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Metabolite-based inter-kingdom communication controls intestinal tissue recovery following chemotherapeutic injury 基于代谢物的王国间交流控制化疗损伤后的肠道组织恢复
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-08-27 DOI: 10.1016/j.chom.2024.07.026
Christopher J. Anderson, Laura Boeckaerts, Pricilla Chin, Javier Burgoa Cardas, Wei Xie, Amanda Gonçalves, Gillian Blancke, Sam Benson, Sebastian Rogatti, Mariska S. Simpson, Anna Davey, Sze Men Choi, Sandrien Desmet, Summer D. Bushman, Geert Goeminne, Peter Vandenabeele, Mahesh S. Desai, Lars Vereecke, Kodi S. Ravichandran

Cytotoxic chemotherapies have devastating side effects, particularly within the gastrointestinal tract. Gastrointestinal toxicity includes the death and damage of the epithelium and an imbalance in the intestinal microbiota, otherwise known as dysbiosis. Whether dysbiosis is a direct contributor to tissue toxicity is a key area of focus. Here, from both mammalian and bacterial perspectives, we uncover an intestinal epithelial cell death-Enterobacteriaceae signaling axis that fuels dysbiosis. Specifically, our data demonstrate that chemotherapy-induced epithelial cell apoptosis and the purine-containing metabolites released from dying cells drive the inter-kingdom transcriptional re-wiring of the Enterobacteriaceae, including fundamental shifts in bacterial respiration and promotion of purine utilization-dependent expansion, which in turn delays the recovery of the intestinal tract. Inhibition of epithelial cell death or restriction of the Enterobacteriaceae to homeostatic levels reverses dysbiosis and improves intestinal recovery. These findings suggest that supportive therapies that maintain homeostatic levels of Enterobacteriaceae may be useful in resolving intestinal disease.

细胞毒性化疗具有破坏性的副作用,尤其是在胃肠道内。胃肠道毒性包括上皮细胞的死亡和损伤以及肠道微生物群的失衡,也就是所谓的菌群失调。菌群失调是否是组织毒性的直接因素是一个关键的关注领域。在这里,我们从哺乳动物和细菌的角度,揭示了肠上皮细胞死亡-肠杆菌信号轴对菌群失调的促进作用。具体来说,我们的数据证明,化疗诱导的上皮细胞凋亡和凋亡细胞释放的含嘌呤代谢物驱动了肠杆菌科细菌的跨领域转录重新布线,包括细菌呼吸的根本转变和促进嘌呤利用依赖性扩增,这反过来又延迟了肠道的恢复。抑制上皮细胞死亡或将肠杆菌科细菌限制在平衡水平可逆转菌群失调并改善肠道恢复。这些研究结果表明,维持肠杆菌平衡水平的支持疗法可能有助于解决肠道疾病。
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引用次数: 0
Engineered probiotic ameliorates ulcerative colitis by restoring gut microbiota and redox homeostasis 工程益生菌通过恢复肠道微生物群和氧化还原平衡改善溃疡性结肠炎
IF 20.6 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-08-27 DOI: 10.1016/j.chom.2024.07.028
Peilin Guo, Wenjing Wang, Wei Wei
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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 Pub Date : 2024-08-27 DOI: 10.1016/j.chom.2024.07.027
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

Aberrant preterm infant gut microbiota assembly predisposes to early-life disorders and persistent health problems. Here, we characterize gut microbiome dynamics over the first 3 months of life in 236 preterm infants hospitalized in three neonatal intensive care units using shotgun metagenomics of 2,512 stools and metatranscriptomics of 1,381 stools. Strain tracking, taxonomic and functional profiling, and comprehensive clinical metadata identify Enterobacteriaceae, enterococci, and staphylococci as primarily exploiting available niches to populate the gut microbiome. Clostridioides difficile lineages persist between individuals in single centers, and Staphylococcus epidermidis lineages persist within and, unexpectedly, between centers. Collectively, antibiotic and non-antibiotic medications influence gut microbiome composition to greater extents than maternal or baseline variables. Finally, we identify a persistent low-diversity gut microbiome in neonates who develop necrotizing enterocolitis after day of life 40. Overall, we comprehensively describe gut microbiome dynamics in response to medical interventions in preterm, hospitalized neonates.

