Beneficial Regulatory Effects of Polymethoxyflavone—Rich Fraction from Ougan (Citrus reticulata cv. Suavissima) Fruit on Gut Microbiota and Identification of Its Intestinal Metabolites in Mice

Polymethoxyflavones (PMFs) are special flavonoids in citrus fruits that have been suggested to be beneficial to human health. However, whether PMFs in citrus fruit alter human gut microbiota is not well understood. The aim of the present study was to investigate the effects of PMF-rich fraction from Ougan (Citrus reticulata cv. Suavissima) on gut microbiota and evaluate the intestinal metabolic profile of PMFs in Institute of Cancer Research mice. The main components of the PMF-rich fraction were nobiletin, tangeretin, and 5-demethylnobiletin. The composition of the gut microbiota was analyzed using 16S ribosomal DNA sequencing. The results showed that after oral administration, the composition of mice gut microbiota was significantly altered. The relative abundance of two probiotics, Lactobacillus and Bifidobacterium, were found to increase significantly. A total of 21 metabolites of PMFs were detected in mice intestinal content by high performance liquid chromatography electrospray ionization tandem mass spectrometry, and they were generated through demethylation, demethoxylation, hydroxylation, and glucuronidation. Our results provided evidence that PMFs have potential beneficial regulatory effects on gut microbiota that in turn metabolize PMFs, which warrants further investigation in human clinical trials

Evaluation of Antioxidant Capacity and Gut Microbiota Modulatory Effects of Different Kinds of Berries

Berries are fairly favored by consumers. Phenolic compounds are the major phytochemicals in berries, among which anthocyanins are one of the most studied. Phenolic compounds are reported to have prebiotic-like effects. In the present study, we identified the anthocyanin profiles, evaluated and compared the antioxidant capacities and gut microbiota modulatory effects of nine common berries, namely blackberry, black goji berry, blueberry, mulberry, red Chinese bayberry, raspberry, red goji berry, strawberry and white Chinese bayberry. Anthocyanin profiles were identified by UPLC-Triple-TOF/MS. In vitro antioxidant capacity was evaluated by four chemical assays (DPPH, ABTS, FRAP and ORAC). In vivo antioxidant capacity and gut microbiota modulatory effects evaluation was carried out by treating healthy mice with different berry extracts for two weeks. The results show that most berries could improve internal antioxidant status, reflected by elevated serum or colonic T-AOC, GSH, T-SOD, CAT, and GSH-PX levels, as well as decreased MDA content. All berries significantly altered the gut microbiota composition. The modulatory effects of the berries were much the same, namely by the enrichment of beneficial SCFAs-producing bacteria and the inhibition of potentially harmful bacteria. Our study shed light on the gut microbiota modulatory effect of different berries and may offer consumers useful consumption guidance

Polymethoxyflavone–Enriched Fraction from Ougan (Citrus reticulata cv. Suavissima) Attenuated Diabetes and Modulated Gut Microbiota in Diabetic KK‑A^y Mice

Diabetes mellitus is a serious, chronic disease worldwide; yet it is largely preventable through physical activity and healthy diets. Ougan (Citrus reticulata cv. Suavissima) is a characteristic citrus variety rich in polymethoxyflavones. In the present study, the anti-diabetic effects of the polymethoxyflavone-enriched fraction from Ougan (OG-PMFs) were investigated. Diabetic KK-Ay mice were supplemented with different doses of OG-PMFs for 5 weeks. Our results demonstrated that OG-PMFs exhibited robust protective effects against diabetes symptoms in KK-Ay mice. The potential mechanisms may partially be attributed to the restoration of hepatic GLUT2 and catalase expression. Notably, OG-PMF administration significantly altered the gut microbiota composition in diabetic KK-Ay, indicated by the suppression of metabolic disease-associated genera Desulfovibrio, Lachnoclostridium, Enterorhabdus, and Ralstonia, implying that the gut microbiota might be another target for OG-PMFs to show effects. Taken together, our results provided a supplementation for the metabolic-protective effects of PMFs and highlighted that OG-PMFs hold great potential to be developed as a functional food ingredient

Effects of Dietary Interventions on Gut Microbiota in Humans and the Possible Impacts of Foods on Patients' Responses to Cancer Immunotherapy

