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Multiomics of parkinsonism cynomolgus monkeys highlights significance of metabolites in interaction between host and microbiota. 帕金森病猴的多组学研究凸显了代谢物在宿主与微生物群相互作用中的重要性。
IF 7.8 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-07-26 DOI: 10.1038/s41522-024-00535-3
Jiang-Mei Gao, Shou-Yue Xia, Geoff Hide, Bi-Hai Li, Yi-Yan Liu, Zhi-Yuan Wei, Xiao-Ji Zhuang, Qing Yan, Yun Wang, Wei Yang, Jian-Huan Chen, Jun-Hua Rao

The gut microbiota has been demonstrated to play a significant role in the pathogenesis of Parkinson's disease (PD). However, conflicting findings regarding specific microbial species have been reported, possibly due to confounding factors within human populations. Herein, our current study investigated the interaction between the gut microbiota and host in a non-human primate (NHP) PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) using a multi-omic approach and a self-controlled design. Our transcriptomic sequencing of peripheral blood leukocytes (PBL) identified key genes involved in pro-inflammatory cytokine dysregulation, mitochondrial function regulation, neuroprotection activation, and neurogenesis associated with PD, such as IL1B, ATP1A3, and SLC5A3. The metabolomic profiles in serum and feces consistently exhibited significant alterations, particularly those closely associated with inflammation, mitochondrial dysfunctions and neurodegeneration in PD, such as TUDCA, ethylmalonic acid, and L-homophenylalanine. Furthermore, fecal metagenome analysis revealed gut dysbiosis associated with PD, characterized by a significant decrease in alpha diversity and altered commensals, particularly species such as Streptococcus, Butyrivibrio, and Clostridium. Additionally, significant correlations were observed between PD-associated microbes and metabolites, such as sphingomyelin and phospholipids. Importantly, PDPC significantly reduced in both PD monkey feces and serum, exhibiting strong correlation with PD-associated genes and microbes, such as SLC5A3 and Butyrivibrio species. Moreover, such multi-omic differential biomarkers were linked to the clinical rating scales of PD monkeys. Our findings provided novel insights into understanding the potential role of key metabolites in the host-microbiota interaction involved in PD pathogenesis.

肠道微生物群已被证实在帕金森病(PD)的发病机制中发挥着重要作用。然而,关于特定微生物物种的研究结果却相互矛盾,这可能是由于人类群体中的混杂因素造成的。在此,我们目前的研究采用多组学方法和自控设计,调查了非人灵长类(NHP)帕金森病模型中肠道微生物群与宿主之间的相互作用,该模型由1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱发。我们对外周血白细胞(PBL)进行了转录组测序,发现了与帕金森病相关的促炎细胞因子失调、线粒体功能调节、神经保护激活和神经发生的关键基因,如IL1B、ATP1A3和SLC5A3。血清和粪便中的代谢组图谱始终表现出显著的变化,尤其是那些与帕金森病的炎症、线粒体功能障碍和神经变性密切相关的代谢组,如TUDCA、乙基丙二酸和L-高苯丙氨酸。此外,粪便元基因组分析显示了与帕金森病相关的肠道菌群失调,其特点是α多样性显著降低和共生菌发生改变,尤其是链球菌、丁弧菌和梭状芽孢杆菌等物种。此外,还观察到与脊髓灰质炎相关的微生物与代谢物(如鞘磷脂和磷脂)之间存在明显的相关性。重要的是,PD 猴粪便和血清中的 PDPC 都明显减少,这与 PD 相关基因和微生物(如 SLC5A3 和丁弧菌)有很强的相关性。此外,这些多组学差异生物标志物还与帕金森病猴的临床评分量表有关。我们的研究结果为了解关键代谢物在帕金森氏症发病机制所涉及的宿主-微生物群相互作用中的潜在作用提供了新的见解。
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引用次数: 0
GmAMT2.1/2.2-dependent ammonium nitrogen and metabolites shape rhizosphere microbiome assembly to mitigate cadmium toxicity. 依赖于 GmAMT2.1/2.2 的铵态氮和代谢产物塑造了根瘤微生物组的组合,以减轻镉的毒性。
IF 7.8 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-07-24 DOI: 10.1038/s41522-024-00532-6
Zhandong Cai, Taobing Yu, Weiyi Tan, Qianghua Zhou, Lingrui Liu, Hai Nian, Tengxiang Lian