早产儿肠道微生物群的异常组合易导致早年疾病和持续性健康问题。在本文中,我们使用霰弹枪元基因组学分析了 2,512 份粪便,并使用元转录组学分析了 1,381 份粪便,从而描述了在三个新生儿重症监护病房住院的 236 名早产儿在出生后头 3 个月的肠道微生物群动态特征。通过菌株追踪、分类和功能分析以及全面的临床元数据发现,肠杆菌科、肠球菌和葡萄球菌主要利用现有的壁龛来填充肠道微生物组。难辨梭状芽孢杆菌菌系在单个中心的个体间持续存在,而表皮葡萄球菌菌系在中心内持续存在,出乎意料的是在中心间也持续存在。总的来说,抗生素和非抗生素药物对肠道微生物组组成的影响程度要大于母体或基线变量。最后,我们发现在出生 40 天后发生坏死性小肠结肠炎的新生儿中,肠道微生物群的多样性持续较低。总之,我们全面描述了早产住院新生儿肠道微生物组对医疗干预的动态响应。
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引用次数: 0
RSV and rhinovirus increase pneumococcal carriage acquisition and density, whereas nasal inflammation is associated with bacterial shedding RSV 和鼻病毒会增加肺炎球菌的携带量和密度,而鼻腔炎症则与细菌脱落有关
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-08-23 DOI: 10.1016/j.chom.2024.07.024
Elena Mitsi, Elissavet Nikolaou, Andre Goncalves, Annie Blizard, Helen Hill, Madlen Farrar, Angela Hyder-Wright, Oluwasefunmi Akeju, Josh Hamilton, Ashleigh Howard, Filora Elterish, Carla Solorzano, Ryan Robinson, Jesus Reiné, Andrea M. Collins, Stephen B. Gordon, Richard E. Moxon, Jeffrey N. Weiser, Debby Bogaert, Daniela M. Ferreira

Epidemiological studies report the impact of co-infection with pneumococcus and respiratory viruses upon disease rates and outcomes, but their effect on pneumococcal carriage acquisition and bacterial load is scarcely described. Here, we assess this by combining natural viral infection with controlled human pneumococcal infection in 581 healthy adults screened for upper respiratory tract viral infection before intranasal pneumococcal challenge. Across all adults, respiratory syncytial virus (RSV) and rhinovirus asymptomatic infection confer a substantial increase in secondary infection with pneumococcus. RSV also has a major impact on pneumococcal density up to 9 days post challenge. We also study rates and kinetics of bacterial shedding through the nose and oral route in a subset. High levels of pneumococcal colonization density and nasal inflammation are strongly correlated with increased odds of nasal shedding as opposed to cough shedding. Protection against respiratory viral infections and control of pneumococcal density may contribute to preventing pneumococcal disease and reducing bacterial spread.

流行病学研究报告了肺炎球菌和呼吸道病毒共同感染对发病率和预后的影响,但对它们对肺炎球菌携带和细菌量的影响却很少描述。在此,我们对 581 名健康成年人进行了鼻内肺炎球菌挑战前上呼吸道病毒感染筛查,通过将自然病毒感染与受控人类肺炎球菌感染相结合来评估这种影响。在所有成年人中,呼吸道合胞病毒(RSV)和鼻病毒无症状感染会大幅增加肺炎球菌的继发感染。RSV 对挑战后 9 天内的肺炎球菌密度也有重大影响。我们还研究了通过鼻腔和口腔途径脱落细菌的比率和动力学。与咳嗽脱落相比,高水平的肺炎球菌定植密度和鼻腔炎症与鼻腔脱落几率的增加密切相关。预防呼吸道病毒感染和控制肺炎球菌密度可能有助于预防肺炎球菌疾病和减少细菌传播。
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引用次数: 0
Salmonella re-engineers the intestinal environment to break colonization resistance in the presence of a compositionally intact microbiota 沙门氏菌重新设计肠道环境,在微生物群组成完整的情况下打破定植阻力
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-08-23 DOI: 10.1016/j.chom.2024.07.025
Andrew W.L. Rogers, Lauren C. Radlinski, Henry Nguyen, Connor R. Tiffany, Thaynara Parente Carvalho, Hugo L.P. Masson, Michael L. Goodson, Lalita Bechtold, Kohei Yamazaki, Megan J. Liou, Brittany M. Miller, Scott P. Mahan, Briana M. Young, Aurore M. Demars, Sophie R. Gretler, Anaïs B. Larabi, Jee-Yon Lee, Derek J. Bays, Renee M. Tsolis, Andreas J. Bäumler

