Post-stress changes in the gut microbiome composition in rats with different levels of nervous system excitability

PLOS ONE RESEARCH ARTICLE Post-stress changes in the gut microbiome composition in rats with different levels of nervous system excitability Alla Shevchenko1, Irina Shalaginova ID1*, Dmitriy Katserov1, Ludmila Matskova ID3, Natalia Shiryaeva2, Natalia Dyuzhikova2 a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 OPEN ACCESS Citation: Shevchenko A, Shalaginova I, Katserov D, Matskova L, Shiryaeva N, Dyuzhikova N (2023) Post-stress changes in the gut microbiome composition in rats with different levels of nervous system excitability. PLoS ONE 18(12): e0295709. https://doi.org/10.1371/journal.pone.0295709 Editor: Brenda A Wilson, University of Illinois Urbana-Champaign, UNITED STATES Received: August 29, 2023 Accepted: November 26, 2023 Published: December 11, 2023 Peer Review History: PLOS recognizes the benefits of transparency in the peer review process; therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. The editorial history of this article is available here: https://doi.org/10.1371/journal.pone.0295709 Copyright: © 2023 Shevchenko et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 1 Educational and Scientific Cluster “Institute of Medicine and Life Sciences (MEDBIO)”, Immanuel Kant Baltic Federal University, Kaliningrad, Russia, 2 Pavlov Institute of Physiology of the Russian Academy of Sciences, Saint-Petersburg, Russia, 3 Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden * Abstract The gut-brain axis is a critical communication system influencing the interactions between the gastrointestinal tract (GI) and the central nervous system (CNS). The gut microbiota plays a significant role in this axis, affecting the development and function of the nervous system. Stress-induced psychopathologies, such as depression and anxiety, have been linked to the gut microbiota, but underlying mechanisms and genetic susceptibility remain unclear. In this study, we examined stress-induced changes in the gut microbiome composition in two rat strains with different levels of nervous system excitability: high threshold (HT strain) and low threshold (LT strain). Rats were exposed to long-term emotional and painful stress using the Hecht protocol, and fecal samples were collected at multiple time points before and after stress exposure. Using 16S rRNA amplicon sequencing, we assessed the qualitative and quantitative changes in the gut microbiota. Our results revealed distinct microbial diversity between the two rat strains, with the HT strain displaying higher diversity compared to the LT strain. Notably, under prolonged stress, the HT strain showed an increase in relative abundance of microorganisms from the genera Faecalibacterium and Prevotella in fecal samples. Additionally, both strains exhibited a decrease in Lactobacillus abundance following stress exposure. Our findings provide valuable insights into the impact of hereditary nervous system excitability on the gut microbiome composition under stress conditions. Understanding the gut-brain interactions in response to stress may open new avenues for comprehending stress-related psychopathologies and developing potential therapeutic interventions targeted at the gut microbiota. However, further research is needed to elucidate the exact mechanisms underlying these changes and their implications for stress-induced disorders. Overall, this study contributes to the growing body of knowledge on the gut-brain axis and its significance in stressrelated neurobiology. Data Availability Statement: All data files are available from the https://www.ncbi.nlm.nih.gov/ bioproject/PRJNA831893. PLOS ONE | https://doi.org/10.1371/journal.pone.0295709 December 11, 2023 1 / 14 PLOS ONE Funding: This research was funded by the Russian Federal Academic Leadership Program Priority 2030 at the Immanuel Kant Baltic Federal University (IKBFU) - Irina Shalaginova, Dmitriy Katserov; Natalia Shiryaeva, Natalia Dyuzhikova by State Program 47 SP «Scientific and technological development of the RF», topic 0134-2019-0002 (Pavlov Institute of Physiology, Russian Academy of Sciences). Competing interests: The authors have declared that no competing interests exist. Stress and the gut microbiome composition in rats with different levels of nervous system excitability Introduction The gastrointestinal tract (GI) and the central nervous system (CNS) interact via the bidirectional biochemical signaling between neurons of the CNS and the GI, the gut–brain axis. There are three main pathways by which the microbiota exerts its effect on the function of the nervous system: through modulation of the immune response; through the metabolism of hormones, neuropeptides and neurotransmitters, and through direct influence on neurons and neural signaling [1]. The enteric nervous system and the vagus nerve provide one of the pathways through which the gut microbiota influences the brain. It has been shown that bacterial metabolites stimulate afferent neurons of the enteric nervous system [2]. Recent research identified sensory gut cells called "neuropod cells" that can form connections with the vagus nerve. These connections enable rapid information transfer from the gut to the brain [3]. The latest data indicate a significant role of the gut microbiota in the dysfunction of the HypothalamicPituitary-Adrenal axis (HPA axis) and, consequently, in neuroendocrine dysregulation [4]. The gut microbiota has recently been identified as a factor that actively influences the functional state of the brain and host behavior. In particular, the gut microbiota plays a role in the development of neuroinflammation, which in recent years has been considered as one of the factors in the pathogenesis of post-stress psychopathologies (such as depression, anxiety disorders). The molecular mechanisms of microbiota-modulated neuroinflammation, acting both locally and systemically, have begun to be elucidated. For example, gut microbiota metabolites have been shown to inhibit host histone deacetylases (HDACs), which, as key modifiers of histones, control the assembly of transcriptional complexes, facilitating the active state of the host genome [5, 6]. Persistent changes in the intestinal microbiota can lead to increased production of proinflammatory cytokines, causing increased intestinal permeability [7]. This can mediate increased transfer of bacterial lipopolysaccharides and neuroactive metabolites into the bloodstream, and eventually into the brain, causing neuroinflammation in mammals [8]. Intestinal dysbiosis may also trigger immune system stimulation, which, combined with increased intestinal barrier permeability, may lead to local and systemic inflammation along wi (...truncated)