Cell host & microbe最新文献

英文中文

Intestinal fungal-host interactions in promoting and maintaining health 肠道真菌与宿主在促进和保持健康方面的相互作用

IF 30.3 1区医学 Q1 MICROBIOLOGY

Cell host & microbe

Pub Date : 2024-10-09 DOI: 10.1016/j.chom.2024.09.010

Jennifer H. Hill, June L. Round

The resident microbiota are a key component of a healthy organism. The vast majority of microbiome studies have focused on bacterial members, which constitute a significant portion of resident microbial biomass. Recent studies have demonstrated how the fungal component of the microbiota, or the mycobiome, influences mammalian biology despite its low abundance compared to other microbes. Fungi are known for their pathogenic potential, yet fungi are also prominent colonizers in healthy states, highlighting their duality. We summarize the characteristics that define the gut mycobiome across life, the factors that can impact its composition, and studies that identify mechanisms of how fungi confer health benefits. The goal of this review is to synthesize our knowledge regarding the composition and function of a healthy mycobiome with a view to inspiring future therapeutic advances.

常驻微生物群是健康生物体的关键组成部分。绝大多数微生物组研究都侧重于细菌，因为细菌在常驻微生物生物量中占很大比例。最近的研究表明，微生物群中的真菌成分或真菌生物群如何影响哺乳动物的生物学，尽管与其他微生物相比，真菌的丰度较低。真菌以其潜在的致病性而闻名，但在健康状态下，真菌也是重要的定植者，这突出了真菌的双重性。我们总结了肠道真菌生物群在整个生命过程中的特征、影响其组成的因素以及确定真菌如何对健康有益的机制的研究。这篇综述的目的是综合我们对健康真菌生物群的组成和功能的认识，以启发未来的治疗进展。

引用次数: 0

Immunity to fungi and vaccine considerations 真菌免疫和疫苗考虑因素

IF 30.3 1区医学 Q1 MICROBIOLOGY

Cell host & microbe

Pub Date : 2024-10-09 DOI: 10.1016/j.chom.2024.09.011

Alexander J. Whitehead, Therese Woodring, Bruce S. Klein

Fungal disease poses a growing threat to public health that our current antifungal therapies are not well equipped to meet. As the population of immunocompromised hosts expands, and ecological changes favor the emergence of fungal pathogens, the development of new antifungal agents, including vaccines, becomes a global priority. Here, we summarize recent advancements in the understanding of fungal pathogenesis, key features of the host antifungal immune response, and how these findings could be leveraged to design novel approaches to deadly fungal disease.

真菌病对公共健康的威胁日益严重，而我们目前的抗真菌疗法还不能很好地应对这一威胁。随着免疫力低下的宿主群体不断扩大，以及生态环境的变化有利于真菌病原体的出现，开发包括疫苗在内的新型抗真菌药物已成为全球的当务之急。在此，我们总结了对真菌致病机理认识的最新进展、宿主抗真菌免疫反应的关键特征，以及如何利用这些发现设计新型方法来治疗致命的真菌疾病。

引用次数: 0

From dysbiosis to homeostasis: Oleic acid matters in the vagina 从菌群失调到平衡：油酸在阴道中的作用

IF 30.3 1区医学 Q1 MICROBIOLOGY

Cell host & microbe

Pub Date : 2024-10-09 DOI: 10.1016/j.chom.2024.09.007

Ri-hua Xie, Hao Liu, Cancan Qi, Yan He

The role of fatty acids in shaping vaginal microbiota remains unclear. In an issue of Cell, Zhu et al. use genomic and transcriptomic analyses to reveal that oleic acid (OA) selectively inhibits L. iners while promoting L. crispatus, suggesting new strategies for the treatment of bacterial vaginosis (BV).

