# PathMap Report Trace Context: #00000130
Hypothesis: Targeted alteration of the oral microbiome via a single polyphenol- and fiber-dense meal plan creates an immediate shift in the microbial composition of involuntary nocturnal microaspiration droplets. Upon entry into the lower respiratory tract, this eubiotic bacterial influx acts as an acute molecular signal that rapidly modulates microglia reactivity and neuroinflammation via the lung-brain axis, bypassing systemic colonic metabolite transport.
Author: Joshua Dungan (PathMap.org)
License: 'THE GLOBAL HUMANITARIAN PROPRIETARY LICENSE (VERSION 1.0.1)' https://pathmap.org/license.pdf
Full provenance JSON trace: https://pathmap.org/download.php/?id=130
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SYSTEM NOTE: The eight-digit ID numbers (e.g., ID 12345678) used in citations below are PubMed ID numbers and can be loaded via https://pubmed.ncbi.nlm.nih.gov/{ID}/ for verification.

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## Primary Synthesis & Clinical Bottom-Line
Scientific synthesis indicates that while the lung microbiome is largely populated by oral taxa via micro-aspiration, and the lung-brain axis mediates neuroinflammation through various pulmonary metabolites and pathogens, the direct link between acute dietary changes, specific altered micro-aspiration, and rapid microglial modulation is not established in the provided literature.

## Novel & Overlooked Insights
- The lung microbiome includes bacteria, archaea, fungi, protozoa, and viruses.
- However, fungi and viruses have not been fully studied compared to bacteria in the lungs.
- The gut-lung-brain (GLB) axis is a multidirectional communication network linking the gastrointestinal tract, respiratory system, and central nervous system (CNS) through neural, endocrine, and immune pathways.
- Emerging evidence suggests that tryptophan (Trp) metabolism serves as a key integrating node within this axis, modulating host-microbe interactions involved in systemic homeostasis.
- Intratracheal transplantation of lung microbiota from anxiety-susceptible donors induced similar behavioral changes in recipient mice, indicating a causal role of the pulmonary microbiota.
- Transcriptomic and immunofluorescence analyses suggested that formononetin acts through modulation of hippocampal microglia.
- Epidemiological and clinical evidence shows a close association between compromised lung health-including chronic obstructive pulmonary disease (COPD), asthma, obstructive sleep apnea (OSA), and pulmonary infections-and cognitive impairment and dementia.
- In a recent issue of Nature, Hosang et al. demonstrate how the lung microbiome regulates the magnitude of autoimmune inflammation in the brain.

## Extracted Custom Discoveries
### Suggested Experiments
- Test the effect of high-polyphenol acute dietary intake on the salivary and nocturnal oropharyngeal microbial composition in human volunteers.
- Evaluate the impact of controlled micro-aspiration of specific oral taxa on hippocampal microglia activation in an animal model.

### Suggested Studies
- A longitudinal study mapping the temporal correlation between oral microbiome fluctuation and pulmonary microbiome composition in subjects prone to nocturnal micro-aspiration.
- Investigate whether dietary modulation of the oral cavity can mitigate neuroinflammation in animal models of lung-brain axis-associated diseases.

### Swansons Literature Based Discovery Candidates
- Modulation of the oral microbiome through rapid dietary shifts can serve as a non-systemic prophylactic intervention to prevent pulmonary-induced microglial overactivation in patients at risk for micro-aspiration-related neurological decline.
- Oral-pulmonary axis (36768494: Oral-lung seeding via micro-aspiration).
- Microglia reactivity and lung-brain axis modulation (41981595: Sevoflurane-induced pulmonary dysbiosis and microglial activation).
- Microglial reactivity/activation.
- Since oral bacteria form the lung microbiome and pulmonary microbes influence microglia, transiently adjusting the oral community via diet could functionally 'program' the aspirations that reach the lung, thereby pre-empting or attenuating neuroinflammatory signaling without relying on systemic colonic metabolic feedback.

### Contradictions Between Evidences
- There is no direct conflict in the evidence; the claim is simply a novel synthesis of disparate fields (oral-lung seeding and pulmonary-induced neuroinflammation) that has not been explicitly tested or confirmed in the provided literature.

### Repurposed Solutions
- The tannic acid nanoparticle treatment for HSV-1 infection (40191045) might be repurposed as a therapeutic platform to selectively modulate or neutralize specific pro-inflammatory microbes in the respiratory tract, potentially altering the signaling landscape of the lung-brain axis.

