Commensal Bacteroides fragilis possesses immune-regulatory characteristics. Consequently, it has been proposed as a potential novel probiotic because of its therapeutic effects on immune imbalance, mental disorders and inflammatory diseases. Macrophages play a central role in the immune response, developing either a classical-M1 or an alternative-M2 phenotype after stimulation with various signals. The interactions between macrophages and B. fragilis, however, remain to be defined. Here, a new isolate of B. fragilis, ZY-312, was shown to possess admirable properties, including tolerance to simulated gastric fluid, intestinal fluid and ox bile and good safety (MOI = 100, 200) and adherent ability (MOI = 100) to LoVo cells. Isolate ZY-312 cell lysate promoted phagocytosis of fluorescent microspheres and pathogenic bacteria in bone marrow-derived macrophage (BMDM) cells. Gene expression of IL-12, iNOS and IL-1β in BMDM cells was increased after treatment with ZY-312, indicating the induction of M1 macrophages, consistent with enhanced secretion of NO. Cell surface expression of CD80 and CD86 was also increased. This study is the first to demonstrate that B. fragilis enhances the phagocytic functions of macrophages, polarising them to an M1 phenotype. Our findings provide insight into the close relationship between B. fragilis and the innate immune system.

Cronobacter sakazakii is an opportunistic pathogenic bacterium that can cause necrotizing enterocolitis (NEC). However, the mechanism of pathogenicity of C. sakazakii is largely unknown. Here we have now demonstrated that apoptotic and pyroptotic stimuli are effectors of C. sakazakii -induced NEC. Previously, we isolated a novel probiotic strain candidate from fecal samples from healthy infants and characterized it as Bacteroides fragilis strain ZY-312. Functional characterization reveals that ZY-312 inhibited C. sakazakii invasion, restoring epithelial barrier dysfunction, decreasing the expression of inflammatory cytokines, and reducing dual cell death (pyroptosis and apoptosis). Furthermore, the presence of ZY-132 was sufficient to hinder the adverse reaction seen with C. sakazakii in a C. sakazakii -induced NEC model. Taking the results together, our study demonstrated the utility of ZY-312 as a promising probiotic agent for the prevention of NEC.

Mitophagy is a conserved cellular process that plays a vital role in maintaining cellular homeostasis by selectively removing dysfunctional mitochondria. Notwithstanding that growing evidence suggests that mitophagy is implicated in pancreatic tumorigenesis, the effect of mitophagy-related genes on pancreatic cancer (PC) prognosis and therapeutic response remains largely unknown. In this study, we sought to construct a mitophagy-related gene signature and assessed its ability to predict the survival, immune activity, mutation status, and chemotherapy response of PC patients. During the screening process, we identified three mitophagy-related genes (PRKN, SRC, VDAC1) from The Cancer Genome Atlas (TCGA) cohort and a 3-gene signature was established. The prognostic model was validated using an International Cancer Genome Consortium (ICGC) cohort and two Gene Expression Omnibus (GEO) cohorts. According to the median risk score, PC patients were divided into high and low-risk groups, and the high-risk group correlated with worse survival in the four cohorts. The risk score was then identified as an independent prognostic predictor, and a predictive nomogram was constructed to guide clinical decision-making. Remarkably, enhanced immunosuppressive levels and higher mutation rates were observed in patients from the high-risk group, which may account for their poor survival. Furthermore, we found that high-risk patients were more sensitive to paclitaxel and erlotinib. In conclusion, a mitophagy-related gene signature is a novel prognostic model that can be used as a predictive indicator and allows prognostic stratification of PC patients.

