An in-line digestive cartridge increases enteral fat and vitamin absorption in a porcine model of short bowel syndrome

Abstract

Background & aims: Short bowel syndrome (SBS) occurs after intestinal loss resulting in parenteral nutrition dependence and micronutrient deficiencies, which may lead to life-limiting complications. ALC-078 is a cartridge containing immobilized lipase that connects in-line with enteral feeding sets and digests fats in enteral nutrition (EN). In this study, we evaluate the efficacy of ALC-078 to improve fat and nutrient absorption in a porcine SBS model.

Methods: Fifteen male Yorkshire piglets were assessed. Animals were randomized to no intestinal resection (n = 5), 75% resection (n = 5), or 75% resection + ALC-078 (n = 5). After recovery, animals were treated for 14 days. Piglets received 60% of nutrition from continuous EN and 40% from chow. The degree of fat malabsorption was determined by the coefficient of fat absorption (CFA) following a 72-h stool collection. Body weight, fat-soluble vitamins, and nutritional markers were assessed.

Results: Adverse events were similar across the three groups (P = 1.00). ALC-078-treated animals had similar weight gain compared to resected piglets. Resected animals had a lower CFA compared to unresected controls (79.3% vs. 95.2%, P = 0.01) while there was no significant difference in the ALC-078 animals (87.1% vs. 95.2%, P = 0.19). Between Study Days 1 and 15, ALC-078 animals had increased concentrations of vitamin D (12.2 vs. 8.7 ng/mL, P = 0.0006), and vitamin E (4.3 vs. 2.5 mg/L, P = 0.03). These markers did not significantly change in untreated resected animals.

Conclusion: ALC-078 increases the absorption of fat-soluble vitamins and may improve fat malabsorption. Future studies should determine whether ALC-078 can reduce PN dependence and if these findings translate to human patients with SBS.

Keywords: Digestive cartridge; Immobilized lipase; Intestinal failure; Micronutrient deficiencies; Short bowel syndrome.

Figure 1.

Weight pattern for the entire study across the three groups. Animals that underwent 75% resection and received treatment with ALC-078 had similar weight gain compared to resected animals that did not receive treatment. Both groups had decreased weight gain compared to unresected control animals as demonstrated by the weight trend for the duration of the study (A) and by the percent weight change from baseline weight at the various timepoints (B). The baseline weight is defined as the animal’s preoperative weight on the day of operation (Study Day -7). Statistical analysis of the experimental groups was done with repeated-measures analysis of covariance (ANCOVA), with adjustment for baseline weight and Holm step-down Bonferroni adjustment for multiple comparisons. Shown are mean ± SE for the raw (unadjusted) data. ***P<0.001.

Figure 2.

Total fat and nitrogen absorption. Stool was collected for 72-hours and was analyzed for fat content (A) to determine the coefficient of fat absorption (CFA) and nitrogen content (B) to determine the coefficient of nitrogen absorption (CNA). Resected animals without treatment had a significantly lower CFA compared to unresected animals. There was no significant difference in the CFA between resected animals treated with ALC-078 and unresected controls. The CNA was also lower for resected animals without treatment compared to unresected controls but this did not reach statistical significance. Statistical analyses of the experimental groups were done using analysis of variance (ANOVA) with a Tukey-Kramer adjustment for multiple comparisons. Results are expressed as mean ± SE.

Figure 3.

Fat-soluble vitamin plasma concentration. The plasma concentration of Vitamin A at Study Day 15 (A) was similar across the three groups and did not change between Days 1 and 15 (D). Plasma concentrations of both Vitamin D (B) and Vitamin E (C) at Day 15 were lower in animals that underwent 75% resection compared to unresected controls. However, there was no statistical difference in the concentrations of Vitamins D and E in resected animals treated with ALC-078 compared to unresected controls. The plasma concentration of Vitamin D significantly increased between Days 1 and 15 (E) in both unresected control animals and ALC-078-treated resected animals but remained the same in the 75% Resection group. A similar pattern was observed between these two timepoints in the plasma concentration of Vitamin E (F). Statistical analysis of the experimental groups was done with repeated-measures analysis of covariance (ANCOVA), with adjustment for baseline vitamin concentration and Holm step-down Bonferroni adjustment for multiple comparisons. Results are expressed as mean ± SE.

Figure 4.

Plasma concentration of triglycerides, cholesterol, and HDL. The plasma triglyceride concentration at Study Day 15 (A) was similar across the three groups and significantly decreased only in ALC-078-treated animals between Days 1 and 15 (D). Cholesterol concentration at Day 15 (B) was significantly lower in animals that underwent 75% resection compared to unresected controls. Similarly, the concentration of HDL at Day 15 (C) was also lower in resected animals, although this did not reach statistical significance. There were no statistical differences in the concentrations of cholesterol and HDL in resected animals treated with ALC-078 compared to unresected controls (B, C). The plasma concentration of cholesterol decreased in resected animals between Days 1 and 15 (E) but remained similar in both unresected control animals and resected animals treated with ALC-078. Finally, the plasma concentration of HDL increased in the ALC-078 treatment group between the two timepoints (F), although this did not reach statistical significance. Statistical analysis of the experimental groups was done with repeated-measures analysis of covariance (ANCOVA), with adjustment for baseline concentrations and Holm step-down Bonferroni adjustment for multiple comparisons. Results are expressed as mean ± SE.