Mechanisms of Qingyi Decoction in Severe Acute Pancreatitis-Associated Acute Lung Injury via Gut Microbiota: Targeting the Short-Chain Fatty Acids-Mediated AMPK/NF-κB/NLRP3 Pathway

Wang, Zhengjian; Liu, Jin; Li, Fan; Ma, Shu‐Rong; Zhao, Liang; Ge, Peng; Wen, Haiyun; Zhang, Hongjie; Liu, Xiaojun; Luo, Yalan; Yao, Jiaqi; Zhang, Guixin; Chen, Hailong

doi:10.1128/spectrum.03664-22

Cited by 8 publications

(8 citation statements)

References 66 publications

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“…SCFAs also play an important role in the immune response of the host and in metabolism. Numerous studies have shown that the gut microbiota can modulate SCFAs to alleviate acute lung injury [54][55][56]. In the present study, heat-inactivated MRSA induced a decrease in SCFAs in ALI in mice, and propolis pretreatment elevated the concentrations of acetic acid and valeric acid to reverse these changes.…”

Section: Discussionsupporting

confidence: 47%

Propolis Alleviates Acute Lung Injury Induced by Heat-Inactivated Methicillin-Resistant Staphylococcus aureus via Regulating Inflammatory Mediators, Gut Microbiota and Serum Metabolites

Li,

Liu,

Guo

et al. 2024

Nutrients

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Propolis has potential anti-inflammatory properties, but little is known about its efficacy against inflammatory reactions caused by drug-resistant bacteria, and the difference in efficacy between propolis and tree gum is also unclear. Here, an in vivo study was performed to study the effects of ethanol extract from poplar propolis (EEP) and poplar tree gum (EEG) against heat-inactivated methicillin-resistant Staphylococcus aureus (MRSA)-induced acute lung injury (ALI) in mice. Pre-treatment with EEP and EEG (100 mg/kg, p.o.) resulted in significant protective effects on ALI in mice, and EEP exerted stronger activity to alleviate lung tissue lesions and ALI scores compared with that of EEG. Furthermore, EEP significantly suppressed the levels of pro-inflammatory mediators in the lung, including TNF-α, IL-1β, IL-6, and IFN-γ. Gut microbiota analysis revealed that both EEP and EEG could modulate the composition of the gut microbiota, enhance the abundance of beneficial microbiota and reduce the harmful ones, and partly restore the levels of short-chain fatty acids. EEP could modulate more serum metabolites and showed a more robust correlation between serum metabolites and gut microbiota. Overall, these results support the anti-inflammatory effects of propolis in the treatment of ALI, and the necessity of the quality control of propolis.

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Section: Discussionsupporting

confidence: 47%

Propolis Alleviates Acute Lung Injury Induced by Heat-Inactivated Methicillin-Resistant Staphylococcus aureus via Regulating Inflammatory Mediators, Gut Microbiota and Serum Metabolites

Li,

Liu,

Guo

et al. 2024

Nutrients

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“…Substantial research has supported that the gut microbiota is closely related to the development and progression of ALI by transmitting gut-lung axis activation. The intestinal flora plays an important role in maintaining the normal immune function of the body, reducing bacterial translocation and improving lung injury [48]. Compared to the control group, the model group with an imbalance in the gut flora showed more obvious gut damage and decreased expression of ZO-1 and occludin [29,49].…”

Section: Discussionmentioning

confidence: 99%

Preventive Effect of the Total Polyphenols from Nymphaea candida on Sepsis-Induced Acute Lung Injury in Mice via Gut Microbiota and NLRP3, TLR-4/NF-κB Pathway

Li,

Qi,

et al. 2024

IJMS

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This study aimed to investigate the preventive effects of the total polyphenols from Nymphaea candida (NCTP) on LPS-induced septic acute lung injury (ALI) in mice and its mechanisms. NCTP could significantly ameliorate LPS-induced lung tissue pathological injury in mice as well as lung wet/dry ratio and MPO activities (p < 0.05). NCTP could significantly decrease the blood leukocyte, neutrophil, monocyte, basophil, and eosinophil amounts and LPS contents in ALI mice compared with the model group (p < 0.05), improving lymphocyte amounts (p < 0.05). Moreover, compared with the model group, NCTP could decrease lung tissue TNF-α, IL-6, and IL-1β levels (p < 0.05) and downregulate the protein expression of TLR4, MyD88, TRAF6, IKKβ, IκB-α, p-IκB-α, NF-κB p65, p-NF-κB p65, NLRP3, ASC, and Caspase1 in lung tissues (p < 0.05). Furthermore, NCTP could inhibit ileum histopathological injuries, restoring the ileum tight junctions by increasing the expression of ZO-1 and occludin. Simultaneously, NCTP could reverse the gut microbiota disorder, restore the diversity of gut microbiota, increase the relative abundance of Clostridiales and Lachnospiraceae, and enhance the content of SCFAs (acetic acid, propionic acid, and butyric acid) in feces. These results suggested that NCTP has preventive effects on septic ALI, and its mechanism is related to the regulation of gut microbiota, SCFA metabolism, and the TLR-4/NF-κB and NLRP3 pathways.

