Mice are widely used as experimental models for gut microbiome (GM) studies, yet the majority of mouse GM members remain uncharacterized. Here, we report the construction of a mouse gut microbial biobank (mGMB) that contains 126 species, represented by 244 strains that have been deposited in the China General Microorganism Culture Collection. We sequence and phenotypically characterize 77 potential new species and propose their nomenclatures. The mGMB includes 22 and 17 species that are significantly enriched in ob/ob and wild-type C57BL/6J mouse cecal samples, respectively. The genomes of the 126 species in the mGMB cover 52% of the metagenomic nonredundant gene catalog (sequence identity ≥ 60%) and represent 93-95% of the KEGG-Orthology-annotated functions of the sampled mouse GMs. The microbial and genome data assembled in the mGMB enlarges the taxonomic characterization of mouse GMs and represents a useful resource for studies of host-microbe interactions and of GM functions associated with host health and diseases.

Background In gut microbiome studies, the cultured gut microbial resource plays essential roles, such as helping to unravel gut microbial functions and host-microbe interactions. Although several major studies have been performed to elucidate the cultured human gut microbiota, up to 70% of the Unified Human Gastrointestinal Genome species have not been cultured to date. Large-scale gut microbial isolation and identification as well as availability to the public are imperative for gut microbial studies and further characterizing human gut microbial functions. Results In this study, we constructed a human Gut Microbial Biobank (hGMB; homepage: hgmb.nmdc.cn) through the cultivation of 10,558 isolates from 31 sample mixtures of 239 fresh fecal samples from healthy Chinese volunteers, and deposited 1170 strains representing 400 different species in culture collections of the International Depository Authority for long-term preservation and public access worldwide. Following the rules of the International Code of Nomenclature of Prokaryotes, 102 new species were characterized and denominated, while 28 new genera and 3 new families were proposed. hGMB represented over 80% of the common and dominant human gut microbial genera and species characterized from global human gut 16S rRNA gene amplicon data (n = 11,647) and cultured 24 “most-wanted” and “medium priority” taxa proposed by the Human Microbiome Project. We in total sequenced 115 genomes representing 102 novel taxa and 13 previously known species. Further in silico analysis revealed that the newly sequenced hGMB genomes represented 22 previously uncultured species in the Unified Human Gastrointestinal Genome (UHGG) and contributed 24 representatives of potentially “dark taxa” that had not been discovered by UHGG. The nonredundant gene catalogs generated from the hGMB genomes covered over 50% of the functionally known genes (KEGG orthologs) in the largest global human gut gene catalogs and approximately 10% of the “most wanted” functionally unknown proteins in the FUnkFams database. Conclusions A publicly accessible human Gut Microbial Biobank (hGMB) was established that contained 1170 strains and represents 400 human gut microbial species. hGMB expands the gut microbial resources and genomic repository by adding 102 novel species, 28 new genera, 3 new families, and 115 new genomes of human gut microbes.

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BackgroundDiabetes mellitus is one of the most important risk factors for atherosclerosis. However, the mechanisms underlying high-glucose-induced atherosclerosis remain unclear. This study was designed to observe the effects of high-glucose stimulation on the permeability of cultured human umbilical vein endothelial cells (HUVECs), and to explore the effects of RhoA–Rho-associated protein kinase (ROCK) signal transduction pathway activation and myosin light chain (MLC) phosphorylation.MethodsHUVECs were cultured in conventional M199 medium to produce endothelial cell monolayers, and stimulated with high-glucose-M199 medium. The transmembrane transport of dextran and THP-1 cells and levels of MLC phosphorylation were measured. The effects of blocking the RhoA-ROCK pathway using dnRhoA or the ROCK inhibitor Y27632 on dextran and THP-1 transport and MLC phosphorylation were observed.ResultsTransendothelial migration of dextran and THP-1 cells were significantly increased by stimulation of HUVEC monolayers with high glucose (P < 0.05). This effect was attenuated by treatment with dnRhoA or Y27632.ConclusionHigh-glucose stimulation upregulated MLC phosphorylation and increased endothelial permeability by activating the RhoA-ROCK signaling pathway in HUVECs in vitro.

