Associations between various markers of intestinal barrier and immune function after a high-intensity exercise challenge

Abstract

Strenuous exercise can result in disruption of intestinal barrier function and occurrence of gastrointestinal symptoms. The aim of this exploratory study was to elucidate systemic effects of increased intestinal permeability after high-intensity exercise. Forty-one endurance-trained subjects performed a 60-min treadmill run at 80% VO₂max. Small intestinal permeability was measured as urinary excretion ratio of lactulose/rhamnose (L/R). Blood, saliva and feces were analyzed for gut barrier and immune-related biomarkers. The exercise challenge increased several markers of intestinal barrier disruption, immune function and oxidative stress. We found a negative correlation between L/R ratio and uric acid (r = -0.480), as well as a positive correlation between the L/R ratio and fecal chromogranin A in male participants (r = 0.555). No significant correlations were found between any of the markers and gastrointestinal symptoms, however, perceived exertion correlated with the combination of IL-6, IL-10 and salivary cortisol (r = 0.492). The lack of correlation between intestinal permeability and gastrointestinal symptoms could be due to minor symptoms experienced in lab settings compared to real-life competitions. The correlation between L/R ratio and uric acid might imply a barrier-protective effect of uric acid, and inflammatory processes due to strenuous exercise seem to play an important role regarding physical exhaustion.

Keywords: gastrointestinal symptoms; high‐intensity exercise; intestinal barrier function; intestinal permeability.

FIGURE 1

Scatter plot of the correlation between Bacteroidota/total 16S rRNA ratio and L/R ratio after the exercise challenge. Black dots represent female participants and open dots represent male participants. The analysis was performed by a two‐tailed Spearman's correlation analysis and corrected for multiplicity by the Benjamin‐Hochberg procedure if p < 0.05. q‐values smaller than 0.05 were considered statistically significant. The graph is shown in log‐scale to improve visualization. Three female and three male participants had too low values of Bacteroidota/total 16S rRNA ratio and are thus not shown in the graph. For one female participant, not enough blood samples were available for 16S rRNA analysis. L/R ratio – urinary lactulose/rhamnose excretion ratio.

FIGURE 2

Scatter plot of the negative correlation between uric acid and L/R ratio after the exercise challenge. Black dots represent female participants and open dots represent male participants. The analysis was performed by a two‐tailed Spearman's correlation analysis and corrected for multiplicity by the Benjamin‐Hochberg procedure if p < 0.05. q‐values smaller than 0.05 were considered statistically significant. The graph is shown in log scale to improve visualization. One female and one male participant had missing values. L/R ratio—urinary lactulose/rhamnose excretion ratio.

FIGURE 3

Scatter plot of the correlation observed in males between fecal chromogranin A (CgA) and L/R ratio after the exercise challenge. The analysis was performed by a two‐tailed Spearman's correlation analysis and corrected for multiplicity by the Benjamin‐Hochberg procedure if p < 0.05. q‐values smaller than 0.05 were considered statistically significant. The graph is shown in log scale to improve visualization. L/R ratio – urinary lactulose/rhamnose excretion ratio.

FIGURE 4

Significant correlation between the combination of IL‐6, IL‐10 and saliva cortisol with local exertion after 60 min. Black dots represent female participants and open dots represent male participants. Data were log2‐transformed and standardized prior to sparse Canonical Correlation analysis (sCCA) between biomarkers and symptoms and exertion after the exercise challenge. FDR estimates (q‐values) were calculated according to Storey (2002). IL—Interleukin.