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Platinum-based chemotherapy failure represents a significant challenge in the management of ovarian cancer (OC) and contributes to disease recurrence and poor prognosis. Recent studies have shed light on the involvement of the gut microbiota in modulating anticancer treatments. However, the precise underlying mechanisms, by which gut microbiota regulates the response to platinum-based therapy, remain unclear. Here, we investigated the role of gut microbiota on the anticancer response of cisplatin and its underlying mechanisms. Our results demonstrate a substantial improvement in the anticancer efficacy of cisplatin following antibiotic-induced perturbation of the gut microbiota in OC-bearing mice. 16S rRNA sequencing showed a pronounced alteration in the composition of the gut microbiome in the cecum contents following exposure to cisplatin. Through metabolomic analysis, we identified distinct metabolic profiles in the antibiotic-treated group, with a notable enrichment of the gut-derived metabolite 3-methylxanthine in antibiotic-treated mice. Next, we employed a strategy combining transcriptome analysis and chemical-protein interaction network databases. We identified metabolites that shared structural similarity with 3-methylxanthine, which interacted with genes enriched in cancer-related pathways. It is identified that 3-methylxanthinesignificantly enhances the effectiveness of cisplatin by promoting apoptosis both in vivo and in vitro . Importantly, through integrative multiomics analyses, we elucidated the mechanistic basis of this enhanced apoptosis, revealing a dopamine receptor D1-dependent pathway mediated by 3-methylxanthine. This study elucidated the mechanism by which gut-derived metabolite 3-methylxanthine mediated cisplatin-induced apoptosis. Our findings highlight the potential translational significance of 3-methylxanthine as a promising adjuvant in conjunction with cisplatin, aiming to improve treatment outcomes for OC patients.IMPORTANCEThe precise correlation between the gut microbiota and the anticancer effect of cisplatin in OC remains inadequately understood. Our investigation has revealed that manipulation of the gut microbiota via the administration of antibiotics amplifies the efficacy of cisplatin through the facilitation of apoptosis in OC-bearing mice. Metabolomic analysis has demonstrated that the cecum content from antibiotic-treated mice exhibits an increase in the levels of 3-methylxanthine, which has been shown to potentially enhance the therapeutic effectiveness of cisplatin by an integrated multiomic analysis. This enhancement appears to be attributable to the promotion of cisplatin-induced apoptosis, with 3-methylxanthine potentially exerting its influence via the dopamine receptor D1-dependent pathway. These findings significantly contribute to our comprehension of the impact of the gut microbiota on the anticancer therapy in OC. Notably, the involvement of 3-methylxanthine suggests its prospective utility as a supplementary component for augmenting treatment outcomes in patients afflicted with ovarian cancer., Competing Interests: The authors declare no conflict of interest.

Background: The results of human observational studies on the correlation between gut microbiota perturbations and polycystic ovary syndrome (PCOS) have been contradictory. This study aimed to perform the first systematic review and meta-analysis to evaluate the specificity of the gut microbiota in PCOS patients compared to healthy women., Methods: Literature through May 22, 2023, was searched on PubMed, Web of Science, Medline, Embase, Cochrane Library, and Wiley Online Library databases. Unreported data in diversity indices were filled by downloading and processing raw sequencing data. Systematic review inclusion: original studies were eligible if they applied an observational case-control design, performed gut microbiota analysis and reported diversity or abundance measures, sampled general pre-menopausal women with PCOS, and are longitudinal studies with baseline comparison between PCOS patients and healthy females. Systematic review exclusion: studies that conducted interventional or longitudinal comparisons in the absence of a control group. Two researchers made abstract, full-text, and data extraction decisions, independently. The Joanna Briggs Institute Critical Appraisal Checklist was used to assess the methodologic quality. Hedge's g standardized mean difference (SMD), confidence intervals (CIs), and heterogeneity (I 2 ) for alpha diversity were calculated. Qualitative syntheses of beta-diversity and microbe alterations were performed., Results: Twenty-eight studies (n = 1022 patients, n = 928 control) that investigated gut microbiota by collecting stool samples were included, with 26 and 27 studies having provided alpha-diversity and beta-diversity results respectively. A significant decrease in microbial evenness and phylogenetic diversity was observed in PCOS patients when compared with control participants (Shannon index: SMD = - 0.27; 95% CI, - 0.37 to - 0.16; phylogenetic diversity: SMD = - 0.39; 95% CI, -- 0.74 to - 0.03). We also found that reported beta-diversity was inconsistent between studies. Despite heterogeneity in bacterial relative abundance, we observed depletion of Lachnospira and Prevotella and enrichment of Bacteroides, Parabacteroides, Lactobacillus, Fusobacterium, and Escherichia/Shigella in PCOS. Gut dysbiosis in PCOS, which might be characterized by the reduction of short-chain fatty acid (SCFA)-producing and bile-acid-metabolizing bacteria, suggests a shift in balance to favor pro-inflammatory rather than anti-inflammatory bacteria., Conclusions: Gut dysbiosis in PCOS is associated with decreased diversity and alterations in bacteria involved in microbiota-host crosstalk., Trial Registration: PROSPERO registration: CRD42021285206, May 22, 2023., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The gut metabolome acts as an intermediary between the gut microbiota and host, and has tremendous diagnostic and therapeutic potential. Several studies have utilized bioinformatic tools to predict metabolites based on the different aspects of the gut microbiome. Although these tools have contributed to a better understanding of the relationship between the gut microbiota and various diseases, most of them have focused on the impact of microbial genes on the metabolites and the relationship between microbial genes. In contrast, relatively little is known regarding the effect of metabolites on the microbial genes or the relationship between these metabolites. In this study, we constructed a computational framework of Microbe-Metabolite INteractions-based metabolic profiles Predictor (MMINP), based on the Two-Way Orthogonal Partial Least Squares (O2-PLS) algorithm to predict the metabolic profiles associated with gut microbiota. We demonstrated the predictive value of MMINP relative to that of similar methods. Additionally, we identified the features that would profoundly impact the prediction performance of data-driven methods (O2-PLS, MMINP, MelonnPan, and ENVIM), including the training sample size, host disease state, and the upstream data processing methods of the different technical platforms. We suggest that when using data-driven methods, similar host disease states and preprocessing methods, and a sufficient number of training samples are necessary to achieve accurate prediction.