## Evaluation Scoring Reference
All analyzed perspectives utilize a standardized 1-7 scoring framework:
- Alignment Score (1-7): How well does the evaluated claim factually align with the provided evidence set?
  [1 = Evidence proves claim strictly false, 2 = Evidence indicates the claim is impossible, 3 = Implausible, 4 = Neutral/Unrelated, 5 = Plausible, 6 = Evidence indicates inevitable, 7 = Evidence proves claim strictly true]
- Consilience Score (1-7): How consilient (in agreement) is the evidence set regarding this claim?
  [1 = Highly Conflicting/Disputed, 4 = Mixed, 7 = Unanimous Agreement]
- Confidence Score (1-7): Implied confidence of the research based on study design and depth.
  [1 = In Vitro/Animal/Preprint, 4 = Observational/Moderate, 7 = Meta-analysis/RCT]

## Evaluated Perspectives & Findings
### Perspective R1: Claim [Run1 Eval1 Synthesis] evaluated against Evidence [N/A]
- Alignment Score: 3/7
- Consilience Score: 2/7
- Directional Logic: High Score = SUPPORTS Original Claim
Even though this fact check looked at unique up-to-date abstracts, new evidence may refute this answer in the future. Although 'Zero Hallucinated Moneyshot Quotes' is programmatically enforced, AI is not always immune to inadvertently/erroneously misinterpreting data. This is not medical or professional advice, but instead, is an opinion calculated by AI based on the literature evaluated.

###[CLAIM EVALUATED AND ANSWER TO USER]
"Targeted alteration of the oral microbiome via a single polyphenol- and fiber-dense meal plan creates an immediate shift in the microbial composition of involuntary nocturnal microaspiration droplets. Upon entry into the lower respiratory tract, this eubiotic bacterial influx acts as an acute molecular signal that rapidly modulates microglia reactivity and neuroinflammation via the lung-brain axis, bypassing systemic colonic metabolite transport."

The claim is currently unsupported and largely speculative based on the provided literature. While the lung microbiome is suggested to be derived from the oral cavity via micro-aspiration, there is no evidence that a "single meal plan" can induce an "immediate shift" in the microbial composition of aspiration droplets, nor is there evidence confirming the ability to "bypass systemic colonic metabolite transport" in modulating microglia reactivity via this specific mechanism.

### [ABSTRACT & REWRITTEN CLAIM]
Scientific synthesis indicates that while the lung microbiome is largely populated by oral taxa via micro-aspiration, and the lung-brain axis mediates neuroinflammation through various pulmonary metabolites and pathogens, the direct link between acute dietary changes, specific altered micro-aspiration, and rapid microglial modulation is not established in the provided literature.

### [INTRODUCTION & JUSTIFICATION]
The lung has traditionally been considered a sterile organ, but contemporary non-culture-dependent techniques have confirmed the presence of low-biomass microbiomes. Due to the limitations of culture techniques, the lung in a healthy state is traditionally considered to be a sterile organ. The species of the lung microbiome are similar to those of the oral microbiome, suggesting that the microbiome is derived passively within the lungs from the oral cavity via micro-aspiration. Elimination, immigration, and relative growth within its communities all contribute to the composition of the lung microbiome. There is a close relationship between the lungs and the brain, which can be called the lung-brain axis. However, the problem now is that it is not well understood how the lung microbiota plays a role in the disease-specifically, whether there is a causal connection between disease and the lung microbiome. Recent evidence suggests that pulmonary dysbiosis, induced by factors like sevoflurane exposure or viral infection, can influence microglial phenotypes. Pulmonary microbes were found to enhance Th1-type immunoreactivity induced by RSV infection and eventually induced M1-type dominant microglia in the brains of mice. This study was able to establish a correlation between the pulmonary microbiome and brain function. Furthermore, metabolites such as sphingosine have been identified as key mediators, where developmental sevoflurane exposure induces microglial activation and cognitive decline via a pulmonary dysbiosis-sphingosine reduction cascade. While the evidence confirms the existence of a lung-brain axis, the claim that a "single" meal plan could alter this axis via immediate aspiration-related microglial modulation is not documented.