Background: Neutrophil extracellular traps (NETs) have been shown to play a pivotal role in promoting metastasis and immune escape in hepatocellular carcinoma (HCC). Therefore, noninvasive tests to detect the formation of NETs in tumors can have significant implications for the treatment and prognoses of patients. Here, we sought to develop and validate a computed tomography (CT)-based radiomics model to predict the gene expression profiles that regulate the formation of NETs in HCC.Methods: This study included 1133 HCC patients from five retrospective cohorts. Based on the mRNA expression levels of 69 biomarkers correlated with NET formation, a 6-gene score (NETs score, NETS) was constructed in cohort 1 from TCIA database (n=52) and validated in cohort 2 (n=232) from ICGC database and cohort 3 (n=365) from TCGA database. And then based on the radiomics features of CT images, a radiomics signature (RNETS) was developed in cohort 1 to predict NETS status (high- or low-NETS). We further employed two cohorts from Nanfang Hospital (Guangzhou, China) to evaluate the predictive power of RNETS in predicting prognosis in cohort 4 (n=347) and the responses to PD-1 inhibitor of HCC patients in cohort 5 (n=137).Results: For NETS, in cohort 1, the area under the curve (AUC) values predicting 1, 2, and 3-year overall survival (OS) were 0.836, 0.879, and 0.902, respectively. The low-NETS was associated with better survival and higher levels of immune cell infiltration. The RNETS yielded an AUC value of 0.853 in distinguishing between high-NETS or low-NETS and patients with low-RNETS were associated with significantly longer survival time in cohort 1 (P<0.001). Notably, the RNETS was competent in predicting disease-free survival (DFS) and OS in cohort 4 (P<0.001). In cohort 5, the RNETS was found to be an independent risk factor for progression-free survival (PFS) (P<0.001). In addition, the objective response rate of HCC patients treated with PD-1 inhibitor was significantly higher in the low-RNETS group (27.8%) than in the high-RNETS group (10.8%).Conclusions: This study revealed that RNETS as a radiomics biomarker could effectively predict prognosis and immunotherapy response in HCC patients.

Researchers are attempting to harness the advantages of the gut–brain axis to prevent neurocognitive disorders by enhancing intestinal health. In this study, four groups of ICR mice were orally gavaged with either phosphate-buffered saline (control and CW groups) or the probiotic strain Lactobacillus johnsonii BS15 (P and PW group; daily amounts of 2 × 10⁸ colony-forming units) for 28 days. From days 22 to 28, the mice in the CW and PW groups were subjected to water-avoidance stress (WAS). The issue of whether psychological stress–induced memory dysfunction can be prevented via L. johnsonii BS15 pretreatment to modulate the gut–brain axis was investigated. Results show that L. johnsonii BS15 enhanced gut development by increasing villus height in the jejunum and ileum as well as villus height:crypt depth ratio in the ileum. L. johnsonii BS15 increased the activities of digestive enzymes, including trypsin and lipase in the jejunum and ileum. The intestinal goblet cell number was also increased by L. johnsonii BS15 pretreatment. Moreover, L. johnsonii BS15 balanced the gut microbiota by increasing the log₁₀ DNA gene copies of Lactobacillus spp. and L. johnsonii and decreasing that of Enterobacteriaceae in the cecum. L. johnsonii BS15 also exerted preventive effects on intestinal permeability WAS by modulating diamine oxidase and _D-lactate levels in the serum and mRNA expression levels of the tight junction proteins claudin-1, occludin, and ZO-1 in the jejunum and ileum. L. johnsonii BS15 pretreatment modulated inflammatory factors, specifically tumor necrosis factor-alpha, interferon-gamma, and interleukin-10. L. johnsonii BS15 pretreatment improved their performance in two behavioral tests, namely the novel object and T-maze tests. This result indicates that psychological stress–induced memory dysfunction possibly could be prevented through the gut–brain axis. In addition, L. johnsonii BS15 exerted beneficial effects on the hippocampus by modulating memory-related functional proteins, especially those related to synaptic plasticity, such as brain-derived neurotrophic factor and stem cell factor. Moreover, L. johnsonii BS15 recovered antioxidant capacity and exerted protective effects on mitochondrion-mediated apoptosis in the hippocampus. Collectively, the modulation of the gut–brain axis by L. johnsonii BS15 could be considered a promising non-invasive treatment modality for psychological stress–induced memory dysfunction.