(P16-021-23) Colonic Amino Acid Absorption

Objectives: To measure the colonic absorption of amino acids (AA) with ²H₁₀-allo-isoleucine: a stable isotope labelled non-protein AA.

Methods: ²H₁₀ allo-isoleucine (5 mg) was instilled into the lumen of ascending colon in 10 adults undergoing check colonoscopy at St. John Medical College, India, during withdrawal of the scope after confirming normalcy of the colon. Blood samples were collected prior to tracer instillation and every 20 min thereafter until 2:3h and then at 3 and 4h. A population pharmacokinetic approach was used to model absorption kinetics using plasma concentrations of ²H₁₀ and ²H₉-allo-isoleucine (since ²H₁₀-allo-isoleucine can be transaminated to the m-1 isotopologue) over the 4h of observation. The absorption was measured using a modified two-compartment model with a pre-absorption compartment describing a zero-order absorption process, along with a sinusoidal function to mimic peristalsis (prior to colonoscopy, the patients were given a prokinetic agent that increased colonic peristalsis). The volume of distribution (Vd) of allo-isoleucine was estimated from a previous study with intravenous (IV) administration of ²H₁₀-allo-isoleucine.

Results: The mean±standard deviation of age and body mass index of the participants was 37.9±11.1y and 22.5±4.6 kg/m² respectively. The Vd, from a dose-dilution calculation from the prior IV administration of ²H₁₀-allo-isoleucine, was estimated at 29.9±3.4% of the body weight. The absorption of ²H₁₀-allo-isoleucine, resulting in steadily increasing plasma concentrations, continued till 4 h. The bioavailability of ²H₁₀-allo-isoleucine was 16.6±5.8%, range 7.7-25.6%, over 4h.

Conclusions: This study directly quantified colonic AA absorption in humans for the first time. This is relevant in plant-based protein consumption, where 25-30% undigested protein could enter the colon: this is usually considered lost. If colonic bioavailability were applied to an intake of 1 g of plant protein/kg/d (ileal digestibility of 70%), where 0.3 g/kg/d would enter the colon, it could account for ~7.5% of the average daily requirement of protein. This is a conservative estimate, as bioavailability was measured for only 4h; AA absorption could continue as transporters are expressed in all parts of the colon. This estimate is exclusive of microbial recycling of nitrogen.

Funding Sources: DBT/Wellcome Trust India Alliance