### [DISCUSSION: NOVEL & OVERLOOKED]
* The lung microbiome includes bacteria, archaea, fungi, protozoa, and viruses.
* However, fungi and viruses have not been fully studied compared to bacteria in the lungs.
* The gut-lung-brain (GLB) axis is a multidirectional communication network linking the gastrointestinal tract, respiratory system, and central nervous system (CNS) through neural, endocrine, and immune pathways.
* Emerging evidence suggests that tryptophan (Trp) metabolism serves as a key integrating node within this axis, modulating host-microbe interactions involved in systemic homeostasis.
* Intratracheal transplantation of lung microbiota from anxiety-susceptible donors induced similar behavioral changes in recipient mice, indicating a causal role of the pulmonary microbiota.
* Transcriptomic and immunofluorescence analyses suggested that formononetin acts through modulation of hippocampal microglia.
* Epidemiological and clinical evidence shows a close association between compromised lung health-including chronic obstructive pulmonary disease (COPD), asthma, obstructive sleep apnea (OSA), and pulmonary infections-and cognitive impairment and dementia.
* In a recent issue of Nature, Hosang et al. demonstrate how the lung microbiome regulates the magnitude of autoimmune inflammation in the brain.

### [EVIDENCE, METHODOLOGY & CITATIONS]
1. ID: 36768494 - "Due to the limitations of culture techniques, the lung in a healthy state is traditionally considered to be a sterile organ."
2. ID: 36768494 - "The species of the lung microbiome are similar to those of the oral microbiome, suggesting that the microbiome is derived passively within the lungs from the oral cavity via micro-aspiration."
3. ID: 36768494 - "Elimination, immigration, and relative growth within its communities all contribute to the composition of the lung microbiome."
4. ID: 36768494 - "There is a close relationship between the lungs and the brain, which can be called the lung-brain axis."
5. ID: 36768494 - "However, the problem now is that it is not well understood how the lung microbiota plays a role in the disease-specifically, whether there is a causal connection between disease and the lung microbiome."
6. ID: 36768494 - "The lung microbiome includes bacteria, archaea, fungi, protozoa, and viruses."
7. ID: 36768494 - "However, fungi and viruses have not been fully studied compared to bacteria in the lungs."
8. ID: 42296911 - "The gut-lung-brain (GLB) axis is a multidirectional communication network linking the gastrointestinal tract, respiratory system, and central nervous system (CNS) through neural, endocrine, and immune pathways."
9. ID: 42296911 - "Emerging evidence suggests that tryptophan (Trp) metabolism serves as a key integrating node within this axis, modulating host-microbe interactions involved in systemic homeostasis."
10. ID: 42296911 - "Trp catabolism follows three divergent pathways: the kynurenine (Kyn) pathway, which is involved in immune tolerance but can generate neuroactive and potentially neurotoxic metabolites; the serotonin pathway, essential for mood and gastrointestinal motility; and the microbial indole pathway, which supports epithelial barrier function through aryl hydrocarbon receptor activation."
11. ID: 42296911 - "These alterations contribute to systemic low-grade inflammation and immune dysregulation, which further propagate cross-organ pathology within the GLB axis. This review synthesizes current evidence on how Trp metabolites may function as cross-organ mediators, contributing to the "leaky gut" and "leaky brain" phenotypes."
12. ID: 42108470 - "Intratracheal transplantation of lung microbiota from anxiety-susceptible donors induced similar behavioral changes in recipient mice, indicating a causal role of the pulmonary microbiota."
13. ID: 42108470 - "Transcriptomic and immunofluorescence analyses suggested that formononetin acts through modulation of hippocampal microglia."
14. ID: 41981595 - "Neonatal sevoflurane exposure in mice induces microglial activation and long-term cognitive deficits, a finding that raises significant concerns for pediatric anesthesia."
15. ID: 41981595 - "Developmental sevoflurane exposure induces microglial activation and cognitive decline via a pulmonary dysbiosis-sphingosine reduction cascade."
16. ID: 41981595 - "Notably, sphingosine-a key membrane lipid-was significantly decreased."
17. ID: 41980215 - "Epidemiological and clinical evidence shows a close association between compromised lung health-including chronic obstructive pulmonary disease (COPD), asthma, obstructive sleep apnea (OSA), and pulmonary infections-and cognitive impairment and dementia."
18. ID: 41890764 - "Melatonin increased gut-derived butyrate levels and restored gut microbiota balance."
19. ID: 41890764 - "Mechanistically, both treatments inhibited the activation of the MAPK/P65/NLRP3 pathway in hippocampal microglia and LPS-stimulated BV2 cells."
20. ID: 41679674 - "Emerging evidence suggests that Parkinson's disease (PD) extends beyond the brain and involves early disturbances along the gut-brain axis."
21. ID: 41679674 - "Conversely, uremic indoles such as indoxyl sulfate (IS) and p-cresyl sulfate (pCS) activate microglia and astrocytes, promote α-synuclein aggregation, and accelerate dopaminergic neuron loss."
22. ID: 41572340 - "Esketamine improved pulmonary function and behavior, reduced neuronal apoptosis and microglial activation, and suppressed MAPK/NF-κB signaling; these effects were partly reversed by Diprovocim."
23. ID: 41572340 - "Microbiota profiling showed dysbiosis of gut and lung communities, with loss of beneficial taxa and expansion of conditional pathogens, whereas esketamine partially restored balance by promoting commensals and reducing potential pathogens."
