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.

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.

The pathogenesis of severe acute pancreatitis-associated acute lung injury (SAP-ALI), which is the leading cause of mortality among hospitalized patients in the intensive care unit, remains incompletely elucidated. The intestinal mucosal immune barrier is a crucial component of the intestinal epithelial barrier, and its aberrant activation contributes to the induction of sustained pro-inflammatory immune responses, paradoxical intercellular communication, and bacterial translocation. In this review, we firstly provide a comprehensive overview of the composition of the intestinal mucosal immune barrier and its pivotal roles in the pathogenesis of SAP-ALI. Secondly, the mechanisms of its crosstalk with gut microbiota, which is called gut-lung axis, and its effect on SAP-ALI were summarized. Finally, a number of drugs that could enhance the intestinal mucosal immune barrier and exhibit potential anti-SAP-ALI activities were presented, including probiotics, glutamine, enteral nutrition, and traditional Chinese medicine (TCM). The aim is to offer a theoretical framework based on the perspective of the intestinal mucosal immune barrier to protect against SAP-ALI.

Acute pancreatitis (AP) represents a significant global health challenge. Despite recent advances in medical treatment, the development of novel therapeutic strategies remains crucial. Rhein, a natural compound of the Chinese herb Rheum, shows promise in the treatment of AP. However, the exact mechanism underlying its therapeutic effect is still not fully understood. To investigate the association between the rhein-related gut microbiota and AP, we conducted antibiotic-mediated microbiota depletion experiments, fecal microbiota transplantation (FMT), and in vitro bacterial culture experiments. Concurrently, we performed 16S rRNA gene sequencing, metagenomic sequencing, and liquid chromatography‒mass spectrometry (LC‒MS) analyses on mouse fecal samples to characterize alterations in the microbiota and metabolome. Transcriptomic studies were also performed to elucidate the mechanisms underlying acinar cell inflammation. Rhein alleviated AP by modulating the gut microbiota, as demonstrated by changes in the gut microbiota composition and improvements in AP after FMT in rhein-treated mice compared with those in cerulein-induced AP mice. Specifically, rhein is concentrated mainly in the stomach and intestines, where it exerts anti-inflammatory effects on acinar cells by antagonizing the TLR4/NF-κB/NLRP3 signaling pathway activated by trimethylamine-N-oxide (TMAO). This mechanism is associated with lipid peroxidation and necrosis mediated by oxidative stress. Clinically, disease severity in patients with AP is positively correlated with serum TMAO concentration. Rhein alleviates AP by modulating the intestinal microbiota to reduce TMAO production, thereby suppressing TMAO-induced activation of the TLR4/NF-κB/NLRP3 signaling pathway and inhibiting acinar cell inflammation.

Background: The mental health of university students, particularly depression, has become a significant public health concern in China. While previous studies have highlighted the link between self-efficacy and mental health, especially concerning depressive symptoms, the potential mediating role of the big five personality traits in this relationship remains underexplored. This study aims to examine the relationships among self-efficacy, the big five personality traits, and depressive symptoms through a mediation model.Methods: This cross-sectional study utilized a multi-stage stratified random sampling method to survey residents across 23 provinces in China, ultimately enrolling 1,193 university students aged 19-25. Measures included the PHQ-9 to assess depressive symptoms, the BFI-10 to evaluate personality traits, and the NGSES for self-efficacy. Hierarchical regression, random forest regression, mediation analyses, and restricted cubic spline (RCS) models were conducted using R software.Results: The prevalence of depressive symptoms among university students was 21.8%. Neuroticism (p<0.001) was a positive predictor of depressive symptoms, while agreeableness (P<0.001) and conscientiousness (P<0.001) were negative predictors. And agreeableness [Effect = -0.028, 95% CI (-0.045, -0.014)], conscientiousness [Effect = -0.043, 95% CI (-0.067, -0.023)], and neuroticism [Effect = -0.048, 95% CI (-0.070, -0.029)] significantly mediated the relationship between self-efficacy and depressive symptoms. Additionally, a potential nonlinear relationship (p for nonlinearity < 0.001) was identified between self-efficacy and depressive symptoms.Conclusions: Self-efficacy shows a direct positive association with depressive symptoms when controlling for personality traits, with neuroticism, agreeableness, and conscientiousness serving as key mediators. This highlights that the effect of self-efficacy on depression depends critically on personality, emphasizing the need to consider these traits in interventions for university students’ mental health.