Alterations of the human gut microbiome in liver cirrhosis.

Liver cirrhosis occurs as a consequence of many chronic liver diseases that are prevalent worldwide. Here we characterize the gut microbiome in liver cirrhosis by comparing 98 patients and 83 healthy control individuals. We build a reference gene set for the cohort containing 2.69 million genes, 36.1% of which are novel. Quantitative metagenomics reveals 75,245 genes that differ in abundance between the patients and healthy individuals (false discovery rate < 0.0001) and can be grouped into 66 clusters representing cognate bacterial species; 28 are enriched in patients and 38 in control individuals. Most (54%) of the patient-enriched, taxonomically assigned species are of buccal origin, suggesting an invasion of the gut from the mouth in liver cirrhosis. Biomarkers specific to liver cirrhosis at gene and function levels are revealed by a comparison with those for type 2 diabetes and inflammatory bowel disease. On the basis of only 15 biomarkers, a highly accurate patient discrimination index is created and validated on an independent cohort. Thus microbiota-targeted biomarkers may be a powerful tool for diagnosis of different diseases.

Novel insights into the mechanism of dynamic changes in microstructure and physicochemical properties of corn straw pretreated by ball milling and feasibility analysis of anaerobic digestion.

In this study, the effects of Ball milling (BM) pretreatment (0-240 min) on the microstructure, physicochemical properties and subsequent methanogenesis performance of corn straw (CS) were explored, and the feasibility analysis was carried out. The results showed that BM pretreatment destroyed the dense structure of the CS, and the particle size was significantly reduced (D50: 13.85 µm), transforming it into a cell-scale granular form. The number of mesopores increased, the pore volume (PV) (0.032 cm3/g) and specific surface area (SSA) (4.738 m2/g) considerably increased, and the water-absorbent property was improved. The crystalline order of cellulose was disrupted and the crystallinity (CrI) (8.61 %) and crystal size (CrS) (3.37) were remarkably reduced. The cross-links between lignocelluloses were broken, and the relative content and functional groups did not alter obviously. The bulk density (BD), repose angle (RA) and slip angle (SA) dramatically increased. As a result, CS was more readily accessible, attached and utilized by microorganisms and enzymes, causing the hydrolysis and acidification of AD to be greatly facilitated. Compared with the untreated group, the cumulative methane production (CMP) increased by 35.83 %-101.97 %, and the lag phase time (λ) was shortened by 33.04 %-71.17 %. The results of redundancy analysis, Pearson analysis and Mantel test showed that BM pretreatment affects the process of AD by changing the physicochemical factors of CS. The normalization analysis showed that particle size (D90) and BD can be used as direct indicators to evaluate the performance of AD and predict the threshold of biodegradation of CS. Energy analysis and energy conversion assessment showed that BM is a green and efficient AD pretreatment strategy. This result provides a theoretical basis for the industrial application of BM pretreatment towards more energy-efficient and sustainable development.

Alterations, Interactions, and Diagnostic Potential of Gut Bacteria and Viruses in Colorectal Cancer.

Gut microbiome alteration was closely associated with colorectal cancer (CRC). Previous studies had demonstrated the bacteria composition changes but lacked virome profiles, trans-kindom interactions, and reliable diagnostic model explorations in CRC. Hence, we performed metagenomic sequencing to investigate the gut microbiome and microbial interactions in adenoma and CRC patients. We found the decreased microbial diversity in CRC and revealed the taxonomic alterations of bacteria and viruses were highly associated with CRC at the species level. The relative abundance of oral-derived species, such as Fusobacterium nucleatum, Fusobacterium hwasookii, Porphyromonas gingivalis, and Bacteroides fragilis, increased. At the same time, butyrate-producing and anti-inflammatory microbes decreased in adenoma and CRC by non-parametric Kruskal-Wallis test. Despite that, the relative abundance of Escherichia viruses and Salmonella viruses increased, whereas some phages, including Enterobacteria phages and Uncultured crAssphage, decreased along with CRC development. Gut bacteria was negatively associated with viruses in CRC and healthy control by correlation analysis (P=0.017 and 0.002, respectively). Viruses were much more dynamic than the bacteria as the disease progressed, and the altered microbial interactions were distinctively stage-dependent. The degree centrality of microbial interactions decreased while closeness centrality increased along with the adenoma to cancer development. Uncultured crAssphage was the key bacteriophage that enriched in healthy controls and positively associated with butyrate-producing bacteria. Diagnostic tests based on bacteria by random forest confirmed in independent cohorts showed better performance than viruses for CRC. In conclusion, our study revealed the novel CRC-associated bacteria and viruses that exhibited specific differences and intensive microbial correlations, which provided a reliable diagnostic panel for CRC.