24. ID: 41378250 - "These factors activated toll-like receptors (TLR2/TLR4), microglia, and astrocytes, increasing levels of interleukin 1 beta, tumor necrosis factor-alpha, and other proinflammatory cytokines."
25. ID: 40383292 - "Parkinson's Disease (PD), a complex neurodegenerative disorder, is increasingly recognized as a systemic condition involving multi-organ interactions."
26. ID: 40339190 - "Western diets (WD) contribute to obesity, and previous reviews have described a role for WD in impaired hippocampal-dependent memory."
27. ID: 40339190 - "Gut microbiota impacts gastrointestinal barrier function, leading to increased circulating proinflammatory bacterial products, increased blood-brain barrier permeability, and neuroinflammation."
28. ID: 39481495 - "Multi-omics analyses uncovered distinctive metabolic responses between the delta and omicron variants, with the former demonstrating dysregulation in synaptic transmission proteins associated with neurocognitive disorders."
29. ID: 39481495 - "These findings underscore the SARS-CoV-2-mediated tissue insult, characterized by modified host metabolites, neurological protein dysregulation, and gut dysbiosis, highlighting the compromised gut-lung-brain axis during acute infection."
30. ID: 39255392 - "Repeated oral inoculation of mice with P. gingivalis results in brain infiltration of bacterial products, increased inflammation, and induction of AD-like biomarkers."
31. ID: 38974208 - "Numerous studies have underscored the mediation of the lung-brain axis by inflammatory responses and hypoxia-induced damage, which are pivotal to the progression of both pulmonary and neurological diseases."
32. ID: 38974208 - "Additionally, we highlight the emerging research on the lung microbiome which, drawing parallels between the gut and lungs in terms of microbiome contents, may play a significant role in modulating brain health."
33. ID: 37721279 - "In the human body, the gut and lung are regarded as the key reactional targets that are initiated by brain ischemic attacks."
34. ID: 37721279 - "Mucosal microorganisms play an important role in immune regulation and metabolism and affect blood-brain barrier permeability."
35. ID: 37522339 - "Pulmonary microbes were found to enhance Th1-type immunoreactivity induced by RSV infection and eventually induced M1-type dominant microglia in the brains of mice."
36. ID: 37522339 - "This study was able to establish a correlation between the pulmonary microbiome and brain function."
37. ID: 36552802 - "An impaired BBB allows the translocation of potentially harmful bacterial products, including LPS, and activated neutrophils/leucocytes into the brain, which results in neuroinflammation and apoptosis."
38. ID: 36552802 - "Chronic neuroinflammation causes neuronal damage and synaptic loss, leading to memory impairment."
39. ID: 35417673 - "In a recent issue of Nature, Hosang et al. demonstrate how the lung microbiome regulates the magnitude of autoimmune inflammation in the brain."
40. ID: 33919550 - "Excessive alcohol use can result in translocation of bacterial products into circulation, increased expression of pro-inflammatory cytokines, and activation of immune cells, including macrophages and/or microglia in the liver and brain."
41. ID: 32971216 - "There is a growing amount of evidence showing a reciprocal relation between the gut microbiota and the brain."
42. ID: 32971216 - "The communication between the microbiota and the brain exists through different pathways: (1) the immune response elicited by bacterial products, coupled with alterations of the intestinal barrier allowing these products to enter the bloodstream, (2) the direct and indirect effects of bacterial metabolites such as short chain fatty acids (SCFAs) or tryptophan on the brain, (3) and the hypothalamic-pituitary-adrenal (HPA) axis, whose peripheral afferents can be influenced by the microbiota, and can in turn activate microglia."
43. ID: 32971216 - "In some but not all patients suffering from alcohol-use-disorder (AUD), alcohol alters the composition of the gut microbiota and the permeability of the intestinal barrier, directly and through dysbiosis."
44. ID: 40191045 - "We found that tannic acid is necessary for binding with HSV-1, with smaller sizes independent of the NPs composition, whereas for larger NPs, only TA-AgNPs can inhibit HSV-1 infection."
45. ID: 40191045 - "Intranasal treatment of HSV-1 infection with TA-Ag/AuNPs results in lower viral titers and a better antiviral response, followed by increased IFN-α, CXCL9, and CXCL10 levels as well as infiltration of T cells and NK cells in the infected sites."
46. ID: 40191045 - "We also found that the application of TA-NPs to the nasal cavities of infected mice induced infiltration of both monocytes and Langerhans cells (LCs), which lasted longer compared to the application of unmodified NPs."
47. ID: 40191045 - "Furthermore, TA-NPs activated monocytes and microglia to produce antiviral cytokines and chemokines better than unmodified NPs, except for the large TA-AuNPs."
48. ID: 40191045 - "Treatment of the mucosal tissues at the early stage of HSV-1 infection helps to modulate specific and effective antiviral immune response by attracting cytotoxic lymphocytes and inducing the production of antiviral cytokines and chemokines."
49. ID: 40191045 - "Furthermore, tannic acid modification is helpful for the removal of nanoparticles from the respiratory tract, which increases the safety of nanoparticle applications to treat infections."
50. ID: 40191045 - "HSV-1 also invades the nervous system where it establishes a lifelong latency-making infection poorly treatable"
51. ID: 36768494 - "Due to the limitations of culture techniques, the lung in a healthy state is traditionally considered to be a sterile organ."
52. ID: 36768494 - "There is a close relationship between the lungs and the brain, which can be called the lung-brain axis."