脂肪酸在塑造阴道微生物群方面的作用仍不清楚。在一期《细胞》杂志上，Zhu 等人利用基因组和转录组分析揭示了油酸（OA）能选择性地抑制 L. iners，同时促进 L. crispatus，为治疗细菌性阴道病（BV）提出了新策略。

引用次数: 0

Host-microbe interaction paradigms in acute and recurrent vulvovaginal candidiasis 急性和复发性外阴阴道念珠菌病的宿主-微生物相互作用范例

IF 30.3 1区医学 Q1 MICROBIOLOGY

Cell host & microbe

Pub Date : 2024-10-09 DOI: 10.1016/j.chom.2024.08.018

Jessie MacAlpine, Michail S. Lionakis

Candida spp. are members of the human mucosal microbiota that can cause opportunistic diseases ranging from superficial infections to life-threatening invasive candidiasis. In humans, the most common infection caused by Candida spp. is vulvovaginal candidiasis (VVC), which affects >70% of women at least once in their lifetime. Of those women, ∼5%–10% develop recurrent VVC (RVVC). In this review, we summarize our current understanding of the host and fungal factors that contribute to susceptibility to VVC and RVVC. We synthesize key findings that support the notion that disease symptoms are driven by neutrophil-associated dysfunction and immunopathology and describe how antifungal immune mechanisms in the vagina are distinct from other mucosal barrier sites. Finally, we highlight key, unanswered research areas within the field that can help us better understand the immunopathogenesis of this infection and facilitate the development of novel preventive, therapeutic, and/or vaccination strategies to combat these common, poorly understood diseases.

念珠菌属是人类粘膜微生物群中的一员，可引起从浅表感染到危及生命的侵袭性念珠菌病等各种机会性疾病。在人类中，念珠菌属引起的最常见感染是外阴阴道念珠菌病（VVC），70%的女性一生中至少会感染一次。在这些妇女中，有 5%-10%会反复感染外阴阴道念珠菌病（RVVC）。在这篇综述中，我们总结了目前对导致 VVC 和 RVVC 易感性的宿主和真菌因素的认识。我们综述了支持疾病症状由中性粒细胞相关功能障碍和免疫病理驱动这一观点的主要发现，并描述了阴道中的抗真菌免疫机制与其他粘膜屏障部位的不同之处。最后，我们强调了该领域中尚未解决的关键研究领域，这些领域可以帮助我们更好地了解这种感染的免疫发病机制，并促进新型预防、治疗和/或疫苗接种策略的开发，以防治这些常见的、鲜为人知的疾病。

引用次数: 0

The RNA landscape of the human commensal Segatella copri reveals a small RNA essential for gut colonization 人类共生动物 Segatella copri 的 RNA 图谱揭示了肠道定植所必需的小 RNA

IF 30.3 1区医学 Q1 MICROBIOLOGY

Cell host & microbe

Pub Date : 2024-10-04 DOI: 10.1016/j.chom.2024.09.008

Youssef El Mouali, Caroline Tawk, Kun D. Huang, Lena Amend, Till Robin Lesker, Falk Ponath, Jörg Vogel, Till Strowig

The bacterium Segatella copri is a prevalent member of the human gut microbiota associated with health and disease states. However, the intrinsic factors that determine its ability to colonize the gut effectively remain largely unknown. By extensive transcriptome mapping of S. copri and examining human-derived samples, we discover a small RNA, which we name Segatella RNA colonization factor (SrcF), and show that SrcF is essential for S. copri gut colonization in gnotobiotic mice. SrcF regulates genes involved in nutrient acquisition, and complex carbohydrates, particularly fructans, control its expression. Furthermore, SrcF expression is strongly influenced by human microbiome composition and by the breakdown of fructans by cohabitating commensals, suggesting that the breakdown of complex carbohydrates mediates interspecies signaling among commensals beyond its established function in generating energy. Together, this study highlights the contribution of a small RNA as a critical regulator in gut colonization.

