Sauna dehydration as a new physiological challenge model for intestinal barrier function

Abstract

The intestinal barrier plays a crucial role in maintaining gut health, and an increased permeability has been linked to several intestinal and extra-intestinal disorders. There is an increasing demand for interventions aimed at strengthening this barrier and for in vivo challenge models to assess their efficiency. This study investigated the effect of sauna-induced dehydration on intestinal barrier function (clinicaltrials.gov: NCT03620825). Twenty healthy subjects underwent three conditions in random order: (1) Sauna dehydration (loss of 3% body weight), (2) non-steroidal anti-inflammatory drug (NSAID) intake, (3) negative control. Intestinal permeability was assessed by a multi-sugar urinary recovery test, while intestinal damage, bacterial translocation and cytokines were assessed by plasma markers. The sauna dehydration protocol resulted in an increase in gastroduodenal and small intestinal permeability. Presumably, this increase occurred without substantial damage to the enterocytes as plasma intestinal fatty acid-binding protein (I-FABP) and liver fatty acid-binding protein (L-FABP) were not affected. In addition, we observed significant increases in levels of lipopolysaccharide-binding protein (LBP), IL-6 and IL-8, while sCD14, IL-10, IFN-ɣ and TNF-α were not affected. These results suggest that sauna dehydration increased intestinal permeability and could be applied as a new physiological in vivo challenge model for intestinal barrier function.

Conflict of interest statement

The authors declare no competing interests

© 2021. The Author(s).

Figures

Figure 1

Intestinal permeability at the different test conditions. (a) Gastroduodenal permeability measured by urinary sucrose recovery (0-5 h). (b) Small intestinal permeability measured by lactulose/rhamnose (L/R) excretion ratio (0-5 h). (c) Colonic permeability measured by urinary sucralose/erythritol (S/E) excretion ratio (5-24 h). The horizontal line marks the median, the vertical line spans through the interquartile range (IQR). The dots represent the individuals.*P < 0.05. **P < 0.01. ***P < 0.001. ****P < 0.0001. ns, non-significant. NSAID, nonsteroidal anti-inflammatory drug.

Figure 2

Plasma fatty acid-binding proteins concentrations at the different test conditions. (a) Plasma concentrations of intestinal fatty acid-binding protein (I-FABP). (b) Plasma concentrations of liver fatty acid-binding protein (L-FABP). The horizontal line marks the median, the vertical line spans through the interquartile range (IQR). The dots represent the individuals. *P < 0.05. ****P < 0.0001. ns, non-significant. NSAID, nonsteroidal anti-inflammatory drug.

Figure 3

Lipopolysaccharide-binding protein and soluble CD14 concentrations at the different test conditions. (a) Plasma concentrations of lipopolysaccharide-binding protein (LBP). (b) Plasma concentrations of soluble CD14 (sCD14). The horizontal line marks the median, the vertical line spans through the interquartile range (IQR). The dots represent the individuals. * P < 0.05. ns, non-significant. NSAID, nonsteroidal anti-inflammatory drug. Data of one participant was excluded from the LBP analysis due to disproportionately high baseline values.

Figure 4

Plasma cytokine concentrations at the control condition and after sauna dehydration. (a) IL-6. (b) IL-8. (c) IL-10. (d) IFN-ɣ. (e) TNF-α. The horizontal line marks the median, the vertical line spans through the interquartile range (IQR). The dots represent the individuals. ***P < 0.001. ****P < 0.0001. ns, non-significant.

Figure 5

Differences between female and male participants. (a) Small intestinal permeability shown as ∆ L/R (L/R sauna–L/R control). (b) Total time in sauna until loss of 3% body weight. The horizontal line marks the median, the vertical line spans through the interquartile range (IQR). The dots represent the individuals.*P < 0.05. ns, non-significant.

Figure 6

Salivary cortisol concentrations over time during the different test conditions. Saliva samples at the control and NSAID visit were collected at similar times of the day as during the sauna condition in order to consider diurnal changes. Median and IQR are shown. p-values indicate significant differences between the control and sauna dehydration condition. *P < 0.05 (sauna dehydration versus control). **P < 0.01 (sauna dehydration versus control). ns, non-significant. NSAID, nonsteroidal anti-inflammatory drug.

Figure 7

Schematic model of the study design. All 20 subjects participated in all three visits in random order: negative control, sauna dehydration and positive control. Visits were separated by a wash-out period of at least five days.