metagenomic sequencing

宏基因组测序
  • 文章类型: Journal Article
    随着微生物组学术研究的兴起,长寿及其决定因素的研究得到了振兴。肠道微生物群已经建立起至关重要的保护作用,新陈代谢,以及在人类健康和疾病中的生理作用。肠道菌群失调已被确定为促成多种疾病发展的重要因素。因此,假设长寿个体的肠道微生物群具有健康的抗衰老相关的肠道微生物是合理的,which,通过延伸,可能为抗衰老治疗和干预提供特定的分子靶标。在本研究中,我们比较了两个不同年龄段中国人的肠道菌群,没有重大疾病的长寿成年人(90岁以上)和老年人(65-74岁)。我们发现,在长寿个体中,Sutterella属和Megamonas属的细菌相对丰度显着降低。此外,我们确定,虽然生物过程如自噬(GO:0006914)和通过半保守复制(GO:0032201)的端粒维持在长寿群体中得到增强,对脂多糖的反应(GO:0032496),烟酰胺腺嘌呤二核苷酸氧化(GO:0006116),S-腺苷蛋氨酸代谢(GO:0046500)减弱。此外,发现两组在氨基酸代谢方面存在差异。我们认为,肠道微生物群的这些组成和功能差异可能与决定寿命或衰老的机制有关。
    The study of longevity and its determinants has been revitalized with the rise of microbiome scholarship. The gut microbiota have been established to play essential protective, metabolic, and physiological roles in human health and disease. The gut dysbiosis has been identified as an important factor contributing to the development of multiple diseases. Accordingly, it is reasonable to hypothesize that the gut microbiota of long-living individuals have healthy antiaging-associated gut microbes, which, by extension, might provide specific molecular targets for antiaging treatments and interventions. In the present study, we compared the gut microbiota of Chinese individuals in two different age groups, long-living adults (aged over 90 years) and elderly adults (aged 65-74 years) who were free of major diseases. We found significantly lower relative abundances of bacteria in the genera Sutterella and Megamonas in the long-living individuals. Furthermore, we established that while biological processes such as autophagy (GO:0006914) and telomere maintenance through semiconservative replication (GO:0032201) were enhanced in the long-living group, response to lipopolysaccharide (GO:0032496), nicotinamide adenine dinucleotide oxidation (GO:0006116), and S-adenosyl methionine metabolism (GO:0046500) were weakened. Moreover, the two groups were found to differ with respect to amino acid metabolism. We suggest that these compositional and functional differences in the gut microbiota may potentially be associated with mechanisms that contribute to determining longevity or aging.
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  • 文章类型: Journal Article
    本研究旨在研究高脂饮食下硒对乳腺癌小鼠肠道菌群的影响。
    将12只雌性BALB/c小鼠随机分为两组:4只T1+硒+高脂饮食组和4只T1+高脂饮食组。小鼠在右侧第4乳腺脂肪垫上注射4个T1细胞,并保持高脂肪饮食。收集粪便样本,提取DNA进行宏基因组测序和生物信息学分析。对相关靶基因和通路进行注释和代谢分析,探讨高脂饮食状态下硒对乳腺癌的干预作用。
    在高脂肪饮食中补充硒改变了患有乳腺癌的小鼠的肠道微生物群的组成和多样性。硒干预组肠道微生物组成差异显著,随着变形杆菌的丰度增加,放线菌,和Verrucomicrobiaphyla和诸如ganmani螺杆菌之类的物种,日本螺旋杆菌,和阿克曼西亚粘虫,而门,比如拟杆菌,Firmicutes,去铁杆菌,和螺旋藻,和物种,例如普雷沃特拉sp。MGM2,肠壁杆菌,鼠乳杆菌,和普雷沃特拉sp。MGM1,均降低。功能分析揭示了与碳水化合物活性酶相关的基因的差异表达,病原体-宿主相互作用,细胞通讯,细胞自动诱导,膜转运蛋白,和毒力因子。此外,预测了硒干预组中37个COGs和48个代谢潜力上升的代谢物。
    硒改变了高脂饮食乳腺癌小鼠肠道菌群的稳态,影响他们的组成,丰度,和相关的新陈代谢。这些发现表明,该机制涉及干扰肠道微生物群稳态,导致肿瘤相关蛋白质和脂肪酸的合成改变,并诱导肿瘤细胞凋亡和焦亡。
    UNASSIGNED: This study aimed to investigate the effect of selenium on gut microbiota in mice with breast cancer under a high-fat diet.
