Vitamin D, a crucial fat-soluble vitamin, is primarily synthesized in the skin upon exposure to ultraviolet radiation and is widely recognized as a bone-associated hormone. However, recent scientific advancements have unveiled its intricate association with gut health. The intestinal barrier serves as a vital component, safeguarding the intestinal milieu and maintaining overall homeostasis. Deficiencies in vitamin D have been implicated in altering the gut microbiome composition, compromising the integrity of the intestinal mucosal barrier, and predisposing individuals to various intestinal pathologies. Vitamin D exerts its regulatory function by binding to vitamin D receptors (VDR) present in immune cells, thereby modulating the production of pro-inflammatory cytokines and influencing the intestinal barrier function. Notably, numerous studies have reported lower serum vitamin D levels among patients suffering from intestinal diseases, including inflammatory bowel disease, irritable bowel syndrome, and celiac disease, highlighting the growing significance of vitamin D in gut health maintenance. This comprehensive review delves into the latest advancements in understanding the mechanistic role of vitamin D in modulating the gut microbiome and intestinal barrier function, emphasizing its pivotal role in immune regulation. Furthermore, we consolidate and present relevant findings pertaining to the therapeutic potential of vitamin D in the management of intestinal diseases.

OBJECTIVE: This study uses a two-sample Mendelian randomization (MR) analysis to delineate the causal influence of gut microbiota on the occurrence of irritable bowel syndrome (IBS), concurrently assessing the potential mediating function of depression within this framework.
METHODS: Several two-sample MR methods were used to assess the causal repercussions of gut microbiota on the onset of both IBS and depression. Following this, gut microbiota and depression, which demonstrated notable causal associations, were integrated as exposure variables in a multivariable Mendelian randomization (MVMR) framework to construct a model encompassing gut microbiota, depression, and IBS. Mediation effects were assessed by examining the indirect pathway of gut microbiota → depression → IBS.
RESULTS: Two-sample MR analysis unveiled a statistically significant causal association (P < 0.05) between specific bacterial group within the gut microbiota, notably p_Actinobacteria(OR = 0.829225), c_Clostridia(OR = 0.798897), s_Desulfovibrio_piger(OR = 1.163912), g_Streptococcus(OR = 1.132735), c_Actinobacteria(OR = 0.829224), and the onset of IBS. In the MVMR analysis, the relationship between depression and IBS was significant across Model 3, Model 7, Model 8, and Model 13 (P < 0.05). Assessment of mediation effects revealed that c_Clostridia and o_Clostridiales indirectly impacted IBS through depression, with masking effect ratios of 168.46 % and 168.44 %, respectively.
CONCLUSIONS: These findings underscore a resilient causal association between the composition of gut microbiota and the initiation of IBS. Furthermore, depression serves as a mediator for particular groups of gut bacteria, thereby contributing to the development of IBS. These observations imply that interventions targeting mental health may potentially alleviate the risk of IBS onset attributable to adverse configurations of gut microbiota.

