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.
This study is the first to characterise gut microbiome in patients with HCC and to report the successful diagnosis model establishment and cross-region validation of microbial markers for HCC. Gut microbiota-targeted biomarkers represent potential non-invasive tools for early diagnosis of HCC.
BackgroundAs part of the tumor microenvironment, the gastric microbiota play vital roles in tumor initiation, progression and metastasis, but stomach microhabitats are not always uniform. We aimed to characterize differences of gastric microbiota in stomach microhabitats associated with gastric cancer (GC) development.MethodsA cohort of 276 GC patients without preoperative chemotherapy was enrolled retrospectively, and 230 normal, 247 peritumoral and 229 tumoral tissues were obtained for gastric microbiota analysis targeting the 16S rRNA gene by MiSeq sequencing. The microbial diversity and composition, bacterial co-occurrence correlations and predictive functional profiles were compared across different microhabitats.FindingsGC-specific stomach microhabitats, not GC stages or types, determine the composition and diversity of the gastric microbiota. Most notably, bacterial richness was decreased in peritumoral and tumoral microhabitats, and the correlation network of abundant gastric bacteria was simplified in tumoral microhabitat. Helicobacter pylori (HP), Prevotella copri and Bacteroides uniformis were significantly decreased, whereas Prevotella melaninogenica, Streptococcus anginosus and Propionibacterium acnes were increased in tumoral microhabitat. Higher HP colonisation influenced the overall structure of the gastric microbiota in normal and peritumoral microhabitats. PiCRUSt analysis revealed that genes associated with nucleotide transport and metabolism and amino acid transport and metabolism were significantly enriched in tumoral microbiota, while gastric acid secretion was significantly higher in HP positive group of the tumoral microbiota.InterpretationOur present study provided new insights into the roles of gastric microbiota in different stomach microhabitats in gastric carcinogenesis, especially the pathogenesis of HP.FundNational Natural Science Foundation of China.
Photodynamic therapy is an effective alternative to traditional treatments due to its minimally invasive nature, negligible systemic toxicity, fewer side effects, and avoidance of drug resistance. However, it is still challenging to design photosensitizers with high singlet oxygen (1O2) quantum yields (QY) due to severe aggregation of the hydrophobic photosensitizers. Herein, we developed a discrete organoplatinum(II) metallacage using therapeutic cis-(PEt3)2Pt(OTf)2 as the building block to improve the 1O2 QY, thus achieving synergistic anticancer efficacy. The metallacage-loaded nanoparticles (MNPs) with tri-modality imaging capability allow precise diagnosis of tumor and real-time monitoring the delivery, biodistribution, and excretion of the MNPs. MNPs exhibited excellent anti-metastatic effect and superior anti-tumor performance against U87MG, drug resistant A2780CIS, and orthotopic tumor models, ablating the tumors without recurrence after a single treatment. Gene chip analyses confirmed the contribution of different therapeutic modalities to the tumor abrogation. This supramolecular platform holds potential in precise cancer theranostics.
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