Frontiers in microbiomes最新文献

{"title":"Fecal microbial transplantation as a novel therapeutic for autism spectrum disorders: a review of the current literature","authors":"Rebecca Gudka, I. Nyinoh","doi":"10.3389/frmbi.2023.1222089","DOIUrl":"https://doi.org/10.3389/frmbi.2023.1222089","url":null,"abstract":"Autism spectrum disorders (ASDs) are complex neurobiological conditions with poor long-term outcomes and limited treatment options. The microbiota–gut–brain axis indicates a pathway by which the gut microbiota links to ASDs. Fecal microbial transplantation (FMT), whereby the gut microbiota is replaced with that of a healthy individual, shows promise for the treatment of neurobiological conditions. This review examines the current evidence for the use of FMT as a therapeutic for ASD.ASDs and their associated gastrointestinal symptoms are improved with FMT, potentially due to the engraftment of features of a healthy gut. Longer treatment regimens that include daily maintenance doses appear to be the most effective long-term therapeutic option, with benefits persisting 2 years post-intervention. Evidence is mixed regarding the use of preparatory treatments. Considering the sex bias in ASD research, small sample sizes and the lack of placebo control arms, randomized controlled trials would be of benefit to the evidence base regarding the use of FMT as a therapeutic option for ASD.FMT is a promising new therapeutic for ASD, but the evidence base is in its infancy.","PeriodicalId":73089,"journal":{"name":"Frontiers in microbiomes","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74753677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of rumen microbiota in lactating Holstein cows fed molasses versus corn grain at two levels of rumen-degradable protein","authors":"E. Guduk, M. Hall, G. Zanton, A. Steinberger, P. Weimer, G. Suen, K. Weigel","doi":"10.3389/frmbi.2023.1204988","DOIUrl":"https://doi.org/10.3389/frmbi.2023.1204988","url":null,"abstract":"We evaluated the influence of diets differing in non-fiber carbohydrates and rumen-degradable protein (RDP) levels on changes in the ruminal bacterial populations in lactating Holstein cows. In all, 12 ruminally cannulated cows were assigned to diets with high or low RDP levels. Within each RDP level, molasses was substituted for corn grain at a concentration of 0%, 5.25%, or 10.5% of diet dry matter in a replicated 3 × 3 Latin square design with 28-day periods. Liquid and solid rumen digesta fractions collected at the end of each period underwent 16S rRNA gene sequencing to identify operational taxonomic units and were analyzed for short-chain fatty acids. Protein degradability affected 6 bacterial genera, whereas carbohydrate alteration impacted 13 genera (p < 0.05). Of the 30 genera with the highest relative abundance, 26 differed by digesta fraction (p < 0.05), with Bacteroidetes genera showing a greater abundance in solids and Firmicutes genera demonstrating a greater prevalence in liquids. Regarding relative abundances, with increasing molasses, Succiniclasticum decreased in liquid (p < 0.05), and CF231, YRC22, Clostridium, Desulfovibrio, BF311, and Oscillospira increased in solids (p < 0.05). In contrast, at higher RDP levels, Succiniclasticum increased while YRC22 and Pseudobutyrivibrio decreased in solids (p < 0.05). Genera with abundances found to be correlated with fermentation products in the liquid included Shuttleworthia, Treponema, Lachnospira, and Schwartzia, which typically have lower relative abundances, showing strong positive correlations with molar proportions (mol%) of propionate, butyrate, and valerate (p < 0.05), and negative correlations with pH and acetate mol% (p < 0.05). Fibrobacter was positively correlated with lactate mol% (p < 0.05). Butyrate mol% exhibited a quadratic increase as molasses increased (p = 0.017), and lactate mol% rose with increased RDP levels (p = 0.042). No treatment effects were detected for pH propionate and valerate mol%; however, we observed a tendency (p = 0.075) for a quadratic effect of molasses treatment on the mol% of acetate. These findings substantiate the pivotal role of diet in shaping rumen microbiota and metabolism, elucidating a nuanced relationship between dietary components, bacterial community structure, and metabolic output. This offers a more detailed understanding of rumen function and the potential for high-precision dietary management in lactating cows.","PeriodicalId":73089,"journal":{"name":"Frontiers in microbiomes","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88950677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial and temporal metagenomics of river compartments reveals viral community dynamics in an urban impacted stream","authors":"Josué Rodríguez-Ramos, Angela Oliverio, Mikayla A. Borton, Robert Danczak, Birgit M. Mueller, Hanna Schulz, Jared Ellenbogen, Rory M. Flynn, Rebecca A. Daly, LeAundra Schopflin, Michael Shaffer, Amy Goldman, Joerg Lewandowski, James C. Stegen, Kelly C. Wrighton","doi":"10.3389/frmbi.2023.1199766","DOIUrl":"https://doi.org/10.3389/frmbi.2023.1199766","url":null,"abstract":"Although river ecosystems constitute a small fraction of Earth’s total area, they are critical modulators of microbially and virally orchestrated global biogeochemical cycles. However, most studies either use data that is not spatially resolved or is collected at timepoints that do not reflect the short life cycles of microorganisms. To