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

Chronic subordinate colony housing (CSC), an established mouse model for chronic psychosocial stress, promotes a microbial signature of gut inflammation, characterized by expansion of Proteobacteria, specifically Helicobacter spp., in association with colitis development. However, whether the presen...

Full description

Bibliographic Details
Main Authors: 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.
Other Authors: Massachusetts Institute of Technology. Division of Comparative Medicine
Format: Article
Language:English
Published: Elsevier BV 2019
Online Access:https://hdl.handle.net/1721.1/122646
_version_ 1811091557159272448
author 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.
author2 Massachusetts Institute of Technology. Division of Comparative Medicine
author_facet Massachusetts Institute of Technology. Division of Comparative Medicine
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.
author_sort Langgartner, Dominik
collection MIT
description Chronic subordinate colony housing (CSC), an established mouse model for chronic psychosocial stress, promotes a microbial signature of gut inflammation, characterized by expansion of Proteobacteria, specifically Helicobacter spp., in association with colitis development. However, whether the presence of Helicobacter spp. during CSC is critically required for colitis development is unknown. Notably, during previous CSC studies performed at Regensburg University (University 1), male specific-pathogen-free (SPF) CSC mice lived in continuous subordination to a physically present and Helicobacter spp.-positive resident. Therefore, it is likely that CSC mice were colonized, during the CSC procedure, with Helicobacter spp. originating from the dominant resident. In the present study we show that employing SPF CSC mice and Helicobacter spp.-free SPF residents at Ulm University (University 2), results in physiological responses that are typical of chronic psychosocial stress, including increased adrenal and decreased thymus weights, decreased adrenal in vitro adrenocorticotropic hormone (ACTH) responsiveness, and increased anxiety-related behavior. However, in contrast to previous studies that used Helicobacter spp.-positive resident mice, use of Helicobacter spp.-negative resident mice failed to induce spontaneous colitis in SPF CSC mice. Consistent with the hypothesis that the latter is due to a lack of Helicobacter spp. transmission from dominant residents to subordinate mice during the CSC procedure, colonization of SPF residents with Helicobacter typhlonius at University 2, prior to the start of the CSC model, rescued the colitis-inducing potential of CSC exposure. Furthermore, using SPF CSC mice and H. typhlonius-free SPF residents at University 1 prevented CSC-induced colitis. In summary, our data support the hypothesis that the presence or absence of exposure to certain pathobionts contributes to individual variability in susceptibility to stress-/trauma-associated pathologies and to reproducibility of stress-related outcomes between laboratories. Keywords: Chronic psychosocial stress; Chronic subordinate colony housing (CSC); Enterohepatic Helicobacter species (EHS); Inflammatory bowel disease (IBD); Microbiota; Colitis; Stress vulnerability; Stress resilience; Inflammation; Pathobionts
first_indexed 2024-09-23T15:04:15Z
format Article
id mit-1721.1/122646
institution Massachusetts Institute of Technology
language English
last_indexed 2024-09-23T15:04:15Z
publishDate 2019
publisher Elsevier BV
record_format dspace
spelling mit-1721.1/1226462022-09-29T12:29:09Z 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. Massachusetts Institute of Technology. Division of Comparative Medicine Massachusetts Institute of Technology. Department of Biological Engineering Chronic subordinate colony housing (CSC), an established mouse model for chronic psychosocial stress, promotes a microbial signature of gut inflammation, characterized by expansion of Proteobacteria, specifically Helicobacter spp., in association with colitis development. However, whether the presence of Helicobacter spp. during CSC is critically required for colitis development is unknown. Notably, during previous CSC studies performed at Regensburg University (University 1), male specific-pathogen-free (SPF) CSC mice lived in continuous subordination to a physically present and Helicobacter spp.