Microbiota regulate social behaviour via stress response neurons in the brain

Wu, Wei; Adame, Mark D.; Liou, Chia Wei; Barlow, Jacob T.; Lai, Tzu Ting; Sharon, Gil; Schretter, Catherine E.; Needham, Brittany D.; Wang, Madelyn I.; Tang, Weiyi; Ousey, James; Lin, Yuan Yuan; Yao, Tzu Hsuan; Abdel-Haq, Reem; Beadle, Keith; Gradinaru, Viviana; Ismagilov, Rustem F.; Mazmanian, Sarkis K.

doi:10.1038/s41586-021-03669-y

Cited by 203 publications

(151 citation statements)

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“…Enterococcus is a Gram-positive opportunistic pathogen that could cause pneumonia and bacteremia in patients with stroke, worsening functional outcome (20). Mechanically, Enterococcus was reported to have interactions with platelets (27) and could modulate neuronal circuits that mediate stress responses (28). It is noteworthy that the pathogenic bacterium Desulfovibrionaceae, previously reported to be elevated in patients with stroke and associated with stroke severity (9), showed a decrease in the unfavorable outcome group in this study, which gives rise to the complicated patterns of microbial dysbiosis influenced by the stroke that worth further investigations.…”

Section: Discussionmentioning

confidence: 99%

Gut Microbiota Dysbiosis in Acute Ischemic Stroke Associated With 3-Month Unfavorable Outcome

Sun

et al. 2022

Front. Neurol.

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BackgroundAlterations in the gut microbiota after ischemic stroke have been demonstrated, whereas the effect on stroke outcome remains to be established.MethodsA total of 132 consecutive patients with acute ischemic stroke were prospectively enrolled. Their gut microbiomes within 24 h of admission were profiled using 16S ribosomal RNA (rRNA) gene (V3–V4 region) sequencing. Microbiota comparisons were made between groups with good outcome (n = 105) and poor outcome (n = 27) based on 3-month modified Rankin Scale scores of 0–2 and 3–6. Propensity score-matching (PSM) analysis was conducted to assess the robustness of our findings. The functional potential was predicted using the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt).ResultsPatients in the poor outcome group were characterized by a significant reduction in the alpha diversity (Shannon index, p = 0.025; Simpson index, p = 0.010), an increase in the pathogenic bacteria (e.g., Enterococcaceae and Enterococcus), and a decrease in the short-chain fatty acids (SCFAs)-producing bacteria (e.g., Bacteroidaceae, Ruminococcaceae, and Faecalibacterium) to those with good outcome group (all p < 0.05). Similar results of microbial composition were obtained after PSM. The PICRUSt revealed that the pathway for membrane transport was relatively dominant in patients with poor outcome (p < 0.05).ConclusionThis study demonstrated that stroke patients with 3-month poor outcome had baseline gut microbiota dysbiosis featured by increased pathogenic bacteria and decreased SCFAs-producing bacteria.

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Section: Discussionmentioning

confidence: 99%

Gut Microbiota Dysbiosis in Acute Ischemic Stroke Associated With 3-Month Unfavorable Outcome

Sun

et al. 2022

Front. Neurol.

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“…Accumulating evidence suggests an involvement of the MGB axis in the modulation of the host's stress response. In Sudo et al's landmark study, germ-free mice showed an enhanced secretion of plasma ACTH and corticosterone, when compared with specificpathogen-free (SPF) mice, under restraint stress [10], and it was later shown that modulation of the gut microbiota could affect the stress response, including the HPA axis [24,25]. Meanwhile, numerous studies, both animal and human, have been performed on the role of probiotics in stress resilience [26][27][28][29][30].…”

Section: Abnormal Stress Responsementioning

confidence: 99%

How Microbes Affect Depression: Underlying Mechanisms via the Gut–Brain Axis and the Modulating Role of Probiotics