Background: Hand, foot and mouth disease (HFMD) is an acute enterovirus-induced disease. Gut microbiota dysbiosis has been identified as a factor that plays an important role in enteral virus infection, but the gut microbiota profile in hand, foot and mouth disease has rarely been studied in a large population., Methods: A total of 749 children (HFMD: n = 262, healthy control: n = 487) aged 2 to 7 years were recruited from hospitals and communities in the period from May to July, 2017. Clinical and demographical information was collected by trained personnel, and fecal samples were collected and processed for 16S ribosomal RNA(rRNA) gene sequencing., Results: We observed a significant alteration in the microbiota profile of children with HFMD compared with that of control children. Patients with enteroviruses A71(EV71) positive had more dysbiotic gut microbiota than those with coxsackievirus A16 (CAV16) positive. We found that Prevotella and Streptococcus were enriched in children with HFMD, whereas beneficial bacteria, including Bifidobacterium and Faecalibacterium , were depleted. Children with synbiotics supplements had lower risk of HFMD and we observed that the gut microbiota of HFMD patients who were administered synbiotics exhibited potential resistance to the dysbiosis detected in HFMD., Conclusions: This study suggested that the gut microbiota of patients with hand, foot and mouth disease exhibits dysbiosis and that synbiotics supplements potentially helps maintain the homeostasis of the gut flora., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Guo, Lan, Wen, Zheng, Rong, Liu, Chen, Yang, Zheng and Wu.)