Cadmium (Cd), a heavy metal, is negatively associated with plant growth. AMT (ammonium transporter) genes can confer Cd resistance and enhance nitrogen (N) uptake in soybeans. The potential of AMT genes to alleviate Cd toxicity by modulating rhizosphere microbiota remains unkonwn. Here, the rhizosphere microbial taxonomic and metabolic differences in three genotypes, i.e., double knockout and overexpression lines and wild type, were identified. The results showed that GmAMT2.1/2.2 genes could induce soybean to recruit beneficial microorganisms, such as Tumebacillus, Alicyclobacillus, and Penicillium, by altering metabolites. The bacterial, fungal, and cross-kingdom synthetic microbial communities (SynComs) formed by these microorganisms can help soybean resist Cd toxicity. The mechanisms by which SynComs help soybeans resist Cd stress include reducing Cd content, increasing ammonium (NH4+-N) uptake and regulating specific functional genes in soybeans. Overall, this study provides valuable insights for the developing microbial formulations that enhance Cd resistance in sustainable agriculture.

重金属镉(Cd)与植物生长呈负相关。AMT(铵转运体)基因可赋予大豆抗镉能力,并提高大豆对氮(N)的吸收。AMT 基因通过调节根瘤微生物群减轻镉毒性的潜力仍有待研究。在此,研究人员确定了三种基因型(即双基因敲除和过表达株系以及野生型)的根瘤微生物分类和代谢差异。结果表明,GmAMT2.1/2.2 基因可通过改变代谢产物诱导大豆吸收有益微生物,如Tumebacillus、Alicyclobacillus 和Penicillium。这些微生物形成的细菌、真菌和跨领域合成微生物群落(SynComs)可以帮助大豆抵抗镉的毒性。SynComs 帮助大豆抵抗镉胁迫的机制包括降低镉含量、增加铵(NH4+-N)吸收和调节大豆的特定功能基因。总之,这项研究为开发提高可持续农业抗镉能力的微生物制剂提供了宝贵的见解。
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引用次数: 0
The Bifidobacterium-dominated fecal microbiome in dairy calves shapes the characteristic growth phenotype of host. 以双歧杆菌为主的乳牛粪便微生物群塑造了宿主的生长表型特征。
IF 7.8 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-07-21 DOI: 10.1038/s41522-024-00534-4
Yimin Zhuang, Shuai Liu, Duo Gao, Yiming Xu, Wen Jiang, Tianyu Chen, Jianxin Xiao, Jingjun Wang, Guobin Hou, Sumin Li, Xinjie Zhao, Yanting Huang, Shangru Li, Siyuan Zhang, Mengmeng Li, Wei Wang, Shengli Li, Zhijun Cao

The dominant bacteria in the hindgut of calves play an important role in their growth and health, which could even lead to lifelong consequences. However, the identification of core probiotics in the hindgut and its mechanism regulating host growth remain unclear. Here, a total of 1045 fecal samples were analyzed by 16S rRNA gene sequencing from the 408 Holstein dairy calves at the age of 0, 14, 28, 42, 56, and 70 days to characterize the dynamic changes of core taxa. Moreover, the mechanisms of nutrient metabolism of calf growth regulated by core bacteria were investigated using multi-omics analyses. Finally, fecal microbiota transplantation (FMT) in mice were conducted to illustrate the potential beneficial effects of core bacteria. Four calf enterotypes were identified and enterotypes dominated by Bifidobacterium and Oscillospiraceae_UCG-005 were representative. The frequency of enterotype conversion shifted from variable to stable. The close relationship observed between phenotype and enterotype, revealing a potential pro-growth effect of Bifidobacterium, might be implemented by promoting the use of carbohydrate, activating the synthesis of volatile fatty acids, amino acids and vitamin B6, and inhibiting methane production in the hindgut. The FMT results indicated the beneficial effect of Bifidobacterium on host growth and hindgut development. These results support the notion that the Bifidobacterium-dominated fecal microbiome would be an important driving force for promoting the host growth in the early life. Our findings provide new insights into the potential probiotic mining and application strategies to promote the growth of young animals or improve their growth retardation.