The gut microbiota prevents harmful microbes from entering the body, a function known as colonization resistance. The enteric pathogen Salmonella enterica serovar (S.) Typhimurium uses its virulence factors to break colonization resistance through unknown mechanisms. Using metabolite profiling and genetic analysis, we show that the initial rise in luminal pathogen abundance was powered by a combination of aerobic respiration and mixed acid fermentation of simple sugars, such as glucose, which resulted in their depletion from the metabolome. The initial rise in the abundance of the pathogen in the feces coincided with a reduction in the cecal concentrations of acetate and butyrate and an increase in epithelial oxygenation. Notably, these changes in the host environment preceded changes in the microbiota composition. We conclude that changes in the host environment can weaken colonization resistance even in the absence of overt compositional changes in the gut microbiota.

肠道微生物群能阻止有害微生物进入人体,这种功能被称为抗定植性。肠道病原体鼠伤寒沙门氏菌(S. Typhimurium)利用其毒力因子通过未知机制打破定植抵抗。通过代谢物分析和基因分析,我们发现腔内病原体丰度的最初上升是由有氧呼吸和葡萄糖等单糖的混合酸发酵共同驱动的,这导致了代谢组中单糖的消耗。粪便中病原体丰度的最初上升与盲肠中乙酸盐和丁酸盐浓度的降低以及上皮含氧量的增加相吻合。值得注意的是,宿主环境的这些变化先于微生物群组成的变化。我们的结论是,即使肠道微生物群的组成没有明显变化,宿主环境的变化也会削弱定植抵抗力。
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引用次数: 0
Unlocking the mind-gut connection: Impact of human microbiome on cognition 解开心灵与肠道的联系:人类微生物群对认知的影响
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-08-14 DOI: 10.1016/j.chom.2024.07.019

This perspective explores the current understanding of the gut microbiota’s impact on cognitive function in apparently healthy humans and in individuals with metabolic disease. We discuss how alterations in gut microbiota can influence cognitive processes, focusing not only on bacterial composition but also on often overlooked components of the gut microbiota, such as bacteriophages and eukaryotes, as well as microbial functionality. We examine the mechanisms through which gut microbes might communicate with the central nervous system, highlighting the complexity of these interactions. We provide a comprehensive overview of the emerging field of microbiota-gut-brain interactions and its significance for cognitive health. Additionally, we summarize novel therapeutic strategies designed to promote cognitive resilience and reduce the risk of cognitive disorders, focusing on interventions that target the gut microbiota. An in-depth understanding of the microbiome-brain axis is imperative for developing innovative treatments aimed at improving cognitive health.

本视角探讨了目前对肠道微生物群对明显健康的人类和代谢性疾病患者认知功能的影响的理解。我们讨论了肠道微生物群的改变如何影响认知过程,不仅关注细菌的组成,还关注肠道微生物群中经常被忽视的成分,如噬菌体和真核生物,以及微生物的功能。我们研究了肠道微生物可能与中枢神经系统沟通的机制,强调了这些相互作用的复杂性。我们全面概述了微生物群-肠道-大脑相互作用这一新兴领域及其对认知健康的意义。此外,我们还总结了旨在促进认知复原力和降低认知障碍风险的新型治疗策略,重点是针对肠道微生物群的干预措施。深入了解微生物组-大脑轴对于开发旨在改善认知健康的创新疗法至关重要。
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引用次数: 0
Maternal antibiotic prophylaxis during cesarean section has a limited impact on the infant gut microbiome 剖腹产期间母体使用抗生素预防对婴儿肠道微生物组的影响有限
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-08-14 DOI: 10.1016/j.chom.2024.07.010

Pregnant women undergoing a cesarean section (CS) typically receive antibiotics prior to skin incision to prevent infections. To investigate if the timing of antibiotics influences the infant gut microbiome, we conducted a randomized controlled trial (NCT06030713) in women delivering via a scheduled CS who received antibiotics either before skin incision or after umbilical cord clamping. We performed a longitudinal analysis on 172 samples from 28 infants at 8 post-birth time points and a cross-sectional analysis at 1 month in 79 infants from 3 cohorts. Although no significant associations with bacterial composition, metabolic pathways, short-chain fatty acids, and bile acids were found, we observed subtle differences between the groups at the bacterial strain level and in the load of antibiotic resistance genes. Rather, feeding mode was a predominant and defining factor impacting infant microbial composition. In conclusion, antibiotic administration during CS has only limited effects on the early-life gut microbiome.

