Altered fecal microbiota composition in all male aggressor‐exposed rodent model simulating features of post‐traumatic stress disorder

The bidirectional role of gut–brain axis that integrates the gut and central nervous system activities has recently been investigated. We studied “cage‐within‐cage resident‐intruder” all‐male model, where subject male mice (C57BL/6J) are exposed to aggressor mice (SJL albino), and gut microbiota‐derived metabolites were identified in plasma after 10 days of exposure. We assessed 16S ribosomal RNA gene from fecal samples collected daily from these mice during the 10‐day study. Alpha diversity using Chao indices indicated no change in diversity in aggressor‐exposed samples. The abundance profile showed the top phyla were Firmicutes and Bacteroidetes, Tenericutes, Verrucomicrobia, Actinobacteria and Proteobacteria, respectively. The phyla Firmicutes and Bacteroidetes are vulnerable to PTSD‐eliciting stress and the Firmicutes/Bacteroidetes ratio increases with stress. Principal coordinate analysis showed the control and aggressor‐exposed samples cluster separately where samples from early time points (day 1‐3) clustered together and were distinct from late time points (day 4‐9). The genus‐based analysis revealed all control time points clustered together and aggressor‐exposed samples had multiple clusters. The decrease in proportion of Firmicutes after aggressor exposure persisted throughout the study. The proportion of Verrucomicrobia immediately decreased and was significantly shifted at most of the later time points. The genus Oscillospira, Lactobacillus, Akkermansia and Anaeroplasma are the top four genera that differed between control and stressor‐exposed mice. The data showed immediate effect on microbiome composition during a 10 day time period of stress exposure. Studying the longitudinal effects of a stressor is an important step toward an improved mechanistic understanding of the microbiome dynamics.

[1]  James T. Morton,et al.  The Microbiome in Posttraumatic Stress Disorder and Trauma-Exposed Controls: An Exploratory Study , 2017, Psychosomatic medicine.

[2]  A. Hoke,et al.  Molecular indicators of stress-induced neuroinflammation in a mouse model simulating features of post-traumatic stress disorder , 2017, Translational Psychiatry.

[3]  M. Surette,et al.  Oral treatment with Lactobacillus rhamnosus attenuates behavioural deficits and immune changes in chronic social stress , 2017, BMC Medicine.

[4]  K. Hinde,et al.  Handling stress may confound murine gut microbiota studies , 2017, PeerJ.

[5]  Rasha Hammamieh,et al.  Genome to Phenome: A Systems Biology Approach to PTSD Using an Animal Model. , 2017, Methods in molecular biology.

[6]  Ajay S. Gulati,et al.  Akkermansia muciniphila mediates negative effects of IFNγ on glucose metabolism , 2016, Nature Communications.

[7]  Shyamal D Peddada,et al.  Immunization with a heat-killed preparation of the environmental bacterium Mycobacterium vaccae promotes stress resilience in mice , 2016, Proceedings of the National Academy of Sciences.

[8]  T. Dinan,et al.  A gut (microbiome) feeling about the brain , 2016, Current opinion in gastroenterology.

[9]  Ron Milo,et al.  Are We Really Vastly Outnumbered? Revisiting the Ratio of Bacterial to Host Cells in Humans , 2016, Cell.

[10]  A. Gasbarrini,et al.  Gut microbiota in autism and mood disorders. , 2016, World journal of gastroenterology.

[11]  R. Milo,et al.  Revised Estimates for the Number of Human and Bacteria Cells in the Body , 2016, bioRxiv.

[12]  J. Versalovic,et al.  Histamine H2 Receptor-Mediated Suppression of Intestinal Inflammation by Probiotic Lactobacillus reuteri , 2015, mBio.

[13]  David A. Spratt,et al.  Same Exposure but Two Radically Different Responses to Antibiotics: Resilience of the Salivary Microbiome versus Long-Term Microbial Shifts in Feces , 2015, mBio.

[14]  Patrice D. Cani,et al.  Crosstalk between Gut Microbiota and Dietary Lipids Aggravates WAT Inflammation through TLR Signaling , 2015, Cell metabolism.

[15]  Bing Ruan,et al.  Altered fecal microbiota composition in patients with major depressive disorder , 2015, Brain, Behavior, and Immunity.

[16]  T. Dinan,et al.  Bifidobacteria modulate cognitive processes in an anxious mouse strain , 2015, Behavioural Brain Research.