    UNASSIGNED: A total of 12 female BALB/c mice were randomly divided into two groups: 4 T1 + selenium+ high-fat diet group and 4 T1 + high-fat diet group. Mice were injected with 4 T1 cells on the right 4th mammary fat pad and kept on a high-fat diet. Fecal samples were collected, and DNA was extracted for metagenomic sequencing and bioinformatics analysis. Relevant target genes and pathways were annotated and metabolically analyzed to explore the intervention effect of selenium on breast cancer in the high-fat diet state.
    UNASSIGNED: Selenium supplementation in the high-fat diet altered the composition and diversity of gut microbiota in mice with breast cancer. The gut microbial composition was significantly different in the selenium intervention group, with an increased abundance of Proteobacteria, Actinobacteria, and Verrucomicrobia phyla and species such as Helicobacter ganmani, Helicobacter japonicus, and Akkermansia muciniphila, while phyla, such as Bacteroidetes, Firmicutes, Deferribacteres, and Spirochaetes, and species, such as Prevotella sp. MGM2, Muribaculum intestinale, Lactobacillus murinus, and Prevotella sp. MGM1, were decreased. Functional analysis revealed differential expression of genes related to carbohydrate-active enzymes, pathogen-host interactions, cell communication, cell auto-induction, membrane transporters, and virulence factors. Furthermore, 37 COGs and 48 metabolites with rising metabolic potential in the selenium intervention group were predicted.
    UNASSIGNED: Selenium alters the homeostasis of gut microbiota in mice with breast cancer on a high-fat diet, affecting their composition, abundance, and associated metabolism. These findings suggest that the mechanism involves interfering with gut microbiota homeostasis, leading to altered synthesis of tumor-associated proteins and fatty acids and inducing tumor cell apoptosis and pyroptosis.
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  • 文章类型: Journal Article
    背景:动员分型(MOB)是一种基于其松弛酶基因的质粒基因组分类方案。不同MOB类别的质粒的宿主范围是多种多样的,MOB对于研究质粒动员至关重要,尤其是抗性基因和毒力因子的传播。然而,由于宏基因组重叠群的高度片段化特征,质粒宏基因组数据的MOB分型具有挑战性。
    结果:我们开发了MOBFinder,一个11类分类器,用于将质粒片段分为10种MOB类型和不可移动的类别。我们首先进行MOB分型以根据松弛酶信息对完整的质粒基因组进行分类,然后从MOB类型得到良好注释的那些完整的质粒基因组构建质粒宏基因组片段(PMF)的人工基准数据集。接下来,基于自然语言模型,我们使用词向量来表征PMF。训练并整合了几种随机森林分类模型以预测不同长度的片段。使用基准数据集评估工具,我们发现MOBFinder的性能优于以前的工具,如MOBscan和MOB-suite,总体准确率比MOB套件高出约59%。此外,平衡的准确性,谐波平均值,某些MOB类型的F1得分高达99%。当应用于2型糖尿病(T2D)患者队列时,MOBFinder提供的见解表明,MOBF型质粒,它广泛存在于大肠杆菌和克雷伯菌中,MOBQ型质粒可能加速T2D患者的抗生素耐药性传播。
    结论:据我们所知,MOBFinder是用于PMF的MOB键入的第一个工具。该工具可在https://github.com/FengTaoSMU/MOBFinder上免费获得。
    BACKGROUND: Mobilization typing (MOB) is a classification scheme for plasmid genomes based on their relaxase gene. The host ranges of plasmids of different MOB categories are diverse, and MOB is crucial for investigating plasmid mobilization, especially the transmission of resistance genes and virulence factors. However, MOB typing of plasmid metagenomic data is challenging due to the highly fragmented characteristics of metagenomic contigs.
