Potential causal association between gut microbiome and posttraumatic stress disorder

The Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group; Anders M. Dale; Mark J. Daly; Nikolaos P. Daskalakis; J. rgen 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; 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; 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 McD Young; Hongyu Zhao; Lori A. Zoellner; Israel Liberzon; Kerry J. Ressler; Magali Haas; Karestan C. Koenen

doi:10.1038/s41398-024-02765-7

Potential causal association between gut microbiome and posttraumatic stress disorder

The Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group, Anders M. Dale, Mark J. Daly, Nikolaos P. Daskalakis, J. rgen 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 GelayeJoel 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, 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, 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 McD Young, Hongyu Zhao, Lori A. Zoellner, Israel Liberzon, Kerry J. Ressler, Magali Haas, Karestan C. Koenen

Research output: Contribution to journal › Article › Academic › peer-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 language	English
Article number	67
Journal	Translational Psychiatry
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41398-024-02765-7
Publication status	Published - 1 Dec 2024

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The Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group, Dale, A. M., Daly, M. J., Daskalakis, N. P., Deckert, J. R., Delahanty, D. L., Dennis, M. F., Disner, S. G., Domschke, K., Dzubur-Kulenovic, A., Erbes, C. R., Evans, A., Farrer, L. A., Feeny, N. C., Flory, J. D., Forbes, D., Franz, C. E., Galea, S., Garrett, M. E., ... Koenen, K. C. (2024). Potential causal association between gut microbiome and posttraumatic stress disorder. Translational Psychiatry, 14(1), Article 67. https://doi.org/10.1038/s41398-024-02765-7

@article{c8bd4248168b41778dcd191197fe821e,

title = "Potential causal association between gut microbiome and posttraumatic stress disorder",

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{\textquoteright}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.",

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

note = "Publisher Copyright: {\textcopyright} 2024, The Author(s).",

year = "2024",

month = dec,

day = "1",

doi = "10.1038/s41398-024-02765-7",

language = "English",

volume = "14",

journal = "Translational Psychiatry",

issn = "2158-3188",

publisher = "Nature Publishing Group",

number = "1",

}

The Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group, Dale, AM, Daly, MJ, Daskalakis, NP, Deckert, JR, Delahanty, DL, Dennis, MF, Disner, SG, Domschke, K, Dzubur-Kulenovic, A, Erbes, CR, Evans, A, Farrer, LA, Feeny, NC, Flory, JD, Forbes, D, Franz, CE, Galea, S, Garrett, ME, Gelaye, B, Gelernter, J, Geuze, E, Gillespie, C, Uka, AG, Gordon, SD, Guffanti, G, Hammamieh, R, Harnal, S, Hauser, MA, Heath, AC, Hemmings, SMJ, Hougaard, DM, Jakovljevic, M, Jett, M, Johnson, EO, Jones, I, Jovanovic, T, Qin, X-J, Junglen, AG, Karstoft, K-I, Kaufman, ML, Kessler, RC, Khan, A, Kimbrel, NA, King, AP, Koen, N, Kranzler, HR, Kremen, WS, Lawford, BR, Lebois, LAM, Lewis, CE, Linnstaedt, SD, Lori, A, Lugonja, B, Lyons, MJ, Maples-Keller, J, Marmar, C, Martin, AR, Martin, NG, Maurer, D, Mavissakalian, MR, McFarlane, A, McGlinchey, RE, McLaughlin, KA, McLean, SA, McLeay, S, Mehta, D, Milberg, WP, Miller, MW, Morey, RA, Morris, CP, Mors, O, Mortensen, PB, Neale, BM, Nelson, EC, Nordentoft, M, Norman, SB, O’Donnell, M, Orcutt, HK, Panizzon, MS, Peters, ES, Peterson, AL, Peverill, M, Pietrzak, RH, Polusny, MA, Rice, JP, Ripke, S, Risbrough, VB, Roberts, AL, Rothbaum, AO, Rothbaum, BO, Roy-Byrne, P, Ruggiero, K, Rung, A, Rutten, BPF, Saccone, NL, Sanchez, SE, Schijven, D, Seedat, S, Seligowski, AV, Seng, JS, Sheerin, CM, Silove, D, Smith, AK, Smoller, JW, Solovieff, N, Sponheim, SR, Stein, DJ, Sumner, JA, Teicher, MH, Thompson, WK, Trapido, E, Uddin, M, Ursano, RJ, van den Heuvel, LL, van Hooff, M, Vermetten, E, Voisey, J, Wang, Y, Wang, Z, Werge, T, Williams, MA, Williamson, DE, Winternitz, S, Wolf, C, Wolf, EJ, Wolff, JD, Yehuda, R, Young, KA, Young, RM, Zhao, H, Zoellner, LA, Liberzon, I, Ressler, KJ, Haas, M & Koenen, KC 2024, 'Potential causal association between gut microbiome and posttraumatic stress disorder', Translational Psychiatry, vol. 14, no. 1, 67. https://doi.org/10.1038/s41398-024-02765-7