-positive resident. Therefore, it is likely that CSC mice were colonized, during the CSC procedure, with Helicobacter spp. originating from the dominant resident. In the present study we show that employing SPF CSC mice and Helicobacter spp.-free SPF residents at Ulm University (University 2), results in physiological responses that are typical of chronic psychosocial stress, including increased adrenal and decreased thymus weights, decreased adrenal in vitro adrenocorticotropic hormone (ACTH) responsiveness, and increased anxiety-related behavior. However, in contrast to previous studies that used Helicobacter spp.-positive resident mice, use of Helicobacter spp.-negative resident mice failed to induce spontaneous colitis in SPF CSC mice. Consistent with the hypothesis that the latter is due to a lack of Helicobacter spp. transmission from dominant residents to subordinate mice during the CSC procedure, colonization of SPF residents with Helicobacter typhlonius at University 2, prior to the start of the CSC model, rescued the colitis-inducing potential of CSC exposure. Furthermore, using SPF CSC mice and H. typhlonius-free SPF residents at University 1 prevented CSC-induced colitis. In summary, our data support the hypothesis that the presence or absence of exposure to certain pathobionts contributes to individual variability in susceptibility to stress-/trauma-associated pathologies and to reproducibility of stress-related outcomes between laboratories. Keywords: Chronic psychosocial stress; Chronic subordinate colony housing (CSC); Enterohepatic Helicobacter species (EHS); Inflammatory bowel disease (IBD); Microbiota; Colitis; Stress vulnerability; Stress resilience; Inflammation; Pathobionts 2019-10-21T16:00:47Z 2019-10-21T16:00:47Z 2016-12 2016-12 2019-10-17T13:23:10Z Article http://purl.org/eprint/type/JournalArticle 0889-1591 https://hdl.handle.net/1721.1/122646 Langgartner, Dominik et al. "Individual differences in stress vulnerability: The role of gut pathobionts in stress-induced colitis." Brain, Behavior, and Immunity 64 (August 2017): 23-32 © Elsevier en http://dx.doi.org/10.1016/j.bbi.2016.12.019 Brain, Behavior, and Immunity Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV Prof. Fox via Howard Silver
spellingShingle 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.
Individual differences in stress vulnerability: The role of gut pathobionts in stress-induced colitis
title Individual differences in stress vulnerability: The role of gut pathobionts in stress-induced colitis
title_full Individual differences in stress vulnerability: The role of gut pathobionts in stress-induced colitis
title_fullStr Individual differences in stress vulnerability: The role of gut pathobionts in stress-induced colitis
title_full_unstemmed Individual differences in stress vulnerability: The role of gut pathobionts in stress-induced colitis
title_short Individual differences in stress vulnerability: The role of gut pathobionts in stress-induced colitis
title_sort individual differences in stress vulnerability the role of gut pathobionts in stress induced colitis
url https://hdl.handle.net/1721.1/122646
work_keys_str_mv AT langgartnerdominik individualdifferencesinstressvulnerabilitytheroleofgutpathobiontsinstressinducedcolitis
AT peterlikdaniel individualdifferencesinstressvulnerabilitytheroleofgutpathobiontsinstressinducedcolitis
AT foertschsandra individualdifferencesinstressvulnerabilitytheroleofgutpathobiontsinstressinducedcolitis
AT fuchslandream individualdifferencesinstressvulnerabilitytheroleofgutpathobiontsinstressinducedcolitis
AT brokmannpetra individualdifferencesinstressvulnerabilitytheroleofgutpathobiontsinstressinducedcolitis
AT florpeterj individualdifferencesinstressvulnerabilitytheroleofgutpathobiontsinstressinducedcolitis
AT shenzeli individualdifferencesinstressvulnerabilitytheroleofgutpathobiontsinstressinducedcolitis
AT foxjamesg individualdifferencesinstressvulnerabilitytheroleofgutpathobiontsinstressinducedcolitis
AT uscholdschmidtnicole individualdifferencesinstressvulnerabilitytheroleofgutpathobiontsinstressinducedcolitis
AT lowrychristophera individualdifferencesinstressvulnerabilitytheroleofgutpathobiontsinstressinducedcolitis
AT reberstefano individualdifferencesinstressvulnerabilitytheroleofgutpathobiontsinstressinducedcolitis