    RESULTS: We developed MOBFinder, an 11-class classifier, for categorizing plasmid fragments into 10 MOB types and a nonmobilizable category. We first performed MOB typing to classify complete plasmid genomes according to relaxase information and then constructed an artificial benchmark dataset of plasmid metagenomic fragments (PMFs) from those complete plasmid genomes whose MOB types are well annotated. Next, based on natural language models, we used word vectors to characterize the PMFs. Several random forest classification models were trained and integrated to predict fragments of different lengths. Evaluating the tool using the benchmark dataset, we found that MOBFinder outperforms previous tools such as MOBscan and MOB-suite, with an overall accuracy approximately 59% higher than that of MOB-suite. Moreover, the balanced accuracy, harmonic mean, and F1-score reached up to 99% for some MOB types. When applied to a cohort of patients with type 2 diabetes (T2D), MOBFinder offered insights suggesting that the MOBF type plasmid, which is widely present in Escherichia and Klebsiella, and the MOBQ type plasmid might accelerate antibiotic resistance transmission in patients with T2D.
    CONCLUSIONS: To the best of our knowledge, MOBFinder is the first tool for MOB typing of PMFs. The tool is freely available at https://github.com/FengTaoSMU/MOBFinder.
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  • 文章类型: Journal Article
    在电动修复(EKR)中,沉积的溶解有机物(DOM)可能会通过清除反应性物种并产生意外的副产物来阻碍修复。然而,它的转变和机制在很大程度上仍然未知。本研究使用负离子电喷雾电离耦合21特斯拉傅里叶变换离子回旋共振质谱(21TFT-ICRMS)对EKR中的水可萃取DOM(WEOM)进行了分子水平表征。结果表明,在鉴定的7000种WEOM化合物中,55%是反应性的,EKR降低了它们的多样性,分子量分布,和双键当量(DBE)通过电化学和微生物氧化还原反应的组合。含杂原子的WEOM(CHON和CHOS)含量丰富(约占WEOM总量的35%),CHOS通常比CHON更具反应性。低电位(1V/cm)促进脱烷基化和脱硫菌的生长,导致了阳极二氧化碳矿化,-SO和-SO3的阳极裂解,-SH2的阴极裂解;高电势(2V/cm)仅富集脱硫细菌,不同的是,导致不饱和和酚类化合物的阳极氧化和阴极氢化,除了-SH2的阴极裂解。可能需要研究这些变化对土壤质量和氮-硫-碳通量的长期影响,以确定EKR的未知风险和新应用。
    In electrokinetic remediation (EKR), the sedimentary dissolved organic matter (DOM) could impede remediation by scavenging reactive species and generating unintended byproducts. Yet its transformation and mechanisms remained largely unknown. This study conducted molecular-level characterization of the water-extractable DOM (WEOM) in EKR using negative-ion electrospray ionization coupled to 21 tesla Fourier transform ion cyclotron resonance mass spectrometry (21 T FT-ICR MS). The results suggested that ∼55 % of the ∼7,000 WEOM compounds identified were reactive, and EKR lowered their diversity, molecular weight distribution, and double-bond equivalent (DBE) through a combination of electrochemical and microbial redox reactions. Heteroatom-containing WEOM (CHON and CHOS) were abundant (∼ 35% of the total WEOM), with CHOS generally being more reactive than CHON. Low electric potential (1 V/cm) promoted the growth of dealkylation and desulfurization bacteria, and led to anodic CO2 mineralization, anodic cleavage of -SO and -SO3, and cathodic cleavage of -SH2; high electric potential (2 V/cm) only enriched desulfurization bacteria, and differently, led to anodic oxygenation and cathodic hydrogenation of unsaturated and phenolic compounds, in addition to cathodic cleavage of -SH2. The long-term impact of these changes on soil quality and nitrogen-sulfur-carbon flux may be need to studied to identify unknown risks and new applications of EKR.
