Potential causal association between gut microbiome and posttraumatic stress disorder

Qiang He, Wenjing Wang, Dingkang Xu, Yang Xiong, Chuanyuan Tao, Chao You, Lu Ma, Junpeng Ma, Caroline M. Nievergelt, Adam X. Maihofer, Torsten Klengel, Elizabeth G. Atkinson, Chia Yen Chen, Karmel W. Choi, Jonathan R.I. Coleman, Shareefa Dalvie, Laramie E. Duncan, Mark W. Logue, Allison C. Provost, Andrew RatanatharathornMurray B. Stein, Katy Torres, Allison E. Aiello, Lynn M. Almli, Ananda B. Amstadter, Søren B. Andersen, Ole A. Andreassen, Paul A. Arbisi, Allison E. Ashley-Koch, S. Bryn Austin, Esmina Avdibegovic, Dragan Babić, Marie Bækvad-Hansen, Dewleen G. Baker, Jean C. Beckham, Laura J. Bierut, Jonathan I. Bisson, Marco P. Boks, Elizabeth A. Bolger, Anders D. Børglum, Bekh Bradley, Megan Brashear, Gerome Breen, Richard A. Bryant, Angela C. Bustamante, Jonas Bybjerg-Grauholm, Joseph R. Calabrese, José M. Caldas-de-Almeida, Anders M. Dale, Mark J. Daly, Nikolaos P. Daskalakis, Jürgen Deckert, Douglas L. Delahanty, Michelle F. Dennis, Seth G. Disner, Katharina Domschke, Alma Dzubur-Kulenovic, Christopher R. Erbes, Alexandra Evans, Lindsay A. Farrer, Norah C. Feeny, Janine D. Flory, David Forbes, Carol E. Franz, Sandro Galea, Melanie E. Garrett, Bizu Gelaye, Joel Gelernter, Elbert Geuze, Charles Gillespie, Aferdita Goci Uka, Scott D. Gordon, Guia Guffanti, Rasha Hammamieh, Supriya Harnal, Michael A. Hauser, Andrew C. Heath, Sian M.J. Hemmings, David Michael Hougaard, Miro Jakovljevic, Marti Jett, Eric Otto Johnson, Ian Jones, Tanja Jovanovic, Xue Jun Qin, Angela G. Junglen, Karen Inge Karstoft, Milissa L. Kaufman, Ronald C. Kessler, Alaptagin Khan, Nathan A. Kimbrel, Anthony P. King, Nastassja Koen, Henry R. Kranzler, William S. Kremen, Bruce R. Lawford, Lauren A.M. Lebois, Catrin E. Lewis, Sarah D. Linnstaedt, Adriana Lori, Bozo Lugonja, Jurjen J. Luykx, Michael J. Lyons, Jessica Maples-Keller, Charles Marmar, Alicia R. Martin, Nicholas G. Martin, Douglas Maurer, Matig R. Mavissakalian, Alexander McFarlane, Regina E. McGlinchey, Katie A. McLaughlin, Samuel A. McLean, Sarah McLeay, Divya Mehta, William P. Milberg, Mark W. Miller, Rajendra A. Morey, Charles Phillip Morris, Ole Mors, Preben B. Mortensen, Benjamin M. Neale, Elliot C. Nelson, Merete Nordentoft, Sonya B. Norman, Meaghan O’Donnell, Holly K. Orcutt, Matthew S. Panizzon, Edward S. Peters, Alan L. Peterson, Matthew Peverill, Robert H. Pietrzak, Melissa A. Polusny, John P. Rice, Stephan Ripke, Victoria B. Risbrough, Andrea L. Roberts, Alex O. Rothbaum, Barbara O. Rothbaum, Peter Roy-Byrne, Ken Ruggiero, Ariane Rung, Bart P.F. Rutten, Nancy L. Saccone, Sixto E. Sanchez, Dick Schijven, Soraya Seedat, Antonia V. Seligowski, Julia S. Seng, Christina M. Sheerin, Derrick Silove, Alicia K. Smith, Jordan W. Smoller, Nadia Solovieff, Scott R. Sponheim, Dan J. Stein, Jennifer A. Sumner, Martin H. Teicher, Wesley K. Thompson, Edward Trapido, Monica Uddin, Robert J. Ursano, Leigh Luella van den Heuvel, Miranda van Hooff, Eric Vermetten, Christiaan H. Vinkers, Joanne Voisey, Yunpeng Wang, Zhewu Wang, Thomas Werge, Michelle A. Williams, Douglas E. Williamson, Sherry Winternitz, Christiane Wolf, Erika J. Wolf, Jonathan D. Wolff, Rachel Yehuda, Keith A. Young, Ross Mc D. Young, Hongyu Zhao, Lori A. Zoellner, Israel Liberzon, Kerry J. Ressler, Magali Haas, Karestan C. Koenen

Research output: Contribution to journalArticlepeer-review

Abstract

Background: The causal effects of gut microbiome and the development of posttraumatic stress disorder (PTSD) are still unknown. This study aimed to clarify their potential causal association using mendelian randomization (MR). Methods: The summary-level statistics for gut microbiome were retrieved from a genome-wide association study (GWAS) of the MiBioGen consortium. As to PTSD, the Freeze 2 datasets were originated from the Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group (PGC-PTSD), and the replicated datasets were obtained from FinnGen consortium. Single nucleotide polymorphisms meeting MR assumptions were selected as instrumental variables. The inverse variance weighting (IVW) method was employed as the main approach, supplemented by sensitivity analyses to evaluate potential pleiotropy and heterogeneity and ensure the robustness of the MR results. We also performed reverse MR analyses to explore PTSD’s causal effects on the relative abundances of specific features of the gut microbiome. Results: In Freeze 2 datasets from PGC-PTSD, eight bacterial traits revealed a potential causal association between gut microbiome and PTSD (IVW, all P < 0.05). In addition, Genus.Dorea and genus.Sellimonas were replicated in FinnGen datasets, in which eight bacterial traits revealed a potential causal association between gut microbiome and the occurrence of PTSD. The heterogeneity and pleiotropy analyses further supported the robustness of the IVW findings, providing additional evidence for their reliability. Conclusion: Our study provides the potential causal impact of gut microbiomes on the development of PTSD, shedding new light on the understanding of the dysfunctional gut-brain axis in this disorder. Our findings present novel evidence and call for investigations to confirm the association between their links, as well as to illuminate the underlying mechanisms.

Original languageEnglish
Article number67
JournalTranslational psychiatry
Volume14
Issue number1
DOIs
StatePublished - Dec 2024

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