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Orally administered probiotics encounter various challenges on their journey through the mouth, stomach, intestine and colon. The health benefits of probiotics are diminished mainly due to the substantial reduction of viable probiotic bacteria under the harsh conditions in the gastrointestinal tract and the colonization resistance caused by commensal bacteria. In this review, we illustrate the factors affecting probiotic viability and their mucoadhesive properties through their journey in the gastrointestinal tract, including a discussion on various mucosadhesion-related proteins on the probiotic cell surface which facilitate colonization.

The low viability during gastrointestinal transit and poor mucoadhesion considerably limits the effectiveness of Ligilactobacillus salivarius Li01 (Li01) in regulating gut microbiota and alleviating inflammatory bowel disease (IBD). In this study, a delivery system was designed through layer-by-layer (LbL) encapsulating a single Li01cell with chitosan and alginate. The layers were strengthened by cross-linking to form a firm and mucoadhesive shell (~10 nm thickness) covering the bacterial cell. The LbL Li01 displayed improved viability under simulated gastrointestinal conditions and mucoadhesive function. Almost no cells could be detected among the free Li01 after 2 h incubation in digestive fluids, while for LbL Li01, the total reduction was around 3 log CFU/mL and the viable number of cells remained above 6 log CFU/mL. Besides, a 5-fold increase in the value of rupture length and a two-fold increase in the number of peaks were found in the (bacteria-mucin) adhesion curves of LbL Li01, compared to those of free Li01. Oral administration with LbL Li01 on colitis mice facilitated intestinal barrier recovery and restoration of the gut microbiota. The improved functionality of Li01 by LbL encapsulation could increase the potential for the probiotic to be used in clinical applications to treat IBD; this should be explored in future studies.

Although Ligilactobacillus salivarius Li01 (Li01) has shown much promise in preventing multiple gastrointestinal diseases, the potential of the probiotic in alleviating constipation and the related mechanisms remain unclear. In this study, the effects of Li01 were evaluated in a loperamide-induced constipation mouse model. The results demonstrated that Li01 intervention can relieve constipation symptoms by improving water content, quantity, and morphology of feces and act as an intestinal barrier structure protector. Furthermore, Li01 can modulate gut motility (gastrointestinal transit rate), the fluid transit-associated expression of aquaporins, and the serum parameters vasoactive intestinal peptide, substance P, and somatostatin. Constipation significantly increased the levels of 5-hydroxytryotamine (5-HT) in serum (p < 0.01) and decreased the levels in the intestine (p < 0.001). Due to its function of elevating the expression of tryptophan hydroxylase 1, this was reversed after Li01 treatment. Li01 also promoted the expression of 5-HT receptor 3 and 4, indicating that the 5-HT signaling pathway may play a critical role in the mechanism by which Li01 alleviate constipation symptoms. Additionally, Li01 significantly altered the gut microbiota composition by enhancing the ratio of Firmicutes/Bacteroidetes and increasing the abundance of Rikenellaceae_RC9 genera. Based on the above results, Li01 may have the potential to effectively alleviate constipation by regulating the 5-HT pathway and alteration of the gut microbiota.

Resveratrol (RSV) has been confirmed to confer multiple health benefits, and the majority of RSV tends to be metabolized in the gut microbiota after oral administration. In this study, the metabolism of RSV was investigated by using mouse models with distinct gut microbiota compositions: germ-free mice colonized with probiotics, conventional mouse, and DSS-induced colitis mouse models. The results demonstrated that in feces, the metabolites of RSV, including resveratrol sulfate (RES-sulfate), resveratrol glucuronide (RES-glucuronide), and dihydroresveratrol, significantly increased after probiotics colonized in germ-free mice. Furthermore, RES-sulfate and RES-glucuronide were below the detectable limit in the feces of conventional mice, with dihydroresveratrol being the dominant metabolite. Compared to the conventional mice, the ratio of Firmicutes/Bacteroides and the abundance of Lactobacillus genera were found significantly elevated in colitis mice after long-term ingestion of RSV, which shifted the metabolism of RSV in return. Our study provided critical implications in further application of RSV in foods and food supplements.

