Elsevier

Biological Psychology

Volume 138, October 2018, Pages 48-55
Biological Psychology

Effects of acute stress provocation on cortisol levels, zonulin and inflammatory markers in low- and high-stressed men

https://doi.org/10.1016/j.biopsycho.2018.08.013Get rights and content

Highlights

  • This study is the first to show fluctuations in gut permeability after psychosocial stress induction.

  • The pro-inflammatory interleukin 6 increased with time after psychosocial stress induction, and was related to age.

  • After stress induction, IL-6 and IL-8 correlated positively with zonulin.

  • This study indicate, that high-stressed participants generally have higher IL-1β values than low-stressed participants.

  • High-stressed participants experienced more abdominal dysfunction than low-stressed participants.

Abstract

The virtual version of the Trier Social Stress Test (V-TSST) is an effective and standardized tool for social stress induction. This study aimed to examine gut permeability and physiological and inflammatory markers of reactivity to acute psychosocial stress. Forty young men were classified as high-stressed (HIGHS) or low-stressed (LOWS) according to the Shirom-Melamed Burnout Questionnaire. Cardiovascular reactivity and gut dysfunction were studied along with cortisol, zonulin and cytokines. Gut permeability was shown to be affected within one hour after the psychosocial stress induction, and shown to be dependent on age. Interleukin-6 increased with time, most pronounced at the end of the one-hour recovery after V-TSST, and was positively correlated to age. HIGHS experienced more abdominal dysfunction compared to LOWS. In conclusion, this study is the first to show fluctuations in gut permeability after psychosocial stress induction. This was partly associated with changes in inflammatory markers.

Introduction

Previous studies have reported that individuals scoring high on scales associated with long-term stress, such as vital exhaustion (Kudielka et al., 2006), allostatic load index (Juster et al., 2011), and exhaustion disorder (Jönsson et al., 2015), respond with reduced hypothalamic-pituitary-adrenal (HPA) axis reactivity (as measured by cortisol) to acute psychosocial stress, induced by the Trier Social Stress Test (TSST) (Kirschbaum, Pirke, & Hellhammer, 1993). Chronic stress has also been related to reduced blood pressure and norepinephrine reactivity to acute stress (Matthews, Gump, & Owens, 2001). In individuals suffering from work-related stress and vital exhaustion, a generally decreased functioning of the parasympathetic nervous system (PNS), quantified by high frequency heart rate variability (HF-HRV), has been observed (Thayer, Yamamoto, & Brosschot, 2010; Watanabe et al., 2002). A dysfunctional reactivity, or general activity, of the stress system has been suggested as a possible link to a number of cardiovascular, endocrine, autoimmune, metabolic, and behavioral disorders (Chrousos, 2009).

The steroid hormone cortisol is released by the adrenals in response to stress and is normally regulated by negative feedback (Brzozowski et al., 2016; Miller and O’Callaghan, 2002). Increased cortisol levels have been related to suppression of the immune system (Tomfohr, Edwards, & Dimsdale, 2012). The amount of cortisol seems to be an objective biological marker of stress (Wosu, Valdimarsdóttir, Shields, Williams, & Williams, 2013), and increased concentrations are related to diseases like coronary heart disease, type 2 diabetes and allergy (Miller and O’Callaghan, 2002; Stenius et al., 2011; Wosu et al., 2013).

Intestinal integrity is an essential barrier and defense mechanism to avoid translocation of luminal antigens. However, situations like stress can weaken the integrity and increase paracellular permeability (Brzozowski et al., 2016) that normally is regulated in a dynamic interplay between the mucosa and luminal content to prevent harmful substances from entering the body. It was recently shown that people exposed to stress by giving a speech in front of an audience experienced increased small-intestinal permeability and increased salivary cortisol (Vanuytsel et al., 2014). This was also observed in participants exposed to cold pain stress (Alonso et al., 2012). The importance of gut health can be exemplified by children having increased risk of developing atopic eczema before the age of two if it proceeds by low gut bacterial diversity (Wang et al., 2008) and high levels of salivary cortisol (Stenius et al., 2011).

Zonulin has been identified as a precursor for haptoglobin-2, and circulating zonulin protein is known to reversibly regulate intestinal permeability by modulating intercellular tight junctions (Tripathi et al., 2009) and is therefore a suitable marker of intestinal permeability (Fasano, 2011). Increased zonulin concentration has been reported in various diseases (Fasano, 2011), and it has been suggested that increased circulating zonulin might be mediated through increased circulating IL-6 (Moreno-Navarrete et al., 2012). Increased permeability, as well as psychosocial stress, has been shown to activate the inflammatory cascade, with increased concentrations of circulating pro-inflammatory cytokines, of which IL-6 is one of the most consistently documented (Rohleder, Aringer, & Boentert, 2012).