[17]  J. Bienenstock,et al.  The gut microbiome restores intrinsic and extrinsic nerve function in germ‐free mice accompanied by changes in calbindin , 2015, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[18]  P. Conti,et al.  Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation. , 2015, Clinical therapeutics.

[19]  Michael Maes,et al.  The gut–brain axis: The role of melatonin in linking psychiatric, inflammatory and neurodegenerative conditions , 2015 .

[20]  M. Jett,et al.  Brain transcriptome profiles in mouse model simulating features of post-traumatic stress disorder , 2015, Molecular Brain.

[21]  B. Luke,et al.  Acute and Chronic Plasma Metabolomic and Liver Transcriptomic Stress Effects in a Mouse Model with Features of Post-Traumatic Stress Disorder , 2015, PloS one.

[22]  M. Conlon,et al.  The Impact of Diet and Lifestyle on Gut Microbiota and Human Health , 2014, Nutrients.

[23]  L. Galland The gut microbiome and the brain. , 2014, Journal of medicinal food.

[24]  T. Dinan,et al.  Bifidobacteria exert strain‐specific effects on stress‐related behavior and physiology in BALB/c mice , 2014, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[25]  David Padua,et al.  Altered brain‐gut axis in autism: Comorbidity or causative mechanisms? , 2014, BioEssays : news and reviews in molecular, cellular and developmental biology.

[26]  S. Dowd,et al.  Exposure to a social stressor disrupts the community structure of the colonic mucosa-associated microbiota , 2014, BMC Microbiology.

[27]  W. D. de Vos,et al.  The first 1000 cultured species of the human gastrointestinal microbiota , 2014, FEMS microbiology reviews.

[28]  Yan Wang,et al.  The role of microbiome in central nervous system disorders , 2014, Brain, Behavior, and Immunity.

[29]  C. Cartier,et al.  Probiotic gut effect prevents the chronic psychological stress‐induced brain activity abnormality in mice , 2014, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[30]  M. Bailey,et al.  Impact of stressor exposure on the interplay between commensal microbiota and host inflammation , 2014, Gut microbes.

[31]  Susan P. Holmes,et al.  Waste Not , Want Not : Why Rarefying Microbiome Data is Inadmissible . October 1 , 2013 , 2013 .

[32]  M. Bailey Influence of stressor-induced nervous system activation on the intestinal microbiota and the importance for immunomodulation. , 2014, Advances in experimental medicine and biology.

[33]  J. Petrosino,et al.  The microbiota modulates gut physiology and behavioral abnormalities associated with autism , 2014 .

[34]  J. Petrosino,et al.  Microbiota Modulate Behavioral and Physiological Abnormalities Associated with Neurodevelopmental Disorders , 2013, Cell.

[35]  D. Macfabe Autism: Metabolism, Mitochondria, and the Microbiome , 2013, Global advances in health and medicine.

[36]  P. Hemarajata,et al.  Lactobacillus reuteri-Specific Immunoregulatory Gene rsiR Modulates Histamine Production and Immunomodulation by Lactobacillus reuteri , 2013, Journal of bacteriology.

[37]  L. Duan,et al.  Bacterial Community Mapping of the Mouse Gastrointestinal Tract , 2013, PloS one.

[38]  P. Bork,et al.  Richness of human gut microbiome correlates with metabolic markers , 2013, Nature.

[39]  Jesse R. Zaneveld,et al.  Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences , 2013, Nature Biotechnology.

[40]  J. Foster,et al.  Gut–brain axis: how the microbiome influences anxiety and depression , 2013, Trends in Neurosciences.

[41]  A. Klindworth,et al.  Evaluation of general 16S ribosomal RNA gene PCR primers for classical and next-generation sequencing-based diversity studies , 2012, Nucleic acids research.

[42]  M. Maes,et al.  Increased IgA and IgM responses against gut commensals in chronic depression: further evidence for increased bacterial translocation or leaky gut. , 2012, Journal of affective disorders.

[43]  Aarti Gautam,et al.  Murine model of repeated exposures to conspecific trained aggressors simulates features of post-traumatic stress disorder , 2012, Behavioural Brain Research.

[44]  V. Théodorou,et al.  Prevention of gut leakiness by a probiotic treatment leads to attenuated HPA response to an acute psychological stress in rats , 2012, Psychoneuroendocrinology.