Currently approved therapeutical strategies for inflammatory bowel diseases (IBD) suffer from variable efficacy and association with risk of serious side effects. Therefore, efforts have been made in searching for alternative therapeutics strategies utilizing gut microbiota manipulation. In this study, we show that the probiotic strain Ligilactobacillus salivarius Li01 (Li01) and the phytochemical prebiotic resveratrol (RSV) have synergistic effect in ameliorating colitis in mice. Oral coadministration of Li01 (109 CFU/d) and RSV (1.5 g/kg/d) promoted restoration of various inflammatory injuries and gut microbiota composition, exhibiting a favorable anti-inflammatory effect in DSS-induced colitis mice. The combination treatment was associated with reductions in the levels of proinflammatory cytokines IL-1β and IL-6 and increases in the levels of the anti-inflammatory cytokine IL-17A in mouse serum. Moreover, the combination treatment was found to alter the composition and metabolism of the gut microbiota, especially influencing the production of short chain fatty acids and anti-inflammatory related molecules. The mechanism underlying the improved anti-inflammatory effect from the RSV and Li01 combination treatment was found to be associated with the environmental sensor mammalian aryl hydrocarbon receptor (AHR) and tryptophan metabolism pathway. Administration of RSV in combination with Li01 in different mouse model led to enhanced conversion of RSV into metabolites, including dihydroresveratrol (DHR), resveratrol-sulfate, and resveratrol-glucuronide. DHR was found to be the dominant metabolite of RSV in conventional and colitis mice. An increased DHR/RSV ratio was confirmed to activate AHR and contribute to an enhanced anti-inflammatory effect. DHR is considered as a potential AHR ligand. The DHR/RSV ratio also affected the serotonin pathway by controlling the expression of Tph1, SERT, and 5-HT7R leading to amelioration of colitis in mice. Our data suggest that treatment with a combination of Li01 and RSV has potential as a therapeutic strategy for IBD; further investigation of this combination in clinical settings is warranted.

Although Ligilactobacillus salivarius Li01 (Li01) has shown much promise in preventing multiple gastrointestinal diseases, the potential of the probiotic in alleviating constipation and the related mechanisms remain unclear. In this study, the effects of Li01 were evaluated in a loperamide-induced constipation mouse model. The results demonstrated that Li01 intervention can relieve constipation symptoms by improving water content, quantity, and morphology of feces and act as an intestinal barrier structure protector. Furthermore, Li01 can modulate gut motility (gastrointestinal transit rate), the fluid transit-associated expression of aquaporins, and the serum parameters vasoactive intestinal peptide, substance P, and somatostatin. Constipation significantly increased the levels of 5-hydroxytryotamine (5-HT) in serum (p < 0.01) and decreased the levels in the intestine (p < 0.001). Due to its function of elevating the expression of tryptophan hydroxylase 1, this was reversed after Li01 treatment. Li01 also promoted the expression of 5-HT receptor 3 and 4, indicating that the 5-HT signaling pathway may play a critical role in the mechanism by which Li01 alleviate constipation symptoms. Additionally, Li01 significantly altered the gut microbiota composition by enhancing the ratio of Firmicutes/Bacteroidetes and increasing the abundance of Rikenellaceae_RC9 genera. Based on the above results, Li01 may have the potential to effectively alleviate constipation by regulating the 5-HT pathway and alteration of the gut microbiota.

Gastrointestinal disease is characterized by gastrointestinal dysfunction with dysbiosis of the microbiome. Probiotics may act as biological agents in treating gastrointestinal diseases through modifying gut microbiota. However, several challenges, including safety, stress resistance, postcolonization quantification, and evaluation models, may hinder the application of probiotics in gastrointestinal diseases. This review introduces the emerging methods for delivering probiotics as well as available materials. Furthermore, we elucidated bacteriocins and their role in helping probiotics obtain a competitive advantage over other strains and challenges of large-scale application. Bacteriocins produced by probiotics also showed promising efficacy in gastrointestinal diseases including the capacity of immune stimulation, intestinal barrier protection, and cytotoxicity against intestinal tumorigenesis. For the quantification of probiotics in complex microbiomes and evaluation methods of probiotic encapsulated delivery systems, recent fluorescent labeling technology and various in vitro and in vivo models were also reviewed. Given the widespread use of probiotic agents in the microecological therapy of gastrointestinal diseases, further understanding of the multiple challenges of probiotic application and the updated methods to improve the colonization and evaluation system of probiotics is of great significance for probiotics as live biotherapeutics.

