Chronic Stress-Induced Depression and Anxiety Priming Modulated by Gut-Brain-Axis Immunity

Westfall, Susan; Caracci, Francesca; Estill, Molly; Frolinger, Tal; Shen, Li; Pasinetti, Giulio Maria

doi:10.3389/fimmu.2021.670500

Cited by 59 publications

(35 citation statements)

References 81 publications

(110 reference statements)

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“…Considering stress-induced behavioral impairment is at least partially a consequence of gut microbiota alteration, supplementation with probiotics has been considered as a potential but promising therapy to counteract the detrimental effects of stress by restoring the microbiota ( Foster et al, 2017 ; Nishida et al, 2019 ; Tian et al, 2020 ; Westfall et al, 2021 ). Our observation revealed that C. butyricum RH2 treatment ameliorated the CFSS-induced anxiety/depression-like symptoms, cognitive decline and the decrease in body weight gain but not in food intake.…”

Section: Discussionmentioning

confidence: 99%

Clostridium butyricum RH2 Alleviates Chronic Foot Shock Stress-Induced Behavioral Deficits in Rats via PAI-1

et al. 2022

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Recent investigations have demonstrated that the chronic stress-induced behavioral disorders can be ameliorated by probiotics including Clostridium butyricum (C. butyricum) via the gut-brain-axis. However, the molecular mechanisms underlying the beneficial effects of C. butyricum on brain remain largely unknown. Here, we investigated whether chronic foot shock stress (CFSS) paradigm used for a hypertensive animal model could induce mood disorders such as anxiety, depression and cognitive impairments. Then, we assessed the impact of C. butyricum RH2 on the behavior disorders and neurobiological alterations in the hippocampus. Male Sprague-Dawley (SD) rats received intermittent electric shocks for consecutive 14 days and were treated with C. butyricum RH2 for 17 days. Anxiety- or depression-like behaviors were evaluated by open field test (OFT), and elevated plus maze (EPM). The Morris water maze test (MWM) was used to evaluate the cognitive functions. CFSS intervention led to mild anxiety- or depression-like behavior or cognitive impairment and C. butyricum RH2 treatment reversed the CFSS-induced symptoms. The serum ACTH or CORT was increased following CFSS but was completely reversed by C. butyricum RH2 treatment. In the hippocampus of CFSS rats, the expressions of BDNF and TrkB were downregulated but proBDNF and P75NTR were upregulated. These expression changes were partially reversed by C. butyricum RH2, suggesting a mode of action on BDNF and proBDNF balance. CFSS exposure resulted in downregulation of tissue-type plasminogen activator (tPA) but upregulation of plasminogen activator inhibitor 1(PAI-1), which could contribute to the decrease in BDNF by reduced conversion from proBDNF to BDNF in the hippocampus. C. butyricum RH2 treatment reversed the upregulated PAI-1 but not the downregulated tPA, which was in parallel with the amelioration of behavioral abnormalities, suggesting a novel tPA independent mechanism for PAI-1 action. Our results demonstrate for the first time that C. butyricum RH2 attenuates stress-induced behavior disorders via inhibiting the expression of brain PAI-1.

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Section: Discussionmentioning

confidence: 99%

Clostridium butyricum RH2 Alleviates Chronic Foot Shock Stress-Induced Behavioral Deficits in Rats via PAI-1

et al. 2022

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“…Whilst physical and mental stresses, either acute or chronic, have a dramatic impact on the immune system, both innate and adaptive immune components could be affected. Humans and animals subjected to stress conditions exhibited significant reduction in lymphocytes [ 140 ], increase in IL-6 production [ 141 ], decrease in IFN-γ [ 142 ], augmentation in regulatory T cells [ 142 ], and alteration in gut microbiota [ 143 ]. The induction of Fas expression on lymphocytes by chronic stress [ 144 ] could account, at least in part, for the lymphopenia development in COVID-19 patients mentioned above.…”

Section: Adaptive Immunity: Cellular Immunity and Resistance To Sars-...mentioning

confidence: 99%

Immune response in COVID-19: what is next?

Wang

Sun

et al. 2022

Cell Death Differ

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The coronavirus disease 2019 (COVID-19) has been a global pandemic for more than 2 years and it still impacts our daily lifestyle and quality in unprecedented ways. A better understanding of immunity and its regulation in response to SARS-CoV-2 infection is urgently needed. Based on the current literature, we review here the various virus mutations and the evolving disease manifestations along with the alterations of immune responses with specific focuses on the innate immune response, neutrophil extracellular traps, humoral immunity, and cellular immunity. Different types of vaccines were compared and analyzed based on their unique properties to elicit specific immunity. Various therapeutic strategies such as antibody, anti-viral medications and inflammation control were discussed. We predict that with the available and continuously emerging new technologies, more powerful vaccines and administration schedules, more effective medications and better public health measures, the COVID-19 pandemic will be under control in the near future.

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“…The combination of probiotics and prebiotics promotes behavioral resilience to chronic stress by normalizing the gut microbiome and promoting T regs expansion, an impact reflecting behavioral responses better than neuroinflammation in limbic regions of brain. The ratio of ileal T regs /Th17 is associated with the production of hippocampal chemokines and IL-1β in the prefrontal cortex ( 124 ). Traditional Chinese Medicine, such as resveratrol, may inhibit neuroinflammation by regulating microbiota-gut-brain axis mediated Th17/T regs and Th1/Th2 polarity shift ( 125 ).…”

Section: T Regs -Related Therapeutic Potential In Saementioning

confidence: 99%

Insight Into Regulatory T Cells in Sepsis-Associated Encephalopathy

et al. 2022

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Sepsis-associated encephalopathy (SAE) is a diffuse central nervous system (CNS) dysfunction during sepsis, and is associated with increased mortality and poor outcomes in septic patients. Despite the high incidence and clinical relevance, the exact mechanisms driving SAE pathogenesis are not yet fully understood, and no specific therapeutic strategies are available. Regulatory T cells (Tregs) have a role in SAE pathogenesis, thought to be related with alleviation of sepsis-induced hyper-inflammation and immune responses, promotion of T helper (Th) 2 cells functional shift, neuroinflammation resolution, improvement of the blood-brain barrier (BBB) function, among others. Moreover, in a clinical point of view, these cells have the potential value of improving neurological and psychiatric/mental symptoms in SAE patients. This review aims to provide a general overview of SAE from its initial clinical presentation to long-term cognitive impairment and summarizes the main features of its pathogenesis. Additionally, a detailed overview on the main mechanisms by which Tregs may impact SAE pathogenesis is given. Finally, and considering that Tregs may be a novel target for immunomodulatory intervention in SAE, different therapeutic options, aiming to boost peripheral and brain infiltration of Tregs, are discussed.

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Chronic Stress-Induced Depression and Anxiety Priming Modulated by Gut-Brain-Axis Immunity

Cited by 59 publications

References 81 publications

Clostridium butyricum RH2 Alleviates Chronic Foot Shock Stress-Induced Behavioral Deficits in Rats via PAI-1

Clostridium butyricum RH2 Alleviates Chronic Foot Shock Stress-Induced Behavioral Deficits in Rats via PAI-1

Immune response in COVID-19: what is next?

Insight Into Regulatory T Cells in Sepsis-Associated Encephalopathy

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