Quality of Life in Cancer Patients: A study involving M. Vaccae in cancer patients, although not showing improvements in cancer outcomes, highlighted its potential to significantly enhance overall quality of life. Patients receiving M. Vaccae alongside chemotherapy reported less decline in their Global Health Status, indicating a more stable overall well-being. Notably, these patients experienced improvements in cognitive functioning and vitality, suggesting enhanced mental clarity and energy levels. Moreover, they reported fewer treatment-related side effects such as nausea and peripheral neuropathy, and relief from debilitating symptoms like bodily pain and difficulty breathing. These findings suggest that M. Vaccae may have broader applications beyond oncological care, potentially improving daily quality of life by reducing discomforts, enhancing mental function, and overall vitality. This positions M. Vaccae as a promising candidate for supporting general well-being in various stressful and physically demanding conditions.
Effects on Serotonin System: A study on M. Vaccae's effect on the serotonin system reveals its potential to positively influence mood and stress-related behaviors. In mice, M. Vaccae selectively activated a specific group of serotonergic neurons in the brainstem, leading to increased serotonin metabolism in brain areas linked to emotional regulation. This activation was distinct from responses to other immune stimulants and was associated with behavioral changes, such as reduced immobility in stress-related tests. These findings suggest that M. Vaccae's unique influence on the serotonin system could offer new ways to manage mood and stress, highlighting its potential as a novel agent for enhancing emotional well-being.
Effects on Serotonin System: In mice, M. Vaccae's effects on the serotonin system suggests it plays a significant role in enhancing stress resilience through microbiome-gut-brain axis signaling. Specifically, M. Vaccae immunization in mice altered the expression of serotonergic genes (Tph2 and Slc6a4) in the dorsal raphe nucleus (DR), a brain region responsive to stress and anxiety. This alteration prevented the typical changes in these genes' expression induced by stressors, demonstrating M. Vaccae's potential to modulate stress responses. Furthermore, M. Vaccae's effect extended to maintaining the diversity of the gut microbiome and stabilizing brainstem serotonergic systems in the face of circadian disruption, hinting at its broader impact on stress and circadian disruptions. These findings highlight M. Vaccae's potential as a therapeutic agent for enhancing stress resilience and mitigating stress-related physiological changes.
References
SRL172 (killed Mycobacterium vaccae) in addition to standard chemotherapy improves quality of life without affecting survival, in patients with advanced non-small-cell lung cancer: phase III results
M.E.R. O’Brien, H. Anderson, E. Kaukel, K. O’Byrne, M. Pawlicki, J. von Pawel, M. Reck, Annals of Oncology, June 2004
Identification of an immune-responsive mesolimbocortical serotonergic system: Potential role in regulation of emotional behavior
C.A. Lowry, J.H. Hollis, A. de Vries, B. Pan, L.R. Brunet, J.R.F. Hunt, J.F.R. Paton et al., IBRO Neuroscience, May 2007
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, Jared D. Heinze, Antonio González, Fernando Vargas, Christopher A. Lowry et al., Frontiers in Physiology, January 2021
M. Vaccae has been extensively studied for its potential benefits in managing anxiety and stress resilience. These studies encompass various models, from animal to human-based research, and offer insights into the bacterium's therapeutic potential.
Stress Resilience in Mice: Immunization with a heat-killed preparation of M. Vaccae has shown to enhance stress resilience in mice. The treatment counteracts stress-induced exaggerated inflammation and pathology, leading to reduced anxiety-like behaviors in situations of chronic psychosocial stress. This finding aligns with the “old friends” hypothesis, suggesting that reintroducing certain microorganisms into our environment could be beneficial for managing inflammatory diseases and stress-related pathologies.
Enhancing Fear Extinction: Immunization with M. Vaccae has shown promising results in enhancing fear extinction (a decline in conditioned fear responses) in stress-related scenarios. In a series of experiments with rats, it was found that while M. Vaccae did not affect the initial acquisition of fear, it significantly prevented the stress-induced resistance to the extinction of auditory-cued fear responses. This suggests that M. Vaccae enhances the ability to overcome fear memories, a key challenge in stress-related psychiatric disorders like PTSD. The study supports the "Old Friends" hypothesis, which links the lack of immunoregulatory inputs to the prevalence of stress-related disorders. By increasing immunoregulation and stress resilience, M. Vaccae immunization could be a potential therapeutic intervention for trauma- and stressor-related disorders, aiding in the management of fear and anxiety responses.