Comparative prevention potential of 10 mouthwashes on intolerable oral mucositis in cancer patients: A Bayesian network analysis.

BACKGROUND: There is a wide variety of mouthwashes currently available for the prevention of intolerable oral mucositis (OM) onset. Because of a lack of evidence from head-to-head randomized controlled trials (RCTs), the relative effects of these mouthwashes in intolerable OM patients remain unclear. This study compared the preventive effect of ten mouthwashes in intolerable OM. METHODS: A literature search was performed of the Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, and MEDLINE (PubMed) databases. Reports published from 1990 to 2019 focusing on mouthwashes for preventing OM were identified. Authors assessed the studies' risk of bias in accordance with the Cochrane Handbook for Systematic Reviews of Interventions, and followed the PRISMA for Network Meta-Analyses Statement. Authors estimated summary odds ratios (ORs) using pairwise and Bayesian network meta-analysis with random effects. RESULTS: Thirty-six RCTs, with a total of 2594 patients, were included in the present study. Bayesian network analysis showed that honey (Odd Ratio [OR] 0.17, 95%CI 0.09 to 0.30), chamomile (OR 0.09, 95% CI 0.01 to 0.52), curcumin (OR 0.23, 95% CI 0.08 to 0.67) and benzydamine (OR 0.26, 95% CI 0.12 to 0.54) mouthwashes were superior to placebo. Honey mouthwashes were more efficacious than chlorhexidine (OR 0.34, 95% CI 0.12 to 0.92), sucralfate (OR 0.26, 95% CI 0.06 to 0.96) and povidone-iodine (OR 0.30, 95% CI 0.11 to 0.82) mouthwashes. Other mouthwashes showed no significant differences. CONCLUSIONS: According to the analysis of rank probabilities, chamomile, honey, curcumin and benzydamine mouthwashes may be the most advantageous in terms of the prevention of intolerable OM.

A rewritable optical storage medium of silk proteins using near-field nano-optics.

Nanoscale lithography and information storage in biocompatible materials offer possibilities for applications such as bioelectronics and degradable electronics for which traditional semiconductor fabrication techniques cannot be used. Silk fibroin, a natural protein renowned for its strength and biocompatibility, has been widely studied in this context. Here, we present the use of silk film as a biofunctional medium for nanolithography and data storage. Using tip-enhanced near-field infrared nanolithography, we demonstrate versatile manipulation and characterize the topography and conformation of the silk in situ. In particular, we fabricate greyscale and dual-tone nanopatterns with full-width at half-maximum resolutions of ~35 nm, creating an erasable 'silk drive' that digital data can be written to or read from. As an optical storage medium, the silk drive can store digital and biological information with a capacity of ~64 GB inch-2 and exhibits long-term stability under various harsh conditions. As a proof-of-principle demonstration, we show that this silk drive can be biofunctionalized to exhibit chromogenic reactions, resistance to bacterial infection and heat-triggered, enzyme-assisted decomposition.

Oral Microbiome Alterations Associated with Early Childhood Caries Highlight the Importance of Carbohydrate Metabolic Activities.

