Gut microbiota dysbiosis has been considered to be an important risk factor that contributes to coronary artery disease (CAD), but limited evidence exists about the involvement of gut microbiota in the disease. Our study aimed to characterize the dysbiosis signatures of gut microbiota in coronary artery disease. The gut microbiota represented in stool samples were collected from 70 patients with coronary artery disease and 98 healthy controls. 16S rRNA sequencing was applied, and bioinformatics methods were used to decipher taxon signatures and function alteration, as well as the microbial network and diagnostic model of gut microbiota in coronary artery disease. Gut microbiota showed decreased diversity and richness in patients with coronary artery disease. The composition of the microbial community changed; Escherichia-Shigella [false discovery rate (FDR = 7.5*10] and Enterococcus (FDR = 2.08*10) were significant enriched, while Faecalibacterium (FDR = 6.19*10), Subdoligranulum (FDR = 1.63*10), Roseburia (FDR = 1.95*10), and Eubacterium rectale (FDR = 2.35*10) were significant depleted in the CAD group. Consistent with the taxon changes, functions such as amino acid metabolism, phosphotransferase system, propanoate metabolism, lipopolysaccharide biosynthesis, and protein and tryptophan metabolism were found to be enhanced in CAD patients. The microbial network revealed that Faecalibacterium and Escherichia-Shigella were the microbiotas that dominated in the healthy control and CAD groups, respectively. The microbial diagnostic model based on random forest also showed probability in identifying those who suffered from CAD. Our study successfully identifies the dysbiosis signature, dysfunctions, and comprehensive networks of gut microbiota in CAD patients. Thus, modulation targeting the gut microbiota may be a novel strategy for CAD treatment.

BackgroundA newly isolated L. acidophilus strain has been reported to have potential anti-inflammatory activities against lipopolysaccharide (LPS) challenge in piglet, while the details of the related inflammatory responses are limited. Here we aimed to analysis the ability of L. acidophilus to regulate inflammatory responses and to elucidate the mechanisms involved in its anti-inflammatory activity.ResultsThe ETEC (enterotoxigenic Escherichia coli) K88-induced up-regulations of IL-1β, IL-8 and TNF-α were obviously inhibited by L. acidophilus while IL-10 was significantly increased. Moreover, L. acidophilus down-regulated pattern recognition receptors TLR (Toll-like receptor) 2 and TLR4 expression in both spleen and mesenteric lymph nodes of ETEC-challenged piglets, in accompanied with the reduced phosphorylation levels of nuclear factor kappa B (NF-κB) p65 and mitogen-activated protein kinase (MAPK) p38 as well in spleen of ETEC-infected piglets. Furthermore, L.acidophilus significantly increased the expression of the negative regulators of TLRs signaling, including Tollip, IRAK-M, A20 and Bcl-3 in spleen of ETEC-challenged piglets.ConclusionsOur findings suggested that L. acidophilus regulated inflammatory response to ETEC via impairing both NF-κB and MAPK signaling pathways in piglets.

The novelty of this study lies in the beneficial effects of C. butyricum on intestinal health, likely by improving intestinal barrier function and alleviating inflammatory reactions.

Chronic functional constipation is a kind of common intestinal disease that occurs in children, adults and elderly people. This disease not only causes great influence to physiological function, but also results in varying degrees of psychological barriers. At present, constipation treatments continue to rely on traditional methods such as purgative therapy and surgery. However, these approaches can disrupt intestinal function. Recent research between intestinal diseases and gut microbiota has gradually revealed a connection between constipation and intestinal flora disturbance, providing a theoretical basis for microbial treatment in chronic constipation. Microbial treatment mainly includes probiotic preparations such as probiotics, prebiotics, synbiotics and fecal microbiota transplantation (FMT). Due to its safety, convenience and curative effect, probiotic preparations have been widely accepted, especially gradually developed FMT with higher curative effects. Microbial treatment improves clinical symptoms, promotes the recovery of intestinal flora, and has no complications during the treatment process. Compared with traditional treatments, microbial treatment in chronic constipation has advantages, and is worthy of further promotion from clinical research to clinical application.

Background: Long noncoding RNAs have been known to be involved in multiple types of malignancies, including invasive breast cancer (IBC). This study aimed to explore the role of long noncoding RNAs in IBC and elucidate the potential molecular mechanisms. Methods: Using TCGA microarray data analysis, we identified a long noncoding RNA, MIR210HG, highly expressed in IBC. Kaplan-Meier method and the log-rank test were used for survival analysis. The gain-of-function experiments were performed to assess the function of MIR210HG in IBC invasion and migration in both in vitro and in vivo settings. Bioinformatic analysis as well as luciferase reporter assay, rescue experiments and western blot assay revealed the mode of action of MIR210HG. Results: The aberrantly enhanced MiR210HG expression predicted poor prognosis and lower survival rate. Knockdown of MiR210HG suppressed IBC cell invasion and metastasis both in vitro and in vivo . MiR-1226-3p was identified and validated to be the target miRNA of MiR210HG. Furthermore, MiR210HG functions as a competing endogenous RNAs (ceRNA) which sponges miR-1226-3p, therefore upregulates the expression of mucin1 (MUC1-C). Conclusions: Our study demonstrated that MiR210HG sponges miR-1226-3p to facilitate invasive breast cancer cell invasion and metastasis by regulating mucin-1c and EMT pathway, revealing the oncogenic role of MiR210HG in IBC cells.