In the present study we aimed to examine intestinal permeability and physiological and inflammatory markers of reactivity to acute psychosocial stress in high-stressed and low-stressed individuals using a virtual version of the TSST (Jönsson et al., 2010).

Section snippets

Participants

Forty-five healthy men aged 19–35 years were recruited through advertisements at Lund University, in student magazines, and via the web from June 2015 to February 2016. The study was conducted in the same time period. It was explicitly stated that we were interested in persons that during the last six months felt either non-stressed or stressed. Only men were included because the menstrual cycle may affect the magnitude of cortisol response to psychosocial stressors (Kudielka, Hellhammer, &

Results

On the day of V-TSST, 17 of the participants had SMBQ ≥ 3.75 and were therefore classified as high-stressed (HIGHS), 23 participants had SMBQ ≤ 2.75 and were classified as low-stressed (LOWS), according to Grossi et al. (2003). Characteristics of participants are presented in Table 1.

Discussion

In line with previous studies (Fich et al., 2014; Jönsson et al., 2010; Jönsson et al., 2015) heart rate, self-reported anxiety and cortisol were increased during V-TSST, indicating that stress induction was successful. Self-reported anxiety was significantly more pronounced in HIGHS than LOWS during the V-TSST. Furthermore, the positive correlations between cortisol in saliva compared to serum confirm the ability to use either body fluid for measurement of this common biological marker of

Funding

This work was supported by Dr. Håkansson’s Foundation, Eslöv, and Probi AB, Lund, Sweden. The funding sources had no role in performing the study; in the collection, analysis and interpretation of data; in writing of the report; and in the decision to submit the article for publication.

Author contribution paragraph

C.L. designed and performed the study, analyzed the biochemical data, interpreted the data, and wrote the manuscript. P.J. designed the study, performed the physiological and statistical analyzes, interpreted data, and wrote the manuscript, H.B. was test leader in V-TSST and contributed to manuscript preparation, G.Ö. participated in the study design and manuscript preparation, J.E. and G.J. participated in the study design and approved the manuscript, S.A. designed the study and participated

Declaration of interest

The authors declare no conflict of interest related to this publication. G.Ö. is employed by Probi AB. C.L. has taken up a position in the public company BioGaia AB after the manuscript first was submitted.

Acknowledgements

All participants are greatly thanked for their participation and Anne-Marie Rohrstock is acknowledged for technical assistance.

References (44)

  • F. Stenius et al.

    Salivary cortisol levels and allergy in children: The ALADDIN birth cohort

    Journal of Allergy and Clinical Immunology

    (2011)
  • L.K. Stenman et al.

    Probiotic with or without fiber controls body fat mass, associated with serum zonulin, in overweight and obese adults—randomized controlled trial

    EBioMedicine

    (2016)
  • J.F. Thayer et al.

    The relationship of autonomic imbalance, heart rate variability and cardiovascular disease risk factors

    International Journal of Cardiology

    (2010)
  • L.M. Tomfohr et al.

    Is obstructive sleep apnea associated with cortisol levels? A systematic review of the research evidence

    Sleep Medicine Reviews

    (2012)
  • M. Wang et al.

    Reduced diversity in the early fecal microbiota of infants with atopic eczema

    Journal of Allergy and Clinical Immunology

    (2008)
  • C. Alonso et al.

    Acute experimental stress evokes a differential gender-determined increase in human intestinal macromolecular permeability

    Neurogastroenterology & Motility

    (2012)
  • G.G. Berntson et al.

    Heart rate variability: Origins, methods, and interpretive caveats

    Psychophysiology

    (1997)
  • B. Brzozowski et al.

    Mechanisms by which stress affects the experimental and clinical inflammatory bowel disease (IBD): Role of brain-gut Axis

    Current Neuropharmacology

    (2016)
  • L.L. Carpenter et al.

    Association between plasma IL-6 response to acute stress and early-life adversity in healthy adults

    Neuropsychopharmacology

    (2010)
  • G.P. Chrousos

    Stress and disorders of the stress system

    Nature Reviews Endocrinology

    (2009)
  • W.B. Ershler et al.

    The role of interleukin-6 in certain age-related diseases

    Drugs & Aging

    (1994)
  • A. Fasano

    Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer

    Physiological Reviews

    (2011)
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