Segatella copri 细菌是人类肠道微生物群中的一种常见成员，与健康和疾病状态有关。然而，决定其有效定植肠道能力的内在因素在很大程度上仍然未知。通过对 S. copri 进行广泛的转录组图谱绘制和对人类来源样本的研究，我们发现了一种小 RNA，并将其命名为 Segatella RNA 定殖因子（SrcF）。SrcF 可调控涉及营养获取的基因，而复杂碳水化合物（尤其是果聚糖）可控制其表达。此外，SrcF 的表达还受到人类微生物群组成以及同居共生动物分解果聚糖的强烈影响，这表明复杂碳水化合物的分解在产生能量的既定功能之外，还介导了共生动物之间的种间信号传递。总之，这项研究强调了小 RNA 作为肠道定植关键调节因子的作用。

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引用次数: 0

Rapid design of bacteriophage cocktails to suppress the burden and virulence of gut-resident carbapenem-resistant Klebsiella pneumoniae 快速设计噬菌体鸡尾酒，抑制肠道耐碳青霉烯类肺炎克雷伯氏菌的负担和毒力

IF 30.3 1区医学 Q1 MICROBIOLOGY

Cell host & microbe

Pub Date : 2024-10-04 DOI: 10.1016/j.chom.2024.09.004

Ella Rotman, Sandra McClure, Joshua Glazier, Jay Fuerte-Stone, Jonathan Foldi, Ali Erani, Rory McGann, Jack Arnold, Huaiying Lin, Sandra Valaitis, Mark Mimee

Antibiotic use can lead to the expansion of multi-drug-resistant pathobionts within the gut microbiome that can cause life-threatening infections. Selective alternatives to conventional antibiotics are in dire need. Here, we describe a Klebsiella PhageBank for the tailored design of bacteriophage cocktails to treat multi-drug-resistant Klebsiella pneumoniae. Using a transposon library in carbapenem-resistant K. pneumoniae, we identify host factors required for phage infection in major Klebsiella phage families. Leveraging the diversity of the PhageBank, we formulate phage combinations that eliminate K. pneumoniae with minimal phage resistance. Optimized cocktails selectively suppress the burden of K. pneumoniae in the mouse gut and drive the loss of key virulence factors that act as phage receptors. Phage-mediated diversification of bacterial populations in the gut leads to co-evolution of phage variants with higher virulence and broader host range. Altogether, the Klebsiella PhageBank charts a roadmap for phage therapy against a critical multidrug-resistant human pathogen.

抗生素的使用会导致肠道微生物群中具有多重耐药性的病原菌增多，从而引发危及生命的感染。传统抗生素的选择性替代品亟待开发。在这里，我们描述了一个克雷伯氏菌噬菌体库（Klebsiella PhageBank），用于定制设计噬菌体鸡尾酒，以治疗多重耐药肺炎克雷伯氏菌。利用耐碳青霉烯类肺炎克雷伯氏菌的转座子文库，我们确定了主要克雷伯氏菌噬菌体家族中噬菌体感染所需的宿主因子。利用噬菌体库的多样性，我们配制出了噬菌体组合，能以最小的噬菌体耐药性消灭肺炎克雷伯氏菌。优化后的鸡尾酒选择性地抑制了小鼠肠道中肺炎克雷伯菌的负担，并促使作为噬菌体受体的关键毒力因子丧失。噬菌体介导的肠道细菌种群多样化导致了噬菌体变种的共同进化，这些变种具有更强的毒力和更广的宿主范围。总之，克雷伯氏菌噬菌体库为噬菌体疗法提供了一个路线图，以对付一种关键的耐多药人类病原体。

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引用次数: 0

Pangenomes of human gut microbiota uncover links between genetic diversity and stress response 人类肠道微生物群的庞基因组揭示了遗传多样性与应激反应之间的联系

IF 30.3 1区医学 Q1 MICROBIOLOGY

Cell host & microbe

Pub Date : 2024-09-30 DOI: 10.1016/j.chom.2024.08.017

Saar Shoer, Lee Reicher, Chunyu Zhao, Katherine S. Pollard, Yitzhak Pilpel, Eran Segal

The genetic diversity of the gut microbiota has a central role in host health. Here, we created pangenomes for 728 human gut prokaryotic species, quadrupling the genes of strain-specific genomes. Each of these species has a core set of a thousand genes, differing even between closely related species, and an accessory set of genes unique to the different strains. Functional analysis shows high strain variability associates with sporulation, whereas low variability is linked with antibiotic resistance. We further map the antibiotic resistome across the human gut population and find 237 cases of extreme resistance even to last-resort antibiotics, with a predominance among Enterobacteriaceae. Lastly, the presence of specific genes in the microbiota relates to host age and sex. Our study underscores the genetic complexity of the human gut microbiota, emphasizing its significant implications for host health. The pangenomes and antibiotic resistance map constitute a valuable resource for further research.

