Frontiers in Physiology (Jan 2021)
Effects of Immunization With the Soil-Derived Bacterium Mycobacterium vaccae on Stress Coping Behaviors and Cognitive Performance in a “Two Hit” Stressor Model
- Christine L. Foxx,
- Christine L. Foxx,
- Jared D. Heinze,
- Jared D. Heinze,
- Antonio González,
- Fernando Vargas,
- Fernando Vargas,
- Michael V. Baratta,
- Michael V. Baratta,
- Ahmed I. Elsayed,
- Ahmed I. Elsayed,
- Jessica R. Stewart,
- Jessica R. Stewart,
- Kelsey M. Loupy,
- Kelsey M. Loupy,
- Mathew R. Arnold,
- Mathew R. Arnold,
- M. C. Flux,
- M. C. Flux,
- Saydie A. Sago,
- Saydie A. Sago,
- Philip H. Siebler,
- Lauren N. Milton,
- Margaret W. Lieb,
- James E. Hassell,
- James E. Hassell,
- David G. Smith,
- Kyo A. K. Lee,
- Kyo A. K. Lee,
- Sandra A. Appiah,
- Sandra A. Appiah,
- Evan J. Schaefer,
- Evan J. Schaefer,
- Morgan Panitchpakdi,
- Morgan Panitchpakdi,
- Nicole C. Sikora,
- Nicole C. Sikora,
- Kelly C. Weldon,
- Kelly C. Weldon,
- Christopher E. Stamper,
- Dominic Schmidt,
- David A. Duggan,
- Yosan M. Mengesha,
- Mikale Ogbaselassie,
- Kadi T. Nguyen,
- Chloe A. Gates,
- K’loni Schnabel,
- Linh Tran,
- Joslynn D. Jones,
- Martha H. Vitaterna,
- Fred W. Turek,
- Monika Fleshner,
- Monika Fleshner,
- Pieter C. Dorrestein,
- Pieter C. Dorrestein,
- Pieter C. Dorrestein,
- Rob Knight,
- Rob Knight,
- Rob Knight,
- Rob Knight,
- Kenneth P. Wright,
- Kenneth P. Wright,
- Christopher A. Lowry,
- Christopher A. Lowry,
- Christopher A. Lowry,
- Christopher A. Lowry,
- Christopher A. Lowry,
- Christopher A. Lowry,
- Christopher A. Lowry
Affiliations
- Christine L. Foxx
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, United States
- Christine L. Foxx
- Center for Microbial Exploration, University of Colorado Boulder, Boulder, CO, United States
- Jared D. Heinze
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, United States
- Jared D. Heinze
- Center for Microbial Exploration, University of Colorado Boulder, Boulder, CO, United States
- Antonio González
- Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla, CA, United States
- Fernando Vargas
- Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA, United States
- Fernando Vargas
- Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, United States
- Michael V. Baratta
- Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO, United States
- Michael V. Baratta
- Center for Neuroscience, University of Colorado Boulder, Boulder, CO, United States
- Ahmed I. Elsayed
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, United States
- Ahmed I. Elsayed
- Center for Microbial Exploration, University of Colorado Boulder, Boulder, CO, United States
- Jessica R. Stewart
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, United States
- Jessica R. Stewart
- Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO, United States
- Kelsey M. Loupy
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, United States
- Kelsey M. Loupy
- Center for Microbial Exploration, University of Colorado Boulder, Boulder, CO, United States
- Mathew R. Arnold
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, United States
- Mathew R. Arnold
- Center for Neuroscience, University of Colorado Boulder, Boulder, CO, United States
- M. C. Flux
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, United States
- M. C. Flux
- Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO, United States
- Saydie A. Sago
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, United States
- Saydie A. Sago
- Center for Microbial Exploration, University of Colorado Boulder, Boulder, CO, United States
- Philip H. Siebler
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, United States
- Lauren N. Milton
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, United States
- Margaret W. Lieb
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, United States
- James E. Hassell
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, United States
- James E. Hassell
- Center for Neuroscience, University of Colorado Boulder, Boulder, CO, United States
- David G. Smith
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, United States
- Kyo A. K. Lee
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, United States
- Kyo A. K. Lee
- Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO, United States
- Sandra A. Appiah
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, United States
- Sandra A. Appiah
- Center for Microbial Exploration, University of Colorado Boulder, Boulder, CO, United States
- Evan J. Schaefer
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, United States
- Evan J. Schaefer
- Center for Microbial Exploration, University of Colorado Boulder, Boulder, CO, United States
- Morgan Panitchpakdi
- Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA, United States
- Morgan Panitchpakdi
- Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, United States
- Nicole C. Sikora
- Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA, United States
- Nicole C. Sikora
- Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, United States
- Kelly C. Weldon
- Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA, United States
- Kelly C. Weldon
- Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, United States
- Christopher E. Stamper
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, United States
- Dominic Schmidt
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, United States
- David A. Duggan