BACKGROUND: Irritable Bowel Syndrome (IBS) is a prevalent gastrointestinal disorder that significantly diminishes the quality of life for affected individuals. The pathophysiology of IBS remains poorly understood, and available therapeutic options for IBS are limited. The crucial roles of brain-gut interaction, which is mediated by the Hypothalamic-Pituitary-Adrenocortical (HPA) axis and the autonomic nervous system in IBS, have attracted increasing attention.
OBJECTIVE: The objective of this study was to examine the impact of paeoniflorin (PF) on anxiety and visceral hypersensitivity in maternal separation-induced IBS-like rats.
METHODS: The IBS-like rat model was established through the implementation of Maternal Separation (MS) and subsequently subjected to various doses of PF administered via oral gavage for 14 days. Anxiety-like behavior was evaluated using the Open Field Test (OFT) and Elevated Plus Maze (EPM) test. The assessment of visceral sensitivity involved the utilization of the Abdominal Withdrawal Reflex (AWR) score and electromyographic (EMG) responses of the external oblique muscle in response to colorectal distention. The levels of adrenocorticotropic hormone (ACTH), corticosterone (CORT), and corticotrophin-releasing hormone (CRH) were examined by ELISA. Quantitative real-time PCR (qRT-PCR) and immunofluorescence were employed to detect the expressions of CRH receptors 1 (CRHR1) and 2 (CRHR2). Glucocorticoid receptors (GR), mineralocorticoid receptor (MR), brain-derived neurotrophic factor (BDNF), tyrosine receptor kinase B (TrkB), and phospholipase C γ1 (PLCγ1) were examined by Western blot.
CONCLUSIONS: The results showed that MS induced anxiety-like behavior and visceral hypersensitivity, while PF treatment attenuated these changes. Furthermore, the HPA axis hyperactivity in MS rats was attenuated by PF treatment, indicated by reduced serum ACTH, CORT, and CRH levels and recovered hippocampal CRHR1 and GR expressions. In addition, PF inhibited BDNF/TrkB signaling by downregulating the protein levels of BDNF, TrkB, and phospho-PLCγ1 in the colon.
CONCLUSIONS: These findings suggest that PF alleviated anxiety and visceral hypersensitivity in MS-induced IBS-like rats, which may be the modulation of HPA axis activity and BDNF/TrkB/PLCγ1 signaling pathway.

IBS is a prevalent clinical condition affecting bowel function. There is a restricted comprehension of its pathogenesis, an absence of particular diagnostic tools, and an insufficiency of efficient pharmacological remedies. MiRNAs are a highly conserved class of non-coding small molecule RNAs, with a length of 20-24 nucleotides. Research has shown the presence of a number of differentially expressed miRNAs in the colonic tissue and peripheral blood of IBS patients. Meanwhile, miRNAs have a critical role in gene expression and the pathology of IBS as they act as significant mediators of post-transcriptional gene silencing. The investigation of miRNA molecular regulatory networks proves useful in examining the convoluted pathogenesis of IBS. This paper presents a review of recent literature on miRNAs associated with IBS, explains how miRNAs contribute to the development of IBS, and assesses the potential usefulness of miRNA analysis for diagnosing and treating IBS.

Traditional Chinese medicine Guchang Zhixie pills(GCZX) is one of the famous varieties of \"Qin medicine\" that has been extensively applied to treating irritable bowel syndrome(IBS). However, despite the acknowledged clinical advantages of GCZX there are significant constraints on its quality control and evaluation. The present study utilized UHPLC-Q-Exactive-Orbitrap-MS to analyze the chemical composition of GCZX. Additionally, network pharmacology approaches were utilized to explore the underlying mechanism by which blood components exert therapeutic effects in the treatment of IBS. Furthermore, the GCZX samples were evaluated for their quality on the basis of the qualitative results obtained from 25 batches of GCZX samples using fingerprinting; subsequently, multivariate statistical analysis methods were employed for further analysis. The results indicated the presence of 198 individual components. Among them, 17 prototype compounds were detected in the serum of rats that were administered with GCZX. The potential therapeutic mechanism of GCZX in the treatment of IBS may be associated with the modulation of the neurological system, the immunological system, and the inflammatory response. Moreover, a total of seven prominent peaks were identified after fingerprint analysis. The range of fingerprint similarity among the 25 batches of samples varied from 0.843 to 1.000. The application of chemometrics analysis successfully facilitated the categorical classification of 25 batches of GCZX into three distinct groups. Seven components hold significant importance and should be duly considered during the quality control process of GCZX. The present study can establish the Q-Markers of GCZX for IBS, thereby providing a foundation for investigating the theoretical underpinnings and elucidating the mechanisms underlying the therapeutic effects of GCZX in the treatment of IBS.