肠道微生物群的遗传多样性对宿主健康起着核心作用。在这里，我们为 728 个人类肠道原核生物物种创建了泛基因组，使菌株特异性基因组的基因数量翻了两番。每个菌种都有一个由一千个基因组成的核心基因组，即使是近缘菌种之间也存在差异，另外还有一个不同菌株特有的附属基因组。功能分析显示，菌株的高变异性与孢子繁殖有关，而低变异性则与抗生素耐药性有关。我们进一步绘制了整个人类肠道群体的抗生素耐药性组图，发现 237 个极端耐药性病例，甚至对最后一种抗生素也有耐药性，其中以肠杆菌科细菌为主。最后，微生物群中特定基因的存在与宿主的年龄和性别有关。我们的研究凸显了人类肠道微生物群的遗传复杂性，强调了其对宿主健康的重要影响。庞基因组和抗生素耐药性图谱是进一步研究的宝贵资源。

引用次数: 0

Clinical sequelae of gut microbiome development and disruption in hospitalized preterm infants 住院早产儿肠道微生物组的发展和破坏带来的临床后遗症

IF 30.3 1区医学 Q1 MICROBIOLOGY

Cell host & microbe

Pub Date : 2024-09-24 DOI: 10.1016/j.chom.2024.09.012

Robert Thänert, Drew J. Schwartz, Eric C. Keen, Carla Hall-Moore, Bin Wang, Nurmohammad Shaikh, Jie Ning, L. Colleen Rouggly-Nickless, Anna Thänert, Aura Ferreiro, Skye R.S. Fishbein, Janice E. Sullivan, Paula Radmacher, Marilyn Escobedo, Barbara B. Warner, Phillip I. Tarr, Gautam Dantas

No Abstract

无摘要

引用次数: 0

Microbiota regulates neonatal disease tolerance to virus-evoked necrotizing enterocolitis by shaping the STAT1-NLRC5 axis in the intestinal epithelium 微生物群通过塑造肠上皮细胞中的 STAT1-NLRC5 轴来调节新生儿对病毒诱发的坏死性小肠结肠炎的疾病耐受性

IF 30.3 1区医学 Q1 MICROBIOLOGY

Cell host & microbe

Pub Date : 2024-09-17 DOI: 10.1016/j.chom.2024.08.013

Saravanan Subramanian, Hua Geng, Longtao Wu, Chao Du, Amy M. Peiper, Heng-Fu Bu, Pauline M. Chou, Xiao Wang, Stephanie C. Tan, Neha R. Iyer, Nazeer Hussain Khan, Ellen L. Zechner, James G. Fox, Rolf Breinbauer, Chao Qi, Bakhtiar Yamini, Jenny P. Ting, Isabelle G. De Plaen, Stephanie M. Karst, Xiao-Di Tan

Microbiota and feeding modes influence the susceptibility of premature newborns to necrotizing enterocolitis (NEC) through mechanisms that remain unknown. Here, we show that microbiota colonization facilitated by breastmilk feeding promotes NOD-like receptor family CARD domain containing 5 (Nlrc5) gene expression in mouse intestinal epithelial cells (IECs). Notably, inducible knockout of the Nlrc5 gene in IECs predisposes neonatal mice to NEC-like injury in the small intestine upon viral inflammation in an NK1.1⁺ cell-dependent manner. By contrast, formula feeding enhances neonatal gut colonization with environment-derived tilivalline-producing Klebsiella spp. Remarkably, tilivalline disrupts microbiota-activated STAT1 signaling that controls Nlrc5 gene expression in IECs through a PPAR-γ-mediated mechanism. Consequently, this dysregulation hinders the resistance of neonatal intestinal epithelium to self-NK1.1⁺ cell cytotoxicity upon virus infection/colonization, promoting NEC development. Together, we discover the underappreciated role of intestinal microbiota colonization in shaping a disease tolerance program to viral inflammation and elucidate the mechanisms impacting NEC development in neonates.

