Diet Induced Intestinal Mucosal Adaptation

Small Intestinal Adaptation to Isocaloric Diets Dominated Either by Fats or Carbohydrates

Human beings are 'omnivores' meaning that all principal components of food (i.e. the macronutrients: carbohydrates, fat, proteins) can be assimilated by the gastrointestinal tract. When the gut mucosa is exposed to dietary changes it adjusts its functional behaviour. For example, a fatty diet demands certain digestive mechanisms, whereas others are needed to take care of a carbohydrate rich diet. Such dietary induced changes in appearance and functionality of the small intestinal mucosa have been described in animals but only little is known about it in man. The present project aims at elucidating in man if a 2 weeks diet dominated by either fat or carbohydrates, but with similar energy content, is associated with changes in the small intestinal mucosal appearance and metabolic signalling capacity.

Study Overview

• Status: Completed
• Conditions: Healthy Conditions
• Intervention / Treatment: Dietary supplement: high fat diet (hfd), then high carbohydrate diet; Dietary supplement: high carbohydrate diet, then high fat diet

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Gothenburg, Sweden, SE41345
    • Dept of Gastrosurgical R&E, Sahlgrenska Universityhospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

healthy volunteer not taking prescribed medications BMI ≤25 kg/m2

Exclusion Criteria:

BMI ≥26 kg/m2 smoker previous or current gastrointestinal disease significant abdominal surgery pregnancy/breast feeding drug intolerance of importance (particularly opiates and midazolam used during endoscopy) history of drug addiction

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: First high fat diet, then high carbohydrate diet; had; first sixty percent fat as the energy source, then sixty percent carbohydrates	Dietary supplement: high fat diet (hfd), then high carbohydrate diet; Sixty % of the energy content is based on fat, then sixty % of the energy content is based on carbohydrates
Experimental: First, high carb diet, then high fat diet; had; first sixty percent carbohydrates as the energy source, the sixty percent fat	Dietary supplement: high carbohydrate diet, then high fat diet; Sixty % of the energy content is based on carbohydrates, then sixty % of the energy content is based on fat

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mucosal Surface Enlargement	The enlargement of the luminal surface area is a morphometric factor, defined as the percentage of the mucosal surface (one dimension in arbitrary units) in relation to the relatively flat area of the muscular mucosae layer from the same histological cuts. Unit: % of the muscular mucosae.	Appearance after 2 weeks of each diet

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glucose Induced Electrogenic Responses In-vitro	Jejunal mucosal biopsies are mounted as a sheet between two different (glucose-free) physiological solutions (in so called Ussing chambers). The electrogenic response to glucose will be measured as follows: Baseline ion-transporting capacity for the luminal to serosa side will be measured as the epithelial current (Iep) in the absence of glucose (unit; µA/cm2). Addition of 10mM glucose on the luminal side increases the ion-transporting capacity. This level will be divided with preceding baseline ion-transporting capacity and is presented as % change from the baseline secretion. The sensitivity of this response to phloridzin is given to confirm to what extent the glucose transporter SGLT1 is involved. Only the completed pairs (high fat diet versus high carbohydrate diet) will be analyzed.	The condition after 2 weeks of each diet
Glycemic Control Following a Test Meal	Blood concentrations of glucose are assessed over 2 hours following a mixed test meal.	The condition after 2 weeks of each diet

Collaborators and Investigators

• Sponsor: Göteborg University
• Collaborators: Sahlgrenska University Hospital
• Investigators: Principal Investigator: Lars Fändriks, MD, PhD, Göteborg University

Publications and helpful links

General Publications

• Elebring E, Wallenius V, Casselbrant A, Docherty NG, Roux CWL, Marschall HU, Fandriks L. A Fatty Diet Induces a Jejunal Ketogenesis Which Inhibits Local SGLT1-Based Glucose Transport via an Acetylation Mechanism-Results from a Randomized Cross-Over Study between Iso-Caloric High-Fat versus High-Carbohydrate Diets in Healthy Volunteers. Nutrients. 2022 May 7;14(9):1961. doi: 10.3390/nu14091961.

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: March 13, 2014
• First Submitted That Met QC Criteria: March 14, 2014
• First Posted (Estimated): March 17, 2014

Study Record Updates

• Last Update Posted (Actual): July 17, 2025
• Last Update Submitted That Met QC Criteria: June 30, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: metabolic control; human; diet; intestinal; mucosa
• Other Study ID Numbers: BUTTER