BACKGROUND: Psychological stress is a major trigger for visceral hypersensitivity (VH) in irritable bowel syndrome. The zinc finger protein ZBTB20 (ZBTB20) is implicated in somatic nociception via modulating transient receptor potential (TRP) channels, but its role in the development of VH is unclear. This study aimed to investigate the role of ZBTB20/TRP channel axis in stress-induced VH.
METHODS: Rats were subjected to water avoidance stress (WAS) for 10 consecutive days. Small interfering RNA (siRNA) targeting ZBTB20 was intrathecally administered. Inhibitors of TRP channels, stress hormone receptors, and nuclear factor kappa-B (NF-κB) were administered. Visceromotor response to colorectal distension was recorded. Dorsal root ganglia (DRGs) were dissected for Western blot, coimmunoprecipitation, and chromatin immunoprecipitation. The DRG-derived neuron cell line was applied for specific research.
RESULTS: WAS-induced VH was suppressed by the inhibitor of TRPV1, TRPA1, or TRPM8, with enhanced expression of these channels in L6-S2 DRGs. The inhibitor of glucocorticoid receptor or β2-adrenergic receptor counteracted WAS-induced VH and TRP channel expression. Concurrently, WAS-induced stress hormone-dependent ZBTB20 expression and NF-κB activation in DRGs. Intrathecally injected ZBTB20 siRNA or an NF-κB inhibitor repressed WAS-caused effect. In cultured DRG-derived neurons, stress hormones promoted nuclear translocation of ZBTB20, which preceded p65 nuclear translocation. And, ZBTB20 siRNA suppressed stress hormone-caused NF-κB activation. Finally, WAS enhanced p65 binding to the promoter of TRPV1, TRPA1, or TRPM8 in rat DRGs.
CONCLUSIONS: ZBTB20 mediates stress-induced VH via activating NF-κB/TRP channel pathway in nociceptive sensory neurons.

Irritable bowel syndrome (IBS) could seriously affect the patient\'s health quality by its recurrence. There is a great medical and social need to explore the mechanisms and new treatment strategies of IBS.
To explore the influence of protease-activated receptor 2 (PAR2) gene knockout on IBS visceral sensitivity, stress behaviors, and colonic electrical activities.
The PAR2 gene knockout and IBS model rats were generated and divided into PAR2+/+ wild control (WC) group, PAR2+/+ wild IBS model (WM) group, PAR2-/- knockout control (KC) group and PAR2-/- knockout IBS model (KM) group. The stress behaviors scores, minimum rectal fluid injection capacity threshold value of abdominal withdrawal reflex (AWR) = 3, and the colonic electrical activities indexes were recorded and the experimental results were analyzed statistically.
(1) PAR2 gene deletion and IBS models were successfully generated. (2) The scores of aggressive and exploratory behaviors in WM and KM groups were higher than WC and KC groups (p < 0.05). The grooming behavior scores in WC and KC groups were higher than the WM and KM groups (p < 0.05). WM group had the highest aggressive and exploratory behavior scores; WC group had the highest grooming behavior scores. (3) The minimum rectal fluid injection capacity threshold value of AWR = 3 in WM and KM groups were lower than WC and KC groups (p < 0.05); WM group had the lowest value. (4) The maximum amplitude and wave frequency of colonic fast and slow waves in WM and WC groups were greater than in the KM and KC groups, respectively (p < 0.05). The amplitude index and number of colonic contraction waves in WM and KM groups were greater than the WC and KC groups (p < 0.05). Colonic electrical activity indexes were highest in the WM group.
The PAR2 gene deletion could have a beneficial effect on visceral sensitivity, stress behaviors and colonic electrical activities in rats with IBS.

