Gastro-intestinal and Hormonal Responses to Systemic Inflammatory Disease

Gastro-intestinal and Hormonal Responses to Systemic Inflammatory Disease: A Human Model Comprising Endotoxemia, Fast and Bed Rest.

The aim of this study is to describe hormonal responses and changes of the gastrointestinal (GI) tract during healthy and catabolic inflammatory conditions. Participants will receive isocaloric, isonitrogenous beverages of either whey or 3-OHB+whey in a randomized crossover design during either healthy (overnight fast) or catabolic conditions (inflammation/endotoxemia + 36 h fast and bed rest).

Background: Endotoxemia (LPS) is known to cause fever, inflammation and nausea, but the underlying mechanisms are unknown. In a human disease model comprising LPS-induced inflammation, 36 hour fast and bed rest the investigators want to investigate mechanisms accounting for the nausea and decreased food intake often observed in hospitalized patients. Aim: This study aims to investigate total transit time and motility of the GI-tract together with the regulation of gut- and appetite hormones following catabolic conditions compared with healthy controlled conditions Hypothesis: Catabolic stress (endotoxemia/inflammation + 36 h fast and bed rest) induces GI-tract and hormonal changes compared with healthy conditions (overnight fast) Interventions: In a randomized crossover design, eight healthy, lean, young men will undergo either: i) Healthy conditions (overnight fast) + whey protein ii) Catabolic conditions (Inflammation (LPS) + 36-hour fast and bed rest*) + whey protein iii) Catabolic conditions (Inflammation (LPS) + 36-hour fast and bed rest*) + 3-ketone/whey protein Beverages will be isonitrogenous with 45 g whey protein + 20 g maltodextrin +/- 50 g of 3-OHB. Bolus/sip administration will be applied (1/3 bolus, 2/3 sip).Beverages will be isocaloric (fat will be added to interventions without 3-OHB) *LPS will be administered (1 ng/kg) the day prior to the study together with fast and bed rest. On the study day LPS (0.5 ng/kg) will be injected.

In a randomized crossover design, eight healthy lean young men will undergo either: i) Healthy conditions (overnight fast) + whey protein ii) Catabolic conditions (Inflammation (LPS) + 36-hour fast and bed rest) + whey protein iii) Catabolic conditions (Inflammation (LPS) + 36-hour fast and bed rest) + 3-OHB/whey protein

Outcome Assessor will be blinded for all interventions and will recieve raw data sequentially numbered, and will therefore not know which data are from the same test object and which intervention was given.

Difference in total gastro-intestinal transit time measured by the Smartpill system between healthy and catabolic conditions. A pooled mean of the catabolic conditions will be used, if there is no difference between first and second exposure to LPS or "catabolic + whey" and "catabolic + 3-OHB/whey" interventions.

Measured from intake of the Smartpill (together with the bolus of the protein beverages at t=210) until excretion with faeces (expected time frame: 2-5 days))

Difference in gastric emptying by Smartpill between healthy and catabolic conditions. A pooled mean of the two catabolic arms during the basal period will be represented

Measured from intake of the Smartpill (t = 210) until it leaves the ventricle (assessed by rise in pH levels, expected time frame: 2-7 hours)

Difference in small intestine passage time by Smartpill between healthy and catabolic conditions. A pooled mean of the two catabolic arms during the basal period will be represented

Measured from the timepoint where Smartpill leaves the ventricle until it enters the colon (assessed by specific predefined motility and pH patterns, expected timeframe 1-3 days)

Difference in colon passage time by Smartpill between healthy and catabolic conditions. A pooled mean of the two catabolic arms during the basal period will be represented

Measured from the timepoint where Smartpill leaves the small intestine until it is excreted with faeces (assessed by specific predefined motility and pH patterns, expected timeframe 1-3 days)

Difference in GI motility measured by Smartpill pressure sensor between healthy and catabolic conditions. A pooled mean of the catabolic conditions will be used, if there is no difference between first and second exposure to LPS or "catabolic + whey" and "catabolic + 3-OHB/whey" interventions. A pooled mean of the two catabolic arms during the basal period will be represented

Measured from intake of the Smartpill (t = 210) until excretion with faeces (expected time frame: 2-5 days)

Difference in body temperature measured by Smartpill between healthy and catabolic conditions. A pooled mean of the two catabolic arms during the basal period will be represented

Measured from intake of the Smartpill (t = 210) until excretion with faeces (expected time frame: 2-5 days)

Difference in pH measured by Smartpill between healthy and catabolic conditions in the ventricle, small intestine and colon . A pooled mean of the catabolic conditions will be used, if there is no difference between first and second exposure to LPS or "catabolic + whey" and "catabolic + 3-OHB/whey" interventions. A pooled mean of the two catabolic arms during the basal period will be represented

Measured from intake of the Smartpill (t = 210) until excretion with faeces (expected time frame: 2-5 days)

Difference in gastric- and appetite hormones (GLP-1, GIP, PYY and ghrelin) (healthy vs catabolic conditions)

Difference in hormones at baseline and throughout the basal period between healthy and catabolic conditions. A pooled mean of the two catabolic arms during the basal period will be represented

Written assesment of various symptoms from the GI tract by a score from 0-6 (0 = no symptoms, 6 = very severe symptoms). A pooled mean of the two catabolic arms during the basal period will be represented

Written assesment of pain-coping (score from 0-6 on each question, 0 = no worries, 6 = severe worrying). A pooled mean of the two catabolic arms during the basal period will be represented

Inclusion Criteria: Between 20-40 years of age Body mass index between 20-30 kg/m^2 Healthy Oral and written consent forms obtained prior to study day Exclusion Criteria: Recent immobilization of an extremity that is not fully rehabilitated Lactose, lidocain or rubber allergies Current disease Use of anabolic steroids Smoking Former major abdominal surgery (Or current problems with the GI tract) >10 hours of exercise/weak Present ketogenic diets or high-protein diets Blood doner that does not want to discontinue blood donations until study completion Pending MR scan