BackgroundThe cultivated gut microbial resource plays essential roles in gut microbiome studies such as unraveling gut microbial functions and host-microbe interactions. Though several major studies have been performed to understand the cultured human gut microbiota, up to 70% of the Unified Human Gastrointestinal Genome species remain uncultivated. Large-scale gut microbial isolation and identification and their access to public are imperative for gut microbial studies and further understanding of the human gut microbial functions.ResultsHere, we report the construction of a human Gut Microbial Biobank (hGMB) (homepage: hgmb.nmdc.cn) by cultivation of 10,558 isolates from 239 feces samples of healthy Chinese volunteers, and deposited 1,170 strains representing 400 different species in culture collections of International Depository Authority for long-term preservation and public access worldwide. The hGMB enriched the existing cultivable gut microbial repository and represented over 80% of the common and dominant human gut microbial genera and species of global human gut 16S rRNA gene amplicon data (n=11,647).Moreover, 102 new species were characterized and denominated and 28 new genera and 3 new families were proposed, following the rules of International Code of Nomenclature of Prokaryotes. The hGMB uncovered 24 “most-wanted” and “medium priority” taxa proposed by the Human Microbiome Project, while the novel-taxon genomes represented 22 previously-uncultured species in Unified Human Gastrointestinal Genome (UHGG) and contributed 24 potentially “dark-taxon” representatives that were not discovered by UHGG. The 115 newly-sequenced hGMB genomes covered over 50% of the known genes (KEGG Orthologs) in the global human gut gene catalogs and over 10% of the “most-wanted” functionally unknown proteins in FUnkFams database.ConclusionsA publicly accessible human Gut Microbial Biobank (hGMB) is established and contains 1,170 strains and represents 400 human gut microbial species. The hGMB expands gut microbial resources and genomic repository by adding 102 novel species, 28 new genera and 3 new families, and 115 new genomes of human gut microbes.

Polygenic risk scores (PRS) have the potential to identify individuals at risk of diseases, optimizing treatment, and predicting survival outcomes. Here, we construct and validate a genome-wide association study (GWAS) derived PRS for nasopharyngeal carcinoma (NPC), using a multi-center study of six populations (6 059 NPC cases and 7 582 controls), and evaluate its utility in a nested case-control study. We show that the PRS enables effective identification of NPC high-risk individuals (AUC = 0.65) and improves the risk prediction with the PRS incremental deciles in each population (Ptrend ranging from 2.79 × 10−7 to 4.79 × 10−44). By incorporating the PRS into EBV-serology-based NPC screening, the test’s positive predictive value (PPV) is increased from an average of 4.84% to 8.38% and 11.91% in the top 10% and 5% PRS, respectively. In summary, the GWAS-derived PRS, together with the EBV test, significantly improves NPC risk stratification and informs personalized screening.

This study was undertaken to determine the differences in the clinicopathology and survival between synchronous bilateral breast cancer (sBBC) and metachronous bilateral breast cancer (mBBC). Additionally, we analyzed the risk factors for single tumors to develop as sBBC or mBBC. Of the 190 bilateral breast cancer (BBC) cases, 84 cases were sBBC and 106 were mBBC. We defined sBBC as two tumors that developed within 12 months, while mBBC was defined as two tumors that developed over more than 12 months. The peak age of onset of the first mBBC tumors was significantly younger than that of sBBC tumors (p = 0.001). There was a higher concordance rate of ER/ER positivity and PR/PR positivity in the first and second tumors of sBBC than mBBC. The two sBBC breast cancers had relatively similar hormone conditions because of the low rate of ER and PR transformation from positive to negative or vice versa. We determined that patients who presented with extracapsular extension (p = 0.008) and ER positivity (p = 0.001) tend to have synchronous cancers, while patients with 3+ HER2 were more likely to develop metachronous tumors. The prognosis for mBBC was better than that for sBBC when the survival time of mBBC was measured from the initial observation of the first tumors.

Oncofetal chondroitin sulfate expression plays an important role in the development of tumors and the pathogenesis of malaria in pregnancy. However, the biosynthesis and functions of these chondroitin sulfates, particularly the tissue-specific regulation either in tumors or placenta, have not been fully elucidated. Here, by examining the glycogenes availability in chondroitin sulfate biosynthesis such as xylosytransferase, chondroitin synthase, sulfotransferase, and epimerase, the conserved or differential CS glycosylation in normal, colorectal cancer (CRC), and placenta tissue were predicted. We found that the expression of seven chondroitin sulfate biosynthetic enzymes, namely B4GALT7, B3GALT6, B3GAT3, CHSY3, CHSY1, CHPF, and CHPF2, were significantly increased, while four other enzymes (XYLT1, CHST7, CHST15, and UST) were decreased in the colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ) patients. In the human placenta, where the distinct chondroitin sulfate is specifically bound with VAR2CSA on Plasmodium parasite-infected RBC, eight chondroitin sulfate biosynthesis enzymes (CSGALNACT1, CSGALNACT2, CHSY3, CHSY1, CHPF, DSE, CHST11, and CHST3) were significantly higher than the normal colon tissue. The similarly up-regulated chondroitin synthases (CHSY1, CHSY3, and CHPF) in both cancer tissue and human placenta indicate an important role of the proteoglycan CS chains length for Plasmodium falciparum VAR2CSA protein binding. Interestingly, twelve highly expressed chondroitin sulfate enzymes were significantly correlated to worse outcomes (prognosis) in both COAD and READ. Furthermore, we showed that the levels of chondroitin sulfate enzymes are significantly correlated with the expression of immuno-regulators and immune infiltration levels in CRCs and placenta, and involved in multiple essential pathways, such as extracellular matrix organization, epithelial-mesenchymal transition, and cell adhesion. Our study provides novel insights into the oncofetal chondroitin sulfate biosynthesis regulation and identifies promising targets and biomarkers of immunotherapy for CRC and malaria in pregnancy.