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  • 文章类型: Journal Article
    我们报告了在Marigat县医院的未分化发热儿童中通过宏基因组学无意中鉴定出的裂谷热病毒的完整编码序列,肯尼亚。关于系统发育,基因组聚集在2017年乌干达人类疫情和2021年Kiambu牛疫情期间获得的序列上,肯尼亚。
    We report on the complete coding sequence of Rift Valley Fever Virus inadvertently identified through metagenomics in a child with undifferentiated fever at Marigat sub-county hospital, Kenya. On phylogeny, the genome clustered with sequences obtained during the 2017 human outbreak in Uganda and the 2021 cattle outbreak in Kiambu, Kenya.
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  • 文章类型: Journal Article
    在季节性低氧条件下,控制富含硫酸盐的水库中硝酸盐还原中硫循环的机制尚不清楚。这项研究采用硝酸盐中的氮和氧同位素分馏,以及宏基因组测序,以阐明水柱中硫氧化和硝酸盐还原过程的复杂性。在阿哈水库,典型的季节性分层水体,我们观察到反硝化共存,细菌硫化物氧化,在低氧条件下减少细菌硫酸盐。丰富的N/S相关基因(nosZ和aprAB/dsrAB)的存在以及N/S物种的波动证实了这一点。在这项研究中观察到较低的15εNO3/18εNO3比率(0.60),与异养反硝化相比,有力地支持了硫驱动反硝化的发生。此外,我们发现细菌硫化物氧化和反硝化的代谢潜力之间存在强正相关(p<0.05),强调通过硫酸盐还原产生的硫化物在增强反硝化中的作用。硫化物驱动的反硝化依赖于∑S2-作为优先被反硝化氧化的主要电子供体。关键属,硫磺,在低氧水体中的反硝化和硫化物氧化过程中都是中心角色。我们的研究提供了令人信服的证据,表明硫化物在调节生态系统中低氧水中的反硝化中起着至关重要的作用,而以前它们对整个氮循环的贡献被低估了。
    The mechanism governing sulfur cycling in nitrate reduction within sulfate-rich reservoirs during seasonal hypoxic conditions remains poorly understood. This study employs nitrogen and oxygen isotope fractionation in nitrate, along with metagenomic sequencing to elucidate the intricacies of the coupled sulfur oxidation and nitrate reduction process in the water column. In the Aha reservoir, a typical seasonally stratified water body, we observed the coexistence of denitrification, bacterial sulfide oxidation, and bacterial sulfate reduction in hypoxic conditions. This is substantiated by the presence of abundant N/S-related genes (nosZ and aprAB/dsrAB) and fluctuations in N/S species. The lower 15εNO3/18εNO3 ratio (0.60) observed in this study, compared to heterotrophic denitrification, strongly supports the occurrence of sulfur-driven denitrification. Furthermore, we found a robust positive correlation between the metabolic potential of bacterial sulfide oxidation and denitrification (p < 0.05), emphasizing the role of sulfide produced via sulfate reduction in enhancing denitrification. Sulfide-driven denitrification relied on ∑S2- as the primary electron donor preferentially oxidized by denitrification. The pivotal genus, Sulfuritalea, emerged as a central player in both denitrification and sulfide oxidation processes in hypoxic water bodies. Our study provides compelling evidence that sulfides assume a critical role in regulating denitrification in hypoxic water within an ecosystem where their contribution to the overall nitrogen cycle was previously underestimated.