Diabetic nephropathy (DN) is a serious and one of the most common microvascular complications of diabetes. There is accumulating evidence to indicate that advanced glycation end products (AGEs), senescent macroprotein derivatives formed at an accelerated rate under conditions of diabetes, play a role in DN. In this study, we found that the serum and urine levels of C-X-C motif chemokine ligand 9 (CXCL9) were significantly elevated in patients with DN compared with healthy controls. Based on an in vitro model of mouse podocyte injury, AGEs decreased the proliferation of podocytes and increased the expression of CXCL9 and C-X-C motif chemokine receptor 3 (CXCR3), and promoted the activation of signal transducer and activator of transcription 3 (STAT3). The knockdown of CXCL9 by the transfection of mouse podoyctes with specific siRNA significantly increased the proliferation and decreased the apoptosis of the podoyctes. Moreover, the levels of inflammatory factors, such as tumor necrosis factor (TNF)-α and interleukin (IL)-6 were also decreased in the podoyctes transfected with siRNA-CXCL9, accompanied by the increased expression of nephrin and podocin, and decreased levels of Bax/Bcl-2 and activated caspase-3. The knockdown of CXCL9 also led to the inactivation of the Janus kinase 2 (JAK2)/STAT3 pathway. Importantly, the use of the JAK2 inhibitor, AG490, and valsartan (angiotensin II receptor antagonist) attenuated the injury induced to mouse podoyctes by AGEs. On the whole, and to the best of our knowledge, this study demonstrates for the first time that AGEs exert pro-apoptotic and pro-inflammatory effects in mouse podoyctes through the CXCL9-mediated activation of the JAK2/STAT3 pathway. Thus, our data provide a potential therapeutic target for DN.

This study was performed to identify changes to microbial composition after treatment with synbiotics in patients with functional constipation and to define the key microbiota in the pathogenesis of functional constipation. Fecal samples from 53 patients diagnosed with chronic functional constipation according to the Rome III criteria were analyzed using 16S rRNA sequencing. After treatment with synbiotics for 1 month, fecal samples were collected from 36 patients; after a total of 3 months, fecal samples were collected from 15 patients. The outcomes were compared with the intestinal microbiota profiles of 53 healthy community volunteers. The microbiota in the constipation group differed from that in the treatment group and healthy group. After synbiotic treatment for 1 and 3 months, the abundance of Escherichia/Shigella decreased, whereas that of Prevotella_9 and Lactococcus increased. Comparison of the microbiota among the three groups showed that Prevotella_9 was the characteristic bacteria that decreased in the constipation group and increased in the treatment group. Synbiotic treatment can improve the microbiota in patients with constipation. Identification of the key bacterial genus is important to reveal the mechanism and provide a reliable theoretical basis of synbiotic treatment. It will also promote relevant research of microbiota treatment and individualized treatments.

Background/Aims: Recent studies have demonstrated that the manipulation of the gut microbiome represents a promising treatment for inflammatory bowel disease (IBD). We previously identified micro integral membrane protein (MIMP) as the smallest domain of surface layer protein from Lactobacillus Plantarum. However, the therapeutic relevance of MIMP in IBD remains unknown. Methods: We initially employed a dextran sodium sulphate (DSS)-induced colitis model and evaluated the effect of MIMP on the inflammation response, intestinal barrier and gut microbiota using histological examination, Fluorescein isothiocyanate-Dextran detection and pyrosequencing analysis respectively. We then established peripheral blood mononuclear cells (PBMCs) and an epithelial CaCO-2 co-culture model to investigate the regulatory role of MIMP in inflammatory cytokines. The level changes of inflammatory cytokines were detected using Enzyme-linked immunosorbent and real-time polymerase chain reaction assay. The involved regulatory mechanisms were investigated mainly using dual luciferase reporter and chromatin immunoprecipitation assay. Results: In the DSS-induced colitis model, we observed that MIMP intervention effectively improved the body weight loss, increased the colon length and decreased disease activity index. Consistently, the inflammation scores in the MIMP treatment group were significantly lower than those in the DSS treatment group. Furthermore, MIMP intervention was found to successfully neutralize DSS treatment by decreasing the expression of pro-inflammatory cytokines (IFN-γ, IL-17 and IL-23) and increasing the expression of anti-inflammatory cytokines (IL-4 and IL-10). Notably, the permeability assay demonstrated that the MIMP treatment group was remarkably lower than that in the DSS treatment group. We also showed that MIMP improved gut microbiota dysbiosis caused by DSS-induced inflammation. Additionally, in PBMCs and the CaCO-2 co-culture model, MIMP showed an obvious suppressive effect on lipopolysaccharide-induced inflammation in a time- and dose-dependent manner. Furthermore, we revealed that MIMP could modulate inflammatory cytokine expression through the toll-like receptor 4 pathway and histone acetylation. Conclusions: Our results suggested that MIMP showed a significant anti-inflammatory effect through regulating the gut barrier, microbiota and inflammatory cytokines. MIMP may have translational relevance as clinically relevant therapy for IBD patients.