Individual differences in stress vulnerability: The role of gut pathobionts in stress-induced colitis

Langgartner, Dominik; Peterlik, Daniel; Foertsch, Sandra; Füchsl, Andrea M.; Brokmann, Petra; Flor, Peter J.; Shen, Zeli; Fox, James G.; Uschold-Schmidt, Nicole; Lowry, Christopher A.; Reber, Stefan O.

doi:10.1016/j.bbi.2016.12.019

Cited by 61 publications

(46 citation statements)

References 63 publications

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“…The same is true for the stress-induced shrinkage of peripheral lymph nodes, initially proposed by Selye as part of the stress triad. The number of viable mesenteric lymph node cells was comparable between CSC and SHC animals, independent of the presence of certain intestinal pathobionts [47]. Further in contrast to the stress triad proposed by Selye, statistical analysis performed in the current study did not support a decrease in spleen weight to be a reliable biomarker of chronic stress.…”

Section: Discussioncontrasting

confidence: 70%

“…These data are in line with results of a recent study from our group, showing that the vulnerability to develop CSC-induced colitis is strongly dependent on the presence of certain intestinal pathobiontic germs [75], as for instance certain enterohepatic Helicobacter spp. [47,76]. In detail, in contrast to non-specific pathogen free (non-SPF) conditions, under which CSC exposure reliably causes spontaneous colitis [17,77], CSC animals did not show any signs of intestinal inflammation when performing the paradigm under SPF conditions.…”

Section: Discussionmentioning

confidence: 99%

“…In detail, in contrast to non-specific pathogen free (non-SPF) conditions, under which CSC exposure reliably causes spontaneous colitis [17,77], CSC animals did not show any signs of intestinal inflammation when performing the paradigm under SPF conditions. Importantly, reintroducing Helicobacter typhlonius into otherwise SPF conditions was able to rescue the colitogenic potential of CSC [47], clearly indicating that stress-induced intestinal inflammation is not representing a nonspecific and stressor independent general consequence of chronic stress in the sense of Selye’s stress triad but rather depends on whether certain pathobionts are present or not during stressor exposure. The same is true for the stress-induced shrinkage of peripheral lymph nodes, initially proposed by Selye as part of the stress triad.…”

Section: Discussionmentioning

confidence: 99%

“…All efforts were made to minimize the number of animals used and their suffering. Some of the animals included in the statistical analysis of the present study were included in a recently published study [16,45–47]. …”

Section: Methodsmentioning

confidence: 99%

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Biomarkers for classification and class prediction of stress in a murine model of chronic subordination stress

et al. 2018

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Selye defined stress as the nonspecific response of the body to any demand and thus an inherent element of all diseases. He reported that rats show adrenal hypertrophy, thymicolymphatic atrophy, and gastrointestinal ulceration, referred to as the stress triad, upon repeated exposure to nocuous agents. However, Selye’s stress triad as well as its extended version including reduced body weight gain, increased plasma glucocorticoid (GC) concentrations, and GC resistance of target cells do not represent reliable discriminatory biomarkers for chronic stress. To address this, we collected multivariate biological data from male mice exposed either to the preclinically validated chronic subordinate colony housing (CSC) paradigm or to single-housed control (SHC) condition. We then used principal component analysis (PCA), top scoring pairs (tsp) and support vector machines (SVM) analyses to identify markers that discriminate between chronically stressed and non-stressed mice. PCA segregated stressed and non-stressed mice, with high loading for some of Selye’s stress triad parameters. The tsp analysis, a simple and highly interpretable statistical approach, identified left adrenal weight and relative thymus weight as the pair with the highest discrimination score and prediction accuracy validated by a blinded dataset (92% p-value < 0.0001; SVM model = 83% accuracy and p-value < 0.0001). This finding clearly shows that simultaneous consideration of these two parameters can be used as a reliable biomarker of chronic stress status. Furthermore, our analysis highlights that the tsp approach is a very powerful method whose application extends beyond what has previously been reported.

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Section: Discussioncontrasting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Biomarkers for classification and class prediction of stress in a murine model of chronic subordination stress

et al. 2018

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“…Interestingly, mice exposed to the chronic subordinate colony housing (CSC) paradigm [73, 133, 134, 334, 368], a preclinically established rodent model for PTSD [336] (for more information, see Table 1), which promotes splenocyte activation, as seen following SDR exposure [124, 335], increased also many circulating pro- and anti-inflammatory cytokines, including IL-1β, IL-6, IL-10, granulocyte colony stimulating factor (G-CSF), and MCP-1 [214]. Although we cannot delineate whether the systemic immune activation seen following CSC exposure is mediated by increased DAMPs or MAMPs, we can exclude involvement of any kind of PAMPs, as these experiments have been performed under specific pathogen-free (SPF) conditions [214, 215]. An interesting study in this context shows that both reducing commensal bacteria using antibiotics and neutralizing LPS using endotoxin inhibitor (EI) attenuate increases in some inflammasome-dependent (IL-1β and IL-18), but not inflammasome-independent (IL-6, IL-10, and MCP-1) inflammatory proteins in the blood of male F344 rats exposed to an acute tail shock stressor [261].…”

Section: Underlying Mechanismsmentioning

confidence: 99%

Old Friends, immunoregulation, and stress resilience

Langgartner

Lowry

Reber³

2018

Pflugers Arch - Eur J Physiol

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There is a considerable body of evidence indicating that chronic adverse experience, especially chronic psychosocial stress/trauma, represents a major risk factor for the development of many somatic and affective disorders, including inflammatory bowel disease (IBD) and posttraumatic stress disorder (PTSD). However, the mechanisms underlying the development of chronic stress-associated disorders are still in large part unknown, and current treatment and prevention strategies lack efficacy and reliability. A greater understanding of mechanisms involved in the development and persistence of chronic stress-induced disorders may lead to novel approaches to prevention and treatment of these disorders. In this review, we provide evidence indicating that increases in immune (re-)activity and inflammation, potentially promoted by a reduced exposure to immunoregulatory microorganisms (“Old Friends”) in today’s modern society, may be causal factors in mediating the vulnerability to development and persistence of stress-related pathologies. Moreover, we discuss strategies to increase immunoregulatory processes and attenuate inflammation, as for instance contact with immunoregulatory Old Friends, which appears to be a promising strategy to promote stress resilience and to prevent/treat chronic stress-related disorders.

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Efficacy of probiotics on stress in healthy volunteers: A systematic review and meta‐analysis based on randomized controlled trials

Zhang

et al. 2020

Brain and Behavior

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Individual differences in stress vulnerability: The role of gut pathobionts in stress-induced colitis

Cited by 61 publications

References 63 publications

Biomarkers for classification and class prediction of stress in a murine model of chronic subordination stress

Biomarkers for classification and class prediction of stress in a murine model of chronic subordination stress

Old Friends, immunoregulation, and stress resilience

Efficacy of probiotics on stress in healthy volunteers: A systematic review and meta‐analysis based on randomized controlled trials

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