address this gap, we assessed how viral and microbial communities change over a 48-hour period by sampling surface water and pore water compartments of the wastewater-impacted River Erpe in Germany. We sampled every 3 hours resulting in 32 samples for which we obtained metagenomes along with geochemical and metabolite measurements. From our metagenomes, we identified 6,500 viral and 1,033 microbial metagenome assembled genomes (MAGs) and found distinct community membership and abundance associated with each river compartment (e.g., Competibacteraceae in surfacewater and Sulfurimonadaceae in pore water). We show that 17% of our viral MAGs clustered to viruses from other ecosystems like wastewater treatment plants and rivers. Our results also indicated that 70% of the viral community was persistent in surface waters, whereas only 13% were persistent in the pore waters taken from the hyporheic zone. Finally, we predicted linkages between 73 viral genomes and 38 microbial genomes. These putatively linked hosts included members of the Competibacteraceae , which we suggest are potential contributors to river carbon and nitrogen cycling via denitrification and nitrogen fixation. Together, these findings demonstrate that members of the surface water microbiome from this urban river are stable over multiple diurnal cycles. These temporal insights raise important considerations for ecosystem models attempting to constrain dynamics of river biogeochemical cycles.","PeriodicalId":73089,"journal":{"name":"Frontiers in microbiomes","volume":"58 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135652426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oligosaccharide feed supplementation reduces plasma insulin in geldings with Equine Metabolic Syndrome","authors":"Alexandra von Münchow, Sarah Torp Yttergren, R. R. Jakobsen, N. Lúthersson, A. K. Hansen, F. Lindenberg","doi":"10.3389/frmbi.2023.1194705","DOIUrl":"https://doi.org/10.3389/frmbi.2023.1194705","url":null,"abstract":"The prevalence of Equine Metabolic Syndrome and insulin dysregulation is increasing in the horse population. Insulin dysregulation is a risk factor for laminitis, which has significant welfare consequences for the horse. Current treatment strategies for Equine Metabolic Syndrome have variable effects on insulin sensitivity. Findings suggest that gut microbiota plays an important role in gastrointestinal barrier protection and metabolic diseases. Dietary supplementation with oligosaccharides has been shown to increase the production of short-chain fatty acids and induce changes in the gut microbiota, with an increase in insulin sensitivity.We hypothesized that dietary oligosaccharide supplementation would ameliorate insulin dysregulation in horses with Equine Metabolic Syndrome.Fifteen horses were included in a cross-over study including two feed supplementations periods with oligosaccharide supplementation or calcium carbonate. Before and after each period plasma insulin, endotoxin, serum amyloid A, and blood glucose concentrations were measured during an oral sugar test and fecal samples were collected.Oligosaccharide supplementation significantly reduced insulin in geldings (p = 0.02). Overall, none of the dominating bacterias changed significantly in relative Δ-abundance. In the gut microbiota of mares, the Akkermansia genus and Clostridiaceae family were significantly more abundant. Within-sample bacterial diversity of horses with insulin concentrations > 60 mIU/L was significantly greater when compared to horses < 60 mIU/L. Horses with insulin concentrations > 60 mIU/L and horses with previous laminitis had a significantly greater beta diversity.Cut-off values for oligosaccharide feed supplementation/placebo dosing instead of dosing by g/kg body weight; owner compliance; single blood sample in oral sugar test; inter-horse variationThis study demonstrated that oligosaccharide supplementation could improve insulin dysregulation in geldings with Equine Metabolic Syndrome suggesting that sex susceptibility might be a factor to consider. Additionally, a tendency of reduction of obesity-associated bacteria was observed. Furthermore, the diversity of the gut microbiota was significantly dependent on laminitis status and insulin concentrations. However, more studies on the effects of oligosaccharide supplementation on insulin dysregulation are needed to improve the dietary management of horses with Equine Metabolic Syndrome.","PeriodicalId":73089,"journal":{"name":"Frontiers in microbiomes","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84260610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of neonatal intensive care unit antibiotics on gut bacterial microbiota of preterm infants: a systematic review","authors":"M. Mulinge, Sylvia Mwanza, H. M. Kabahweza, D. Wamalwa, R. Nduati","doi":"10.3389/frmbi.2023.1180565","DOIUrl":"https://doi.org/10.3389/frmbi.2023.1180565","url":null,"abstract":"Preterm infants encounter an unnatural beginning to life, with housing in neonatal intensive care units (NICUs) where they are exposed to antibiotics. Although the effectiveness of antibiotics in infection control is well established, the short- and long-term unintended effects on the microbiota of preterm infants receiving antibiotic treatment are yet to be quantified. Our aim was to investigate the unintended consequences of NICU antibiotics on preterm infants’ gut microbiota. We searched three electronic databases—Embase, PubMed, and Scopus—for records from 2010 to October 2022. Eligibility criteria included intervention and observational studies that collected stool samples and analyzed microbiota data on the effect of antibiotics on the gut microbiota of preterm infants using 16S rRNA sequencing. