Preimmunization with a heat-killed preparation of Mycobacterium vaccae enhances fear extinction in the fear-potentiated startle paradigm

Fox, James H.; Hassell, James E.; Siebler, Philip H.; Arnold, Mathew R.; Lamb, Andrew K.; Smith, David Glenn; Day, Heidi E.W.; Smith, Tessa M.; Simmerman, Emma M.; Outzen, Alexander A.; Holmes, Kaley S.; Brazell, Christopher; Lowry, Christopher A.

doi:10.1016/j.bbi.2017.08.014

Cited by 41 publications

(31 citation statements)

References 71 publications

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“…We observed no effects of ATMs, or differences between sex. Our data contrast with previous reports that microbiota modulate extinction in male rodents (Bravo et al, 2011;Chu et al, 2019;Fox et al, 2017;Savignac et al, 2015). However, in agreement with previous work that high levels of ovarian hormones facilitate aversive extinction (Milad et al, 2009;Velasco, Florido, Milad, & Andero, 2019), we found that female ATM mice and controls in diestrus/proestrus, but not estrus/metestrus, showed reduced freezing during the final 5 presentations of cued expression.…”

Section: Gut Microbiome and Aversive Conditioningsupporting

confidence: 69%

“…Various probiotics (microbiota beneficial to health) have been found to enhance aspects of aversive conditioning in male rodents, including learning, cued and context recall, and extinction (Bravo et al, 2011;Fox et al, 2017;Savignac, Tramullas, Kiely, Dinan, & Cryan, 2015). In contrast, germ-free (GF) male mice exhibit impaired cued aversive memory recall and extinction (Chu et al, 2019;Hoban et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

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Sex-specific gut microbiota modulation of aversive conditioning and basolateral amygdala dendritic spine density

Geary

Wilk

Barton

et al. 2020

Preprint

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Gut microbiota influence numerous aspects of host biology, including brain structure and function. Growing evidence implicates gut microbiota in aversive conditioning and anxiety-related behaviors, but research has focused almost exclusively on males. To investigate sex-specific effects of gut dysbiosis on aversive learning and memory, adult female and male C57BL/6N mice were orally administered a moderate dose of non-absorbable antimicrobial medications (ATMs; neomycin, bacitracin, pimaricin) or a control over 10 days. Changes in gut microbiome composition were analyzed by 16S rRNA sequencing. Open field behavior, cued aversive learning, context recall, and cued recall were assessed. Following behavioral testing, the morphology of basolateral amygdala (BLA) principal neuron dendrites and spines was characterized. Results revealed that ATMs induced distinct but overlapping patterns of gut dysbiosis across sex, with stronger effects in females. There were also sex-specific effects on behavior and neuroanatomy. Treated males but not females exhibited altered locomotor and anxiety-like behavior in the novel open field test. Treated females but not males showed impairments in aversive memory acquisition and cued recall. Context recall remained intact in both sexes, as did dendritic structure of BLA principal neurons. However, ATMs exerted sex-specific effects on spine density. A second experiment was conducted to isolate gut perturbation to cued recall. Results revealed no effect of ATMs on recall of a previously consolidated fear memory, suggesting that gut dysbiosis preferentially impacts aversive learning. These data shed new light on how gut microbiota interact with sex to influence aversive conditioning, anxiety-like behavior, and BLA dendritic spine architecture.SignificanceGut microbiota can influence brain function and behavior, including trauma and anxiety-related disorders. Although these disorders disproportionately affect women, preclinical research has focused almost exclusively on male rodent models. We investigated the impact of antimicrobial administration on gut microbiome structure, aversive conditioning, open field behavior, and basolateral amygdala principal neuron morphology in female and male mice. Results showed that treatment exerted wide-ranging effects, many of which were sex-specific. Our findings underscore the importance of studying sex differences and support a role for microbial modulation of aversive learning, anxiety-like behavior, and amygdala spine patterning.

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Section: Gut Microbiome and Aversive Conditioningsupporting

confidence: 69%

Section: Introductionmentioning

confidence: 99%

Sex-specific gut microbiota modulation of aversive conditioning and basolateral amygdala dendritic spine density

Geary

Wilk

Barton

et al. 2020

Preprint

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“…Letzteres zeigte sich darin, dass die Vorbehandlung mit einem anti-CD25-Antikörper, jedoch nicht die Vorbehandlung mit einem Kontrollantikörper, die stressprotektiven Effekte der Präimmunisierung mit M. vaccae verhinderte. Zudem konnten wir unter Verwendung des fear-potentiated startle (FPS) Paradigmas in Ratten zeigen, dass die wiederholte Immunisierung mit Hitze inaktiviertem M. vaccae im Vergleich zur Behandlung mit Vehikel die Extinktion von erlernter Furcht zwischen und während den jeweiligen Sitzungsdurchgängen, jedoch nicht die basale startle-response auf akustische Reize und den Erwerb oder die Expression von Furchtgedächtnis, verbessert [433]. Die basale startle-response auf akustische Reize ist ein sensibler Messwert für allgemeine Angstzustände bzw.…”

Section: Förderung Von Stress-bzw Traumaresilienz Durch Die Behandluunclassified

“…die Expression von Angst [434]. Interessanterweise hatte M. vaccae in unserer PTBS-Mausstudie auch keinen Einfluss auf Letzteres [372]; nur Angst als Folge von psychosozialer Traumatisierung [372] und FPS [433] wurden durch eine vorangegangene Verabreichung von M. vaccae abgeschwächt. Die Effekte von M. vaccae auf die Extinktion von erlernter Furcht sind von besonderer Bedeutung, da traumatisch bedingte Angstzustände und affektive Störungen, einschließlich der PTBS, mit chronifizierten Erinnerungen an das erlebte traumatische Erlebnis charakterisiert einhergehen.…”