Globally, dental caries is the most prevalent chronic oral disease and affects roughly half of all children. The aim of this report was to use metagenomic analyses to investigate the relationship between the oral microbiome and caries in preschool children. A total of 25 preschoolers, aged 3 to 5 years old with severe early childhood caries (ECC), and 19 age-matched, caries-free children as controls were recruited. Saliva samples were collected from the participants and were subjected to metagenomic analyses, whereby the oral microbial communities were investigated. The metagenomic analyses revealed substantial microbiota differences between the two groups, indicating apparent shifts of the oral microbiome present in the ECC group. At the species level, the ECC-enriched microbes included Prevotella amnii, Shuttleworthia satelles, Olsenella uli, and Anaeroglobus geminatus Interestingly, Actinomyces odontolyticus and Actinomyces graevenitzii exhibited apparent differences at the strain level but not the species level between the ECC and control groups. Functional examination showed that the ECC group displayed extensive alterations in metabolic genes/pathways/modules, including enriched functions in sugar metabolism. Finally, an SVM (support vector machine) classifier comprising seven species was developed and generated a moderately good performance in predicting caries onset (area under the receiver operating characteristic curve [AUC] = 78.33%). Together, these findings indicate that caries is associated with considerable changes in the oral microbiome, some of which can potentially be exploited as therapeutic targets or diagnostic markers. (This study has been registered at ClinicalTrials.gov under registration no. NCT02341352.)IMPORTANCE Dental caries is a highly prevalent oral disease that can lead to severe dental damage and may greatly compromise the quality of life of the affected individuals. Previous studies, including those based on 16S rRNA gene, have revealed that the oral microbiota plays a prominent role in development of the disease. But the approach of those studies was limited in analyzing several key microbiome traits, including species- or strain-level composition and functional profile. Here, we performed metagenomic analyses for a cohort of preschool children with or without caries. Our results showed that caries was associated with extensive microbiota differences at various taxonomic and functional levels. Some caries-associated species had not been previously reported, some of which may have significant clinical implications. A microbiome gene catalogue from children with caries was constructed for the first time. The results demonstrated that caries is associated with alterations of the oral microbiome, including changes in microbial composition and metabolic functional profile.

A metagenomic study of the gut microbiome in Behcet's disease.

BACKGROUND: Behcet's disease (BD) is a recalcitrant, multisystemic inflammatory disease that can lead to irreversible blindness. Microbial agents have been considered to contribute to the pathogenesis of this disease, but the underlying mechanisms remain unclear. In this study, we investigated the association of gut microbiome composition with BD as well as its possible roles in the development of this disease. METHODS: Fecal and saliva samples were collected from 32 active BD patients and 74 healthy controls. DNA extracted from fecal samples was subjected to metagenomic analysis, whereas DNA extracted from saliva samples was subjected to 16S rRNA gene sequencing analysis. The results were used to compare the composition and biological function of the microbiome between patients and healthy controls. Lastly, transplantation of pooled fecal samples from active BD patients into B10RIII mice undergoing experimental autoimmune uveitis (EAU) was performed to determine the causal relationship between the gut microbiome and BD. RESULTS: Fecal samples from active BD patients were shown to be enriched in Bilophila spp., a sulfate-reducing bacteria (SRB) and several opportunistic pathogens (e.g., Parabacteroides spp. and Paraprevotella spp.) along with a lower level of butyrate-producing bacteria (BPB) Clostridium spp. and methanogens (Methanoculleus spp. Methanomethylophilus spp.). Analysis of microbial functions revealed that capsular polysaccharide transport system, oxidation-reduction process, type III, and type IV secretion systems were also increased in active BD patients. Network analysis showed that the BD-enriched SRB and opportunistic pathogens were positively correlated with each other, but they were negatively associated with the BPB and methanogens. Animal experiments revealed that fecal microbiota transplantation with feces from BD patients significantly exacerbated EAU activity and increased the production of inflammatory cytokines including IL-17 and IFN-γ. CONCLUSIONS: Our findings revealed that BD is associated with considerable gut microbiome changes, which is corroborated by a mouse study of fecal microbiota transplants. A model explaining the association of the gut microbiome composition with BD pathogenesis is proposed.

Tongue Coating and the Salivary Microbial Communities Vary in Children with Halitosis.

Halitosis is a common symptom mainly caused by microbial activities in the oral cavity. Here, we used 16S rRNA gene pyrosequencing and metagenomic sequencing to examine oral microbial compositions and their functional variations in children with halitosis. We found that the tongue coating of subjects with halitosis had greater bacterial richness than those of healthy subjects. The relative abundance and prevalence of Leptotrichia wadei and Peptostreptococcus stomatis were higher in tongue coating samples from children with halitosis than those from children without halitosis; Prevotella shahii had higher relative abundance and prevalence in saliva samples from children with halitosis. We present the first comprehensive evaluation of the co-occurrence networks of saliva and tongue coating communities under healthy and halitosis conditions, and investigated patterns of significant differences between these communities. Moreover, we observed that bacterial genes associated with responses to infectious diseases and terpenoid and polyketide metabolism were enriched in subjects with halitosis, but not in healthy subjects. Hydrogen sulphide (H2S)-related metabolic pathways suggested that there was higher microbial production and less usage of H2S in subjects with halitosis. Thus, the mechanism of halitosis was implied for the first time via metagenomic sequencing.