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and the quality of the studies was judged using the Cochrane Collaboration Tool for assessing risk of bias (RoB2) for clinical trials, while non-randomized studies were assessed using the Newcastle–Ottawa Scale (NOS). The initial searches yielded 7,605 papers, of which 21 were included in the review. The selected studies examined 3,669 stool samples that were collected longitudinally from 878 preterm infants in seven different countries. Preterm infants exposed to antibiotics had a reduced bacterial diversity, an increased relative abundance of pathogenic bacteria such as Enterobacteriaceae, and a decrease or absence of symbiotic bacteria such as Bifidobacterium spp., which have been shown to assist in immunity development. Antibiotic discontinuation restored diversity, with variances linked to the antibiotic spectrum and treatment duration in some but not all cases. Breastfeeding confounded the association between antibiotic use and dysbiosis. Intriguingly, the reduction of γ-aminobutyric acid (GABA), a crucial neurotransmitter for early brain development, was linked to the depletion of Veillonella spp. Despite the apparent benefits of using antibiotics on preterm infants, we conclude that they should be used only when absolutely necessary and for a short period of time. Mothers’ milk is recommended to hasten the restoration of disrupted microbiota.","PeriodicalId":73089,"journal":{"name":"Frontiers in microbiomes","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84837707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intestinal and fecal pH in human health","authors":"R. Yamamura, Kumi Y. Inoue, K. Nishino, S. Yamasaki","doi":"10.3389/frmbi.2023.1192316","DOIUrl":"https://doi.org/10.3389/frmbi.2023.1192316","url":null,"abstract":"Gut microbiota has been reported to be closely related to host energy metabolism and immunity, and thus influence the development and progression of various human diseases. To date, the gut microbial metabolites such as short-chain fatty acids, defensins, cathelicidins, and lactoferrin in feces have been investigated as biomarkers associated with various disease conditions. In this review, we introduce intestinal and fecal pH, which is relatively easy and rapid to measure compared to the composition of the gut microbiota and its metabolites. In particular, this review presents the distribution of pH in the human body, its role and clinical significance, and various factors that affect intestinal and fecal pH, including the gut microbiota and its metabolites.","PeriodicalId":73089,"journal":{"name":"Frontiers in microbiomes","volume":"71 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86244957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Foliar fungal communities in agroecosystems depend on crop identity and neighboring vegetation","authors":"B. Whitaker, R. Heiniger, C. Hawkes","doi":"10.3389/frmbi.2023.1216462","DOIUrl":"https://doi.org/10.3389/frmbi.2023.1216462","url":null,"abstract":"Agricultural intensification causes plant diversity loss and environmental homogenization, which may result in changes to plant-microbiome interactions mediating plant growth and stress tolerance. We hypothesized that foliar fungal microbiomes would depend on plant traits and environmental filters, constrained by neighboring vegetation expected to serve as a fungal source. Thus, we sampled foliar fungi from four crops (three annual and one perennial), four sites per crop, and three varieties per annual crop, across a 500-km expanse in North Carolina, USA and tested the role of host traits, environmental traits, and vegetative landcover on foliar fungal community structure. Crop species and site were major determinants of community structure, primarily due to differences in plant size and growing season. Site consistently explained 10× more variation in community structure than host variety across the annual crops. Finally, reduced natural vegetative cover surrounding farms was correlated with decreased fungal richness and more homogeneous microbiome assembly. Based on these results, we posit that foliar fungal assembly in crops results from host and environmental filters acting on inputs from the nearby vegetation. Future efforts at agricultural microbiome management must therefore consider landscape management and will require an improved understanding of how agricultural intensification alters microbial source pools.","PeriodicalId":73089,"journal":{"name":"Frontiers in microbiomes","volume":"47 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75143291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring associations between skin, the dermal microbiome, and ultraviolet radiation: advancing possibilities for next-generation sunscreens","authors":"M. L. Smith, C. O'Neill, Mark R Dickinson, Bhaven Chavan, A. McBain","doi":"10.3389/frmbi.2023.1102315","DOIUrl":"https://doi.org/10.3389/frmbi.2023.1102315","url":null,"abstract":"Recent studies have provided strong evidence of a functional link between the microbiota of the skin and overall host health. While sunscreens offer protection against acute and chronic