接受剖腹产(CS)的孕妇通常会在切开皮肤前接受抗生素治疗,以预防感染。为了研究抗生素的使用时间是否会影响婴儿的肠道微生物组,我们对按计划进行剖宫产的产妇进行了一项随机对照试验(NCT06030713),这些产妇在皮肤切开前或脐带夹闭后接受抗生素治疗。我们在出生后的 8 个时间点对 28 名婴儿的 172 份样本进行了纵向分析,并在 1 个月时对来自 3 个队列的 79 名婴儿进行了横断面分析。虽然没有发现细菌组成、代谢途径、短链脂肪酸和胆汁酸有明显的关联,但我们观察到各组之间在细菌菌株水平和抗生素耐药基因负荷方面存在微妙的差异。相反,喂养方式是影响婴儿微生物组成的主要决定性因素。总之,在分娩过程中使用抗生素对婴儿早期肠道微生物组的影响有限。
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引用次数: 0
Navigating beyond associations: Opportunities to establish causal relationships between the gut microbiome and colorectal carcinogenesis 超越关联:在肠道微生物组和结直肠癌发生之间建立因果关系的机会
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-08-14 DOI: 10.1016/j.chom.2024.07.008

The gut microbiota has been recognized as an important determinant in the initiation and progression of colorectal cancer (CRC), with recent studies shining light on the molecular mechanisms that may contribute to the interactions between microbes and the CRC microenvironment. Despite the increasing wealth of associations being established in the field, proving causality remains challenging. Obstacles include the high variability of the microbiome and its context, both across individuals and across time. Additionally, there is a lack of large and representative cohort studies with long-term follow-up and/or appropriate sampling methods for studying the mucosal microbiome. Finally, most studies focus on CRC, whereas interactions between host and bacteria in early events in carcinogenesis remain elusive, reinforced by the heterogeneity of CRC development. Here, we discuss these current most prominent obstacles, the recent developments, and research needs.

肠道微生物群已被认为是结直肠癌(CRC)发生和发展的重要决定因素,最近的研究揭示了微生物与 CRC 微环境之间相互作用的分子机制。尽管该领域正在建立越来越多的关联,但证明因果关系仍然具有挑战性。障碍包括微生物组及其环境在个体间和时间上的高度可变性。此外,还缺乏长期随访的大型代表性队列研究和/或研究粘膜微生物组的适当取样方法。最后,大多数研究都集中在 CRC 上,而宿主和细菌在癌变早期事件中的相互作用仍然难以捉摸,CRC 发展的异质性也加剧了这一点。在此,我们将讨论这些当前最突出的障碍、最新进展和研究需求。
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引用次数: 0
Lost in translation: Cesarean antibiotics and the infant microbiome 翻译中的迷失:剖腹产抗生素与婴儿微生物组
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-08-14 DOI: 10.1016/j.chom.2024.07.018

In this issue of Cell Host & Microbe, Sinha et al. describe their randomized trial assessing whether antibiotics given for maternal benefit prior to Cesarean disrupted the infants’ microbiomes. Despite pre-incision antibiotics reaching the neonate, there was no meaningful alteration to the infant microbiome—especially when compared with breastmilk feeding.

在本期《细胞宿主与amp; 微生物》(Cell Host & Microbe)杂志上,辛哈(Sinha)等人介绍了他们进行的随机试验,该试验评估了剖腹产前服用抗生素是否会破坏婴儿的微生物组。尽管新生儿在剖腹产前服用了抗生素,但婴儿的微生物组没有发生明显变化,尤其是与母乳喂养相比。
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引用次数: 0
Bacteroides acidifaciens drives a liver detox program 酸性乳杆菌推动肝脏排毒计划
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-08-14 DOI: 10.1016/j.chom.2024.07.011

Alcohol-associated liver disease is a leading cause of chronic liver conditions, yet there are limited effective therapies. In this issue of Cell Host & Microbe, Shen et al. demonstrate that soluble dietary fiber enhances intestinal Bacteroides acidifaciens, which ameliorates alcohol-associated liver injury in mice by activating hepatic ornithine aminotransferase.

酒精相关性肝病是慢性肝病的主要病因,但有效的治疗方法却很有限。在本期《细胞宿主与amp; 微生物》(Cell Host & Microbe)杂志上,Shen 等人证明了可溶性膳食纤维能增强肠道酸乳杆菌的作用,而酸乳杆菌能通过激活肝脏鸟氨酸氨基转移酶来改善小鼠的酒精相关性肝损伤。
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引用次数: 0
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