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“…To the extent of our knowledges, our research constitutes the first wide-ranging, in-depth MR analysis aimed at examining the cause-and-effect relationship between intestinal microbiota and pancreatitis at a genetic prediction scale. Prior research probing the relationship between gut microbiota and pancreatitis has predominantly utilized animal models as the primary mode of investigation (Zhang et al, 2019;Zhu et al, 2019;Glaubitz et al, 2023;Hu et al, 2023;Jiao et al, 2023;Wang Z. et al, 2023). These findings might bear significance for public health initiatives that are targeted toward mitigating the risk associated with pancreatitis.…”

Section: Discussionmentioning

confidence: 99%

Causal link between gut microbiota and four types of pancreatitis: a genetic association and bidirectional Mendelian randomization study

Wang,

Qin,

Ran

et al. 2023

Front. Microbiol.

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BackgroundA number of recent observational studies have indicated a correlation between the constitution of gut microbiota and the incidence of pancreatitis. Notwithstanding, observational studies are unreliable for inferring causality because of their susceptibility to confounding, bias, and reverse causality, the causal relationship between specific gut microbiota and pancreatitis is still unclear. Therefore, our study aimed to investigate the causal relationship between gut microbiota and four types of pancreatitis.MethodsAn investigative undertaking encompassing a genome-wide association study (GWAS) comprising 18,340 participants was undertaken with the aim of discerning genetic instrumental variables that exhibit associations with gut microbiota, The aggregated statistical data pertaining to acute pancreatitis (AP), alcohol-induced AP (AAP), chronic pancreatitis (CP), and alcohol-induced CP (ACP) were acquired from the FinnGen Consortium. The two-sample bidirectional Mendelian randomization (MR) approach was utilized. Utilizing the Inverse-Variance Weighted (IVW) technique as the cornerstone of our primary analysis. The Bonferroni analysis was used to correct for multiple testing, In addition, a number of sensitivity analysis methodologies, comprising the MR-Egger intercept test, the Cochran’s Q test, MR polymorphism residual and outlier (MR-PRESSO) test, and the leave-one-out test, were performed to evaluate the robustness of our findings.ResultsA total of 28 intestinal microflora were ascertained to exhibit significant associations with diverse outcomes of pancreatitis. Among them, Class Melainabacteria (OR = 1.801, 95% CI: 1.288–2.519, p = 0.008) has a strong causality with ACP after the Bonferroni-corrected test, in order to assess potential reverse causation effects, we used four types of pancreatitis as the exposure variable and scrutinized its impact on gut microbiota as the outcome variable, this analysis revealed associations between pancreatitis and 30 distinct types of gut microflora. The implementation of Cochran’s Q test revealed a lack of substantial heterogeneity among the various single nucleotide polymorphisms (SNP).ConclusionOur first systematic Mendelian randomization analysis provides evidence that multiple gut microbiota taxa may be causally associated with four types of pancreatitis disease. This discovery may contribute significant biomarkers conducive to the preliminary, non-invasive identification of Pancreatitis. Additionally, it could present viable targets for potential therapeutic interventions in the disease’s treatment.

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Mechanisms of Qingyi Decoction in Severe Acute Pancreatitis-Associated Acute Lung Injury via Gut Microbiota: Targeting the Short-Chain Fatty Acids-Mediated AMPK/NF-κB/NLRP3 Pathway

Abstract: Gut microbiota affects the severity of SAP-ALI and intestinal barrier function. During SAP, a significant increase in the relative abundance of gut pathogens ( Escherichia , Enterococcus , Enterobacter , Peptostreptococcus , Helicobacter ) was observed.

Cited by 8 publications

References 66 publications

Propolis Alleviates Acute Lung Injury Induced by Heat-Inactivated Methicillin-Resistant Staphylococcus aureus via Regulating Inflammatory Mediators, Gut Microbiota and Serum Metabolites

Propolis Alleviates Acute Lung Injury Induced by Heat-Inactivated Methicillin-Resistant Staphylococcus aureus via Regulating Inflammatory Mediators, Gut Microbiota and Serum Metabolites

Preventive Effect of the Total Polyphenols from Nymphaea candida on Sepsis-Induced Acute Lung Injury in Mice via Gut Microbiota and NLRP3, TLR-4/NF-κB Pathway

Causal link between gut microbiota and four types of pancreatitis: a genetic association and bidirectional Mendelian randomization study

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