dermatological damage by reflecting, absorbing and scattering ultraviolet radiation, their impact on the skin microbiota is poorly understood. The use of sunscreens may affect the skin microbiota directly or indirectly through mechanisms associated with UV protection, and conversely, the microbiota could mediate or alleviate UV-induced skin damage. Here we consider opportunities for the development of improved sunscreens including formulas that work in tandem with skin commensal microorganisms or which minimise direct effects on the skin microbiota.","PeriodicalId":73089,"journal":{"name":"Frontiers in microbiomes","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90480452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Premise plumbing bacterial communities in four European cities and their association with Legionella","authors":"M. Scaturro, F. Del Chierico, Y. Motro, Angeliki Chaldoupi, A. Flountzi, Jacob Moran-Gilad, A. Girolamo, Thomai Koutsiomani, B. Krogulska, D. Lindsay, R. Matuszewska, Georgios T. Papageorgiou, K. Pancer, Nikolaos Panoussis, M. Rota, S. Uldum, E. Velonakis, Dominique L. Chaput, M. Ricci","doi":"10.3389/frmbi.2023.1170824","DOIUrl":"https://doi.org/10.3389/frmbi.2023.1170824","url":null,"abstract":"Introduction Legionella species are Gram negative, facultative, intracellular bacteria found in natural and engineered water systems. Understanding the bacterial interactions underlying the success of Legionella in aquatic environments could be beneficial for control. Materials and methods We aimed to profile, by 16S rRNA gene amplicon sequencing (V3-V4), the bacterial communities in premise plumbing systems of buildings in four European cities (Copenhagen, Warsaw, Rome, Athens), and identify positive and negative associations of specific community members to culturable Legionella. Results The coarse taxonomic composition was similar across the four cities, but Copenhagen and Warsaw had richer, more diverse communities than Athens and Rome, with a greater number of city-specific amplicon sequence variants (ASVs). The cities had statistically significant differences in bacterial communities at the ASV level, with relatively few shared ASVs. Out of 5,128 ASVs, 73 were classified as Legionella, and one or more of these were detected in most samples from each city (88.1% overall). Interestingly, the relative abundance of Legionella ASVs did not correlate with Legionella culture status. Overall, 44.2% of samples were Legionella culture positive: 71.4% in Warsaw, 62.2% in Athens, 22.2% in Rome, and 15.2% in Copenhagen. 54 specific ASVs and 42 genera had significant positive or negative associations with culturable Legionella. Negative associations included Staphylococcus, Pseudomonas, and Acinetobacter. Positive associations included several Nitrospira ASVs and one classified as Nitrosomodaceae oc32, ASVs in the amoeba-associated genera Craurococcus-Caldovatus and Reyranella, and the predatory genus Bdellovibrio. Discussion Some of these associations are well supported by laboratory studies, but others are the opposite of what was expected. This highlights the difficulties in translating pure culture results to in complex real-life scenarios. However, these positive and negative associations held across the four cities, across multiple buildings and plumbing compartments. This is important because developing better control measures, including probiotic approaches, will require an understanding of ecological relationships that can be generalised across different engineered water systems.","PeriodicalId":73089,"journal":{"name":"Frontiers in microbiomes","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84883271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prebiotic capacity of novel bioengineered wheat arabinoxylans in a batch culture model of the human gut microbiota","authors":"Emmanuel N. Njoku, W. Mottawea, H. Hassan, R. Hammami","doi":"10.3389/frmbi.2023.1156797","DOIUrl":"https://doi.org/10.3389/frmbi.2023.1156797","url":null,"abstract":"Arabinoxylan (AX) is an essential component of dietary fiber with potential prebiotic properties. However, owing to its complex structure, fermentation of AX by gut microbes is structure dependent. In this study, we evaluated the effect of bioengineered wheat AX on the metabolism and composition of gut microbiota using an in vitro fermentation model. We compared the effect of bioengineered AX with that of untreated AX and a control. Structurally modified AX did not significantly alter gut microbiome composition within 48 h of treatment; however, it enhanced the abundance of health-promoting bacterial taxa, such as Bacteroides, Bifidobacterium, Anaerofustis, and Eubacterium. Furthermore, the bioengineered AX significantly increased the level of acetate produced over 24 h. The amount of microbiota-generated butyrate was significantly increased 24 h after adding α-L-arabinofuranosidase-treated AX. AX treated with the α-L-arabinofuranosidase B25 enzyme induced higher levels of production of total short-chain fatty acids by the microbiota from four donors. The results of this study provide evidence that enzymatic structural modification of AX has the potential to modulate gut microbiome composition and metabolic activities.","PeriodicalId":73089,"journal":{"name":"Frontiers in microbiomes","volume":"688 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76877087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}