@article{doney_chronic_2024,

title = {Chronic Stress Exposure Alters the Gut Barrier: Sex-Specific Effects on Microbiota and Jejunum Tight Junctions},

author = {E. Doney and L. Dion-Albert and F. Coulombe-Rozon and N. Osborne and R. Bernatchez and S. E. J. Paton and F. N. Kaufmann and R. O. Agomma and J. L. Solano and R. Gaumond and K. A. Dudek and J. K. Szyszkowicz and F. Aardema and L. A. Bentaleb and J. Beauchamp and H. Bendahmane and E. Benoit and L. Bergeron and A. Bertone and N. Bertrand and F. -A. Berube and P. Blanchet and J. Boissonneault and C. J. Bolduc and J. -P. Bonin and F. Borgeat and R. Boyer and C. Breault and J. -J. Breton and C. Briand and J. Brodeur and K. Brule and L. Brunet and S. Carriere and C. Chartrand and R. Chenard-Soucy and T. Chevrette and E. Cloutier and R. Cloutier and H. Cormier and G. Cote and J. Cyr and P. David and L. De Benedictis and M. -C. Delisle and P. Deschenes and C. D. Desjardins and G. Desmarais and J. -L. Dubreucq and M. Dumont and A. Dumais and G. Ethier and C. Feltrin and A. Felx and H. Findlay and L. Fortier and D. Fortin and L. Fortin and N. Francois and V. Gagne and M. -P. Gagnon and M. -C. Gignac-Hens and C. -E. Giguere and R. Godbout and C. Grou and S. Guay and F. Guillem and N. Hachimi-Idrissi and C. Herry and S. Hodgins and S. Homayoun and B. Jemel and C. Joyal and E. Kouassi and R. Labelle and D. Lafortune and M. Lahaie and S. Lahlafi and P. Lalonde and P. Landry and V. Lapaige and G. Larocque and C. Larue and M. Lavoie and J. -J. Leclerc and T. Lecomte and C. Lecours and L. Leduc and M. -F. Lelan and A. Lemieux and A. Lesage and A. Letarte and J. Lepage and A. Levesque and O. Lipp and D. Luck and S. Lupien and F. -A. Lusignan and R. Lusignan and A. J. Luyet and A. Lynhiavu and J. -P. Melun and C. Morin and L. Nicole and F. Noel and L. Normandeau and K. O'Connor and C. Ouellette and V. Parent and M. -H. Parizeau and J. -F. Pelletier and J. Pelletier and M. Pelletier and P. Plusquellec and D. Poirier and S. Potvin and G. Prevost and M. -J. Prevost and P. Racicot and M. -F. Racine-Gagne and P. Renaud and N. Ricard and S. Rivet and M. Rolland and M. Sasseville and G. Safadi and S. Smith and N. Smolla and E. Stip and J. Teitelbaum and A. Thibault and L. Thibault and S. Thibault and F. Thomas and C. Todorov and V. Tourjman and C. Tranulis and S. Trudeau and G. Trudel and N. Vacri and L. Valiquette and C. Vanier and K. Villeneuve and M. Villeneuve and P. Vincent and M. Wolfe and L. Xiong and A. Zizzi and M. Lebel and A. Doyen and A. Durand and F. Lavoie-Cardinal and M. -C. Audet and C. Menard and Cecile Lepage on behalf of Signature Consortium},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85162172419&doi=10.1016%2fj.bpsgos.2023.04.007&partnerID=40&md5=aae4250eee5bd708599126cf76c3f5d7},

doi = {10.1016/j.bpsgos.2023.04.007},

issn = {26671743 (ISSN)},

year  = {2024},

date = {2024-01-01},

journal = {Biological Psychiatry Global Open Science},

volume = {4},

number = {1},

pages = {213–228},

abstract = {Background: Major depressive disorder (MDD) is the leading cause of disability worldwide. Of individuals with MDD, 30% to 50% are unresponsive to common antidepressants, highlighting untapped causal biological mechanisms. Dysfunction in the microbiota-gut-brain axis has been implicated in MDD pathogenesis. Exposure to chronic stress disrupts blood-brain barrier integrity; still, little is known about intestinal barrier function in these conditions, particularly for the small intestine, where absorption of most foods and drugs takes place. Methods: We investigated how chronic social or variable stress, two mouse models of depression, impact the jejunum intestinal barrier in males and females. Mice were subjected to stress paradigms followed by analysis of gene expression profiles of intestinal barrier–related targets, fecal microbial composition, and blood-based markers. Results: Altered microbial populations and changes in gene expression of jejunum tight junctions were observed depending on the type and duration of stress, with sex-specific effects. We used machine learning to characterize in detail morphological tight junction properties, identifying a cluster of ruffled junctions in stressed animals. Junctional ruffling is associated with inflammation, so we evaluated whether lipopolysaccharide injection recapitulates stress-induced changes in the jejunum and observed profound sex differences. Finally, lipopolysaccharide-binding protein, a marker of gut barrier leakiness, was associated with stress vulnerability in mice, and translational value was confirmed on blood samples from women with MDD. Conclusions: Our results provide evidence that chronic stress disrupts intestinal barrier homeostasis in conjunction with the manifestation of depressive-like behaviors in a sex-specific manner in mice and, possibly, in human depression. © 2023 The Authors},

note = {Publisher: Elsevier Inc.},

keywords = {animal experiment, animal model, animal tissue, article, chronic social defeat, chronic stress, chronic variable stress, claudin 3, Claudins, controlled study, corticosterone, corticosterone blood level, Cytokines, enzyme linked immunosorbent assay, female, human, immunohistochemistry, intestine flora, jejunum, lipopolysaccharide, lipopolysaccharide binding protein, Machine learning, major depression, male, mouse, nonhuman, pathogenesis, protein expression, real time polymerase chain reaction, sex difference, sex differences, social stress, tight junction, Variable stress},

pubstate = {published},

tppubtype = {article}

}