TY - JOUR

T1 - Potential causal association between gut microbiome and posttraumatic stress disorder

AU - The Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group

AU - He, Qiang

AU - Wang, Wenjing

AU - Xu, Dingkang

AU - Xiong, Yang

AU - Tao, Chuanyuan

AU - You, Chao

AU - Ma, Lu

AU - Ma, Junpeng

AU - Nievergelt, Caroline M.

AU - Maihofer, Adam X.

AU - Klengel, Torsten

AU - Atkinson, Elizabeth G.

AU - Chen, Chia Yen

AU - Choi, Karmel W.

AU - Coleman, Jonathan R.I.

AU - Dalvie, Shareefa

AU - Duncan, Laramie E.

AU - Logue, Mark W.

AU - Provost, Allison C.

AU - Ratanatharathorn, Andrew

AU - Stein, Murray B.

AU - Torres, Katy

AU - Aiello, Allison E.

AU - Almli, Lynn M.

AU - Amstadter, Ananda B.

AU - Andersen, Søren B.

AU - Andreassen, Ole A.

AU - Arbisi, Paul A.

AU - Ashley-Koch, Allison E.

AU - Austin, S. Bryn

AU - Avdibegovic, Esmina

AU - Babić, Dragan

AU - Bækvad-Hansen, Marie

AU - Baker, Dewleen G.

AU - Beckham, Jean C.

AU - Bierut, Laura J.

AU - Bisson, Jonathan I.

AU - Boks, Marco P.

AU - Bolger, Elizabeth A.

AU - Børglum, Anders D.

AU - Bradley, Bekh

AU - Brashear, Megan

AU - Breen, Gerome

AU - Bryant, Richard A.

AU - Bustamante, Angela C.

AU - Bybjerg-Grauholm, Jonas

AU - Calabrese, Joseph R.

AU - Caldas-de-Almeida, José M.

AU - Luykx, Jurjen J.

AU - Vinkers, Christiaan H.

AU - Dale, Anders M.

AU - Daly, Mark J.

AU - Daskalakis, Nikolaos P.

AU - Deckert, J. rgen

AU - Delahanty, Douglas L.

AU - Dennis, Michelle F.

AU - Disner, Seth G.

AU - Domschke, Katharina

AU - Dzubur-Kulenovic, Alma

AU - Erbes, Christopher R.

AU - Evans, Alexandra

AU - Farrer, Lindsay A.

AU - Feeny, Norah C.

AU - Flory, Janine D.

AU - Forbes, David

AU - Franz, Carol E.

AU - Galea, Sandro

AU - Garrett, Melanie E.

AU - Gelaye, Bizu

AU - Gelernter, Joel

AU - Geuze, Elbert

AU - Gillespie, Charles

AU - Uka, Aferdita Goci

AU - Gordon, Scott D.

AU - Guffanti, Guia

AU - Hammamieh, Rasha

AU - Harnal, Supriya

AU - Hauser, Michael A.

AU - Heath, Andrew C.

AU - Hemmings, Sian M. J.

