Wenrui Wu

Alterations and correlations of the gut microbiome, metabolism and immunity in patients with primary biliary cirrhosis.

We selected 42 early-stage primary biliary cirrhosis (PBC) patients and 30 healthy controls (HC). Metagenomic sequencing of the 16S rRNA gene was used to characterize the fecal microbiome. UPLC-MS/MS assaying of small molecules was used to characterize the metabolomes of the serum, urine and feces. Liquid chip assaying of serum cytokines was used to characterize the immune profiles. The gut of PBC patients were depleted of some potentially beneficial bacteria, such as Acidobacteria, Lachnobacterium sp., Bacteroides eggerthii and Ruminococcus bromii, but were enriched in some bacterial taxa containing opportunistic pathogens, such as γ-Proteobacteria, Enterobacteriaceae, Neisseriaceae, Spirochaetaceae, Veillonella, Streptococcus, Klebsiella, Actinobacillus pleuropneumoniae, Anaeroglobus geminatus, Enterobacter asburiae, Haemophilus parainfluenzae, Megasphaera micronuciformis and Paraprevotella clara. Several altered gut bacterial taxa exhibited potential interactions with PBC through their associations with altered metabolism, immunity and liver function indicators, such as those of Klebsiella with IL-2A and Neisseriaceae with urinary indoleacrylate. Many gut bacteria, such as some members of Bacteroides, were altered in their associations with the immunity and metabolism of PBC patients, although their relative abundances were unchanged. Consequently, the gut microbiome is altered and may be critical for the onset or development of PBC by interacting with metabolism and immunity.

Pre- and post-diagnosis physical activity is associated with survival benefits of colorectal cancer patients: a systematic review and meta-analysis

Objective Physical activity is associated with reduced risk of colorectal cancer. However, whether physical activity could impart cancer patients’ survival benefits remains uncertain. The aim of this study is to systematically evaluate the relationship between physical activity and colorectal cancer mortality. Results Our meta-analysis included 11 studies involving 17,295 patients with a follow-up period ranging from 3.8 to 11.9 years. Results indicated that physical activity was inversely associated with overall (RR = 0.81, 95% CI = 0.72–0.91) and colorectal cancer-specific mortality (RR = 0.79, 95% CI = 0.71–0.89) before the diagnosis of cancer, respectively. For physical activity after diagnosis, the pooled RRs of colorectal cancer-specific and total mortality were 0.77 (95% CI, 0.63–0.94) and 0.71 (95% CI, 0.63–0.81), respectively. Similar inverse associations between exercise and prognosis were found among colorectal cancer survivors who had high-level exercise compared with those who had low-level exercise or were inactive. There was no obvious evidence for publication bias among studies. Materials and Methods We performed a systematic data search in PubMed, Cochrane Library databases and Web of Science for relevant articles before Jan 2016. We adopted adjusted estimates to calculate pooled relative risks (RRs) with 95% confidence intervals (CI) by the random-effects model. The publication bias was assessed by Beggs test. Conclusions Our meta-analysis provides comprehensive evidence that physical activity, whether before or after the diagnosis of colorectal cancer, is related to reduced overall and cancer-specific mortality. Our findings may have significant public health implications and more prospective randomized clinical trials should be warranted to certify this protective association.

Influences of the Gut Microbiota on DNA Methylation and Histone Modification

The gut microbiota is a vast ensemble of microorganisms inhabiting the mammalian gastrointestinal tract that can impact physiologic and pathologic processes. However, our understanding of the underlying mechanism for the dynamic interaction between host and gut microbiota is still in its infancy. The highly evolved epigenetic modifications allow hosts to reprogram the genome in response to environmental stimuli, which may play a key role in triggering multiple human diseases. In spite of increasing studies in gut microbiota and epigenetic modifications, the correlation between them has not been well elaborated. Here, we review current knowledge of gut microbiota impacts on epigenetic modifications, the major evidence of which centers on DNA methylation and histone modification of the immune system.

Integrated transcriptomic and proteomic analysis of the bile stress response in probiotic Lactobacillus salivarius LI01