## Logical Systems Map (Logical Gates)
- "Dietary modification" -> "Dysbiosis"
- "Dysbiosis" -> "Respiratory Aspiration"
- "Respiratory Aspiration" -> "Microglia"

## Verified Verbatim Quotes
- "Due to the limitations of culture techniques, the lung in a healthy state is traditionally considered to be a sterile organ."
- "The species of the lung microbiome are similar to those of the oral microbiome, suggesting that the microbiome is derived passively within the lungs from the oral cavity via micro-aspiration."
- "Elimination, immigration, and relative growth within its communities all contribute to the composition of the lung microbiome."
- "There is a close relationship between the lungs and the brain, which can be called the lung-brain axis."
- "However, the problem now is that it is not well understood how the lung microbiota plays a role in the disease-specifically, whether there is a causal connection between disease and the lung microbiome."
- "The lung microbiome includes bacteria, archaea, fungi, protozoa, and viruses."
- "However, fungi and viruses have not been fully studied compared to bacteria in the lungs."
- "The gut-lung-brain (GLB) axis is a multidirectional communication network linking the gastrointestinal tract, respiratory system, and central nervous system (CNS) through neural, endocrine, and immune pathways."
- "Emerging evidence suggests that tryptophan (Trp) metabolism serves as a key integrating node within this axis, modulating host-microbe interactions involved in systemic homeostasis."
- "Trp catabolism follows three divergent pathways: the kynurenine (Kyn) pathway, which is involved in immune tolerance but can generate neuroactive and potentially neurotoxic metabolites; the serotonin pathway, essential for mood and gastrointestinal motility; and the microbial indole pathway, which supports epithelial barrier function through aryl hydrocarbon receptor activation."
- "These alterations contribute to systemic low-grade inflammation and immune dysregulation, which further propagate cross-organ pathology within the GLB axis. This review synthesizes current evidence on how Trp metabolites may function as cross-organ mediators, contributing to the "leaky gut" and "leaky brain" phenotypes."
- "Intratracheal transplantation of lung microbiota from anxiety-susceptible donors induced similar behavioral changes in recipient mice, indicating a causal role of the pulmonary microbiota."
- "Transcriptomic and immunofluorescence analyses suggested that formononetin acts through modulation of hippocampal microglia."
- "Neonatal sevoflurane exposure in mice induces microglial activation and long-term cognitive deficits, a finding that raises significant concerns for pediatric anesthesia."
- "Developmental sevoflurane exposure induces microglial activation and cognitive decline via a pulmonary dysbiosis-sphingosine reduction cascade."
- "Notably, sphingosine-a key membrane lipid-was significantly decreased."
- "Epidemiological and clinical evidence shows a close association between compromised lung health-including chronic obstructive pulmonary disease (COPD), asthma, obstructive sleep apnea (OSA), and pulmonary infections-and cognitive impairment and dementia."
- "Melatonin increased gut-derived butyrate levels and restored gut microbiota balance."
- "Mechanistically, both treatments inhibited the activation of the MAPK/P65/NLRP3 pathway in hippocampal microglia and LPS-stimulated BV2 cells."
- "Emerging evidence suggests that Parkinson's disease (PD) extends beyond the brain and involves early disturbances along the gut-brain axis."
- "Conversely, uremic indoles such as indoxyl sulfate (IS) and p-cresyl sulfate (pCS) activate microglia and astrocytes, promote α-synuclein aggregation, and accelerate dopaminergic neuron loss."
- "Esketamine improved pulmonary function and behavior, reduced neuronal apoptosis and microglial activation, and suppressed MAPK/NF-κB signaling; these effects were partly reversed by Diprovocim."
- "Microbiota profiling showed dysbiosis of gut and lung communities, with loss of beneficial taxa and expansion of conditional pathogens, whereas esketamine partially restored balance by promoting commensals and reducing potential pathogens."
- "These factors activated toll-like receptors (TLR2/TLR4), microglia, and astrocytes, increasing levels of interleukin 1 beta, tumor necrosis factor-alpha, and other proinflammatory cytokines."
- "Parkinson's Disease (PD), a complex neurodegenerative disorder, is increasingly recognized as a systemic condition involving multi-organ interactions."
- "Western diets (WD) contribute to obesity, and previous reviews have described a role for WD in impaired hippocampal-dependent memory."