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, United States
- Yosan M. Mengesha
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, United States
- Mikale Ogbaselassie
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, United States
- Kadi T. Nguyen
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, United States
- Chloe A. Gates
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, United States
- K’loni Schnabel
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, United States
- Linh Tran
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, United States
- Joslynn D. Jones
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, United States
- Martha H. Vitaterna
- Center for Sleep and Circadian Biology, Department of Neurobiology, Northwestern University, Evanston, IL, United States
- Fred W. Turek
- Center for Sleep and Circadian Biology, Department of Neurobiology, Northwestern University, Evanston, IL, United States
- Monika Fleshner
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, United States
- Monika Fleshner
- Center for Neuroscience, University of Colorado Boulder, Boulder, CO, United States
- Pieter C. Dorrestein
- Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla, CA, United States
- Pieter C. Dorrestein
- Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA, United States
- Pieter C. Dorrestein
- Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, United States
- Rob Knight
- Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla, CA, United States
- Rob Knight
- Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA, United States
- Rob Knight
- Department of Computer Science and Engineering, Jacobs School of Engineering, University of California, San Diego, La Jolla, CA, United States
- Rob Knight
- 0Department of Bioengineering, Jacobs School of Engineering, University of California, San Diego, La Jolla, CA, United States
- Kenneth P. Wright
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, United States
- Kenneth P. Wright
- Center for Neuroscience, University of Colorado Boulder, Boulder, CO, United States
- Christopher A. Lowry
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, United States
- Christopher A. Lowry
- Center for Microbial Exploration, University of Colorado Boulder, Boulder, CO, United States
- Christopher A. Lowry
- Center for Neuroscience, University of Colorado Boulder, Boulder, CO, United States
- Christopher A. Lowry
- 1Veterans Health Administration, Rocky Mountain Mental Illness Research Education and Clinical Center, Rocky Mountain Regional Veterans Affairs Medical Center, Aurora, CO, United States
- Christopher A. Lowry
- 2Military and Veteran Microbiome: Consortium for Research and Education, Aurora, CO, United States
- Christopher A. Lowry
- 3Department of Physical Medicine and Rehabilitation and Center for Neuroscience, University of Colorado Anschutz Medical Campus, Aurora, CO, United States
- Christopher A. Lowry
- 4inVIVO Planetary Health, Worldwide Universities Network, West New York, NJ, United States
- DOI
- https://doi.org/10.3389/fphys.2020.524833
- Journal volume & issue
-
Vol. 11
Abstract
Previous studies demonstrate that Mycobacterium vaccae NCTC 11659 (M. vaccae), a soil-derived bacterium with anti-inflammatory and immunoregulatory properties, is a potentially useful countermeasure against negative outcomes to stressors. Here we used male C57BL/6NCrl mice to determine if repeated immunization with M. vaccae is an effective countermeasure in a “two hit” stress exposure model of chronic disruption of rhythms (CDR) followed by acute social defeat (SD). On day –28, mice received implants of biotelemetric recording devices to monitor 24-h rhythms of locomotor activity. Mice were subsequently treated with a heat-killed preparation of M. vaccae (0.1 mg, administered subcutaneously on days –21, –14, –7, and 27) or borate-buffered saline vehicle. Mice were then exposed to 8 consecutive weeks of either stable normal 12:12 h light:dark (LD) conditions or CDR, consisting of 12-h reversals of the LD cycle every 7 days (days 0–56). Finally, mice were exposed to either a 10-min SD or a home cage control condition on day 54. All mice were exposed to object location memory testing 24 h following SD. The gut microbiome and metabolome were assessed in fecal samples collected on days –1, 48, and 62 using 16S rRNA gene sequence and LC-MS/MS spectral data, respectively; the plasma metabolome was additionally measured on day 64. Among mice exposed to normal LD conditions, immunization with M. vaccae induced a shift toward a more proactive behavioral coping response to SD as measured by increases in scouting and avoiding an approaching male CD-1 aggressor, and decreases in submissive upright defensive postures. In the object location memory test, exposure to SD increased cognitive function in CDR mice previously immunized with M. vaccae. Immunization with M. vaccae stabilized the gut microbiome, attenuating CDR-induced reductions in alpha diversity and decreasing within-group measures of beta diversity. Immunization with M. vaccae also increased the relative abundance of 1-heptadecanoyl-sn-glycero-3-phosphocholine, a lysophospholipid, in plasma. Together, these data support the hypothesis that immunization with M. vaccae stabilizes the gut microbiome, induces a shift toward a more proactive response to stress exposure, and promotes stress resilience.
Keywords