Lactobacillus salivarius LI01, isolated from healthy humans, has demonstrated probiotic properties in the prevention and treatment of liver failure. Tolerance to bile stress is crucial to allow lactobacilli to survive in the gastrointestinal tract and exert their benefits. In this work, we used a Digital Gene Expression transcriptomic and iTRAQ LC-MS/MS proteomic approach to examine the characteristics of LI01 in response to bile stress. Using culture medium with or without 0.15% ox bile, 591 differentially transcribed genes and 347 differentially expressed proteins were detected in LI01. Overall, we found the bile resistance of LI01 to be based on a highly remodeled cell envelope and a reinforced bile efflux system rather than on the activity of bile salt hydrolases. Additionally, some differentially expressed genes related to regulatory systems, the general stress response and central metabolism processes, also play roles in stress sensing, bile-induced damage prevention and energy efficiency. Moreover, bile salts appear to enhance proteolysis and amino acid uptake (especially aromatic amino acids) by LI01, which may support the liver protection properties of this strain. Altogether, this study establishes a model of global response mechanism to bile stress in L. salivarius LI01. BIOLOGICAL SIGNIFICANCE L. salivarius strain LI01 exhibits not only antibacterial and antifungal properties but also exerts a good health-promoting effect in acute liver failure. As a potential probiotic strain, the bile-tolerance trait of strain LI01 is important, though this has not yet been explored. In this study, an analysis based on DGE and iTRAQ was performed to investigate the gene expression in strain LI01 under bile stress at the mRNA and protein levels, respectively. To our knowledge, this work also represents the first combined transcriptomic and proteomic analysis of the bile stress response mechanism in L. salivarius.

Bifidobacterium pseudocatenulatum LI09 and Bifidobacterium catenulatum LI10 attenuate D-galactosamine-induced liver injury by modifying the gut microbiota

The gut microbiota is altered in liver diseases, and several probiotics have been shown to reduce the degree of liver damage. We hypothesized that oral administration of specific Bifidobacterium strains isolated from healthy guts could attenuate liver injury. Five strains were tested in this study. Acute liver injury was induced by D-galactosamine after pretreating Sprague-Dawley rats with the Bifidobacterium strains, and liver function, liver and ileum histology, plasma cytokines, bacterial translocation and the gut microbiome were assessed. Two strains, Bifidobacterium pseudocatenulatum LI09 and Bifidobacterium catenulatum LI10, conferred liver protection, as well as alleviated the increase in plasma M-CSF, MIP-1α and MCP-1 and bacterial translocation. They also ameliorated ileal mucosal injury and gut flora dysbiosis, especially the enrichment of the opportunistic pathogen Parasutterella and the depletion of the SCFA-producing bacteria Anaerostipes, Coprococcus and Clostridium XI. Negative correlations were found between MIP-1α / MCP-1 and Odoribacter (LI09 group) and MIP-1α / M-CSF and Flavonifractor (LI10 group). Our results indicate that the liver protection effects might be mediated through gut microbiota modification, which thus affect the host immune profile. The desirable characteristics of these two strains may enable them to serve as potential probiotics for the prevention or adjuvant treatment of liver injury.

Protective Effect of Akkermansia muciniphila against Immune-Mediated Liver Injury in a Mouse Model

Accumulating evidence indicates that gut microbiota participates in the pathogenesis and progression of liver diseases. The severity of immune-mediated liver injury is associated with different microbial communities. Akkermansia muciniphila can regulate immunologic and metabolic functions. However, little is known about its effects on gut microbiota structure and function. This study investigated the effect of A. muciniphila on immune-mediated liver injury and potential underlying mechanisms. Twenty-two C57BL/6 mice were assigned to three groups (N = 7–8 per group) and continuously administrated A. muciniphila MucT or PBS by oral gavage for 14 days. Mouse feces were collected for gut microbiota analysis on the 15th day, and acute liver injury was induced by Concanavalin A (Con A, 15 mg/kg) injection through the tail vein. Samples (blood, liver, ileum, colon) were assessed for liver injury, systemic inflammation, and intestinal barrier function. We found that oral administration of A. muciniphila decreased serum ALT and AST and alleviated liver histopathological damage induced by Con A. Serum levels of pro-inflammatory cytokines and chemokines (IL-2, IFN-γ, IL-12p40, MCP-1, MIP-1a, MIP-1b) were substantially attenuated. A. muciniphila significantly decreased hepatocellular apoptosis; Bcl-2 expression increased, but Fas and DR5 decreased. Further investigation showed that A. muciniphila enhanced expression of Occludin and Tjp-1 and inhibited CB1 receptor, which strengthened intestinal barriers and reduced systemic LPS level. Fecal 16S rRNA sequence analysis indicated that A. muciniphila increased microbial richness and diversity. The community structure of the Akk group clustered distinctly from that of mice pretreated with PBS. Relative abundance of Firmicutes increased, and Bacteroidetes abundance decreased. Correlation analysis showed that injury-related factors (IL-12p40, IFN-γ, DR5) were negatively associated with specific genera (Ruminococcaceae_UCG_009, Lachnospiraceae_UCG_001, Akkermansia), which were enriched in mice pretreated with A. muciniphila. Our results suggested that A. muciniphila MucT had beneficial effects on immune-mediated liver injury by alleviating inflammation and hepatocellular death. These effects may be driven by the protective profile of the intestinal community induced by the bacteria. The results provide a new perspective on the immune function of gut microbiota in host diseases.