- "Gut microbiota impacts gastrointestinal barrier function, leading to increased circulating proinflammatory bacterial products, increased blood-brain barrier permeability, and neuroinflammation."
- "Multi-omics analyses uncovered distinctive metabolic responses between the delta and omicron variants, with the former demonstrating dysregulation in synaptic transmission proteins associated with neurocognitive disorders."
- "These findings underscore the SARS-CoV-2-mediated tissue insult, characterized by modified host metabolites, neurological protein dysregulation, and gut dysbiosis, highlighting the compromised gut-lung-brain axis during acute infection."
- "Repeated oral inoculation of mice with P. gingivalis results in brain infiltration of bacterial products, increased inflammation, and induction of AD-like biomarkers."
- "Numerous studies have underscored the mediation of the lung-brain axis by inflammatory responses and hypoxia-induced damage, which are pivotal to the progression of both pulmonary and neurological diseases."
- "Additionally, we highlight the emerging research on the lung microbiome which, drawing parallels between the gut and lungs in terms of microbiome contents, may play a significant role in modulating brain health."
- "In the human body, the gut and lung are regarded as the key reactional targets that are initiated by brain ischemic attacks."
- "Mucosal microorganisms play an important role in immune regulation and metabolism and affect blood-brain barrier permeability."
- "Pulmonary microbes were found to enhance Th1-type immunoreactivity induced by RSV infection and eventually induced M1-type dominant microglia in the brains of mice."
- "This study was able to establish a correlation between the pulmonary microbiome and brain function."
- "An impaired BBB allows the translocation of potentially harmful bacterial products, including LPS, and activated neutrophils/leucocytes into the brain, which results in neuroinflammation and apoptosis."
- "Chronic neuroinflammation causes neuronal damage and synaptic loss, leading to memory impairment."
- "In a recent issue of Nature, Hosang et al. demonstrate how the lung microbiome regulates the magnitude of autoimmune inflammation in the brain."
- "Excessive alcohol use can result in translocation of bacterial products into circulation, increased expression of pro-inflammatory cytokines, and activation of immune cells, including macrophages and/or microglia in the liver and brain."
- "There is a growing amount of evidence showing a reciprocal relation between the gut microbiota and the brain."
- "The communication between the microbiota and the brain exists through different pathways: (1) the immune response elicited by bacterial products, coupled with alterations of the intestinal barrier allowing these products to enter the bloodstream, (2) the direct and indirect effects of bacterial metabolites such as short chain fatty acids (SCFAs) or tryptophan on the brain, (3) and the hypothalamic-pituitary-adrenal (HPA) axis, whose peripheral afferents can be influenced by the microbiota, and can in turn activate microglia."
- "In some but not all patients suffering from alcohol-use-disorder (AUD), alcohol alters the composition of the gut microbiota and the permeability of the intestinal barrier, directly and through dysbiosis."
- "We found that tannic acid is necessary for binding with HSV-1, with smaller sizes independent of the NPs composition, whereas for larger NPs, only TA-AgNPs can inhibit HSV-1 infection."
- "Intranasal treatment of HSV-1 infection with TA-Ag/AuNPs results in lower viral titers and a better antiviral response, followed by increased IFN-α, CXCL9, and CXCL10 levels as well as infiltration of T cells and NK cells in the infected sites."
- "We also found that the application of TA-NPs to the nasal cavities of infected mice induced infiltration of both monocytes and Langerhans cells (LCs), which lasted longer compared to the application of unmodified NPs."
- "Furthermore, TA-NPs activated monocytes and microglia to produce antiviral cytokines and chemokines better than unmodified NPs, except for the large TA-AuNPs."
- "Treatment of the mucosal tissues at the early stage of HSV-1 infection helps to modulate specific and effective antiviral immune response by attracting cytotoxic lymphocytes and inducing the production of antiviral cytokines and chemokines."
- "Furthermore, tannic acid modification is helpful for the removal of nanoparticles from the respiratory tract, which increases the safety of nanoparticle applications to treat infections."
- "HSV-1 also invades the nervous system where it establishes a lifelong latency-making infection poorly treatable"