Prevention of PTSD-like Symptoms: In experiments involving sleep disruption and acute stress, M. Vaccae immunization in mice prevented the development of a sleep and behavioral phenotype resembling human post-traumatic stress disorder (PTSD). This suggests that M. Vaccae could be a novel approach to increase resilience to stress, particularly in the context of sleep disruption, which is a known risk factor for stress-related psychiatric disorders
Enhanced Coping Behaviors and Cognitive Performance: M. Vaccae also showed promise in a “two-hit” stress exposure model involving chronic disruption of rhythms followed by acute social defeat. Mice immunized with M. Vaccae exhibited proactive behavioral coping responses and enhanced cognitive performance, suggesting an improved stress resilience. Furthermore, M. Vaccae stabilized the gut microbiome, which is increasingly recognized as playing a crucial role in mental health
Reduction of Neuroinflammation and Anxiety-like Behavior: Another significant aspect of M. Vaccae's action is its effect on neuroimmune processes. In rats, M. Vaccae immunization induced an anti-inflammatory state in the brain, particularly in the hippocampus, and blocked stress-induced neuroinflammatory processes and anxiety-like behaviors. This demonstrates M. Vaccae's potential in moderating the neuroinflammatory and behavioral effects of stress
Physiological Responses in Human Soil-Mixing Activities: In a human-based study, participants engaged in soil-mixing activities with soil containing M. Vaccae showed immediate physiological responses indicative of psychological health improvements. These included changes in brain activity and heart rate, suggesting a stabilizing effect on the autonomic nervous system.
M. Vaccae has demonstrated a broad spectrum of benefits in the context of anxiety and stress management. Its effects range from enhancing stress resilience and coping behaviors to modulating neuroinflammatory processes and affecting human physiological responses. These findings underscore the potential of M. Vaccae as a natural and effective approach for managing anxiety and stress-related disorders.
References
Immunization with a heat-killed preparation of the environmental bacterium Mycobacterium vaccae promotes stress resilience in mice
Stefan O. Reber, Philip H. Siebler, Nina C. Donner, Christopher A. Lowry et al., PNAS, May 2016
Immunization with a heat-killed preparation of Mycobacterium vaccae NCTC 11659 enhances auditory-cued fear extinction in a stress-dependent manner
James E Hassell, Michael V Baratta, Isabella P Fallon, Philip H Siebler, Bree L Karns, Christopher A. Lowry et al., Brain, Behavior, and Immunity, January 2023
Immunization with a heat-killed bacterium, Mycobacterium vaccae NCTC 11659, prevents the development of cortical hyperarousal and a PTSD-like sleep phenotype after sleep disruption and acute stress in mice
Samuel J. Bowers, Sophie Lambert, Shannon He, Christopher A. Lowry, Monika Fleshner, Kenneth P. Wright, Fred W. Turek, Martha H. Vitaterna, SLEEP: Oxford University Press, December 2020
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, Jared D. Heinze, Antonio González, Fernando Vargas, Christopher A. Lowry et al., Frontiers in Physiology, January 2021
Immunization with Mycobacterium vaccae induces an anti-inflammatory milieu in the CNS: attenuation of stress-induced microglial priming, alarmins and anxiety-like behavior
Matthew G. Frank, Laura K. Fonken, Samuel D. Dolzani, Jessica L. Annis, Philip H. Siebler, Dominic Schmidt, Linda R. Watkins, Steven F. Maier, and Christopher A. Lowry, Brain, Behavior, and Immunity, May 2018
Physiological Responses of Adults during Soil-mixing Activities Based on the Presence of Soil Microorganisms: A Metabolomics Approach
Seon-Ok Kim, Su Young Son, Min Ji Kim, Choong Hwan Lee, Sin-Ae Park, Journal of the American Society for Horticultural Science, April 2022
Counteracting Stress-Induced Inflammation: M. Vaccae shows potential in protecting against inflammation exacerbated by stress and trauma. In a study with mice subjected to combined physical and psychosocial trauma, oral administration of heat-killed M. Vaccae helped maintain healthy levels of regulatory T cells (Tregs), crucial for immune balance. It also prevented glucocorticoid resistance, a common issue in stress-related disorders, by directly influencing myeloid cells. This effect included inhibiting the stress-induced upregulation of toll-like receptor (TLR)4 in specific immune cells (PMN-MDSCs) and mitigating the rise of TLR2 in neutrophils, a process partially mediated by Tregs. These findings suggest that M. Vaccae can effectively counteract stress-induced inflammatory responses, highlighting its potential as a therapeutic agent to prevent the escalation of inflammation linked to stress and trauma-related psychiatric disorders.