犊牛后肠中的优势菌对其生长和健康起着重要作用,甚至可能导致终身后果。然而,后肠中核心益生菌的鉴定及其调控宿主生长的机制仍不清楚。本文通过 16S rRNA 基因测序分析了 408 头荷斯坦奶牛在 0、14、28、42、56 和 70 日龄时的 1045 份粪便样本,以描述核心类群的动态变化。此外,还利用多组学分析方法研究了核心菌调控犊牛生长的营养代谢机制。最后,对小鼠进行了粪便微生物群移植(FMT),以说明核心菌的潜在有益作用。研究发现了四种小牛肠型,其中以双歧杆菌和Oscillospiraceae_UCG-005为主的肠型具有代表性。肠型转换的频率从可变到稳定。观察到的表型与肠型之间的密切关系揭示了双歧杆菌潜在的促生长效应,可能是通过促进碳水化合物的利用,激活挥发性脂肪酸、氨基酸和维生素 B6 的合成,以及抑制后肠甲烷的产生来实现的。FMT 结果表明,双歧杆菌对宿主的生长和后肠发育有益。这些结果支持了一种观点,即双歧杆菌主导的粪便微生物组将成为促进宿主早期生长的重要动力。我们的发现为潜在益生菌的挖掘和应用策略提供了新的见解,以促进幼年动物的生长或改善其生长迟缓。
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引用次数: 0
Topical prebiotic nitrate: optimizing the 'hang-time', source and dose for specific oral or systemic effects. 局部使用硝酸益生菌:优化 "悬挂时间"、来源和剂量,以达到特定的口服或全身效果。
IF 7.8 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-07-18 DOI: 10.1038/s41522-024-00528-2
Bob T Rosier, Alex Mira

In our opinion, the 'hang-time' of nitrate-containing products discussed in the letter by Green and Green is an interesting variable that should be considered when nitrate-based treatment or prevention strategies are designed. However, due to direct nitrate recycling after nitrate intake, products with a long 'hang-time' (e.g., chewing gum) may not always have an advantage compared to products with a short 'hang-time' (e.g., vegetable juices). We argue that extending the 'hang-time' is especially relevant and potentially beneficial for different applications, such as using a low nitrate dose to stimulate the oral effects, reaching oral tissues that may otherwise not be exposed to dietary nitrate (e.g., periodontal pockets), and providing a longer nitrate exposure in individuals with an impaired salivary flow. Apart from the 'hang-time', other important variables are the nitrate dose and source (e.g., different salts and vegetable extracts), as well as the desired effect (e.g., an oral effect versus systemic effects). Finally, we believe that the alterations in salivary microbiota observed before and after chewing three nitrate-rich gums over a period of ~5 h, as reported by Green and Green, could be considered beneficial. However, the oral microbiota composition is affected by the circadian rhythm and the effect of gum mastication should be evaluated. These results should thus be confirmed by a placebo-controlled study, where these confounding factors can be accounted for.

我们认为,格林和格林在信中讨论的含硝酸盐产品的 "悬挂时间 "是一个有趣的变量,在设计基于硝酸盐的治疗或预防策略时应加以考虑。然而,由于摄入硝酸盐后硝酸盐会被直接回收利用,与 "滞留时间 "较短的产品(如蔬菜汁)相比,"滞留时间 "较长的产品(如口香糖)并不总是具有优势。我们认为,延长 "悬挂时间 "对于不同的应用尤其重要,而且可能有益,例如使用低剂量硝酸盐来刺激口腔效应,使硝酸盐进入可能无法接触到膳食硝酸盐的口腔组织(如牙周袋),以及为唾液流量受损的人提供更长的硝酸盐接触时间。除了 "滞留时间 "外,其他重要变量还包括硝酸盐的剂量和来源(如不同的盐类和植物提取物),以及所期望的效果(如口腔效果和全身效果)。最后,我们认为 Green 和 Green 所报告的在咀嚼三种富含硝酸盐的口香糖前后约 5 小时内观察到的唾液微生物群的变化可以被认为是有益的。然而,口腔微生物群的组成受昼夜节律的影响,因此应评估咀嚼口香糖的影响。因此,这些结果应通过安慰剂对照研究加以证实,因为安慰剂对照研究可以考虑这些干扰因素。
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引用次数: 0
Topical prebiotic nitrate: can extending the 'hang-time' in the mouth improve oral-vascular health outcomes? 局部使用硝酸益生菌:延长在口腔中的 "停留时间 "能否改善口腔血管健康状况?
IF 7.8 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-07-18 DOI: 10.1038/s41522-024-00527-3
Juliana Green, Shawn J Green
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引用次数: 0
Recent advances in the pathogenesis and prevention strategies of dental calculus. 牙结石发病机制和预防策略的最新进展。
IF 7.8 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-07-13 DOI: 10.1038/s41522-024-00529-1
Yu Wei, Gao-Peng Dang, Zhao-Yang Ren, Mei-Chen Wan, Chen-Yu Wang, Hong-Bo Li, Tong Zhang, Franklin R Tay, Li-Na Niu

