Damage to the colon mucus barrier, the first line of defense against microorganisms, is an important determinant of intestinal diseases such as inflammatory bowel disease and colorectal cancer, and disorder in extraintestinal organs. The mucus layer has attracted the attention of the scientific community in recent years, and with the discovery of new mucosal components, it has become increasingly clear that the mucosal barrier is a complex system composed of many components. Moreover, certain components are jointly involved in regulating the structure and function of the mucus barrier. Therefore, a comprehensive and systematic understanding of the functional components of the mucus layer is clearly warranted. In this review, we summarize the various functional components of the mucus layer identified thus far and describe their unique roles in shaping mucosal structure and function. Furthermore, we detail the mechanisms underlying mucus secretion, including baseline and stimulated secretion. In our opinion, baseline secretion can be categorized into spontaneous Ca²⁺ oscillation-mediated slow and continuous secretion and stimulated secretion, which is mediated by massive Ca²⁺ influx induced by exogenous stimuli. This review extends the current understanding of the intestinal mucus barrier, with an emphasis on host defense strategies based on fortification of the mucus layer.

Pre-eclampsia (PE) is the most common complication of pregnancy and seriously threatens the health and safety of the mother and child. Studies have shown that an imbalance in gut microbiota can affect the progression of PE. Trimethylamine N-oxide (TMAO) is an intestinal microbiota-derived metabolite that is thought to be involved in the occurrence of PE; however, its causal relationship and mechanism remain unclear. In this clinical cohort study, including 28 patients with eclampsia and 39 matched healthy controls, fecal samples were collected for 16S rRNA gene sequencing, and serum was collected for targeted metabolomics research. The results showed that the level of TMAO and the abundance of its source bacteria had significantly increased in patients with PE, and were positively correlated with the clinical progression of PE. Fecal microbiota transplantation (FMT) was applied to an antibiotic-depleted-treated mouse model and targeted inhibition of TMAO. The results of the FMT experiment revealed that mice that received fecal microbiota transplantation from patients with PE developed typical PE symptoms and increased oxidative stress and inflammatory damage, both of which were reversed by 3,3-Dimethyl-1-butanol (DMB), a TMAO inhibitor, which also improved pregnancy outcomes in the model mice. Similar results were obtained in the classical NG-Nitroarginine methyl ester (L-NAME) induced PE mouse model. Mechanistically, TMAO promotes the progression of PE by regulating inflammatory and oxidative stress-related signaling pathways, affecting the migration and angiogenesis of vascular endothelial cells, as well as the migration and invasion of trophoblast cells. Our results reveal the role and mechanism of gut microbiota and TMAO in the progression of PE, provides new ideas for exploring the pathogenesis and therapeutic targets of PE, and determines the potential application value of TMAO as a target for PE intervention.

Astragaloside IV (AS-IV) is one of the main pharmacologically active compounds found in Astragalus membranaceus. AS-IV has protective effects against ischemia-reperfusion injury (IRI), but its mechanism of action has not yet been determined. This study aims to investigate the effect of AS-IV on IRI and its effect on the PI3K/Akt/HO-1 signaling pathway through in vitro experiments. Firstly, a cell culture model of myocardiocyte hypoxia-reoxygenation (H/R) injury was replicated. After AS-IV treatment, cell viability, reactive oxygen species ( ROS) levels, as well as the content or activity of the cellular factors lactate dehydrogenase(LDH), superoxide dismutase (SOD), malondialdehyde (MDA), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), were measured to evaluate the effect of treatment with AS-IV. The effect of AS-IV on HO-1 protein expression and nuclear Nrf2 and Bach1 protein expression was determined by Western blotting. Finally, a reversal of the effect of AS-IV treatment was observed following co-incubation with a PI3K inhibitor. Our results show that AS-IV has good protective effect on H/R injury and has anti-oxidative stress and anti-inflammatory effects. It can regulate the expression of Nrf2 and Bach1 proteins in the nucleus and promote the expression of HO-1 protein, while a PI3K inhibitor can partially reverse the above effects. This study suggests that the PI3K/Akt/HO-1 signaling pathway may be a key signaling pathway for the anti-IRI effect of AS-IV.

Background: The change in the characteristics of the gut microbiota is linked to gestational diabetes mellitus (GDM). However, whether and how the gut microbiota‐derived metabolites change in GDM is uncertain. Here, we aimed to determine associations between the gut microbiota‐derived metabolites and GDM.Methods: Using targeted metabolomics approaches, 7 types of short‐chain fatty acids (SCFAs), 38 types of bile acids (BAs), and 5 types of trimethylamine N‐oxide (TMAO), and its derivatives of serum samples were obtained from pregnant women with GDM (n = 24), and healthy pregnant controls (HC, n = 28) were detected to identify the metabolic signature of GDM to investigate the potential biomarkers. Moreover, we assessed the associations between gut microbiota‐derived metabolites and clinical parameters.Results: In our study, the gut microbiota‐derived metabolites signatures were significantly different between GDM and HC. Quantitative results showed the levels of isobutyric acid, isovaleric acid, valeric acid, caproic acid, GUDCA, THDCA + TUDCA, and LCA‐3S were significantly higher in GDM, but the level of TMAO and its derivatives did not change significantly. Some altered gut microbiota‐derived metabolites were significantly correlated with glucose and lipid levels. Receiver‐operating characteristic (ROC) analysis of generalized linear models showed that gut microbiota‐derived metabolites may be potential biomarkers of GDM.Conclusion: This study highlights gut microbiota‐derived metabolites alterations in GDM and correlation of the clinical indicators, which provides a new direction for future studies aiming to novel serum biomarker for early detection or target of drug therapy of GDM.

Background: Ulcerative colitis (UC) is a chronic inflammatory disorder of the colon with a continuously remitting and relapsing course. Its etiology is closely related to abnormal interactions between host and gut microbiota. The mucus barrier lining the gastrointestinal tract is necessary to coordinate host and gut microbiota interaction by nourishing and modulating the microbiota. Differential effects of the anti-inflammatory fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on UC progression in mice were firstly addressed by our previous work; here, the mechanism for their respective effects were further uncovered from host–microbiome crosstalk based on mucus barrier modulation to pave the way for UC therapy. Methods: Assessment of the disease activity index and histopathology score was conducted in mice with dextran sodium sulfate (DSS)-induced colitis pre-treated with different doses of EPA and DHA. Mucin generation, glycosylation and secretion were evaluated by a combination of electron microscopy, specific mucous staining, and qPCR. Western blotting was used to analyze the underlying molecular events. Fecal short chain fatty acids were detected using gas chromatography, and the gut microbial composition was analyzed using 16S rRNA sequencing. Results: Compared with DHA, the more potent inhibitory effect of high dose EPA on DSS-induced colitis was reconfirmed, which was underlain by a reinforced mucus layer as indicated by increased mucin granule release, mucus layer stratification and markedly upregulated expression of the key modulators involved in goblet cell differentiation. In turn a remarkably enhanced mucus barrier in the EPA group functioned to modulate the gut microbiome, as demonstrated by the enriched abundance of the phylum Bacteroidetes and mucin-degrading bacterium Akkermansia muciniphila producing acetic and propionic acids. Conclusions: EPA and DHA differentially coordinate the interaction between the host and the gut microbiota and relieve mucus barrier disruption in DSS-induced colitis. EPA may develop into a promising adjunctive therapy for UC.