Inhibition of Allergic Inflammation: In a study in mice, M. Vaccae, administered by mouth, showed promising results in reducing allergic reactions. This treatment increased beneficial immune responses, particularly IL-10 and IFN-gamma, which help calm inflammation. In mice with lung allergies, a single dose of M. Vaccae significantly reduced the number of inflammatory cells, especially eosinophils, which are often high in allergic reactions. It also encouraged the production of IL-10, a key molecule in controlling inflammation. Notably, taking M. Vaccae orally was just as effective as injecting it. This finding opens up a new, user-friendly way of using M. Vaccae to potentially treat inflammatory allergic conditions.
Reduction in Tuberculosis-related Inflammation: In a study investigating the effects of M. Vaccae on Tuberculosis (TB)-related inflammation, patients receiving M. Vaccae alongside standard TB treatment showed a significant improvement in inflammation markers compared to those on TB drugs alone. M. Vaccae effectively reduced erythrocyte sedimentation rate (ESR) and leukocyte counts, both key indicators of inflammation in TB. Additionally, the study noted improvements in hemoglobin content, indicating a potential reduction in TB-related anemia, which is often exacerbated by inflammation. The effect of oral M. Vaccae showed promise in TB-related inflammation, suggesting possible benefits in various conditions where inflammation is a key concern.
Impact on Human Monocyte-derived Macrophages: M. Vaccae's effects extend to human immune cells as well. When human monocyte-derived macrophages were exposed to M. Vaccae, there was a polarization towards an anti-inflammatory state. This is particularly relevant as chronic low-grade inflammation is a risk factor for various psychiatric disorders, including stress-related conditions.
References
Mycobacterium vaccae protects against glucocorticoid resistance resulting from combined physical and psychosocial trauma in mice
Dominik Langgartner, Mattia Amoroso, Elena Kempter, Monika Kustermann, Jasmin Scheurer, Christopher A. Lowry, Gudrun Strauß, Stefan O. Reber, Brain, Behavior, and Immunity, March 2023
Intragastric administration of Mycobacterium vaccae inhibits severe pulmonary allergic inflammation in a mouse model
J. R. F. Hunt, R. Martinelli, V. C. Adams, G. A. W. Rook, L. Rosa Brunet, Clinical and Experimental Allergy, May 2005
Phase III, placebo-controlled, randomized, double-blind trial of tableted, therapeutic TB vaccine (V7) containing heat-killed M. vaccae administered daily for one month
Aldar S. Bourinbaiar, Allen I. Bain, Cynthia Stanford, John Stanford et al., Journal of Clinical Tuberculosis and Other Mycobacterial Diseases, February 2020
Mycobacterium vaccae NCTC 11659, a Soil-Derived Bacterium with Stress Resilience Properties, Modulates the Proinflammatory Effects of LPS in Macrophages
Holbrook EM, Zambrano CA, Wright CTO, Dubé EM, Stewart JR, Sanders WJ, Frank MG, MacDonald AS, Reber SO, Lowry CA, International Journal of Molecular Sciences, March 2023
Anxiety-Related Behavior and Learning in Mice: A study examining the effects of M. Vaccae on mice demonstrated significant improvements in anxiety-related behaviors and learning abilities. Mice fed with M. Vaccae showed a notable reduction in anxiety-related behaviors and improved performance in complex maze tasks. They completed mazes twice as fast as control mice, with these effects persisting for about a week after the treatment was stopped. Additionally, the M. Vaccae-treated mice exhibited more exploratory behaviors, indicating a positive influence on cognitive functions without affecting overall activity levels