- "Due to the limitations of culture techniques, the lung in a healthy state is traditionally considered to be a sterile organ."
- "The species of the lung microbiome are similar to those of the oral microbiome, suggesting that the microbiome is derived passively within the lungs from the oral cavity via micro-aspiration."
- "Elimination, immigration, and relative growth within its communities all contribute to the composition of the lung microbiome."
- "There is a close relationship between the lungs and the brain, which can be called the lung-brain axis."
- "However, the problem now is that it is not well understood how the lung microbiota plays a role in the disease-specifically, whether there is a causal connection between disease and the lung microbiome."
- "The lung microbiome includes bacteria, archaea, fungi, protozoa, and viruses."
- "However, fungi and viruses have not been fully studied compared to bacteria in the lungs."
- "The gut-lung-brain (GLB) axis is a multidirectional communication network linking the gastrointestinal tract, respiratory system, and central nervous system (CNS) through neural, endocrine, and immune pathways."
- "Emerging evidence suggests that tryptophan (Trp) metabolism serves as a key integrating node within this axis, modulating host-microbe interactions involved in systemic homeostasis."
- "Trp catabolism follows three divergent pathways: the kynurenine (Kyn) pathway, which is involved in immune tolerance but can generate neuroactive and potentially neurotoxic metabolites; the serotonin pathway, essential for mood and gastrointestinal motility; and the microbial indole pathway, which supports epithelial barrier function through aryl hydrocarbon receptor activation."
- "These alterations contribute to systemic low-grade inflammation and immune dysregulation, which further propagate cross-organ pathology within the GLB axis. This review synthesizes current evidence on how Trp metabolites may function as cross-organ mediators, contributing to the "leaky gut" and "leaky brain" phenotypes."
- "Intratracheal transplantation of lung microbiota from anxiety-susceptible donors induced similar behavioral changes in recipient mice, indicating a causal role of the pulmonary microbiota."
- "Transcriptomic and immunofluorescence analyses suggested that formononetin acts through modulation of hippocampal microglia."
- "Neonatal sevoflurane exposure in mice induces microglial activation and long-term cognitive deficits, a finding that raises significant concerns for pediatric anesthesia."
- "Developmental sevoflurane exposure induces microglial activation and cognitive decline via a pulmonary dysbiosis-sphingosine reduction cascade."
- "Notably, sphingosine-a key membrane lipid-was significantly decreased."
- "Epidemiological and clinical evidence shows a close association between compromised lung health-including chronic obstructive pulmonary disease (COPD), asthma, obstructive sleep apnea (OSA), and pulmonary infections-and cognitive impairment and dementia."
- "Melatonin increased gut-derived butyrate levels and restored gut microbiota balance."
- "Mechanistically, both treatments inhibited the activation of the MAPK/P65/NLRP3 pathway in hippocampal microglia and LPS-stimulated BV2 cells."
- "Emerging evidence suggests that Parkinson's disease (PD) extends beyond the brain and involves early disturbances along the gut-brain axis."
- "Conversely, uremic indoles such as indoxyl sulfate (IS) and p-cresyl sulfate (pCS) activate microglia and astrocytes, promote α-synuclein aggregation, and accelerate dopaminergic neuron loss."
- "Esketamine improved pulmonary function and behavior, reduced neuronal apoptosis and microglial activation, and suppressed MAPK/NF-κB signaling; these effects were partly reversed by Diprovocim."
- "Microbiota profiling showed dysbiosis of gut and lung communities, with loss of beneficial taxa and expansion of conditional pathogens, whereas esketamine partially restored balance by promoting commensals and reducing potential pathogens."
- "These factors activated toll-like receptors (TLR2/TLR4), microglia, and astrocytes, increasing levels of interleukin 1 beta, tumor necrosis factor-alpha, and other proinflammatory cytokines."
- "Parkinson's Disease (PD), a complex neurodegenerative disorder, is increasingly recognized as a systemic condition involving multi-organ interactions."
- "Western diets (WD) contribute to obesity, and previous reviews have described a role for WD in impaired hippocampal-dependent memory."
- "Gut microbiota impacts gastrointestinal barrier function, leading to increased circulating proinflammatory bacterial products, increased blood-brain barrier permeability, and neuroinflammation."
