Signaling inflammation across the gut-brain axis

Agirman, Gulistan; Yu, Kristie; Hsiao, Elaine Y.

doi:10.1126/science.abi6087

Cited by 398 publications

(240 citation statements)

References 65 publications

Supporting

Mentioning

234

Contrasting

Unclassified

Order By: Relevance

“…For one, microaspiration during respiratory activity, such as oral breathing, affects the lung microbiota [ 7 ]. In addition, dietary patterns dynamically affect the microbiome profile of the GI tract either by microbial contamination or by supplying specific nutrients for microbial commensals, even manipulating the pathophysiology of cancerous diseases [ 8 , 9 ] as well as regulating immune responses across the gut–brain axis [ 10 , 11 ]. As such, along with the revolution of human microbiome research, much effort has been dedicated to figuring out the relationship between the oral and gut microbiota, which has been dubbed the “oral–gut–brain axis” [ 12 , 13 , 14 , 15 , 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Leaky Gum: The Revisited Origin of Systemic Diseases

Park¹,

Park²,

Lee³

et al. 2022

Cells

View full text Add to dashboard Cite

The oral cavity is the gateway for microorganisms into your body where they disseminate not only to the directly connected respiratory and digestive tracts but also to the many remote organs. Oral microbiota, travelling to the end of the intestine and circulating in our bodies through blood vessels, not only affect a gut microbiome profile but also lead to many systemic diseases. By gathering information accumulated from the era of focal infection theory to the age of revolution in microbiome research, we propose a pivotal role of “leaky gum”, as an analogy of “leaky gut”, to underscore the importance of the oral cavity in systemic health. The oral cavity has unique structures, the gingival sulcus (GS) and the junctional epithelium (JE) below the GS, which are rarely found anywhere else in our body. The JE is attached to the tooth enamel and cementum by hemidesmosome (HD), which is structurally weaker than desmosome and is, thus, vulnerable to microbial infiltration. In the GS, microbial biofilms can build up for life, unlike the biofilms on the skin and intestinal mucosa that fall off by the natural process. Thus, we emphasize that the GS and the JE are the weakest leaky point for microbes to invade the human body, making the leaky gum just as important as, or even more important than, the leaky gut.

show abstract

Section: Introductionmentioning

confidence: 99%

Leaky Gum: The Revisited Origin of Systemic Diseases

Park¹,

Park²,

Lee³

et al. 2022

Cells

View full text Add to dashboard Cite

show abstract

“…Previous studies have demonstrated that disorders of the intestines can aggravate the inflammation of the central nervous system ( Agirman et al, 2021 ). In our study, we discovered that the gavage of periodontitis salivary microbiota aggravated ischemic stroke and exacerbated inflammation in the ischemic brain.…”

Section: Discussionmentioning

confidence: 99%

Periodontitis Salivary Microbiota Aggravates Ischemic Stroke Through IL-17A

et al. 2022

View full text Add to dashboard Cite

Although epidemiological studies suggest that periodontitis is tightly associated with ischemic stroke, its impact on ischemic stroke and the underlysing mechanisms are poorly understood. Recent studies have shown that alteration in gut microbiota composition influences the outcomes of ischemic stroke. In the state of periodontitis, many oral pathogenic bacteria in the saliva are swallowed and transmitted to the gut. However, the role of periodontitis microbiota in the pathogenesis and progression of ischemic stroke is unclear. Therefore, we hypothesized that the periodontitis salivary microbiota influences the gut immune system and aggravates ischemic stroke. Mice receiving gavage of periodontitis salivary microbiota showed significantly worse stroke outcomes. And these mice also manifested more severe neuroinflammation, with higher infiltration of inflammatory cells and expression of inflammatory cytokines in the ischemic brain. More accumulation of Th17 cells and IL-17+ γδ T cells were observed in the ileum. And in Kaede transgenic mice after photoconversion. Migration of CD4+ T cells and γδ T cells from the ileum to the brain was observed after ischemic stroke in photoconverted Kaede transgenic mice. Furthermore, the worse stroke outcome was abolished in the IL-17A knockout mice. These findings suggest that periodontitis salivary microbiota increased IL-17A-producing immune cells in the gut, likely promoted the migration of these cells from the gut to the brain, and subsequently provoked neuroinflammation after ischemic stroke. These findings have revealed the role of periodontitis in ischemic stroke through the gut and provided new insights into the worse outcome of ischemic stroke coexisting with periodontitis in clinical trials.

show abstract

“…While the responsible microbiotal products remain to identified in many cases, a voluminous literature documents the profound influence of the microbiota on host inflammatory responses in the gut, lung, brain, and skin ( Agirman et al., 2021 ; Blander et al., 2017 ; Chen et al., 2018 ; Rosshart et al., 2019 ).…”

Section: Inflammation-regulating Metabolitesmentioning

confidence: 99%

Nonresolving inflammation redux

Nathan

2022

Immunity

View full text Add to dashboard Cite

Signaling inflammation across the gut-brain axis

Cited by 398 publications

References 65 publications

Leaky Gum: The Revisited Origin of Systemic Diseases

Leaky Gum: The Revisited Origin of Systemic Diseases

Periodontitis Salivary Microbiota Aggravates Ischemic Stroke Through IL-17A

Nonresolving inflammation redux

Contact Info

Product

Resources

About