accumulation in tissue can not be excluded. To prevent this iatrogenic toxicity, the aluminum contamination of parenteral nutrition should be assessed regularly.

Outcome of home parenteral nutrition in 251 children over a 14-y period: report of a single center.

BACKGROUND Parenteral nutrition (PN) is the main treatment for intestinal failure. OBJECTIVE We aimed to review the indications for home parenteral nutrition (HPN) in children and describe the outcome over a 14-y period from a single center. DESIGN We conducted a retrospective study that included all children who were referred to our institution and discharged while receiving HPN between 1 January 2000 and 31 December 2013. The indications for HPN were divided into primary digestive diseases (PDDs) and primary nondigestive diseases (PNDDs). We compared our results to a previous study that was performed in our unit from 1980 to 2000 and included 302 patients. RESULTS A total of 251 patients were included: 217 (86%) had a PDD. The mean ± SD age at HPN onset was 0.7 ± 0.3 y, with a mean duration of 1.9 ± 0.4 y. The indications for HPN were short bowel syndrome (SBS) (59%), PNDD (14%), congenital enteropathies (10%), chronic intestinal pseudo-obstruction syndromes (9%), inflammatory bowel diseases (5%), and other digestive diseases (3%). By 31 December 2013, 52% of children were weaned off of HPN, 9% of the PDD subgroup had intestinal transplantation, and 10% died mostly because of immune deficiency. The major complications of HPN were catheter-related bloodstream infections (CRBSIs) (1.7/1000 d of PN) and intestinal failure-associated liver disease (IFALD) (51 children; 20% of cohort). An increased rate of CRBSIs was observed compared with our previous study, but we saw a decreasing trend since 2012. No noteworthy deceleration of growth was observed in SBS children 6 mo after weaning off HPN. CONCLUSIONS SBS was the major indication for HPN in our cohort. IFALD and CRBSIs were potentially life-threatening problems. Nevertheless, complication rates were low, and deaths resulted mostly from the underlying disease.

Enteral nutrition modifies gut-associated lymphoid tissue in rat regardless of the molecular form of nitrogen supply.

BACKGROUND It has been suggested that beneficial effect of elemental enteral diets in the treatment of inflammatory bowel diseases could be mediated by the suppression of protein dietary antigens. The objective of the present work was to study the effect of enteral diet on gut associated lymphoid tissue and on gastric Lactobacillus flora, in rat. METHODS The effects of three molecular forms of nitrogen supply: amino acids, oligopeptides or whole casein, were compared in rats on continuous enteral diet. Frozen sections of small bowel were studied with monoclonal antibodies anti-CD5, -CD4, -CD8, -CD25, -macrophages, -MHC II. The Lactobacillus flora was also enumerated in the stomach, in order to assess the effect of ED on rat flora. RESULTS Growth and mucosa morphology were identical in control and enteral groups. Rats on enteral diet showed, whatever was the molecular form of nitrogen supply, a decrease in CD5+, CD4+ and CD8+ intraepithelial cell numbers, but not in lamina propria cell number, and a decreased MHC II epithelial expression, when compared to control rats. The enterally fed rats also showed a decrease in Lactobacillus gastric contents. CONCLUSIONS The current study demonstrates that continuous enteral nutrition modifies MHC II epithelial expression and gut associated lymphoid tissue cell number in rat, whatever is the molecular form of nitrogen supply. Intestinal flora could be responsible, at least for part, for these results.

Effect of an Elemental vs a Complex Diet on L-Citrulline Production From L-Arginine in Rat Isolated Enterocytes

BACKGROUND L-Arginine and L-glutamine are highly metabolized by intestinal cells, leading to various metabolites, including L-citrulline, which is required for optimal growth. Elemental diets, used in clinical practice to treat growth failure and malnutrition, are very different from complex diets normally consumed. The aim of the present study was to assess the effects of an elemental diet compared with a complex diet on L-arginine metabolism in rat isolated enterocytes and its modulation by L-glutamine. METHODS Rats were fed the elemental diet (group ED) or the control diet (group C) for 14 days. Villus enterocytes then were isolated, and metabolic capacities or enzyme activities were assessed. RESULTS The incubation of enterocytes isolated from group C with 0.1 mmol/L L-[U-14C]-arginine led to the production of 125 +/- 25 pmol L-citrulline/10(6) cells per 30 minutes. This production showed a twofold increase in the presence of 2 mmol/L L-glutamine. In group ED, L-citrulline synthesis from L-arginine was markedly lower in the absence or in the presence of L-glutamine. This coincided with lower carbamoylphosphate synthase I activity and carbamoylphosphate (CP) content of enterocytes. Other L-arginine and L-glutamine metabolic pathways were not affected. Similar results were obtained when the elemental diet was administered continuously through a gastric catheter or fed by mouth. CONCLUSIONS L-Glutamine favors the synthesis of L-citrulline from L-arginine in isolated enterocytes, probably via an increase in CP production. Changing the diet composition, from a complex to an elemental diet, results in an alteration of the enterocyte capacity to synthesize L-citrulline from L-arginine, irrespective of the rhythm of delivery.