Age-Associated Neuroinflammatory Responses: Research on aged rats indicated that M. Vaccae immunization can mitigate age-related neuroinflammatory responses, particularly in the amygdala and hippocampus. These brain regions are crucial for cognitive processes, and the study found that M. Vaccae treatment reduced microglial activation and morphological changes associated with aging. This suggests that M. Vaccae could play a role in preserving cognitive function in the context of aging
Protection Against Surgery-Induced Cognitive Dysfunction: Another study focused on the potential of M. Vaccae to protect against cognitive dysfunction following surgery in aged rats. The rats immunized with M. Vaccae were shielded from postoperative cognitive impairments typically observed in aged subjects. The immunization also shifted the proinflammatory environment in the hippocampus towards an anti-inflammatory state, indicating a protective effect against neuroinflammatory challenges that can impact cognitive health
Alzheimer’s Disease and Neuroprotection: In a study related to Alzheimer's Disease, a neurodegenerative condition with an inflammatory component, M. Vaccae showed promising results. Immunization with M. Vaccae in rats led to changes in the protein profiles of plasma and cerebrospinal fluid, suggesting altered immune activity and lipid metabolism. This alteration, including the upregulation of anti-inflammatory markers like interleukin-4 in the hippocampus, aligns with the hypothesis that M. Vaccae can protect against inflammation-related cognitive impairments potentially triggered by infections.
References
Ingestion of Mycobacterium vaccae decreases anxiety-related behavior and improves learning in mice
Dorothy M. Matthews, Susan M. Jenks, Behavioural Processes, June 2013
Mycobacterium vaccae immunization in rats ameliorates features of age-associated microglia activation in the amygdala and hippocampus
Kevin Sanchez, Jeffrey S. Darling, Reha Kakkar, Sienna L. Wu, Andrew Zentay, Christopher A. Lowry & Laura K. Fonken, Scientific Reports – Nature, February 2022
Mycobacterium vaccae immunization protects aged rats from surgery-elicited neuroinflammation and cognitive dysfunction
Laura K. Fonken, Matthew G. Frank, Heather M. D'Angelo, Jared D. Heinze, Linda R. Watkins, Christopher A. Lowry, Steven F. Maier, Neurobiology of Aging, November 2018
Alzheimer’s Disease: Protective Effects of Mycobacterium vaccae, a Soil-Derived Mycobacterium with Anti-Inflammatory and Anti-Tubercular Properties, on the Proteomic Profiles of Plasma and Cerebrospinal Fluid in Rats
Kelsey M. Loupy, Thomas Lee, Cristian A. Zambrano, Ahmed I. Elsayed, Heather M. D'Angelo, Laura K. Fonken, Matthew G. Frank, Steven F. Maier, Christopher A. Lowry, Journal of Alzheimer's Disease, November 2020
Safety
"Killed M. vaccae is safe: three decades of clinical studies in more than 20 countries failed to reveal any adverse side-effects except local reaction at the site of injection"¹
"Repeated intradermal injections of heat-killed Mycobacterium vaccae have been found to be safe in several studies. Five doses were used in a successful trial of M. vaccae for the prevention of TB in more than 1000 HIV-positive Tanzanians, and multiple doses have also been administered in cancer trials. No serious adverse events were recorded. "²
"The heat-killed vaccine [M. Vaccae] has been demonstrated to be safe in HIV- and non-HIV-infected adults. Side effects due to M. Vaccae have been mild and infrequent."³
References
¹ Randomized, placebo-controlled phase II trial of heat-killed Mycobacterium vaccae (Longcom batch) formulated as an oral pill (V7)
Efremenko et al., Human Vaccines & Immunotherapeutics, June 2013
² Mycobacteria, Immunoregulation, and Autoimmunity
Graham A.W. Rook, The Value of BCG and TNF in Autoimmunity, 2014
³ Immunotherapy of Tuberculosis
Robert F. Wallis, John L. Johnson, Tuberculosis - A Comprehensive Clinical Reference, November 2009