Objective: The objective of the study was to evaluate associations among diet quality, serum uremic toxin concentrations, and the gut microbiota profile in adults undergoing hemodialysis therapy., Design and Methods: This is a cross-sectional analysis of baseline data from a clinical trial involving adults receiving hemodialysis therapy. Usual dietary intake was determined using a diet history method administered by Accredited Practising Dietitians. Two approaches were used for diet quality assessment: (1) using three a priori defined plant-based diet indices-an overall plant-based diet index (PDI), a healthy PDI, and an unhealthy PDI and (2) classification of food group intake. Serum uremic toxins (p-cresyl sulfate and indoxyl sulfate (IS); free and total) were determined by ultra-performance liquid chromatography. Gut microbiota composition was established through sequencing the 16S rRNA gene in stool samples., Results: Twenty-two adults (median age 70.5 [interquartile range: 59-76], 64% male) were included in the final analysis. Higher adherence to the PDI was associated with lower total IS levels (P = .028), independent of dialysis adequacy, urinary output, and blood albumin levels. In contrast, higher adherence to the unhealthy PDI was associated with increases in both free and total IS. Several other direct and inverse associations between diet quality with uremic toxins, microbial relative abundances, and diversity metrics were also highlighted. Diet-associated taxa showed significantly different trends of association with serum uremic toxin concentrations (P < .05). Higher adherence to the PDI was negatively associated with relative abundances of Haemophilus and Haemophilus parainfluenzae that were related to elevated total IS levels. In contrast, increased intake of food items considered unhealthy, such as animal fats, sweets and desserts, were associated with bacteria linked to higher IS and p-cresyl sulfate (total and free) concentrations., Conclusions: The quality of diet and food selections may influence uremic toxin production by the gut microbiota in adults receiving hemodialysis. Well-designed dietary intervention trials that adopt multi-omic technologies appropriate for the functional annotation of the gut microbiome are needed to validate our findings and establish causality., (Copyright © 2020 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: Pre-eclampsia (PE) is one of the malignant metabolic diseases that complicate pregnancy. Gut dysbiosis has been identified for causing metabolic diseases, but the role of gut microbiome in the pathogenesis of PE remains unknown., Design: We performed a case-control study to compare the faecal microbiome of PE and normotensive pregnant women by 16S ribosomal RNA (rRNA) sequencing. To address the causative relationship between gut dysbiosis and PE, we used faecal microbiota transplantation (FMT) in an antibiotic-treated mouse model. Finally, we determined the microbiome translocation and immune responses in human and mouse placental samples by 16S rRNA sequencing, quantitative PCR and in situ hybridisation., Results: Patients with PE showed reduced bacterial diversity with obvious dysbiosis. Opportunistic pathogens, particularly Fusobacterium and Veillonella , were enriched, whereas beneficial bacteria, including Faecalibacterium and Akkermansia , were markedly depleted in the PE group. The abundances of these discriminative bacteria were correlated with blood pressure (BP), proteinuria, aminotransferase and creatinine levels. On successful colonisation, the gut microbiome from patients with PE triggered a dramatic, increased pregestational BP of recipient mice, which further increased after gestation. In addition, the PE-transplanted group showed increased proteinuria, embryonic resorption and lower fetal and placental weights. Their T regulatory/helper-17 balance in the small intestine and spleen was disturbed with more severe intestinal leakage. In the placenta of both patients with PE and PE-FMT mice, the total bacteria, Fusobacterium , and inflammatory cytokine levels were significantly increased., Conclusions: This study suggests that the gut microbiome of patients with PE is dysbiotic and contributes to disease pathogenesis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

At present, the pathophysiology of autism spectrum disorder (ASD) remains unclear. Increasing evidence suggested that gut microbiota plays a critical role in gastrointestinal symptoms and behavioral impairment in ASD patients. The primary aim of this systematic review is to investigate potential evidence for the characteristic dysbiosis of gut microbiota in ASD patients compared with healthy controls (HCs). The MEDLINE, EMBASE, Web of Science and Scopus were systematically searched before March 2018. Human studies that compared the composition of gut microbiota in ASD patients and HCs using culture-independent techniques were included. Independent data extraction and quality assessment of studies were conducted according to PRISMA statement and Newcastle-Ottawa Scale. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was used to infer biological functional changes of the shifted microbiota with the available data in four studies. Sixteen studies with a total sample size of 381 ASD patients and 283 HCs were included in this systematic review. The quality of the studies was evaluated as medium to high. The overall changing of gut bacterial community in terms of β-diversity was consistently observed in ASD patients compared with HCs. Furthermore, Bifidobacterium, Blautia, Dialister, Prevotella, Veillonella, and Turicibacter were consistently decreased, while Lactobacillus, Bacteroides, Desulfovibrio, and Clostridium were increased in patients with ASD relative to HCs in certain studies. This systematic review demonstrated significant alterations of gut microbiota in ASD patients compared with HCs, strengthen the evidence that dysbiosis of gut microbiota may correlate with behavioral abnormality in ASD patients. However, results of inconsistent changing also existed and further big-sampled well-designed studies are needed. Generally, as a potential mediator of risk factors, the gut microbiota could be a novel target for ASD patients in the future.

The gut microbiota has been implicated in glucose intolerance and its progression towards type-2 diabetes mellitus (T2DM). Relevant randomized clinical trial with prebiotic intervention was inadequate. We sought to evaluate the impact of fructooligosaccharides (FOS) and galactooligosaccharides (GOS) on glycemia during oral glucose tolerance test (OGTT) and intestinal microbiota. A randomized double-blind cross-over study was performed with 35 adults treated with FOS and GOS for 14 days (16 g/day). Faeces sampling, OGTT and anthropometric parameters were performed. Short-term intake of high-dose prebiotics had adverse effect on glucose metabolism, as in FOS intervention demonstrated by OGTT (P < 0.001), and in GOS intervention demonstrated by fasting glucose (P < 0.05). A significant increase in the relative abundance of Bifidobacterium was observed both in FOS and GOS group, while the butyrate-producing bacteria like Phascolarctobacterium in FOS group and Ruminococcus in GOS group were decreased. A random forest model using the initial microbiota was developed to predict OGTT levels after prebiotic intervention with relative success (R = 0.726). Our study alerted even though FOS and GOS increased Bifidobacterium, they might have adverse effect on glucose metabolism by reducing butyrate-producing microbes. Individualized prebiotics intervention based on gut microbiome needs to be evaluated in future.