Administration of Lactobacillus salivarius LI01 or Pediococcus pentosaceus LI05 prevents CCl 4 -induced liver cirrhosis by protecting the intestinal barrier in rats

Alterations in the gut microbiome have been reported in liver cirrhosis, and probiotic interventions are considered a potential treatment strategy. This study aimed to evaluate the effects and mechanisms of Lactobacillus salivarius LI01, Pediococcus pentosaceus LI05, Lactobacillus rhamnosus GG, Clostridium butyricum MIYAIRI and Bacillus licheniformis Zhengchangsheng on CCl4-induced cirrhotic rats. Only administration of LI01 or LI05 prevented liver fibrosis and down-regulated the hepatic expression of profibrogenic genes. Serum endotoxins, bacterial translocations (BTs), and destruction of intestinal mucosal ultrastructure were reduced in rats treated with LI01 or LI05, indicating maintenance of the gut barrier as a mechanism; this was further confirmed by the reduction of not only hepatic inflammatory cytokines, such as TNF-α, IL-6, and IL-17A, but also hepatic TLR2, TLR4, TLR5 and TLR9. Metagenomic sequencing of 16S rRNA gene showed an increase in potential beneficial bacteria, such as Elusimicrobium and Prevotella, and a decrease in pathogenic bacteria, such as Escherichia. These alterations in gut microbiome were correlated with profibrogenic genes, gut barrier markers and inflammatory cytokines. In conclusion, L. salivarius LI01 and P. pentosaceus LI05 attenuated liver fibrosis by protecting the intestinal barrier and promoting microbiome health. These results suggest novel strategies for the prevention of liver cirrhosis.

A new perspective on C-reactive protein in H7N9 infections.

OBJECTIVES The avian influenza H7N9 virus can cause cytokine overproduction and result in severe pneumonia and acute respiratory distress syndrome. Many studies have focused on hypercytokinemia during avian influenza infection. This study examined the association between C-reactive protein (CRP) and cytokines. METHODS The plasma cytokine and chemokine profiles of 57 H7N9 patients were investigated using a multiplex immunoassay. The CRP levels of patients with H7N9 and patients with H1N1 were also compared. Further, the association between cytokines and CRP in H7N9 infections was explored. RESULTS Compared with H1N1 virus, it was found that H7N9 virus induced higher expression of CRP, leading to cytokine storms. Several cytokines, including MIP-1β, MCP-1, IP-10, and IL-6, were observed to have significantly positive relationships with CRP levels, whereas IL-17A was negatively associated with CRP levels. CONCLUSIONS These findings suggest that CRP may be used as an early indicator to identify high-risk patients, to assess disease progression, and to determine the development of hypercytokinemia.

Pattern of distant extrahepatic metastases in primary liver cancer: a SEER based study

Background and Aims: Primary liver cancer remains still the common cause of cancer-related deaths globally and the prognosis for patients with extrahepatic metastasis is poor. The aim of our study was to assess extrahepatic metastatic pattern of different histological subtypes and evaluate prognostic effects of extrahepatic metastasis in patients with advanced disease. Methods: Based on the Surveillance, Epidemiology and End Results (SEER) database, eligible patients diagnosed with primary liver cancer was identified between 2010 to 2012. We adopted Chi-square test to compared metastasis distribution among different histological types. We compared survival difference of patients with different extrahepatic metastasises by Kaplan-Meier analysis. Cox proportional hazard models were performed to identify other prognostic factors of overall survival. Results: We finally identified 8677 patients who were diagnosed with primary liver cancer from 2010 to 2012 and 1775 patients were in distant metastasis stages. Intrahepatic cholangiocarcinoma was more invasive and had a higher percentage of metastasis compared with hepatocellular carcinoma. Lung was the most common metastasis and brain was the least common site for both hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Extrahepatic metastasis could consider as an independent prognostic factor for patients with liver cancer. Patients with brain metastasis had the worst prognosis, compared with other metastasis in overall survival (OS) and cancer-specific survival (CSS) analysis. Conclusions: Different histological subtypes of liver cancer had different metastasis patterns. There were profound differences in risk of mortality among distant extrahepatic metastatic sites. Results from our studies would provide some information for follow-up strategies and future studies.

Draft Genome Sequence of Lactobacillus panis DSM 6035T, First Isolated from Sourdough

ABSTRACT We report a draft genome sequence of Lactobacillus panis DSM 6035T, isolated from sourdough. The genome of this strain is 2,082,789 bp long, with 47.9% G+C content. A total of 2,047 protein-coding genes were predicted.