Metabolic markers of protein maldigestion after a 15N test meal in minipigs with pancreatic exocrine insufficiency.

The effect of pancreatic exocrine insufficiency (PEI) on protein malabsorption is little documented, partly due to methodological barriers. We aimed to validate biomarkers of protein malabsorption using a 15N test meal in a minipig model of PEI. Six pancreatic duct-ligated minipigs were used as a model of PEI and four nonoperated animals as a control. All animals were equipped with an ileocecal reentrant cannula. Minipigs were given a test meal containing [15N]casein. The PEI animals repeated the test three times, in the absence of any pancreatic enzymes, or after pancreatic substitution at two levels [ A or B: 7,500 or 75,000 (lipase) and 388 or 3881 (protease) FIP U]. Ileal chyme, urine, and blood were collected postprandially. Nitrogen and 15N were measured in digestive and metabolic pools. We obtained a gradient of ileal protein digestibility from 29 ± 11% in PEI to 89 ± 6% in the controls and a dose- dependent response of enzymes. Insulin and gastric inhibitory polypeptide secretions were decreased by PEI, an effect that was counteracted with the enzymes at level B. The total recovery of 15N in urinary urea and plasma proteins was 14 ± 5.1% in the control group and decreased to 5.5 ± 2.1% by PEI. It was dose dependently restored by the treatment. Both 15N recovery in plasma and urine were correlated to protein digestibility. We confirm that the 15N transfer in those pools is a sensitive marker of protein malabsorption. Nevertheless, an optimization of the test meal conditions would be necessary in the view of implementing a clinical test. NEW & NOTEWORTHY We designed an intervention study to create a gradient of ileal protein digestibility in minipigs with pancreatic exocrine insufficiency and to validate reliable metabolic markers using a 15N oral meal test. 15N recovery in plasma proteins and to a higher extent in urine was sensitive to protein malabsorption. This test is minimally invasive and could be used to reveal protein malabsorption in patients.

The Pancreatic Duct Ligated (Mini)pig as a Model for Pancreatic Exocrine Insufficiency in Man.

Modern therapy of pancreatic exocrine insufficiency (PEI) using pancreatic enzyme replacement therapy (PERT) has largely been very effective and has greatly helped in improving the nutritional status of patients with PEI and in increasing the life expectancy in cystic fibrosis. It is believed that the use of predictable large animal models could play an important role in assessing and developing new therapies. This article reviews the pancreatic duct ligated (adult) minipig as a chronic model of total PEI, with a detailed look at the influence of PEI and response to PERT on prececal compared to fecal digestibility, to directly investigate effects on protein and starch digestion and absorption. In addition, the piglet with PEI is reviewed as a model for PEI in young patients with the aim of further improving the therapy and nutritional status of young patients with cystic fibrosis.

Endogenous praecaecal and total tract losses of nitrogen in pancreatic duct-ligated minipigs.

The pancreatic duct-ligated minipig (PL) is an established model of pancreatic exocrine insufficiency (PEI) with a significant decrease of nutrient digestibility. This study aimed to quantify and compare endogenous losses of nitrogen (N) (ileal and faecal) in minipigs receiving an almost N-free diet. Altogether, 12 Göttingen minipigs (7 PL and 5 control animals) fitted with an re-entrant ileo-caecal fistula were used. In Study 1, ileal digesta was collected over a period of 12 h on seven consecutive days, including one 24 h collection, when animals were fed a diet containing 0.49 g N/kg dry matter (DM). In Study 2, faeces were collected for 10 consecutive days. In Group PL, the amount and DM content of ileal digesta were higher (p < 0.05), while N concentration was lower than in the Control. The ileo-caecal N flux [g/kg DM intake] was about 2.5 times higher in Group PL (5.47 ± 1.15) than in the Control (1.91 ± 0.59) (p < 0.05). The amount of faeces did not differ, but faecal N losses were higher in Group PL (p < 0.05). Endogenous faecal N losses [g N/kg DM intake] of the Control group (1.17 ± 0.72) were comparable with earlier studies, while those of Group PL were 2.6 times higher (3.09 ± 1.34). In contrast, urinary excretion of N did not differ between the Control and Group PL. In conclusion, PEI caused markedly increased endogenous N losses. Therefore, the impact of reduced digestibility of nutrients on endogenous N losses might be relevant for apparent protein digestibility rates and should be taken into account.