A key role of the subdiaphragmatic vagus nerve in the depression-like phenotype and abnormal composition of gut microbiota in mice after lipopolysaccharide administration

Zhang, Jiancheng; Ma, Li; Chang, Lijia; Pu, Yaoyu; Qu, Youge; Hashimoto, Kenji

doi:10.1038/s41398-020-00878-3

Cited by 155 publications

(105 citation statements)

References 59 publications

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“…The subdiaphragmatic vagus nerve serves as a major modulatory pathway between the brain and gut microbiota. Very recently, we demonstrated that lipopolysaccharide produces a depression-like phenotype and abnormal composition of gut microbiota via the subdiaphragmatic vagus nerve [38]. In this study, we found that the ingestion of L. intestinalis and L. reuteri did not induce depression-and anhedonia-like behaviors, increase plasma IL-6 levels, or reduce synaptic protein expression in the PFC in vagotomized mice.…”

Section: Discussionmentioning

confidence: 47%

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Ingestion of Lactobacillus intestinalis and Lactobacillus reuteri causes depression- and anhedonia-like phenotypes in antibiotic-treated mice via the vagus nerve

Wang

Ishima

Zhang

et al. 2020

J Neuroinflammation

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121

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Background: The brain-gut-microbiota axis plays a role in the pathogenesis of stress-related disorders such as depression. In this study, we examined the effects of fecal microbiota transplantation (FMT) in mice with antibiotictreated microbiota depletion. Methods: The fecal microbiota was obtained from mice subjected to chronic social defeat stress (CSDS) and control (no CSDS) mice. FMT from these two groups was performed to antibiotic-treated mice. 16S rRNA analysis was performed to examine the composition of gut microbiota. Furthermore, the effects of subdiaphragmatic vagotomy in depression-like phenotypes after ingestion of microbes were examined. Results: The ingestion of fecal microbiota from CSDS-susceptible mice resulted in an anhedonia-like phenotype, higher plasma levels of interleukin-6 (IL-6), and decreased expression of synaptic proteins in the prefrontal cortex (PFC) in antibiotic-treated mice but not in water-treated mice. 16S rRNA analysis suggested that two microbes (Lactobacillus intestinalis and Lactobacillus reuteri) may be responsible for the anhedonia-like phenotype in antibiotic-treated mice after FMT. Ingestion of these two microbes for 14 days led to depression-and anhedonialike phenotypes, higher plasma IL-6 levels, and decreased expression of synaptic proteins in the PFC of antibiotictreated mice. Interestingly, subdiaphragmatic vagotomy significantly blocked the development of behavioral abnormalities, elevation of plasma IL-6 levels, and downregulation of synaptic proteins in the PFC after ingestion of these two microbes. Conclusions: These findings suggest that microbiota depletion using an antibiotic cocktail is essential for the development of FMT-induced behavioral changes and that the vagus nerve plays a key role in behavioral abnormalities in antibiotic-treated mice after the ingestion of L. intestinalis and L. reuteri. Therefore, it is likely that the brain-gut-microbiota axis participates in the pathogenesis of depression via the vagus nerve.

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Section: Discussionmentioning

confidence: 47%

“…1 c): Sham surgery or subdiaphragmatic vagotomy (SDV) was performed under anesthesia with 5% isoflurane. Mice were put under a microscope (Leica LEICA S9E, Germany), and hair was removed from the abdomen [ 38 ]. The esophagus of each mouse was exposed to the full view.…”

Section: Methodsmentioning

confidence: 99%

Ingestion of Lactobacillus intestinalis and Lactobacillus reuteri causes depression- and anhedonia-like phenotypes in antibiotic-treated mice via the vagus nerve

Wang

Ishima

Zhang

et al. 2020

J Neuroinflammation

Self Cite

121

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“…Collectively, our results suggest that gut microbiota composition alteration elicited by SD after sepsis plays key roles in the aggravation of systemic in ammation. It is evidenced that the communication between the brain and the endogenous and exogenous microorganisms in the gut could be modulated by the subdiaphragmatic vagus nerve [19,[43][44][45][46][47]. Our data showed that SDV abrogated post-septic SDmediated aggravation of systemic in ammation and multi-organ injuries.…”

Section: Discussionmentioning

confidence: 60%

“…Previous studies demonstrate that the ingestion of bene cial bacteria or selective serotonin reuptake inhibitors could alleviate stress-induced anxiety and depression-like behaviors via the subdiaphragmatic vagus nerve, which could be abolished by SDV [47,48]. We previously found that LPS at a dose of 0.5 mg/kg produces a depression-like phenotype and triggers in ammation via the subdiaphragmatic vagus nerve [19]. Abnormal composition of gut microbiota is observed after administration of 0.5 mg/kg LPS.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have shown that stimulation of cervical vagus nerve can decrease the production of proin ammatory cytokines in experimental models of systemic in ammation, including lethal endotoxemia, hemorrhagic shock, and ischemia-reperfusion injury [14][15][16][17][18]. However, we previously found that subdiaphragmatic vagotomy (SDV) performed 14 days prior to LPS injection could attenuate intraperitoneally injection with 0.5 mg/kg LPS-mediated intestinal ora disorder, and increase in spleen weight and plasma levels of IL-6 and TNF-α in mice [19], indicating that different branches of the vagus nerve could play different roles under pathological conditions. We speculated that the dorminated speci c microorganisms in the intestinal ora after LPS treatment might lead to systemic in ammation through the subdiaphragmatic vagus nerve.…”