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  • 文章类型: Journal Article
    将针叶人工林转变为阔叶或阔叶针叶混合人工林是亚热带中国森林经营战略的趋势。然而,这种转化对土壤磷(P)循环微生物功能基因的影响尚不清楚。
    从0-20、20-40和40-60cm收集土壤样品(表土,中间层,和底土,分别)在针叶松马尾松(PM)下,阔叶红回肠(EF),及其在亚热带中国的混合(PM/EF)人工林。利用宏基因组测序技术研究了人工林转换后土壤P循环功能基因的相对丰度和分子生态网络结构的变化。
    PM林分表层土壤中P循环基因的组成与PM/EF和EF林分存在显着差异(p<0.05),总磷(TP)是造成这种差异的主要因素。将PM人工林改造为EF人工林后,随着土壤TP含量的降低,表层和中层的磷溶解和矿化基因的相对丰度显着增加。P-饥饿反应调控基因的丰度在底土中也显著增加(p<0.05),这可能受到土壤有机碳(SOC)的影响。三个人工林下所有土壤层的显性基因均为phoR,glpP,GCD,ppk,和ppx。将PM转化为EF人工林明显增加了表层土壤中的gcd丰度(p<0.05),TP和NO3--N是主要影响因素。在将PM转化为PM/EF种植园后,P循环基因的分子生态网络结构较为复杂;随着PM人工林的转化,网络中的关键基因被修饰。
    将PM转化为EF种植园主要提高了微生物在表土上的磷酸盐溶解潜力,而将PM转化为PM/EF种植园可能增强了微生物P循环基因对环境变化的结构稳定性。
    UNASSIGNED: Transforming coniferous plantation into broadleaved or mixed broadleaved-coniferous plantations is the tendency of forest management strategies in subtropical China. However, the effects of this conversion on soil phosphorus (P) cycling microbial functional genes are still unknown.
    UNASSIGNED: Soil samples were collected from 0-20, 20-40, and 40-60 cm (topsoil, middle layer, and subsoil, respectively) under coniferous Pinus massoniana (PM), broadleaved Erythrophleum fordii (EF), and their mixed (PM/EF) plantation in subtropical China. Used metagenomic sequencing to examine the alterations of relative abundances and molecular ecological network structure of soil P-cycling functional genes after the conversion of plantations.
    UNASSIGNED: The composition of P-cycling genes in the topsoil of PM stand was significantly different from that of PM/EF and EF stands (p < 0.05), and total phosphorus (TP) was the main factor causing this difference. After transforming PM plantation into EF plantation, the relative abundances of P solubilization and mineralization genes significantly increased in the topsoil and middle layer with the decrease of soil TP content. The abundances of P-starvation response regulation genes also significantly increased in the subsoil (p < 0.05), which may have been influenced by soil organic carbon (SOC). The dominant genes in all soil layers under three plantations were phoR, glpP, gcd, ppk, and ppx. Transforming PM into EF plantation apparently increased gcd abundance in the topsoil (p < 0.05), with TP and NO3 --N being the main influencing factors. After transforming PM into PM/EF plantations, the molecular ecological network structure of P-cycling genes was more complex; moreover, the key genes in the network were modified with the transformation of PM plantation.
    UNASSIGNED: Transforming PM into EF plantation mainly improved the phosphate solubilizing potential of microorganisms at topsoil, while transforming PM into PM/EF plantation may have enhanced structural stability of microbial P-cycling genes react to environmental changes.
