LB041 - INESTINAL REHABILITATION IS DRIVEN BY A NOVEL CHYME RECIRCULATION SYSTEM

LB041

INESTINAL REHABILITATION IS DRIVEN BY A NOVEL CHYME RECIRCULATION SYSTEM

S. Mehta¹, C. Manithody¹, K. Kurashima¹, M. Swiderska-Syn¹, S. Miyata¹, M. Nazzal¹, A. Bagwe¹, S. Jain¹, M. Guzman¹, S. Besmer¹, M. McHale¹, C.-J. Lin¹, J. Long¹, A. Jain^1,*

¹Saint Louis University, St. Louis, United States

Rationale: Short bowel syndrome (SBS) is a devastating condition. In absence of enteral nutrition (EN), patients are dependent on Total Parenteral Nutrition (TPN) and suffer from of intestinal failure associated liver disease and gut atrophy. Intestinal adaptation (IA) and enteral autonomy (EA) remains the clinical goal. We hypothesized EA can be achieved using our DREAM system, (US patent 63/413,988) which allows EN via the stomach and then a mechanism for cyclical recirculation of nutrient rich distal intestinal content into proximal bowel enabling full EN despite SBS.

Methods: 24 neonatal pigs were randomly allocated to receive enteral nutrition (EN; n=8); TPN-SBS that received TPN only (n=8); or DREAM that were transitioned to EN by day 3 (n=8). Liver, gut, and serum were collected for histology,
and serum biochemistry. Pairwise t-tests were used for normally distributed data, otherwise pairwise Mann-Whitney U test were conducted. All tests were 2-tailed using a significance level of 0.05.

Results: TPN-SBS piglets had significant cholestasis vs DREAM (p=0.001) with no statistical difference between DREAM and EN (p=0.14). The mean serum conjugated bilirubin for EN was 0.037 mg/dL, TPN-SBS 1.2 mg/dL, and DREAM 0.05 mg/dL. Serum bile acids were significantly elevated in TPN-SBS animals vs EN (p=0.007) and DREAM (p=0.03). The mean serum bile acids were EN 9.1 mg/dL, TPN-SBS 33.42 mg/dL, and DREAM 8.4 mg/dL. The mean GGT, a marker of cholangiocytic injury was significantly higher in TPN-SBS vs EN (p<0.001) and DREAM (p<0.001) with values of EN 21.2 U/L, TPN-SBS 47.9 U/L, and DREAM 22.5 U/L. p=0.89 DREAM vs EN. To evaluate gut growth, we measured the lineal gut mass (LGM), calculated as the weight of the bowel per centimeter. There was significant preservation in gut atrophy with DREAM. The mean proximal gut LGM was EN 0.21 g/cm, TPN-SBS 0.11 g/cm, and DREAM 0.31 g/cm (p=0.004, TPN-SBS vs DREAM). Likewise, the distal gut LGM was for EN 0.34 g/cm, TPN-SBS 0.13 g/cm, and DREAM 0.43 g/cm (p=0.006, TPN-SBS vs DREAM). On IHC, DREAM has similar hepatic CK-7 (marker for bile duct epithelium), p=0.18 and hepatic Cyp7A1, p=0.3 vs EN. We next evaluated IHC for LGR5 positive intestinal stem cells, capable of self-renewal and differentiation. No statistical differences were noted between EN and DREAM, p=0.18. 

Conclusion: Our DREAM methodology resulted in a significant reduction in cholestasis injury markers as well as prevented gut atrophy in comparison to TPN-SBS piglets. DREAM presents a novel method which enables early full EN despite SBS. This methodology highlights a major advancement in the management of SBS and could bring a paradigm change in life saving therapeutic strategies for patients by driving intestinal adaptation and ultimate EN autonomy

Disclosure of Interest: None declared