[45]  Qiang Feng,et al.  A metagenome-wide association study of gut microbiota in type 2 diabetes , 2012, Nature.

[46]  H. Flint,et al.  Role of the gut microbiota in nutrition and health , 2018, British Medical Journal.

[47]  Francisco Guarner,et al.  The gut microbiota in IBD , 2012, Nature Reviews Gastroenterology &Hepatology.

[48]  D. Macfabe,et al.  Short-chain fatty acid fermentation products of the gut microbiome: implications in autism spectrum disorders , 2012, Microbial ecology in health and disease.

[49]  M. Hartmann,et al.  Early life antibiotic‐driven changes in microbiota enhance susceptibility to allergic asthma , 2012, EMBO reports.

[50]  B. de Las Rivas,et al.  Tyramine and Phenylethylamine Biosynthesis by Food Bacteria , 2012, Critical reviews in food science and nutrition.

[51]  B. Berger,et al.  The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gut–brain communication , 2011, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[52]  John F. Cryan,et al.  Brain–Gut–Microbe Communication in Health and Disease , 2011, Front. Physio..

[53]  John F. Cryan,et al.  Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve , 2011, Proceedings of the National Academy of Sciences.

[54]  G. Michel,et al.  Environmental and Gut Bacteroidetes: The Food Connection , 2011, Front. Microbio..

[55]  S. Dowd,et al.  Exposure to a social stressor alters the structure of the intestinal microbiota: Implications for stressor-induced immunomodulation , 2011, Brain, Behavior, and Immunity.

[56]  H. Forssberg,et al.  Normal gut microbiota modulates brain development and behavior , 2011, Proceedings of the National Academy of Sciences.

[57]  P. Arck,et al.  Is there a ‘gut–brain–skin axis’? , 2010, Experimental dermatology.

[58]  Laxman Yetukuri,et al.  The gut microbiota modulates host energy and lipid metabolism in mice[S] , 2010, Journal of Lipid Research.

[59]  William A. Walters,et al.  QIIME allows analysis of high-throughput community sequencing data , 2010, Nature Methods.

[60]  Haixing Li,et al.  Lactic acid bacterial cell factories for gamma-aminobutyric acid , 2010, Amino Acids.

[61]  P. Bork,et al.  A human gut microbial gene catalogue established by metagenomic sequencing , 2010, Nature.

[62]  S. Dowd,et al.  Stressor Exposure Disrupts Commensal Microbial Populations in the Intestines and Leads to Increased Colonization by Citrobacter rodentium , 2010, Infection and Immunity.

[63]  Rob Knight,et al.  PyNAST: a flexible tool for aligning sequences to a template alignment , 2009, Bioinform..

[64]  Mark D. Robinson,et al.  edgeR: a Bioconductor package for differential expression analysis of digital gene expression data , 2009, Bioinform..

[65]  Jerrold R. Turner,et al.  Intestinal mucosal barrier function in health and disease , 2009, Nature Reviews Immunology.

[66]  J. Foster,et al.  Effects of gut microbiota on the brain: implications for psychiatry. , 2009, Journal of psychiatry & neuroscience : JPN.

[67]  M. Phillips Gut Reaction: Environmental Effects on the Human Microbiota , 2009, Environmental health perspectives.

[68]  P. Toivanen,et al.  Fecal microbiota in early rheumatoid arthritis. , 2008, The Journal of rheumatology.

[69]  Seppo Salminen,et al.  The Mucin Degrader Akkermansia muciniphila Is an Abundant Resident of the Human Intestinal Tract , 2007, Applied and Environmental Microbiology.

[70]  P. Turnbaugh,et al.  Microbial ecology: Human gut microbes associated with obesity , 2006, Nature.

[71]  Eoin L. Brodie,et al.  Greengenes, a Chimera-Checked 16S rRNA Gene Database and Workbench Compatible with ARB , 2006, Applied and Environmental Microbiology.

[72]  Roeland Kindt,et al.  Tree diversity analysis: a manual and software for common statistical methods for ecological and biodiversity studies , 2006 .

[73]  F. Bäckhed,et al.  Obesity alters gut microbial ecology. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[74]  E. Purdom,et al.  Diversity of the Human Intestinal Microbial Flora , 2005, Science.

[75]  F. Powrie,et al.  Dendritic cells and the intestinal bacterial flora: a role for localized mucosal immune responses. , 2003, The Journal of clinical investigation.