Inflammatory bowel disease has been a growing concern of lots of people globally, including both adults and children. As a chronic inflammatory disease of the intestine, even though the etiology of inflammatory bowel disease is still unclear, the available evidence from clinic observations has suggested a close association with microorganisms. The oral microbiota possesses the characteristics of a large number and abundant species, second only to the intestinal microbiota in the human body; as a result, it successfully attracts the attention of researchers. The highly diverse commensal oral microbiota is not only a normal part of the oral cavity but also has a pronounced impact on the pathophysiology of general health. Numerous studies have shown the potential associations between the oral microbiota and inflammatory bowel disease. Inflammatory bowel disease can affect the composition of the oral microbiota and lead to a range of oral pathologies. In turn, there are a variety of oral microorganisms involved in the development and progression of inflammatory bowel disease, including Streptococcus spp., Fusobacterium nucleatum, Porphyromonas gingivalis, Campylobacter concisus, Klebsiella pneumoniae, Saccharibacteria (TM7), and Candida albicans. Based on the above analysis, the purpose of this review is to summarize this relationship of mutual influence and give further insight into the detection of flora as a target for the diagnosis and treatment of inflammatory bowel disease to open up a novel approach in future clinical practice.

Due to mucin’s important protective effect on epithelial tissue, it has garnered extensive attention. The role played by mucus in the digestive tract is undeniable. On the one hand, mucus forms “biofilm” structures that insulate harmful substances from direct contact with epithelial cells. On the other hand, a variety of immune molecules in mucus play a crucial role in the immune regulation of the digestive tract. Due to the enormous number of microorganisms in the gut, the biological properties of mucus and its protective actions are more complicated. Numerous pieces of research have hinted that the aberrant expression of intestinal mucus is closely related to impaired intestinal function. Therefore, this purposeful review aims to provide the highlights of the biological characteristics and functional categorization of mucus synthesis and secretion. In addition, we highlight a variety of the regulatory factors for mucus. Most importantly, we also summarize some of the changes and possible molecular mechanisms of mucus during certain disease processes. All these are beneficial to clinical practice, diagnosis, and treatment and can provide some potential theoretical bases. Admittedly, there are still some deficiencies or contradictory results in the current research on mucus, but none of this diminishes the importance of mucus in protective impacts.

Intestinal diseases have always posed a serious threat to human health, with inflammatory bowel disease (IBD) being one of them. IBD is an autoimmune disease characterized by chronic inflammation, including ulcerative colitis (UC) and Crohn’s disease (CD). The “alarm” cytokine IL-33, which is intimately associated with Th2 immunity, is a highly potent inflammatory factor that is considered to have dual functions—operating as both a pro-inflammatory cytokine and a transcriptional regulator. IL-33 has been shown to play a crucial role in both the onset and development of IBD. Therefore, this review focuses on the pathogenesis of IBD, the major receptor cell types, and the activities of IL-33 in innate and adaptive immunity, as well as its underlying mechanisms and conflicting conclusions in IBD. We have also summarized different medicines targeted to IL-33-associated diseases. Furthermore, we have emphasized the role of IL-33 in gastrointestinal cancer and parasitic infections, giving novel prospective therapeutic utility in the future application of IL-33.

(1) Background: Depression is the most prevalent psychiatric symptom present among individuals of all ages and backgrounds, impacting an estimated 300 million people globally. Therefore, it demands a significant amount of attention when it comes to managing depression. A growing amount of data reveal that probiotics and fatty acids could be beneficial to depression. However, the opposing position maintains that they have no influence on depression. A network meta-analyses of existing datasets aid in the estimation of comparative efficacy as well as in achieving an understanding of the relative merits of different therapies. The purpose of this study was to investigate the current evidence for probiotic or fatty acid depression therapy and to establish a practical alternative for depression patients using a meta-analysis and metagenomic data from a Wistar–Kyoto (WKY) depressed rat model. (2) Methods: Probiotic data were obtained from seven randomized controlled trial studies (n = 394), and fatty acid data were obtained from 24 randomized controlled trial studies (n = 1876). Meanwhile, a metagenomics analysis of data on animal gut flora was also applied to validate the preceding evidence. (3) Results: The fatty acid studies were separated into three sections based on the duration of probiotic delivery: ≤8 weeks, 9–12 weeks, and >12 weeks. The results were as follows: for ≤8 weeks, MD = −1.65 (95% CI: −2.96–−0.15), p = 0.01; for 9–12 weeks, MD = −2.22 (95% CI: −3.03–−1.22), p < 0.001; for >12 weeks, MD = −1.23 (95% CI: −2.85–0.39), p = 0.14. Regarding the probiotics, the meta-analysis revealed MD = −2.19 (95% CI: −3.38–−2.43), p < 0.001. The research presented herein illustrates that probiotics and fatty acids may successfully lower depression scores. Additionally, the probiotics were drastically reduced in the WKY rats. (4) Conclusions: According to the data, a depression intervention utilizing probiotics outperformed the control, implying that the use of probiotics and fatty acids may be a successful strategy for depression treatment.

Mast cells have vital functions in allergic responses and parasite ejection, while the underlying mechanisms remain unclear. Meanwhile, MCs are essential for the maintenance of GI barrier function, and their interactions with neurons, immune cells, and epithelial cells have been related to various gastrointestinal (GI) disorders. An increasing number of investigations are being disclosed, with a lack of inner connections among them. This review aims to highlight their properties and categorization and further delve into their participation in GI diseases via interplay with neurons and immune cells. We also discuss their roles in diseases like inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). Based on the evidence, we advocated for their potential application in clinical practices and advocated future research prospects.

Intestinal homeostasis requires immune tolerance, barrier integrity, tissue repair, and microbiota mutualism. Interleukin-10 (IL-10) is essential, but not merely as an immunosuppressant. Although IL-10 signals via the IL-10R—JAK1/TYK2—STAT3 axis, its outputs are cell-type and context dependent. In macrophages, IL-10 restrains IL-23 production, inflammasome activation, IL-1β release, and metabolic reprogramming. In T cells, it limits pathogenic T helper 17 cell (Th17) responses while stabilizing regulatory cells and promoting metabolically driven IL-10 production. In the epithelium, IL-10 maintains barrier integrity by limiting apoptosis, endoplasmic reticulum (ER) stress, and mucus defects. IL-10 and the gut microbiota engage in reciprocal regulation: microbial metabolites and structural components enhance IL-10 production and receptor responsiveness, whereas IL-10 signaling preserves microbial diversity and ecological resilience. This may help to explain why systemic recombinant IL-10 failed in Crohn’s disease (CD)—increasing ligand abundance alone is unlikely to recapitulate endogenous localization or restore refractory target cells. Emerging strategies aim to tune IL-10 signaling through gut-selective delivery, engineered cytokines, conditionally activated prodrugs, regulatory cell approaches, and microbiome or metabolic interventions. Clinical translation requires biomarkers of IL-10R expression, STAT3 responsiveness, macrophage metabolic state, microbial signatures, and acquired IL-10 hyporesponsiveness. Despite the established role of IL-10 in intestinal homeostasis, systemic IL-10 therapy has failed in clinical trials, and there is a lack of effective strategies to restore IL-10 signaling in a spatially and cell-specific manner. The spatially organized, metabolically conditioned homeostatic IL-10 signaling—largely inferred from model systems and awaiting direct spatial validation in human intestine—offers a roadmap for more precise therapy in inflammatory bowel disease and related intestinal disorders.