Poster Topical Area: Dietary Bioactive Components

Location: Hall D

Poster Board Number: 283

P08-025 - Compartmental data analysis to determine whole body short-chain fatty acid (SCFA) production using a pulse of stable tracers in humans

Monday, Jun 11
8:00 AM – 3:00 PM

Objective: Short-chain fatty acids are important to maintain intestinal health. In this study, we estimated the short-chain fatty acid (SCFA) production of the human microbiome via a pulse of stable tracers and using compartmental data analysis.

Methods: A two-compartmental model, containing plasma and tissue pools, was designed to describe extra- and intracellular kinetics of the SCFA acetate (C2), propionate (C3) and butyrate (C4). We gave 14 healthy older adults an 8 ml pulse containing acetate-[13C2], propionate-[1-13C] and butyrate-[1-13C] and sampled plasma regularly for 1 hour. We measured the tracer enrichments in plasma by GC-MS/MS. The open-source software R was used to estimate SCFA de novo intracellular production (F02) and rate of appearance (Ra) through three major steps: 1- fitting the function f(t)=Aexp(-at)+Bexp(-bt) on experimental Tracer-Tracee Ratios (TTR), 2- development of the tracer model, and 3- calculations of the tracee parameters. We used the curve-peeling approach, the Levenberg-Marquardt algorithm, outlier detection and tuning up of convergence criteria which significantly reduced running time and optimized functions’ parameters. After an evaluation of goodness of fit, a-priori identifiable models for tracer and then tracee were developed based on physiological considerations and the fitted f(t).

Results: The function f(t) was fitted independently for each subject. Precision of the functions’ parameters was assessed by model-coefficient-of-variation (m-CV). High precision (Table 1) for parameters illustrates the goodness of fit. Tracee parameters (F12 flux from extracellular (Q1) to intracellular compartment (Q2), show a 8-12 fold higher intracellular production (F02) of the SCFA than estimated from the rate of appearance (Ra) that is usually measured with a primed constant infusion protocol (Table 2).

Conclusions: We developed a compartmental analysis approach to estimate SCFA transport between extracellular and intracellular compartments and intracellular production in humans. We hypothesize that compartmental analysis estimates the SCFA production in the microbiome, mainly present in the large intestine.

Funding Source: none
Table 1

Table 2

CoAuthors: Sarah Kirschner, MS – Texas A&M University; Marielle Engelen, PhD – Texas A&M University; Ivan Ivanov, PhD – Texas A&M University; Ulisses Braga-Neto, PhD – Texas A&M University; Nicolaas Deutz, MD, PhD – Texas A&M University

Parisa Ghane

Graduate Student
Texas A&M University
College Station, Texas