Weaning Off Prognosis Factors of Home Parenteral Nutrition for Children With Primary Digestive Disease

Objectives: The aim of the present study was to describe the indications for home parenteral nutrition (HPN) in children with primary digestive diseases and to identify factors associated with weaning off. Methods: All the children initially discharged on HPN between January 1, 2000, and December 31, 2009, for chronic intestinal failure (IF) were included. The associations between clinical factors and weaning off of HPN were assessed using a multivariable Cox regression model. Results: Among the 151 children (boys = 58%) included in this study, 98 (65%) presented with short bowel syndrome (SBS), 17 (11%) with digestive neuromuscular disorders, 14 (9%) with mucosal diseases, 13 (9%) with inflammatory bowel disease, and 9 (6%) with other primary digestive diseases. The probability of survival was ∼100%. At the end of the follow-up, the probability for weaning off of HPN was 0.73 (95% confidence interval 0.54–0.84) but varied according to the underlying cause of IF (for example, SBS and inflammatory bowel disease had a better prognosis). The median time until weaning off was 21 months (95% confidence interval 18–38 months). Unfavourable prognostic factors for weaning off of HPN included a bowel remnant of <40 cm, the presence of <50% of the colon, and daily lipid intakes >1.5 g · kg−1 · day−1. Underlying disease was also associated with weaning off. Conclusions: HPN is a safe therapeutic option for children with chronic IF requiring long-term nutritional management. Prognostic factors for weaning off of HPN were identified, and they highlight the relevance of SBS anatomy and parenteral nutrition caloric intake. The outcome of children on HPN was primarily dependent on the underlying disease.

Luminal fermentation and colonocyte metabolism in a rat model of enteral nutrition.

Large intestinal fermentation and nutrient metabolism in colonocytes were investigated in a rat model of enteral feeding. Male Wistar rats (240–280 g) were submitted to 7 or 14 days of treatment: intragastric feeding (elemental formula) versus oral feeding (isocaloric and isonitrogenous diet, containing 5% purified cellulose) in the control group. Fermentation products and bacterial populations were analyzed in cecal contents. Colonic cells were isolated and tested for their capacities to metabolize [1-14C] butyrate and [U-14C]glutamine. After 7 days of enteral nutrition, short-chain fatty acid concentrations represented 52% of those measured in the control group, but colonocyte metabolism remained unchanged. After 14 days of enteral nutrition, short-chain fatty acid concentrations were still decreasing, although bacterial counts remained unchanged. In parallel, ammonia and lactate concentrations were significantly increased. The capacities to utilize butyrate and glutamine in colonocytes were only slightly affected. However, there was a dramatic increase in the ratio of β-OH-butyrate to acetoacetate fluxes, suggesting a more reduced redox mitochondrial state associated with enteral feeding.

Endothelial Function and Mechanical Properties of the Common Carotid Artery in Children on Parenteral Nutrition

Intravenous administration of nutrition mixtures induces endothelial damage and arterial wall remodeling in animal models. To study endothelial function and common carotid artery mechanical properties in children receiving parenteral nutrition, we used noninvasive ultrasonic measurements in 18 children on parenteral nutrition and 18 controls. No difference appeared in the geometry of the common carotid artery (intima media thickness, systolic and diastolic diameters) between the patients on parenteral nutrition and the controls. The incremental elastic modulus was significantly higher in the patients on parenteral nutrition (1.8 ± 0.4 versus 1.4 ± 0.5 4 mm Hg · 103, p < 0.05) reflecting alteration of the elastic properties of the arterial wall independent of the vessel geometry. The flow-mediated dilatation of the brachial artery was significantly lower in the patients on parenteral nutrition (6 ± 3 versus 8 ± 3%, p < 0.05), whereas the dilatation after glyceryl trinitrate administration was similar (22 ± 9 versus 25 ± 9%). Children on parenteral nutrition exhibit endothelial dysfunction and altered stiffness of the common carotid artery. The noninvasive methods used in this study may prove useful for objectively determining the effects of various preventive methods.

Effect of an Elemental vs a Complex Diet on Polyamine Metabolism in Rat Isolated Enterocytes

BACKGROUND Polyamines play an important role in the proliferation and differentiation of enterocytes. Ornithine decarboxylase (ODC) is the rate-limiting enzyme for polyamine biosynthesis. Elemental diets, providing easily absorbable nutrients such as free amino acids, are used in clinical practice to treat growth failure and malnutrition. They are very different from complex diets normally consumed. Little information is available about the influence of elemental diets on metabolic capacities of enterocytes. This study was undertaken in rats to assess the effects on polyamine metabolism of an elemental diet compared with a complex diet. METHODS Rats were fed the elemental diet (group ED) or the control diet (group C) for 14 days. The dietary intakes were isocaloric and isonitrogenous in groups C and ED. Villous enterocytes were then isolated and metabolic capacities or enzyme activities were assessed. RESULTS Both the enterocyte capacity to decarboxylate ornithine through ODC (measured in viable enterocytes) and ODC activity (measured in homogenates) were severely decreased in group ED. The polyamine content in enterocytes, however, was maintained at a similar level in both groups. This coincided with a decrease in the main enzymatic activity responsible for putrescine catabolism (ie, diamine oxidase activity) in group ED. CONCLUSIONS Although nutrition manipulation was shown to alter polyamine biosynthesis in this study, the polyamine homeostasis was probably maintained, at least in part, through down-regulation of diamine oxidase.