Nutritional response to chyme reinfusion therapy in intestinal failure – a pilot study

Main aim is to determine the protein absorption and net balance, as well as the change in colonic fibre fermentation after undergoing to Chyme Reinfusion Therapy by using stable isotope tracer techniques. Further to explore the impact on body composition and primary systemic mineral and vitamin status. Condition observed: Adult patients with type 2 intestinal failure and suitability for chyme reinfusion therapy (CRT) (double enterostomy, entero-atmospheric fistula (EAF) or proximal ileostomy with an accessible distal limb), and younger than 70 years. Healthy subjects, matched for gender and age as a reference group. Measurements of protein and fibre metabolism will take place in one time point for healthy control participants and in two time points for T2IF participants: Healthy Participants - As suits the clinic/ team schedule and the participant following recruitment - one visit only at the Human Nutrition Research centre at Massey University Albany Campus, Auckland, New Zealand. In total, 8 hours of participant's time will be required. T2IF Participants - First: Before starting CRT, after surgery and in a general ward following safe commencement of drinking fluids. - Second: After the initiation of CRT for at least 21 days either in hospital or at the Human Nutrition Research Centre at Massey University. On each of the two days (the days before and after establishment of CRT) of investigation (8 hours per day), the data collection will start in the early morning after overnight fasting. In total, 16 hours of participant's time across these two time points will be required. Participants will not receive PN during this period to prevent interference, and missed nutrition will be compensated afterwards. For all participants: Day 1 of investigation for protein absorption, whole body protein and fibre metabolism will involve: • Having a peripheral catheter placed in a superficial vein of the lower arm or access will be from a peripheral venous line already in place for clinical care for stable isotope infusion • A second peripheral catheter will be placed for arterialised venous blood sampling in a superficial dorsal vein of the contralateral hand. The hand will be placed in a thermostatically controlled heated box, a technique to mimic direct arterial sampling. • Having a blood sample taken via their peripheral line to measure natural background isotope enrichments of phenylalanine (Phe) and tyrosine (Tyr) and three SCFA (acetate, propionate and butyrate) in their body prior to infusion. Methods are adapted from Jonker et al (Jonker, Deutz, Schols, et al., 2019). • Next, a primed, constant intravenous infusion of L-[ring-13C6]-Phe ([13C6]-Phe: prime = 270 µmol; infusion = 270 µmol x h-1) and L-[U-13C9, 15N]-Tyr ([U-13C9, 15N]-Tyr: prime = 8.5 µmol; infusion = 8.5 µmol x h-1) will be infused to assess net whole-body protein balance (protein synthesis minus protein breakdown) (Jonker, Deutz, Schols, et al., 2019). • At the same time, a one-off pulse IV solution containing 89.0 mmol/L acetate [1,2-13C2], 13.1 mmol/L propionate [1-13C], and 10.9 mmol/L butyrate [1-13C] will also be given. Methods are adapted from Kirschner et al (Kirschner et al., 2023). • Over the next 30 mins, four blood samples will be taken at 4, 8, 15 and 30 minutes to determine whole body SCFA production (Kirschner et al., 2023). • After two hours of priming: 1. the participant will start sipping a spirulina-flavoured stable isotope tracer-enriched oral nutritional supplement (ONS) drink e.g. Fresubin Energy, every 30 minutes for the next five hours. The ONS dosage for each participant will be determined as one-third of their total daily protein needs, estimated using Dietary Recommended Intakes (DRI). If the participants in the patient group are unable to drink this, they will receive it enterally through a feeding tube (when feeding tube is present). The ONS drinks are tracer-enriched with 3.14 mg/kg body weight free L-[1-13C]-Phe and 1861 mg intrinsically-labelled 15N-spirulina containing 51 mg L-[1-15N] Phe for the purpose of measuring net protein absorption. Methods are adapted from Engelen et al (Engelen et al., 2014). 2. six blood samples will be taken in 60-minute intervals to measure the amounts of Phe and Tyr. • In the T2IF patient group, CRT will be performed using the InsidesTM System (Registered Class 2b device with CE marking, The Insides Company, Auckland, NZ) every 60 min or as required. Four chyme samples will be collected from the patient's stoma bag throughout the day: one at the start, one at the end (after 8 hours) and two in between that must be at least 120 minutes apart (to determine isotope content). Day 2 of investigation at the end of the study will be a repeat procedure for the T2IF patients only. Arterialised venous blood samples will be collected by a certified phlebotomist or research nurse. Isotope infusion will be conducted by the research nurse or trained researcher (physiologist). The Insides System is part of the CRT that is prescribed by the hospital. Patients will receive CRT regardless of their participation in this study. The following data will also be collected during the study: - Body composition. - Weighed diet record x 3 – before, during and after receiving CRT. - Dietary diversity and quality questionnaires x 3 - before, during and after receiving CRT. - Micronutrient status – blood sampling (Vitamin B12, Folate, selenium, Vitamin D, Copper, Zinc, Iron). - Patient experience assessment – short patient interview in person or via videoconference call. - Clinician perceptions regarding CRT – short interview in person or videoconference call. References used: Jonker, R., Deutz, N. E. P., Ligthart-Melis, G. C., Zachria, A. J., Veley, E. A., Harrykissoon, R., & Engelen, M. (2019). Preserved anabolic threshold and capacity as estimated by a novel stable tracer approach suggests no anabolic resistance or increased requirements in weight stable COPD patients. Clin Nutr, 38(4), 1833-1843. https://doi.org/10.1016/j.clnu.2018.07.018 Kirschner, S. K., Ghane, P., Park, J. K., Simbo, S. Y., Ivanov, I., Braga-Neto, U. M., Ten Have, G. A. M., Thaden, J. J., Engelen, M., & Deutz, N. E. P. (2023). Short-chain fatty acid production in accessible and inaccessible body pools as assessed by novel stable tracer pulse approach is reduced by aging independent of presence of COPD. Metabolism, 141, 155399. https://doi.org/10.1016/j.metabol.2023.155399 Engelen, M. P., Com, G., Anderson, P. J., & Deutz, N. E. (2014). New stable isotope method to measure protein digestibility and response to pancreatic enzyme intake in cystic fibrosis. Clin Nutr, 33(6), 1024-1032. https://doi.org/10.1016/j.clnu.2013.11.004