Section: Introductionmentioning

confidence: 98%

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A key role of gut microbiota-vagus nerve axis and gut microbiota-spleen axis in sleep deprivation-mediated aggravation of systemic inflammation after LPS administration

Zhang

Xie

et al. 2020

Preprint

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Background: Sleep deprivation (SD) is shown to be correlated with exacerbated systemic inflammation after sepsis. However, the underlying mechanisms remain unclear. Methods: In this study, mice were intraperitoneally injected with lipopolysaccharide (LPS) followed by 3 consecutive days of SD. The subdiaphragmatic vagotomy (SDV) was performed 2 weeks before LPS injection. The pseudo germ-free mouse model was created by administering antibiotics for 14 consecutive days, and then fecal microbiota transplant (FMT) was performed by gavaging supernatant from fecal suspension of septic mice with or without SD into pseudo germ-free mice with or without SDV or splenectomy. Splenectomy was performed 14 days prior to antibiotics administration.Results: We found that SD after LPS administration increased the plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), reduced IL-10 plasma leve, increased spleen weight, and promoted pathological injury and IL-6 expression in lung, liver and kidney. Post-septic sleep deprivation had no effects on the diversity of gut microbiota. However, the relative abundance of Proteobacteria and its subgroups were increased in septic mice received SD. Pseudo germ-free mice transplanted with fecal bacteria from septic mice subjected to SD developed splenomegaly, systemic inflammation, organ inflammation and damage as their donors do. Intriguingly, SDV abolished the aggravated effects of SD on splenomegaly and inflammatory organ injury in septic mice received SD or in pseudo germ-free mice transplanted with fecal bacteria from septic mice subjected to SD. Furthermore, Splenectomy also abrogated the increase in IL-6 and TNF-α plasma levels and the decrease in IL-10 plasma level in pseudo germ-free mice transplanted with fecal bacteria from septic mice subjected to SD. Conclusions: Taken together, our results suggest that gut microbiota-vagus nerve axis and gut microbiota-spleen axis could play key roles in modulating systemic inflammation induced by SD after LPS administration.

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Gut microbiome and neurosurgery: Implications for treatment

Willman

Reddy

et al. 2022

Clinical and Translational Dis

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Introduction: The aim of this review is to summarize the current understanding of the gut-brain axis (GBA), its impact on neurosurgery, and its implications for future treatment. Background: An abundance of research has established the existence of a collection of pathways between the gut microbiome and the central nervous system (CNS), commonly known as the GBA. Complicating this relationship, the gut microbiome bacterial diversity appears to change with age, antibiotic exposure and a number of external and internal factors. Methods: In this paper, we present the current understanding of the key protective and deleterious roles the gut microbiome plays in the pathogenesis of several common neurosurgical concerns. Results: Specifically, we examine how spinal cord injury, traumatic brain injury and stroke may cause gut microbial dysbiosis. Furthermore, this link appears to be bidirectional as gut dysbiosis contributes to secondary CNS injury in each of these ailment settings. This toxic cycle may be broken, and the future secondary damage rescued by timely, therapeutic, gut microbiome modification. In addition, a robust gut microbiome appears to improve outcomes in brain tumour treatment. There are several primary routes by which microbiome dysbiosis may be ameliorated, including faecal microbiota transplant, oral probiotics, bacteriophages, genetic modification of gut microbiota and vagus nerve stimulation. Conclusion: The GBA represents an important component of patient care in the field of neurosurgery. Future research may illuminate ideal methods of therapeutic microbiome modulation in distinct pathogenic settings.

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A key role of the subdiaphragmatic vagus nerve in the depression-like phenotype and abnormal composition of gut microbiota in mice after lipopolysaccharide administration

Cited by 155 publications

References 59 publications

Ingestion of Lactobacillus intestinalis and Lactobacillus reuteri causes depression- and anhedonia-like phenotypes in antibiotic-treated mice via the vagus nerve

Ingestion of Lactobacillus intestinalis and Lactobacillus reuteri causes depression- and anhedonia-like phenotypes in antibiotic-treated mice via the vagus nerve

A key role of gut microbiota-vagus nerve axis and gut microbiota-spleen axis in sleep deprivation-mediated aggravation of systemic inflammation after LPS administration

Gut microbiome and neurosurgery: Implications for treatment

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