Suda

Matsuda

2022

IJMS

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Accumulating evidence suggests that the gut microbiome influences the brain functions and psychological state of its host via the gut–brain axis, and gut dysbiosis has been linked to several mental illnesses, including major depressive disorder (MDD). Animal experiments have shown that a depletion of the gut microbiota leads to behavioral changes, and is associated with pathological changes, including abnormal stress response and impaired adult neurogenesis. Short-chain fatty acids such as butyrate are known to contribute to the up-regulation of brain-derived neurotrophic factor (BDNF), and gut dysbiosis causes decreased levels of BDNF, which could affect neuronal development and synaptic plasticity. Increased gut permeability causes an influx of gut microbial components such as lipopolysaccharides, and the resultant systemic inflammation may lead to neuroinflammation in the central nervous system. In light of the fact that gut microbial factors contribute to the initiation and exacerbation of depressive symptoms, this review summarizes the current understanding of the molecular mechanisms involved in MDD onset, and discusses the therapeutic potential of probiotics, including butyrate-producing bacteria, which can mediate the microbiota–gut–brain axis.

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“…Depleted microbiota is associated with increased hippocampal noradrenaline and reduced serotonin levels ( de Palma et al, 2015 ; Hoban et al, 2016 ), increased neuronal activation in areas associated with stress response, such as the paraventricular nucleus of the hypothalamus (PVN) and bed nucleus of the stria terminalis (BNST) ( Wu et al, 2021 ), and decreased gene expression of glucocorticoid receptors and CHF in the hippocampus and amygdala ( Hoban et al, 2016 ). Likewise, mice with depleted microbiota have increased basal corticosterone levels and HPA reactivity in response to acute stress, which can be reversed by microbiota recolonization ( Clarke et al, 2013 ; Wu et al, 2021 ). Moreover, chronic probiotic treatment reduces the corticosterone reactivity to acute stress and improves depressive phenotype ( Bravo et al, 2011 ; Liang et al, 2015 ).…”

Section: The Roles Of Microbiota On Depression Anxiety and Microrna E...mentioning

confidence: 99%

“…Remarkably, GF rodents tend to present reduced anxiety- and depression-like behaviors ( Heijtz et al, 2011 ; Clarke et al, 2013 ; de Palma et al, 2015 ; Wu et al, 2021 ) and are resilient to behavioral impairments induced by maternal separation ( de Palma et al, 2015 ). Such aberrant profile is associated with reduced hippocampal BDNF expression, increased hippocampal and striatal serotonin levels, and plasma tryptophan concentrations ( Heijtz et al, 2011 ; Clarke et al, 2013 ).…”

Section: The Roles Of Microbiota On Depression Anxiety and Microrna E...mentioning

confidence: 99%

The Role of MicroRNA and Microbiota in Depression and Anxiety

Rosa

Formolo

et al. 2022

Front. Behav. Neurosci.

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Depression and anxiety are devastating disorders. Understanding the mechanisms that underlie the development of depression and anxiety can provide new hints on novel treatments and preventive strategies. Here, we summarize the latest findings reporting the novel roles of gut microbiota and microRNAs (miRNAs) in the pathophysiology of depression and anxiety. The crosstalk between gut microbiota and the brain has been reported to contribute to these pathologies. It is currently known that some miRNAs can regulate bacterial growth and gene transcription while also modulate the gut microbiota composition, suggesting the importance of miRNAs in gut and brain health. Treatment and prevention strategies for neuropsychiatric diseases, such as physical exercise, diet, and probiotics, can modulate the gut microbiota composition and miRNAs expressions. Nonetheless, there are critical questions to be addressed to understand further the mechanisms involved in the interaction between the gut microbiota and miRNAs in the brain. This review summarizes the recent findings of the potential roles of microbiota and miRNA on the neuropathology of depression and anxiety, and its potential as treatment strategies.

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Microbiota regulate social behaviour via stress response neurons in the brain

Cited by 203 publications

References 48 publications

Gut Microbiota Dysbiosis in Acute Ischemic Stroke Associated With 3-Month Unfavorable Outcome

Gut Microbiota Dysbiosis in Acute Ischemic Stroke Associated With 3-Month Unfavorable Outcome

How Microbes Affect Depression: Underlying Mechanisms via the Gut–Brain Axis and the Modulating Role of Probiotics

The Role of MicroRNA and Microbiota in Depression and Anxiety

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