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  • 文章类型: Journal Article
    卷心菜是大白菜的主要疾病和严重威胁,它是由病原体油菜黄体虫引起的。这种病原体是一种专性生物营养原生生物,可以以静止孢子的形式在土壤中持续存在超过18年,可以很容易地通过许多代理人传播,给全球大白菜生产造成重大经济损失。根际微生物在植物病害的发生和发展中起着重要作用。根际微生物的变化可以揭示植物病害的严重程度,并为其防治提供依据。这里,我们通过使用宏基因组测序研究了不同严重程度的根际微生物群,为了探索植物健康之间的关系,根际微生物群落,和土壤环境;然后,我们确定了根肿病的潜在生物标志物微生物。结果表明,根际根际土壤微生物群落组成和结构受到根际根际土壤,微生物的功能也受到了极大的影响。从获得的结果中确定了四种在根瘤病的生物防治中具有巨大潜力的不同微生物;它们是假单胞菌属,Gemmatatimonas,鞘氨醇单胞菌,和诺卡迪亚.土壤pH值,有机质含量,总氮,和阳离子交换能力是调节植物微生物组组装的主要环境因素。此外,当植物受到病原体入侵时,微生物环境信息处理得到了极大的加强,但当疾病变得严重时就会减弱。特别是,氧化磷酸化和甘油-1-磷酸酶可能在增强大白菜对根瘤病的抗性中起关键作用。这项工作揭示了大白菜之间的相互作用和潜在的机制,土壤环境因子,clubroot病,微生物群落结构和功能,这可能为使用微生物或代谢方法开发抗病栽培技术的进一步研究提供新的基础。
    Clubroot is a major disease and severe threat to Chinese cabbage, and it is caused by the pathogen Plasmodiophora brassicae Woron. This pathogen is an obligate biotrophic protist and can persist in soil in the form of resting spores for more than 18 years, which can easily be transmitted through a number of agents, resulting in significant economic losses to global Chinese cabbage production. Rhizosphere microbiomes play fundamental roles in the occurrence and development of plant diseases. The changes in the rhizosphere microorganisms could reveal the severity of plant diseases and provide the basis for their control. Here, we studied the rhizosphere microbiota after clubroot disease infections with different severities by employing metagenomic sequencing, with the aim of exploring the relationships between plant health, rhizosphere microbial communities, and soil environments; then, we identified potential biomarker microbes of clubroot disease. The results showed that clubroot disease severity significantly affected the microbial community composition and structure of the rhizosphere soil, and microbial functions were also dramatically influenced by it. Four different microbes that had great potential in the biocontrol of clubroot disease were identified from the obtained results; they were the genera Pseudomonas, Gemmatimonas, Sphingomonas, and Nocardioides. Soil pH, organic matter contents, total nitrogen, and cation exchange capacity were the major environmental factors modulating plant microbiome assembly. In addition, microbial environmental information processing was extremely strengthened when the plant was subjected to pathogen invasion, but weakened when the disease became serious. In particular, oxidative phosphorylation and glycerol-1-phosphatase might have critical functions in enhancing Chinese cabbage\'s resistance to clubroot disease. This work revealed the interactions and potential mechanisms among Chinese cabbage, soil environmental factors, clubroot disease, and microbial community structure and functions, which may provide a novel foundation for further studies using microbiological or metabolic methods to develop disease-resistant cultivation technologies.
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  • 文章类型: Journal Article
    土壤施用有机肥和生物投入不可避免地影响其质量,农业化学指标,和微生物群。可持续农业是基于不断学习如何正确管理可用土壤,水,和生物资源。研究的目的是确定使用不同有机肥料及其与生物投入的组合施肥的贫瘠土壤中微生物群落和碳储量的变化。使用NGS方法进行微生物种群的遗传分析。我们的研究表明,有机肥料的施用会影响土壤微生物区系及其群落的分类结构。特定的细菌群,比如芽孢杆菌,是由有机施肥促进的,同时,施用家禽粪便后,大多数处理中的假单胞菌和子囊菌的丰度降低。宏基因组分析证实,生物输入的使用增加了木霉属的相对丰度。真菌;同时,与未使用生物输入的处理相比,在固氮菌代表中未发现显著变化.施肥对所有研究的农业化学指标均有积极影响。当我们使用粒状家禽粪便时,土壤中积累的Corg和Nmin浓度较高,和我们用牛粪时的PHKCl。
    The application of organic fertilizers and biological inputs to soil inevitably affects its quality, agrochemical indicators, and microbiota. Sustainable agriculture is based on continuously learning about how to properly manage available soil, water, and biological resources. The aim of the study was to determine changes in microorganism communities and carbon stocks in infertile soils for fertilization using different organic fertilizers and their combinations with bio-inputs. Genetic analysis of microorganism populations was performed using the NGS approach. Our study showed that the application of organic fertilizers affects the soil microbiota and the taxonomic structure of its communities. Specific groups of bacteria, such as Bacillota, were promoted by organic fertilization, meanwhile the abundance of Pseudomonadota and Ascomycota decreased in most treatments after the application of poultry manure. Metagenomic analysis confirmed that the use of bio-inputs increased the relative abundance of Trichoderma spp. fungi; meanwhile, a significant change was not found in the representatives of Azotobacter compared to the treatments where the bio-inputs were not used. The positive influence of fertilization appeared on all the studied agrochemical indicators. Higher concentrations of Corg and Nmin accumulated in the soil when we used granulated poultry manure, and pHKCl when we used cattle manure.