- "Multi-omics analyses uncovered distinctive metabolic responses between the delta and omicron variants, with the former demonstrating dysregulation in synaptic transmission proteins associated with neurocognitive disorders."
- "These findings underscore the SARS-CoV-2-mediated tissue insult, characterized by modified host metabolites, neurological protein dysregulation, and gut dysbiosis, highlighting the compromised gut-lung-brain axis during acute infection."
- "Repeated oral inoculation of mice with P. gingivalis results in brain infiltration of bacterial products, increased inflammation, and induction of AD-like biomarkers."
- "Numerous studies have underscored the mediation of the lung-brain axis by inflammatory responses and hypoxia-induced damage, which are pivotal to the progression of both pulmonary and neurological diseases."
- "Additionally, we highlight the emerging research on the lung microbiome which, drawing parallels between the gut and lungs in terms of microbiome contents, may play a significant role in modulating brain health."
- "In the human body, the gut and lung are regarded as the key reactional targets that are initiated by brain ischemic attacks."
- "Mucosal microorganisms play an important role in immune regulation and metabolism and affect blood-brain barrier permeability."
- "Pulmonary microbes were found to enhance Th1-type immunoreactivity induced by RSV infection and eventually induced M1-type dominant microglia in the brains of mice."
- "This study was able to establish a correlation between the pulmonary microbiome and brain function."
- "An impaired BBB allows the translocation of potentially harmful bacterial products, including LPS, and activated neutrophils/leucocytes into the brain, which results in neuroinflammation and apoptosis."
- "Chronic neuroinflammation causes neuronal damage and synaptic loss, leading to memory impairment."
- "In a recent issue of Nature, Hosang et al. demonstrate how the lung microbiome regulates the magnitude of autoimmune inflammation in the brain."
- "Excessive alcohol use can result in translocation of bacterial products into circulation, increased expression of pro-inflammatory cytokines, and activation of immune cells, including macrophages and/or microglia in the liver and brain."
- "There is a growing amount of evidence showing a reciprocal relation between the gut microbiota and the brain."
- "The communication between the microbiota and the brain exists through different pathways: (1) the immune response elicited by bacterial products, coupled with alterations of the intestinal barrier allowing these products to enter the bloodstream, (2) the direct and indirect effects of bacterial metabolites such as short chain fatty acids (SCFAs) or tryptophan on the brain, (3) and the hypothalamic-pituitary-adrenal (HPA) axis, whose peripheral afferents can be influenced by the microbiota, and can in turn activate microglia."
- "In some but not all patients suffering from alcohol-use-disorder (AUD), alcohol alters the composition of the gut microbiota and the permeability of the intestinal barrier, directly and through dysbiosis."
- "We found that tannic acid is necessary for binding with HSV-1, with smaller sizes independent of the NPs composition, whereas for larger NPs, only TA-AgNPs can inhibit HSV-1 infection."
- "Intranasal treatment of HSV-1 infection with TA-Ag/AuNPs results in lower viral titers and a better antiviral response, followed by increased IFN-α, CXCL9, and CXCL10 levels as well as infiltration of T cells and NK cells in the infected sites."
- "We also found that the application of TA-NPs to the nasal cavities of infected mice induced infiltration of both monocytes and Langerhans cells (LCs), which lasted longer compared to the application of unmodified NPs."
- "Furthermore, TA-NPs activated monocytes and microglia to produce antiviral cytokines and chemokines better than unmodified NPs, except for the large TA-AuNPs."
- "Treatment of the mucosal tissues at the early stage of HSV-1 infection helps to modulate specific and effective antiviral immune response by attracting cytotoxic lymphocytes and inducing the production of antiviral cytokines and chemokines."
- "Furthermore, tannic acid modification is helpful for the removal of nanoparticles from the respiratory tract, which increases the safety of nanoparticle applications to treat infections."
- "HSV-1 also invades the nervous system where it establishes a lifelong latency-making infection poorly treatable"
- "Due to the limitations of culture techniques, the lung in a healthy state is traditionally considered to be a sterile organ."
- "There is a close relationship between the lungs and the brain, which can be called the lung-brain axis."