Section: Förderung Von Stress-bzw Traumaresilienz Durch Die Behandluunclassified

„Old Friends“, Immunregulation und Stressresilienz

Langgartner¹,

Lowry²,

Reber³

2020

Nervenheilkunde

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ZUSAMMENFASSUNGEs gibt zahlreiche Hinweise darauf, dass chronische negative Erfahrungen, insbesondere chronischer psychosozialer Stress, einen wesentlichen Risikofaktor für die Entstehung vieler somatischer und affektiver Störungen darstellen, einschließlich chronischer entzündlicher Darmerkrankungen (CED) und der posttraumatischen Belastungsstörung (PTBS). Die Mechanismen, die der Entstehung chronischer stressbedingter Erkrankungen zugrunde liegen, sind jedoch noch weitgehend unbekannt und die derzeitigen Behandlungs- und Präventionsstrategien sind unzureichend wirksam und zuverlässig. Ein besseres Verständnis der Mechanismen, die an der Entstehung und Aufrechterhaltung chronischer stressbedingter Erkrankungen beteiligt sind, kann zu neuen Ansätzen in der Prävention und Behandlung dieser Erkrankungen führen. In diesem 2-teiligen Review fassen wir die theoretischen Grundlagen (Teil 1) sowie die zugrunde liegenden Mechanismen (Teil 2) zusammen, welche die Hypothese stützen, dass ein Anstieg der Immun(re)aktivität und des Entzündungsgeschehens in der heutigen modernen Gesellschaft, potenziell gefördert durch einen verminderten Kontakt mit immunregulatorischen Mikroorganismen („Old Friends“), ursächlich an der gesteigerten Anfälligkeit für stressbedingte Pathologien sein könnte. Darüber hinaus diskutieren wir den künstlich herbeigeführten Kontakt mit Old Friends als vielversprechende Strategie zur Förderung der Stressresilienz und zur Vorbeugung/Behandlung chronischer stressbedingter Erkrankungen.

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“…M. rutilum was first identified in soils collected from Hawaii and is known for its ability to degrade polycyclic hydrocarbon pollutants (5). Both species are rapidly growing and are closely related to M. vaccae, which has been well-studied for its potential benefits to human health (64). While M. novocastrense has been found very rarely in infected tissue, it is not generally considered to be pathogenic (65,66).…”

Section: Figmentioning

confidence: 99%

A Global Survey of Mycobacterial Diversity in Soil

Walsh

Gebert

Delgado‐Baquerizo

et al. 2019

Appl Environ Microbiol

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Mycobacteria are a diverse bacterial group ubiquitous in many soil and aquatic environments. Members of this group have been associated with human and other animal diseases, including the nontuberculous mycobacteria (NTM), which are of growing relevance to public health worldwide. Although soils are often considered an important source of environmentally acquired NTM infections, the biodiversity and ecological preferences of soil mycobacteria remain largely unexplored across contrasting climates and ecosystem types. Using a culture-independent approach by combining 16S rRNA marker gene sequencing with mycobacterium-specific hsp65 gene sequencing, we analyzed the diversity, distributions, and environmental preferences of soil-dwelling mycobacteria in 143 soil samples collected from a broad range of ecosystem types. The surveyed soils harbored highly diverse mycobacterial communities that span the full extent of the known mycobacterial phylogeny, with most soil mycobacteria (97% of mycobacterial clades) belonging to previously undescribed lineages. While mycobacteria tended to have higher relative abundances in cool, wet, and acidic soil environments, several individual mycobacterial clades had contrasting environmental preferences. We identified the environmental preferences of many mycobacterial clades, including the clinically relevant Mycobacterium avium complex that was more commonly detected in wet and acidic soils. However, most of the soil mycobacteria detected were not closely related to known pathogens, calling into question previous assumptions about the general importance of soil as a source of NTM infections. Together, this work provides novel insights into the diversity, distributions, and ecological preferences of soil mycobacteria and lays the foundation for future efforts to link mycobacterial phenotypes to their distributions. IMPORTANCE Mycobacteria are common inhabitants of soil, and while most members of this bacterial group are innocuous, some mycobacteria can cause environmentally acquired infections of humans and other animals. Human infections from nontuberculous mycobacteria (NTM) are increasingly prevalent worldwide, and some areas appear to be “hotspots” for NTM disease. While exposure to soil is frequently implicated as an important mode of NTM transmission, the diversity, distributions, and ecological preferences of soil mycobacteria remain poorly understood. We analyzed 143 soils from a range of ecosystems and found that mycobacteria and lineages within the group often exhibited predictable preferences for specific environmental conditions. Soils harbor large amounts of previously undescribed mycobacterial diversity, and lineages that include known pathogens were rarely detected in soil. Together, these findings suggest that soil is an unlikely source of many mycobacterial infections. The biogeographical patterns we documented lend insight into the ecology of this important group of soil-dwelling bacteria.

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Preimmunization with a heat-killed preparation of Mycobacterium vaccae enhances fear extinction in the fear-potentiated startle paradigm

Cited by 41 publications

References 71 publications

Sex-specific gut microbiota modulation of aversive conditioning and basolateral amygdala dendritic spine density

Sex-specific gut microbiota modulation of aversive conditioning and basolateral amygdala dendritic spine density

„Old Friends“, Immunregulation und Stressresilienz

A Global Survey of Mycobacterial Diversity in Soil

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