Immunization with a heat-killed preparation of Mycobacterium vaccae NCTC 11659 enhances auditory-cued fear extinction in a stress-dependent manner

Hassell, James E.; Baratta, Michael V.; Fallon, Isabella P.; Siebler, Philip H.; Karns, Bree L; Nguyen, Kadi T.; Gates, Chloé A.; Frank, Marion E.; Maier, Steven F.; Lowry, Christopher A.

doi:10.1016/j.bbi.2022.09.003

Cited by 6 publications

(3 citation statements)

References 65 publications

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“…Immunization of rats with modified myelin basic protein before chronic mild stress induces autoreactive T cells and reduces depressive behaviors [ 214 ]. Resilience to stress can also be promoted by immunization against Mycobacterium [ 215 ], or by attenuation of inflammation via sphingosine-1-phosphate receptor 3 ( S1PR3 ) overexpression in the medial prefrontal cortex of rats [ 216 ]. Finally, clinical studies have confirmed that emotion regulation strategies can attenuate inflammatory responses [ 217 ].…”

Section: Hallmark 6: Homeostatic Resiliencementioning

confidence: 99%

The missing hallmark of health: psychosocial adaptation

López-Otín,

Kroemer

2024

CST

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The eight biological hallmarks of health that we initially postulated (Cell. 2021 Jan 7;184(1):33-63) include features of spatial compartmentalization (integrity of barriers, containment of local perturbations), maintenance of homeostasis over time (recycling & turnover, integration of circuitries, rhythmic oscillations) and an array of adequate responses to stress (homeostatic resilience, hormetic regulation, repair & regeneration). These hallmarks affect all eight somatic strata of the human body (molecules, organelles, cells, supracellular units, organs, organ systems, systemic circuitries and meta-organism). Here we postulate that mental and socioeconomic factors must be added to this 8×8 matrix as an additional hallmark of health (“psychosocial adaptation”) and as an additional stratum (“psychosocial interactions”), hence building a 9×9 matrix. Potentially, perturbation of each of the somatic hallmarks and strata affects psychosocial factors and vice versa. Finally, we discuss the (patho)physiological bases of these interactions and their implications for mental health improvement.

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Section: Hallmark 6: Homeostatic Resiliencementioning

confidence: 99%

The missing hallmark of health: psychosocial adaptation

López-Otín,

Kroemer

2024

CST

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“…Microbial components of the environment such as soil have been shown to be particularly effective in balancing human physiology. For example, Mycobacterium vaccae is a soil borne bacterium that is particularly effective against stress, anxiety, and select psychiatric disorders [31][32][33][34]. Research by Holbrook et al [35] using strain NCTC 11659 demonstrated that macrophages are on the targets with shifts in cytokines facilitating a reduction in neuroinflammation.…”

Section: Using Microbial Reservoirs For Human Microbiome Restoration:...mentioning

confidence: 99%

Using the Internet of Microbes to Survive the Assault on the Human Microbiome

Dietert

2023

AJBSR

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The past several years has seen what has amounted to an assault on the human microbiome. Public health institutions tasked with protecting the public from hazardous toxic exposures have failed either to remove hazardous products or to adequately alert the public to the presence of dangerous microbial toxicants in specific pharmaceuticals (e.g., proton pump inhibitors), food (e.g., emulsifiers), and household products (e.g., many household cleaners). This lack of attention to the microbiome in general (i.e., as per the need for a robust microbiome to facilitate pathogen colonization resistance) and to microbiome safety specifically was compounded by Covid-19 pandemic-related mandates.Several Covid-related mandates further degraded the human microbiome by restricting supportive microbial exchanges involving human-human contact, human-nature emersions (e.g., closed beaches and restricted park access), and even seed-based gardening (as occurred in Michigan). In the absence of a much-needed medical and public health focus on our microbiome, this article provides examples for self-empowerment in which connecting to the internet of microbes can be both health promoting and self-supporting.The examples described concern a)The benefits of soil-plant-human activities such as gardening and traditional farm activities as well as b) Exposure to animals as might occur on a farm resulting in microbiome-immune driven protection against some chronic diseases.

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“…Subsequent studies in mice demonstrated that immunization with M. vaccae NCTC 11659 provided long-term protection from allergic airway inflammation in a manner dependent on induction of regulatory T cells (Treg) and production of anti-inflammatory cytokines, including IL-10 and TGF-β1 ([ 43 ]; for review, see [ 5 , 44 ]. We have since described in detail the effects of immunization with a heat-killed preparation of M. vaccae NCTC 11659 to prevent: (1) stress-induced increases in spontaneous colitis; (2) stress-induced exaggeration of secretion of proinflammatory cytokines, including IL-6, from mesenteric lymph node cells treated with anti-CD3 antibody ex vivo; and (3) stress-induced increases in anxiety-like defensive behavioral responses [ 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ], including effects relevant to three of the four major diagnostic criteria for PTSD (see Supplementary Table S4 in [ 45 ]; see Table 1 in [ 56 ].…”

Section: Introductionmentioning

confidence: 99%

Mycobacterium vaccae NCTC 11659, a Soil-Derived Bacterium with Stress Resilience Properties, Modulates the Proinflammatory Effects of LPS in Macrophages

Holbrook

Zambrano

Wright

et al. 2023

IJMS

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Inflammatory conditions, including allergic asthma and conditions in which chronic low-grade inflammation is a risk factor, such as stress-related psychiatric disorders, are prevalent and are a significant cause of disability worldwide. Novel approaches for the prevention and treatment of these disorders are needed. One approach is the use of immunoregulatory microorganisms, such as Mycobacterium vaccae NCTC 11659, which have anti-inflammatory, immunoregulatory, and stress-resilience properties. However, little is known about how M. vaccae NCTC 11659 affects specific immune cell targets, including monocytes, which can traffic to peripheral organs and the central nervous system and differentiate into monocyte-derived macrophages that, in turn, can drive inflammation and neuroinflammation. In this study, we investigated the effects of M. vaccae NCTC 11659 and subsequent lipopolysaccharide (LPS) challenge on gene expression in human monocyte-derived macrophages. THP-1 monocytes were differentiated into macrophages, exposed to M. vaccae NCTC 11659 (0, 10, 30, 100, 300 µg/mL), then, 24 h later, challenged with LPS (0, 0.5, 2.5, 250 ng/mL), and assessed for gene expression 24 h following challenge with LPS. Exposure to M. vaccae NCTC 11659 prior to challenge with higher concentrations of LPS (250 ng/mL) polarized human monocyte-derived macrophages with decreased IL12A, IL12B, and IL23A expression relative to IL10 and TGFB1 mRNA expression. These data identify human monocyte-derived macrophages as a direct target of M. vaccae NCTC 11659 and support the development of M. vaccae NCTC 11659 as a potential intervention to prevent stress-induced inflammation and neuroinflammation implicated in the etiology and pathophysiology of inflammatory conditions and stress-related psychiatric disorders.

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Immunization with a heat-killed preparation of Mycobacterium vaccae NCTC 11659 enhances auditory-cued fear extinction in a stress-dependent manner

Cited by 6 publications

References 65 publications

The missing hallmark of health: psychosocial adaptation

The missing hallmark of health: psychosocial adaptation

Using the Internet of Microbes to Survive the Assault on the Human Microbiome

Mycobacterium vaccae NCTC 11659, a Soil-Derived Bacterium with Stress Resilience Properties, Modulates the Proinflammatory Effects of LPS in Macrophages

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