AU - Hougaard, David Michael

AU - Jakovljevic, Miro

AU - Jett, Marti

AU - Johnson, Eric Otto

AU - Jones, Ian

AU - Jovanovic, Tanja

AU - Qin, Xue-Jun

AU - Junglen, Angela G.

AU - Karstoft, Karen-Inge

AU - Kaufman, Milissa L.

AU - Kessler, Ronald C.

AU - Khan, Alaptagin

AU - Kimbrel, Nathan A.

AU - King, Anthony P.

AU - Koen, Nastassja

AU - Kranzler, Henry R.

AU - Kremen, William S.

AU - Lawford, Bruce R.

AU - Lebois, Lauren A. M.

AU - Lewis, Catrin E.

AU - Linnstaedt, Sarah D.

AU - Lori, Adriana

AU - Lugonja, Bozo

AU - Lyons, Michael J.

AU - Maples-Keller, Jessica

AU - Marmar, Charles

AU - Martin, Alicia R.

AU - Martin, Nicholas G.

AU - Maurer, Douglas

AU - Mavissakalian, Matig R.

AU - McFarlane, Alexander

AU - McGlinchey, Regina E.

AU - McLaughlin, Katie A.

AU - McLean, Samuel A.

AU - McLeay, Sarah

AU - Mehta, Divya

AU - Milberg, William P.

AU - Miller, Mark W.

AU - Morey, Rajendra A.

AU - Morris, Charles Phillip

AU - Mors, Ole

AU - Mortensen, Preben B.

AU - Neale, Benjamin M.

AU - Nelson, Elliot C.

AU - Nordentoft, Merete

AU - Norman, Sonya B.

AU - O’Donnell, Meaghan

AU - Orcutt, Holly K.

AU - Panizzon, Matthew S.

AU - Peters, Edward S.

AU - Peterson, Alan L.

AU - Peverill, Matthew

AU - Pietrzak, Robert H.

AU - Polusny, Melissa A.

AU - Rice, John P.

AU - Ripke, Stephan

AU - Risbrough, Victoria B.

AU - Roberts, Andrea L.

AU - Rothbaum, Alex O.

AU - Rothbaum, Barbara O.

AU - Roy-Byrne, Peter

AU - Ruggiero, Ken

AU - Rung, Ariane

AU - Rutten, Bart P. F.

AU - Saccone, Nancy L.

AU - Sanchez, Sixto E.

AU - Schijven, Dick

AU - Seedat, Soraya

AU - Seligowski, Antonia V.

AU - Seng, Julia S.

AU - Sheerin, Christina M.

AU - Silove, Derrick

AU - Smith, Alicia K.

AU - Smoller, Jordan W.

AU - Solovieff, Nadia

AU - Sponheim, Scott R.

AU - Stein, Dan J.

AU - Sumner, Jennifer A.

AU - Teicher, Martin H.

AU - Thompson, Wesley K.

AU - Trapido, Edward

AU - Uddin, Monica

AU - Ursano, Robert J.

AU - van den Heuvel, Leigh Luella

AU - van Hooff, Miranda

AU - Vermetten, Eric

AU - Voisey, Joanne

AU - Wang, Yunpeng

AU - Wang, Zhewu

AU - Werge, Thomas

AU - Williams, Michelle A.

AU - Williamson, Douglas E.

AU - Winternitz, Sherry

AU - Wolf, Christiane

AU - Wolf, Erika J.

AU - Wolff, Jonathan D.

AU - Yehuda, Rachel

AU - Young, Keith A.

AU - Young, Ross McD

AU - Zhao, Hongyu

AU - Zoellner, Lori A.

AU - Liberzon, Israel

AU - Ressler, Kerry J.

AU - Haas, Magali

AU - Koenen, Karestan C.

PY - 2024/12/1

Y1 - 2024/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85184147737&partnerID=8YFLogxK

U2 - 10.1038/s41398-024-02765-7

DO - 10.1038/s41398-024-02765-7

M3 - Article

C2 - 38296956

SN - 2158-3188

VL - 14

JO - Translational Psychiatry

JF - Translational Psychiatry

IS - 1

M1 - 67

ER -

Potential causal association between gut microbiome and posttraumatic stress disorder

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