Background: Irritable bowel syndrome (IBS) is a group of functional intestinal disorders characterized by abdominal pain, bloating, and changes in bowel habits, and/or stool characteristics. Recent studies have shown that there has been a significant advancement in the study of visceral hypersensitivity in IBS. Through the use of bibliometrics, this study aims to provide a comprehensive overview of the knowledge structure and research hotpots of visceral hypersensitivity in IBS. Methods: Publications related to visceral hypersensitivity in IBS from 2012 to 2022 were searched on the web of science core collection (WoSCC) database. CiteSpace.6.1. R2 and Vosviewer 1.6.17 were used to perform bibliometric analysis. Results: A total of 974 articles led by China and the United States from 52 countries were included. Over the past decade, the number of articles on visceral hypersensitivity and IBS has steadily increased year by year. China, the United States, and Belgium are the main countries in this field. Univ Oklahoma, Univ Gothenburg, and Zhejiang University are the main research institutions. Simren, Magnus, Greenwood-van meerveld, Beverley, and Tack, Jan are the most published authors in this research field. The research on the causes, genes, and pathways involved in visceral hypersensitivity in IBS and the mechanism of IBS are the main topics and hotspots in this field. This study also found that gut microbiota may be related to the occurrence of visceral hypersensitivity, and probiotics may be a new method for the treatment of visceral hypersensitivity and pain, which may become a new direction for research in this field. Conclusion: This is the first bibliometric study to comprehensively summarize the research trends and developments of visceral hypersensitivity in IBS. This information provides the research frontier and hot topics in this field in recent years, which will provide a reference for scholars studying this field.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a newly identified phlebovirus associated with severe hemorrhagic fever in humans. Studies have shown that SFTSV nucleoprotein (N) induces BECN1-dependent autophagy to promote viral assembly and release. However, the function of other SFTSV proteins in regulating autophagy has not been reported. In this study, we identify SFTSV NSs, a nonstructural protein that forms viroplasm-like structures in the cytoplasm of infected cells as the virus component mediating SFTSV-induced autophagy. We found that SFTSV NSs-induced autophagy was inclusion body independent, and most phenuivirus NSs had autophagy-inducing effects. Unlike N protein-induced autophagy, SFTSV NSs was key in regulating autophagy by interacting with the host\'s vimentin in an inclusion body-independent manner. NSs interacted with vimentin and induced vimentin degradation through the K48-linked ubiquitin-proteasome pathway. This negatively regulating Beclin1-vimentin complex formed and promoted autophagy. Furthermore, we identified the NSs-binding domain of vimentin and found that overexpression of wild-type vimentin antagonized the induced effect of NSs on autophagy and inhibited viral replication, suggesting that vimentin is a potential antiviral target. The present study shows a novel mechanism through which SFTSV nonstructural protein activates autophagy, which provides new insights into the role of NSs in SFTSV infection and pathogenesis. IMPORTANCE Severe fever with thrombocytopenia syndrome virus (SFTSV) is a newly emerging tick-borne pathogen that causes multifunctional organ failure and even death in humans. As a housekeeping mechanism for cells to maintain steady state, autophagy plays a dual role in viral infection and the host\'s immune response. However, the relationship between SFTSV infection and autophagy has not been described in detail yet. Here, we demonstrated that SFTSV infection induced complete autophagic flux and facilitated viral proliferation. We also identified a key mechanism underlying NSs-induced autophagy, in which NSs interacted with vimentin to inhibit the formation of the Beclin1-vimentin complex and induced vimentin degradation through K48-linked ubiquitination modification. These findings may help us understand the new functions and mechanisms of NSs and may aid in the identification of new antiviral targets.

Dysregulation of gut homeostasis is associated with irritable bowel syndrome (IBS), a chronic functional gastrointestinal disorder affecting approximately 11.2% of the global population. The poorly understood pathogenesis of IBS has impeded its treatment. Here, we report that the E3 ubiquitin ligase tripartite motif-containing 27 (TRIM27) is weakly expressed in IBS but highly expressed in inflammatory bowel disease (IBD), a frequent chronic organic gastrointestinal disorder. Accordingly, knockout of Trim27 in mice causes spontaneously occurring IBS-like symptoms, including increased visceral hyperalgesia and abnormal stool features, as observed in IBS patients. Mechanistically, TRIM27 stabilizes β-catenin and thus activates Wnt/β-catenin signaling to promote intestinal stem cell (ISC) self-renewal. Consistent with these findings, Trim27 deficiency disrupts organoid formation, which is rescued by reintroducing TRIM27 or β-catenin. Furthermore, Wnt/β-catenin signaling activator treatment ameliorates IBS symptoms by promoting ISC self-renewal. Taken together, these data indicate that TRIM27 is critical for maintaining gut homeostasis, suggesting that targeting the TRIM27/Wnt/β-catenin axis could be a potential treatment strategy for IBS. Our study also indicates that TRIM27 might serve as a potential biomarker for differentiating IBS from IBD.