Clear-cell renal cell carcinoma (ccRCC) is a highly aggressive malignancy that originates in the kidney. It often exhibits a limited response or can be refractory to a wide range of anti-cancer therapies, including tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors. Ferroptosis is a form of oxidative, iron-dependent cell death characterized by lipid peroxidation. Targeting ferroptosis may offer a promising alternative therapeutic strategy for cancer cells that are resistant to existing treatments. The impact of ferroptosis-related genes on the prognosis of ccRCC patients is still not fully understood. In this study, we identified 30 differentially expressed ferroptosis-related genes in ccRCC samples compared to normal tissues using data from The Cancer Genome Atlas (TCGA). Lasso regression analyses, along with Kaplan-Meier analysis, were conducted to identify genes associated with prognosis. Based on scRNA-seq and spatial transcriptome analysis, we identified specificity of MIOX in ccRCC. Furthermore, MIOX demonstrated the highest significance, highlighting its independent prognostic value as a single gene in ccRCC. Our findings suggest that MIOX could serve as potential targets for therapeutic interventions in ccRCC.

Background The underlying mechanism of brain glucose hypometabolism, an invariant neurodegenerative feature that tightly correlates with cognitive impairment and disease progression of Alzheimer’s disease (AD), remains elusive. Methods Positron emission tomography with 2-[ 18 F]fluoro-2-deoxy- d -glucose (FDG-PET) was used to evaluate brain glucose metabolism, presented as the rate of 2-[ 18 F]fluoro-2-deoxy- d -glucose standardized uptake value ratio (FDG SUVR) in patients with AD or control subjects and in mice with or without thiamine deficiency induced by a thiamine-deprived diet. Brain amyloid-β (Aβ) deposition in patients with clinically diagnosed AD was quantified by performing assays using 11 C-Pittsburgh compound B PET. The levels of thiamine metabolites in blood samples of patients with AD and control subjects, as well as in blood and brain samples of mice, were detected by high-performance liquid chromatography with fluorescence detection. Results FDG SUVRs in frontal, temporal, and parietal cortices of patients with AD were closely correlated with the levels of blood thiamine diphosphate (TDP) and cognitive abilities, but not with brain Aβ deposition. Mice on a thiamine-deprived diet manifested a significant decline of FDG SUVRs in multiple brain regions as compared with those in control mice, with magnitudes highly correlating with both brain and blood TDP levels. There were no significant differences in the changes of FDG SUVRs in observed brain regions between amyloid precursor protein/presenilin-1 and wild-type mice following thiamine deficiency. Conclusions We demonstrate, for the first time to our knowledge, in vivo that TDP reduction strongly correlates with brain glucose hypometabolism, whereas amyloid deposition does not. Our study provides new insight into the pathogenesis and therapeutic strategy for AD.

To clarify the precipitation forecast skills of climate forecast operations in the flood season in Liaoning Province of China, this study examines the forecast accuracies of China’s national and provincial operational climate prediction products and the self-developed objective prediction methods and climate model products by Shenyang Regional Climate Center (SRCC) in the flood season in Liaoning. Furthermore, the forecast accuracies of the main influencing factors on the precipitation in the flood season of Liaoning are assessed. The results show that the SRCC objective methods have a relatively high accuracy. The European Centre for Medium-Range Weather Forecasts (ECMWF) sub-seasonal forecast initialized at the sub-nearest time has the best performance in June. The National Climate Center (NCC) Climate System Model sub-seasonal forecast initialized at the sub-nearest time, and the ECMWF seasonal and sub-seasonal forecasts initialized at the nearest time, perform the best in July. The NCC sub-seasonal forecast initialized at the sub-nearest time has the best performance in August. For the accuracy of the SRCC objective method, the more significant the equatorial Middle East Pacific sea surface temperature (SST) anomaly is, the higher the evaluation score of the dynamic–analogue correction method is. The more significant the North Atlantic SST tripole is, the higher the score of the hybrid downscaling method is. For the forecast accuracy of the main influencing factors of precipitation, the tropical Atlantic SST and the north–south anti-phase SST in the northwest Pacific can well predict the locations of the southern vortex and the northern vortex in early summer, respectively. The warm (clod) SST in China offshore has a good forecast performance on the weak (strong) southerly wind in midsummer in Northeast China. The accuracy of using the SST in the Nino 1+2 areas to predict the north–south location of the western Pacific subtropical high is better than that of using Kuroshio SST. The accuracy of predicting northward-moving typhoons from July to September by using the SST in the west-wind-drift area is better than using the SST in the Nino 3 area. The above conclusions are of great significance for improving the short-term climate prediction in Liaoning.