Search

The pivotal roles of gut microbiota in severe acute pancreatitis-associated acute lung injury (SAP-ALI) are increasingly revealed, and recent discoveries in the gut-lung axis have provided potential approaches for treating SAP-ALI. Qingyi decoction (QYD), a traditional Chinese medicine (TCM), is commonly used in clinical to treat SAP-ALI. However, the underlying mechanisms remain to be fully elucidated. Herein, by using a caerulein plus lipopolysaccharide (LPS)-induced SAP-ALI mice model and antibiotics (Abx) cocktail-induced pseudogermfree mice model, we tried to uncover the roles of the gut microbiota by administration of QYD and explored its possible mechanisms. Immunohistochemical results showed that the severity of SAP-ALI and intestinal barrier functions could be affected by the relative depletion of intestinal bacteria. The composition of gut microbiota was partially recovered after QYD treatment with decreased Firmicutes / Bacteroidetes ratio and increased relative abundance in short-chain fatty acids (SCFAs)-producing bacteria. Correspondingly increased levels of SCFAs (especially propionate and butyrate) in feces, gut, serum, and lungs were observed, generally consistent with changes in microbes. Western-blot analysis and RT-qPCR results indicated that the AMPK/NF-κB/NLRP3 signaling pathway was activated after oral administration of QYD, which was found to be possibly related to the regulatory effects on SCFAs in the intestine and lungs. In conclusion, our study provides new insights into treating SAP-ALI through modulating the gut microbiota and has prospective practical value for clinical use in the future. IMPORTANCE 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. At the same time, QYD treatment decreased pathogenic bacteria and increased the relative abundance of SCFAs-producing bacteria ( Bacteroides , Roseburia , Parabacteroides , Prevotella , Akkermansia ). In addition, The AMPK/NF-κB/NLRP3 pathway mediated by SCFAs along the gut-lung axis may play an essential role in preventing the pathogenesis of SAP-ALI, which allows for reduced systemic inflammation and restoration of the intestinal barrier., Competing Interests: The authors declare no conflict of interest.

Immunogenic cell death (ICD) is a form of programmed cell death with a strong sense of inflammatory detection, whose powerful situational awareness can cause the reactivation of aberrant immunity. However, the role of ICD in the pathogenesis of severe acute pancreatitis (SAP) has yet to be investigated. This study aims to explore the pivotal genes associated with ICD in SAP and how they relate to immune infiltration and short-chain fatty acids (SCFAs), in order to provide a theoretical foundation for further, in-depth mechanistic studies. We downloaded GSE194331 datasets from the Gene Expression Omnibus (GEO). The use of differentially expressed gene (DEG) analysis; weighted gene co-expression network analysis (WGCNA) and least absolute shrinkage and selection operator (LASSO) regression analysis allowed us to identify a total of three ICD-related hub genes ( LY96 , BCL2 , IFNGR1 ) in SAP. Furthermore, single sample gene set enrichment analysis (ssGSEA) demonstrated that hub genes are closely associated with the infiltration of specific immune cells, the activation of immune pathways and the metabolism of SCFAs (especially butyrate). These findings were validated through the analysis of gene expression patterns in both clinical patients and rat animal models of SAP. In conclusion, the first concept of ICD in the pathogenesis of SAP was proposed in our study. This has important implications for future investigations into the pro-inflammatory immune mechanisms mediated by damage-associated molecular patterns (DAMPs) in the late stages of SAP.

The role of gut microbiota in regulating the intestinal homeostasis, as well as the pathogenesis of severe acute pancreatitis-associated lung injury (PALI) is widely recognized. The bioactive functions of metabolites with small molecule weight and the detail molecular mechanisms of PALI mediated by "gut-lung axis" have gradually raised the attentions of researchers. Several studies have proved that short-chain fatty acids (SCFAs) produced by gut microbiome play crucial roles and varied activities in the process of PALI. However, relevant reviews reporting SCFAs in the involvement of PALI is lacking. In this review, we firstly introduced the synthetic and metabolic pathways of SCFAs, as well as the transport and signal transduction routes in brief. Afterwards, we focused on the possible mechanisms and clues of SCFAs to participate in the fight against PALI which referred to the inhibition of pathogen proliferation, anti-inflammatory effects, enhancement of intestinal barrier functions, and the maintenance and regulation of immune homeostasis via pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). In addition, the latest reported pathological and physiological mechanisms of the gut-lung axis involved in PALI were reviewed. Finally, we summarized the potential therapeutic interventions of PALI by targeting SCFAs, including dietary fiber supplementation, direct supplementation of SCFAs/prebiotics/probiotics, and drugs administration, which is expected to provide new sights for clinical use in the future., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Severe acute pancreatitis (SAP), one of the most serious abdominal emergencies in general surgery, is characterized by acute and rapid onset as well as high mortality, which often leads to multiple organ failure (MOF). Acute lung injury (ALI), the earliest accompanied organ dysfunction, is the most common cause of death in patients following the SAP onset. The exact pathogenesis of ALI during SAP, however, remains unclear. In recent years, advances in the microbiota-gut-lung axis have led to a better understanding of SAP-associated lung injury (PALI). In addition, the bidirectional communications between intestinal microbes and the lung are becoming more apparent. This paper aims to review the mechanisms of an imbalanced intestinal microbiota contributing to the development of PALI, which is mediated by the disruption of physical, chemical, and immune barriers in the intestine, promotes bacterial translocation, and results in the activation of abnormal immune responses in severe pancreatitis. The pathogen-associated molecular patterns (PAMPs) mediated immunol mechanisms in the occurrence of PALI via binding with pattern recognition receptors (PRRs) through the microbiota-gut-lung axis are focused in this study. Moreover, the potential therapeutic strategies for alleviating PALI by regulating the composition or the function of the intestinal microbiota are discussed in this review. The aim of this study is to provide new ideas and therapeutic tools for PALI patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Li, Liu, Luo, Guo, Yang, Xu, Ma and Chen.)