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  • 文章类型: Journal Article
    背景:对术前治疗反应的准确评估可以为局部晚期直肠癌(LARC)提供更合适的个性化治疗方案,这仍然是一个巨大的挑战,尤其是新辅助免疫疗法加放化疗(nICRT)。
    方法:这种前瞻性,多中心队列研究纳入了来自6个接受nICRT的中心的LARC患者。评估了nICRT过程中肠道微生物组的动态变化。开发并验证了物种水平的肠道微生物组预测(SPEED)模型,以预测对nICRT的病理完全反应(pCR)。
    结果:共纳入50例患者,在不同的时间点从33名患者中收集了75份粪便样本,pCR率达到42.4%(14/33)。观察到乳杆菌和真杆菌在nICRT后增加。此外,基线时,在应答者和非应答者之间观察到肠道微生物组存在显著差异.在响应者中发现了明显较高的幼虫螺旋体细菌和Blautuawexlerae,而拟杆菌,普雷沃氏菌,在无反应者中发现了卟啉菌。SPEED模型显示出优异的预测性能,在训练队列中曲线下面积为98.80%(95%置信区间[CI]:95.67%-100%),在验证队列中曲线下面积为77.78%(95%CI:65.42%-88.29%)。
    结论:在微卫星稳定(MSS)/错配修复精通(pMMR)患者中,程序性死亡1(PD-1)阻断加并发长疗程CRT显示出良好的pCR率,并且耐受性良好。SPEED模型可用于基于基线肠道微生物组预测pCR到nICRT,具有较高的鲁棒性和准确性,从而协助临床医生为LARC患者提供个性化管理。
    背景:这项研究由中国国家自然科学基金(82202884)资助。
    BACKGROUND: Accurate evaluation of the response to preoperative treatment enables the provision of a more appropriate personalized therapeutic schedule for locally advanced rectal cancer (LARC), which remains an enormous challenge, especially neoadjuvant immunotherapy plus chemoradiotherapy (nICRT).
    METHODS: This prospective, multicenter cohort study enrolled patients with LARC from 6 centers who received nICRT. The dynamic variation in the gut microbiome during nICRT was evaluated. A species-level gut microbiome prediction (SPEED) model was developed and validated to predict the pathological complete response (pCR) to nICRT.
    RESULTS: A total of 50 patients were enrolled, 75 fecal samples were collected from 33 patients at different time points, and the pCR rate reached 42.4% (14/33). Lactobacillus and Eubacterium were observed to increase after nICRT. Additionally, significant differences in the gut microbiome were observed between responders and non-responders at baseline. Significantly higher abundances of Lachnospiraceaebacterium and Blautiawexlerae were found in responders, while Bacteroides, Prevotella, and Porphyromonas were found in non-responders. The SPEED model showcased a superior predictive performance with areas under the curve of 98.80% (95% confidence interval [CI]: 95.67%-100%) in the training cohort and 77.78% (95% CI: 65.42%-88.29%) in the validation cohort.
    CONCLUSIONS: Programmed death 1 (PD-1) blockade plus concurrent long-course CRT showed a favorable pCR rate and is well tolerated in microsatellite-stable (MSS)/mismatch repair-proficient (pMMR) patients with LARC. The SPEED model can be used to predict the pCR to nICRT based on the baseline gut microbiome with high robustness and accuracy, thereby assisting clinical physicians in providing individualized management for patients with LARC.
    BACKGROUND: This research was funded by the China National Natural Science Foundation (82202884).
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