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Oral microbiota signatures in post-traumatic stress disorder (PTSD) veterans

Abstract

Post-traumatic stress disorder (PTSD) represents a global public health concern, affecting about 1 in 20 individuals. The symptoms of PTSD include intrusiveness (involuntary nightmares or flashbacks), avoidance of traumatic memories, negative alterations in cognition and mood (such as negative beliefs about oneself or social detachment), increased arousal and reactivity with irritable reckless behavior, concentration problems, and sleep disturbances. PTSD is also highly comorbid with anxiety, depression, and substance abuse. To advance the field from subjective, self-reported psychological measurements to objective molecular biomarkers while considering environmental influences, we examined a unique cohort of Israeli veterans who participated in the 1982 Lebanon war. Non-invasive oral 16S RNA sequencing was correlated with psychological phenotyping. Thus, a microbiota signature (i.e., decreased levels of the bacteria sp_HMT_914, 332 and 871 and Noxia) was correlated with PTSD severity, as exemplified by intrusiveness, arousal, and reactivity, as well as additional psychopathological symptoms, including anxiety, hostility, memory difficulties, and idiopathic pain. In contrast, education duration correlated with significantly increased levels of sp_HMT_871 and decreased levels of Bacteroidetes and Firmicutes, and presented an inverted correlation with adverse psychopathological measures. Air pollution was positively correlated with PTSD symptoms, psychopathological symptoms, and microbiota composition. Arousal and reactivity symptoms were correlated with reductions in transaldolase, an enzyme controlling a major cellular energy pathway, that potentially accelerates aging. In conclusion, the newly discovered bacterial signature, whether an outcome or a consequence of PTSD, could allow for objective soldier deployment and stratification according to decreases in sp_HMT_914, 332, 871, and Noxia levels, coupled with increases in Bacteroidetes levels. These findings also raise the possibility of microbiota pathway-related non-intrusive treatments for PTSD.

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Fig. 1: Psychological measures are highly correlated and positively influenced by air pollution.
Fig. 2: Oral microbiota diversity associated with clinical and psychological issues.
Fig. 3: Single taxon distribution analysis distinguishes affected and unaffected individuals.
Fig. 4: The oral microbiota profile linked with exaggerated anxiety, arousal, and reactivity is opposed to the microbiota composition associated with education.
Fig. 5: Oral microbiota signatures in PTSD veterans.

Code availability

Repository code:  BioProject ID PRJNA844909 (web site link: https://github.com/shepp-hub/oral_microbiome_ptsd).

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Acknowledgements

This work was supported in part by a MAF’AT grant to IG and ZS. EL-L’s doctoral research was supported by a Harry and Sadie Lasky Foundation Fellowship. SS was supported by an Eshkol fellowship from the Israel Ministry of Science and Technology, and The BioInnovation Fellowship and Mentorship by Teva. IG was further supported by ERA-NET neuron ADNPinMED, Holly and Jonathan Strelzik (American Friends of Tel Aviv University), and Drs. Ronith and Armand Stemmer (French Friends of Tel Aviv University). VOKL, JCKL, and IG were also supported by a Catalyst Award, US National Academy of Medicine. VOKL and JCKL are also supported in part by the Theme-based Research Scheme of the Research Grants Council of the Hong Kong SAR Government, under Grant No. T41-709/17-N. We acknowledge the assistance of Ruiqiao Bai, HKU-AI WiSe, The University of Hong Kong, in collecting the PM2.5 data.

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Contributions

EL-L designed the study, contacted and interviewed the study participants, handled all the psychological questionnaires, collected DNA, summarized the results, and significantly contributed to paper writing. This study is in partial fulfillment of the PhD requirements of EL-L. GS performed all the bioinformatics, analyzed all data and provided all graphs, as well as edited the paper. SS helped in experimental design, DNA preparation for sequencing, and paper editing. NS provided bioinformatics expertise. JCKL and VOKL provided the air pollutant data and analyzed the correlation between air pollution and PTSD variables. MMH and SB provided microbiota expertise. ABY helped with the study cohort and funding. AS-S mentored EL-L and was instrumental in the design and execution of the study, focusing on the detailed psychological assessment. ZS provided the study cohort, connected the collaborating parties, and contributed to the psychological/sociological assessments. IG oversaw the study, provided biochemical, physiological and neuroscience expertise, integrated the data, and significantly contributed to paper writing.

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Correspondence to Illana Gozes.

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Levert-Levitt, E., Shapira, G., Sragovich, S. et al. Oral microbiota signatures in post-traumatic stress disorder (PTSD) veterans. Mol Psychiatry (2022). https://doi.org/10.1038/s41380-022-01704-6

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