none15si: The gut microbiota-the community of microorganisms in the gut-has been implicated in many physical and mental disorders in addition to intestinal diseases. Diets are the most studied and promising factors for altering it. Indeed, certain dietary interventions that increase fiber intake rapidly change levels of certain nutrients that can modify the composition of the microbiota, promoting richness and diversity. Recent intriguing evidence from several human clinical trials suggested that the composition and diversity of patients' gut microbiotas at baseline can influence their responses to cancer immunotherapy. If the factors that influence the gut microbiota were fully understood, it is conceivable that manipulating them could boost therapeutic responses in cancer patients. In this review, we investigate the possibility of using fruits, vegetables, or whole grains to enhance response to cancer therapies in humans, as current evidence suggests that these dietary components can manipulate and enhance diversity of the gut microbiota. Accordingly, dietary interventions with locally available fruits, vegetables, and whole grains might be an affordable and safe approach to enhancing the diversity of the gut microbiota before immunotherapy, in turn improving patients' responses to their treatments.noneWang, Li-Shu; Mo, Yue Yang; Huang, Yi-Wen; Echeveste, Carla Elena; Wang, Hsin-Tzu; Chen, Jiali; Oshima, Kiyoko; Yearsley, Martha; Simal-Gandaraf, Jesus; Battino, Maurizio; Xiao, Jianbo; Chen, Jiebiao; Sun, Chongde; Yu, Jianhua; Bai, WeibinWang, Li-Shu; Mo, Yue Yang; Huang, Yi-Wen; Echeveste, Carla Elena; Wang, Hsin-Tzu; Chen, Jiali; Oshima, Kiyoko; Yearsley, Martha; Simal-Gandaraf, Jesus; Battino, Maurizio; Xiao, Jianbo; Chen, Jiebiao; Sun, Chongde; Yu, Jianhua; Bai, Weibi

Effects of Dietary Interventions on Gut Microbiota in Humans and the Possible Impacts of Foods on Patients’ Responses to Cancer Immunotherapy

The gut microbiota—the community of microorganisms in the gut—has been implicated in many physical and mental disorders in addition to intestinal diseases. Diets are the most studied and promising factors for altering it. Indeed, certain dietary interventions that increase fiber intake rapidly change levels of certain nutrients that can modify the composition of the microbiota, promoting richness and diversity. Recent intriguing evidence from several human clinical trials suggested that the composition and diversity of patients’ gut microbiotas at baseline can influence their responses to cancer immunotherapy. If the factors that influence the gut microbiota were fully understood, it is conceivable that manipulating them could boost therapeutic responses in cancer patients. In this review, we investigate the possibility of using fruits, vegetables, or whole grains to enhance response to cancer therapies in humans, as current evidence suggests that these dietary components can manipulate and enhance diversity of the gut microbiota. Accordingly, dietary interventions with locally available fruits, vegetables, and whole grains might be an affordable and safe approach to enhancing the diversity of the gut microbiota before immunotherapy, in turn improving patients’ responses to their treatments

Identifying cis-mediators for trans-eQTLs across many human tissues using genomic mediation analysis

The impact of inherited genetic variation on gene expression in humans is well-established. The majority of known expression quantitative trait loci (eQTLs) impact expression of local genes (cis-eQTLs). More research is needed to identify effects of genetic variation on distant genes (trans-eQTLs) and understand their biological mechanisms. One common trans-eQTLs mechanism is "mediation" by a local (cis) transcript. Thus, mediation analysis can be applied to genome-wide SNP and expression data in order to identify transcripts that are "cis-mediators" of trans-eQTLs, including those "cis-hubs" involved in regulation of many trans-genes. Identifying such mediators helps us understand regulatory networks and suggests biological mechanisms underlying trans-eQTLs, both of which are relevant for understanding susceptibility to complex diseases. The multitissue expression data from the Genotype-Tissue Expression (GTEx) program provides a unique opportunity to study cis-mediation across human tissue types. However, the presence of complex hidden confounding effects in biological systems can make mediation analyses challenging and prone to confounding bias, particularly when conducted among diverse samples. To address this problem, we propose a new method: Genomic Mediation analysis with Adaptive Confounding adjustment (GMAC). It enables the search of a very large pool of variables, and adaptively selects potential confounding variables for each mediation test. Analyses of simulated data and GTEx data demonstrate that the adaptive selection of confounders by GMAC improves the power and precision of mediation analysis. Application of GMAC to GTEx data provides new insights into the observed patterns of cis-hubs and trans-eQTL regulation across tissue types

Large eQTL meta-analysis reveals differing patterns between cerebral cortical and cerebellar brain regions

© 2020, The Author(s). The availability of high-quality RNA-sequencing and genotyping data of post-mortem brain collections from consortia such as CommonMind Consortium (CMC) and the Accelerating Medicines Partnership for Alzheimer’s Disease (AMP-AD) Consortium enable the generation of a large-scale brain cis-eQTL meta-analysis. Here we generate cerebral cortical eQTL from 1433 samples available from four cohorts (identifying >4.1 million significant eQTL for >18,000 genes), as well as cerebellar eQTL from 261 samples (identifying 874,836 significant eQTL for >10,000 genes). We find substantially improved power in the meta-analysis over individual cohort analyses, particularly in comparison to the Genotype-Tissue Expression (GTEx) Project eQTL. Additionally, we observed differences in eQTL patterns between cerebral and cerebellar brain regions. We provide these brain eQTL as a resource for use by the research community. As a proof of principle for their utility, we apply a colocalization analysis to identify genes underlying the GWAS association peaks for schizophrenia and identify a potentially novel gene colocalization with lncRNA RP11-677M14.2 (posterior probability of colocalization 0.975)