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Randomized Controlled Trial
. 2022 Sep;10(18):e15462.
doi: 10.14814/phy2.15462.

Prolonged lipopolysaccharide-induced illness elevates glucagon-like peptide-1 and suppresses peptide YY: A human-randomized cross-over trial

Katrine Brodersen  1   2   3 , Maike Mose  2 , Ulla Ramer Mikkelsen  4 , Jens Otto Lunde Jørgensen  2   5 , Michael Festersen Nielsen  1 , Niels Møller  2 , Anne-Marie Wegeberg  6 , Christina Brock  6   7 , Bolette Hartmann  8 , Jens Juul Holst  8 , Nikolaj Rittig  2   3
Affiliations
Randomized Controlled Trial

Prolonged lipopolysaccharide-induced illness elevates glucagon-like peptide-1 and suppresses peptide YY: A human-randomized cross-over trial

Katrine Brodersen et al. Physiol Rep. 2022 Sep.

Abstract

Severe systemic inflammation is associated with nausea, loss of appetite, and delayed gastric emptying, which increases hospitalization admission length and mortality rate. There is a lack of human controlled studies exploring gastric emptying rates and underlying mechanisms during inflammatory conditions. We aimed to investigate if systemic inflammation in young men delays gastro-intestinal transit times, lowers motility, and affects gastrointestinal hormone secretion. This substudy of a randomized crossover trial investigated eight healthy young men on two separate occasions; (I) following an overnight fast (healthy conditions/HC) and (II) fasting and bedrest combined with two lipopolysaccharide (LPS) injections of 1 ng kg-1 following an overnight fast and 0.5 ng kg-1 following another 24 h (systemic inflammation/SI). A standardized protein beverage and a SmartPill capsule (a wireless gastrointestinal monitoring system) were swallowed during each occasion. Whole gut transit time was comparable between HC and SI. SI decreased gastric mean pressure peak amplitude (p = 0.04) and increased pH rise across the pylorus and small bowel pH (p = 0.02) compared with HC. Glucagon-like peptide-1 was elevated during SI compared with HC (p = 0.04). Peptide YY was lower during SI compared with HC (p = 0.007). Prolonged LPS exposure combined with fasting and bedrest elevated glucagon-like peptide 1 concentrations, which may play a role for the nausea and loss of appetite typically associated with SI.

Keywords: endotoxemia; gastrointestinal hormones; gastrointestinal motility; gastrointestinal transit times; inflammation; wireless motility capsule.

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Conflict of interest statement

URM is employed at ARLA Foods Ingredients P/S and contributed to the study design and final draft of the manuscript, but was not involved in data collection, analysis or decision to publish. Furthermore, ARLA Foods did not have any influence on study conduct or interpretation. The remaining authors have no further conflict of interest to declare.

Figures

FIGURE 1
FIGURE 1
Flowchart of the study days. Flowchart showing healthy conditions and prolonged systemic inflammatory conditions. LPS, lipopolysaccharide. Created with BioRender.
FIGURE 2
FIGURE 2
SmartPill output. An example of the SmartPill output measure is shown with pH (green vertical axis), temperature (blue vertical axis) and pressure (red vertical axis) during time (horizontal axis). Whole gastrointestinal transit time (WGTT), gastric emptying time (GET), small bowel transit time (SBTT) and colonic transit time (CTT).
FIGURE 3
FIGURE 3
Gastrointestinal hormone. (a) Glucagon‐like peptide 1 (GLP‐1), (b) glucose‐dependent insulinotropic peptide (GIP), (c) Ghrelin and (d) PYY measured during a basal period followed by consumption of a protein beverage bolus followed by a sip regime of the beverage throughout the study. Interventions were healthy conditions (a 12 h overnight fast) and systemic inflammation (dual lipopolysaccharide exposure combined with a 36 h fast and bedrest).
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