BackgroundA gluten-free diet (GFD) is the most commonly adopted special diet worldwide. It is an effective treatment for coeliac disease and is also often followed by individuals to alleviate gastrointestinal complaints. It is known there is an important link between diet and the gut microbiome, but it is largely unknown how a switch to a GFD affects the human gut microbiome.MethodsWe studied changes in the gut microbiomes of 21 healthy volunteers who followed a GFD for four weeks. We collected nine stool samples from each participant: one at baseline, four during the GFD period, and four when they returned to their habitual diet (HD), making a total of 189 samples. We determined microbiome profiles using 16S rRNA sequencing and then processed the samples for taxonomic and imputed functional composition. Additionally, in all 189 samples, six gut health-related biomarkers were measured.ResultsInter-individual variation in the gut microbiota remained stable during this short-term GFD intervention. A number of taxon-specific differences were seen during the GFD: the most striking shift was seen for the family Veillonellaceae (class Clostridia), which was significantly reduced during the intervention (p = 2.81 × 10−05). Seven other taxa also showed significant changes; the majority of them are known to play a role in starch metabolism. We saw stronger differences in pathway activities: 21 predicted pathway activity scores showed significant association to the change in diet. We observed strong relations between the predicted activity of pathways and biomarker measurements.ConclusionsA GFD changes the gut microbiome composition and alters the activity of microbial pathways.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-016-0295-y) contains supplementary material, which is available to authorized users.
Purpose: The gut microbiome is involved in antitumor immunotherapy and chemotherapy responses; however, evidence-based research on the role of gut microbiome in predicting response to neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC) remains scarce. This prospective, longitudinal study aimed to evaluate the feasibility of the gut microbiome in predicting nCRT responses. Experimental Design: We collected 167 fecal samples from 84 patients with LARC before and after nCRT and 31 specimens from healthy individuals for 16S rRNA sequencing. Patients were divided into responders and nonresponders according to pathologic response to nCRT. After identifying microbial biomarkers related to nCRT responses, we constructed a random forest classifier for nCRT response prediction of a training cohort of baseline samples from 37 patients and validated the classifier in another cohort of 47 patients. Results: We observed significant microbiome alterations represented by a decrease in LARC-related pathogens and an increase in Lactobacillus and Streptococcus during nCRT. Furthermore, a prominent microbiota difference between responders and nonresponders was noticed in the baseline samples. Microbes related with butyrate production, including Roseburia, Dorea, and Anaerostipes, were overrepresented in responders, whereas Coriobacteriaceae and Fusobacterium were overrepresented in nonresponders. Ten biomarkers were selected for the response-prediction classifier, including Dorea, Anaerostipes, and Streptococcus, which yielded an area under the curve value of 93.57% [95% confidence interval (CI), 85.76%–100%] in the training cohort and 73.53% (95% CI, 58.96%–88.11%) in the validation cohort. Conclusions: The gut microbiome offers novel potential biomarkers for predicting nCRT responses, which has important manifestations in the clinical management of these patients.
Background/Aims: Ovarian cancer is often diagnosed at later stages with poor prognosis. Recent studies have associated the expression of deubiquitylase USP7 with the survival of ovarian cancers. Being a cysteine protease, USP7 could become a target for pharmacological intervention. Therefore, in this study, we assessed the influence of its inhibitor P5091 on ovarian cancer cells. Methods: Ovarian cancer cells were treated with P5091, and cell proliferation was measured with MTT assay; cell morphology was inspected under a phase-contrast microscope; cell cycle and cell death were examined by flow cytometry. To gain mechanistic insights into its effects, immunoblotting was performed to detect USP7, HDM2, p53, p21, apoptosis and autophagy related proteins. Results: P5091 effectively suppressed the growth of ovarian cancer cells, caused cell cycle blockage, and induced necrosis and apoptosis with more severe phenotypes observed in HeyA8 cells with wild-type p53 than in OVCAR-8 cells with mutant p53. P5091 also prompted autophagy, with more efficient p62 degradation in HeyA8. Conclusion: P5091 shows efficacy in suppressing ovarian cancers harbouring wild-type and mutant p53. Its effects seemed to be enhanced by wild-type p53. The potency of this USP7 inhibitor also correlated with autophagy to some extent. Therefore, the pharmacological targeting of USP7 may serve as a potential therapeutic strategy and warrants further investigation.
Opa‐interacting protein 5 antisense RNA 1 (OIP5‐AS1) is a long intergenic noncoding RNA, which has been suggested to be dysregulated in human cancers and served as tumor suppressor or promoter depending on tumor types. However, the role of OIP5‐AS1 in bladder cancer was still unknown. In our study, OIP5‐AS1 was overexpressed in bladder cancer, and associated with clinical progression and short overall survival. The loss‐of‐function studies suggested downregulation of OIP5‐AS1 expression decreased cell viability, induced cell‐cycle arrest and promoted cell apoptosis in bladder cancer. There was a positive association between OIP5‐AS1 expression and OIP5 expression in bladder cancer tissues. Moreover, downregulation of OIP5‐AS1 expression reduced messenger RNA and protein levels of OIP5 in bladder cancer cell lines. In conclusion, OIP5‐AS1 is a useful biomarker for predicting clinical progression and poor prognosis and promotes cell proliferation through modulating OIP5 expression.
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