Duodenal Proteome Modifications in Response to Enteral Nutrient Intake in Healthy Humans

A comprehensive analysis of how different nutrients affect protein expression in the human duodenum

Published: June 2023 24 Participants Proteomic Analysis

Introduction

The duodenum serves as a crucial interface between ingested nutrients and the human body, playing a pivotal role in nutrient sensing, digestion, and absorption. Recent advances in proteomic technologies have enabled detailed characterization of the duodenal proteome and its dynamic responses to nutritional stimuli .

This study investigates how different enteral nutrients modulate the duodenal proteome in healthy human subjects. Understanding these modifications provides insights into the molecular mechanisms of nutrient sensing and may inform nutritional interventions for various gastrointestinal disorders .

Proteomic Profiling

Comprehensive analysis of protein expression changes in response to nutrient exposure.

Nutrient Challenges

Controlled administration of different nutrient types to assess specific proteomic responses.

Dynamic Response

Temporal analysis of proteome modifications following nutrient exposure.

Methodology

Study Participants

24 healthy volunteers (12 male, 12 female) aged 25-45 years with normal BMI (20-25 kg/m²) were recruited .

Nutrient Interventions

  • Carbohydrate-rich solution (75g glucose)
  • Protein-rich solution (30g whey protein)
  • Fat-rich solution (30g lipid emulsion)
  • Mixed nutrient solution
Participant Demographics

Experimental Protocol

Baseline Assessment

Fasting blood samples and duodenal biopsies collected after overnight fast .

Nutrient Administration

Randomized, crossover design with one-week washout period between interventions.

Sample Collection

Duodenal biopsies collected at 30, 60, and 120 minutes post-nutrient administration.

Proteomic Analysis

Liquid chromatography-mass spectrometry (LC-MS/MS) for protein identification and quantification .

Analytical Approach

1
Protein Extraction and Digestion

Tissue samples homogenized and proteins extracted using optimized protocols.

2
LC-MS/MS Analysis

High-resolution mass spectrometry with data-dependent acquisition.

3
Bioinformatics

MaxQuant for protein identification and Perseus for statistical analysis.

Results

Differentially Expressed Proteins by Nutrient Type

Carbohydrate Response

Glucose administration resulted in significant upregulation of 42 proteins and downregulation of 18 proteins .

Key Upregulated Proteins:
SGLT1 - Sodium/glucose cotransporter 1
GLUT2 - Glucose transporter 2
AMY2A - Pancreatic alpha-amylase
Protein Expression Timeline - Carbohydrates
Protein Expression Timeline - Proteins

Protein Response

Whey protein intake modulated 67 proteins, with particularly strong effects on peptide transporters and digestive enzymes .

Key Modulated Proteins:
PEPT1 - Peptide transporter 1
ACE - Angiotensin-converting enzyme
DPP4 - Dipeptidyl peptidase 4
Functional Pathway Enrichment Analysis

3.2x

Average increase in nutrient transporter expression

127

Proteins significantly modified across all nutrient types

15

Metabolic pathways significantly enriched

Discussion

This study demonstrates that enteral nutrient intake induces rapid and specific modifications to the duodenal proteome in healthy humans. The proteomic responses were nutrient-specific, with distinct patterns observed for carbohydrates, proteins, and fats .

The upregulation of nutrient transporters following their respective nutrient challenges highlights the adaptive capacity of the duodenum to optimize nutrient absorption. The temporal patterns of protein expression suggest coordinated regulatory mechanisms that may involve both transcriptional and post-translational processes .

Key Insight

The duodenal proteome demonstrates remarkable plasticity in response to nutrient intake, with changes observable within 30 minutes of nutrient exposure.

These findings have implications for understanding the molecular basis of nutrient sensing and may inform nutritional strategies for conditions such as malabsorption syndromes, obesity, and diabetes. The identification of nutrient-responsive proteins could serve as biomarkers for assessing duodenal function or as targets for therapeutic interventions .

Limitations and Future Directions

While this study provides comprehensive proteomic data, it does not establish causal relationships between protein changes and functional outcomes. Future research should integrate proteomic data with metabolic measurements and employ intervention studies to establish functional significance.