微生物群和喂养方式影响早产新生儿对坏死性小肠结肠炎（NEC）的易感性，其机制尚不清楚。在这里，我们发现母乳喂养促进了微生物群的定植，从而促进了小鼠肠上皮细胞（IECs）中 NOD 样受体家族 CARD domain containing 5（Nlrc5）基因的表达。值得注意的是，诱导性敲除 IECs 中的 Nlrc5 基因会使新生小鼠在病毒性炎症时容易受到 NK1.1+ 细胞依赖性的小肠 NEC 样损伤。值得注意的是，替利瓦林会破坏微生物群激活的 STAT1 信号，这种信号通过 PPAR-γ 介导的机制控制 IEC 中 Nlrc5 基因的表达。因此，这种失调阻碍了新生儿肠上皮细胞在病毒感染/定植时对自身 NK1.1+ 细胞毒性的抵抗力，从而促进了 NEC 的发生。我们共同发现了肠道微生物群定植在形成对病毒性炎症的疾病耐受程序中未被重视的作用，并阐明了影响新生儿 NEC 发生的机制。

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引用次数: 0

Networks of human milk microbiota are associated with host genomics, childhood asthma, and allergic sensitization 母乳微生物群网络与宿主基因组学、儿童哮喘和过敏致敏有关

IF 30.3 1区医学 Q1 MICROBIOLOGY

Cell host & microbe

Pub Date : 2024-09-17 DOI: 10.1016/j.chom.2024.08.014

Zhi Yi Fang, Sara A. Stickley, Amirthagowri Ambalavanan, Yang Zhang, Amanda M. Zacharias, Kelsey Fehr, Shirin Moossavi, Charisse Petersen, Kozeta Miliku, Piushkumar J. Mandhane, Elinor Simons, Theo J. Moraes, Malcolm R. Sears, Michael G. Surette, Padmaja Subbarao, Stuart E. Turvey, Meghan B. Azad, Qingling Duan

The human milk microbiota (HMM) is thought to influence the long-term health of offspring. However, its role in asthma and atopy and the impact of host genomics on HMM composition remain unclear. Through the CHILD Cohort Study, we followed 885 pregnant mothers and their offspring from birth to 5 years and determined that HMM was associated with maternal genomics and prevalence of childhood asthma and allergic sensitization (atopy) among human milk-fed infants. Network analysis identified modules of correlated microbes in human milk that were associated with subsequent asthma and atopy in preschool-aged children. Moreover, reduced alpha-diversity and increased Lawsonella abundance in HMM were associated with increased prevalence of childhood atopy. Genome-wide association studies (GWASs) identified maternal genetic loci (e.g., ADAMTS8, NPR1, and COTL1) associated with HMM implicated with asthma and atopy, notably Lawsonella and alpha-diversity. Thus, our study elucidates the role of host genomics on the HMM and its potential impact on childhood asthma and atopy.

母乳微生物群（HMM）被认为会影响后代的长期健康。然而，它在哮喘和过敏症中的作用以及宿主基因组学对 HMM 组成的影响仍不清楚。我们通过儿童队列研究（CHILD Cohort Study）对 885 名怀孕母亲及其后代进行了从出生到 5 岁的跟踪研究，确定了 HMM 与母体基因组学以及母乳喂养婴儿的儿童哮喘和过敏致敏（atopy）发病率有关。网络分析确定了人乳中与学龄前儿童日后哮喘和过敏相关的微生物模块。此外，人乳中α-多样性的减少和劳森氏菌丰度的增加与儿童过敏症发病率的增加有关。全基因组关联研究（GWAS）发现了与哮喘和过敏症相关的母体遗传位点（如 ADAMTS8、NPR1 和 COTL1），特别是劳森菌和α-多样性。因此，我们的研究阐明了宿主基因组学对 HMM 的作用及其对儿童哮喘和过敏症的潜在影响。

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