Dental calculus severely affects the oral health of humans and animal pets. Calculus deposition affects the gingival appearance and causes inflammation. Failure to remove dental calculus from the dentition results in oral diseases such as periodontitis. Apart from adversely affecting oral health, some systemic diseases are closely related to dental calculus deposition. Hence, identifying the mechanisms of dental calculus formation helps protect oral and systemic health. A plethora of biological and physicochemical factors contribute to the physiological equilibrium in the oral cavity. Bacteria are an important part of the equation. Calculus formation commences when the bacterial equilibrium is broken. Bacteria accumulate locally and form biofilms on the tooth surface. The bacteria promote increases in local calcium and phosphorus concentrations, which triggers biomineralization and the development of dental calculus. Current treatments only help to relieve the symptoms caused by calculus deposition. These symptoms are prone to relapse if calculus removal is not under control. There is a need for a treatment regime that combines short-term and long-term goals in addressing calculus formation. The present review introduces the mechanisms of dental calculus formation, influencing factors, and the relationship between dental calculus and several systemic diseases. This is followed by the presentation of a conceptual solution for improving existing treatment strategies and minimizing recurrence.

牙结石严重影响人类和动物宠物的口腔健康。牙结石沉积会影响牙龈外观并引起炎症。牙结石不清除会导致牙周炎等口腔疾病。除了对口腔健康产生不利影响外,一些全身性疾病也与牙结石沉积密切相关。因此,查明牙结石的形成机制有助于保护口腔和全身健康。口腔中的生理平衡是由大量生物和物理化学因素造成的。细菌是其中重要的组成部分。当细菌平衡被打破时,牙结石就开始形成。细菌在局部聚集并在牙齿表面形成生物膜。细菌会促进局部钙和磷浓度的增加,从而引发生物矿化和牙结石的形成。目前的治疗方法只能缓解牙结石沉积引起的症状。如果不控制牙结石的清除,这些症状很容易复发。因此,我们需要一种短期和长期目标相结合的治疗方法来解决牙结石形成的问题。本综述将介绍牙结石形成的机制、影响因素以及牙结石与多种全身性疾病之间的关系。随后介绍了改进现有治疗策略和尽量减少复发的概念性解决方案。
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引用次数: 0
Metaproteomics-informed stoichiometric modeling reveals the responses of wetland microbial communities to oxygen and sulfate exposure. 以元蛋白组学为依据的化学计量学模型揭示了湿地微生物群落对氧气和硫酸盐暴露的反应。
IF 7.8 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-07-03 DOI: 10.1038/s41522-024-00525-5
Dongyu Wang, Pieter Candry, Kristopher A Hunt, Zachary Flinkstrom, Zheng Shi, Yunlong Liu, Neil Q Wofford, Michael J McInerney, Ralph S Tanner, Kara B De Leόn, Jizhong Zhou, Mari-Karoliina H Winkler, David A Stahl, Chongle Pan

Climate changes significantly impact greenhouse gas emissions from wetland soil. Specifically, wetland soil may be exposed to oxygen (O2) during droughts, or to sulfate (SO42-) as a result of sea level rise. How these stressors - separately and together - impact microbial food webs driving carbon cycling in the wetlands is still not understood. To investigate this, we integrated geochemical analysis, proteogenomics, and stoichiometric modeling to characterize the impact of elevated SO42- and O2 levels on microbial methane (CH4) and carbon dioxide (CO2) emissions. The results uncovered the adaptive responses of this community to changes in SO42- and O2 availability and identified altered microbial guilds and metabolic processes driving CH4 and CO2 emissions. Elevated SO42- reduced CH4 emissions, with hydrogenotrophic methanogenesis more suppressed than acetoclastic. Elevated O2 shifted the greenhouse gas emissions from CH4 to CO2. The metabolic effects of combined SO42- and O2 exposures on CH4 and CO2 emissions were similar to those of O2 exposure alone. The reduction in CH4 emission by increased SO42- and O2 was much greater than the concomitant increase in CO2 emission. Thus, greater SO42- and O2 exposure in wetlands is expected to reduce the aggregate warming effect of CH4 and CO2. Metaproteomics and stoichiometric modeling revealed a unique subnetwork involving carbon metabolism that converts lactate and SO42- to produce acetate, H2S, and CO2 when SO42- is elevated under oxic conditions. This study provides greater quantitative resolution of key metabolic processes necessary for the prediction of CH4 and CO2 emissions from wetlands under future climate scenarios.

气候变化会严重影响湿地土壤的温室气体排放。具体来说,湿地土壤可能会在干旱期间受到氧气(O2)的影响,或因海平面上升而受到硫酸盐(SO42-)的影响。目前还不清楚这些压力因素是如何单独或共同影响湿地中驱动碳循环的微生物食物网的。为了研究这个问题,我们整合了地球化学分析、蛋白质基因组学和化学计量学模型,以描述 SO42- 和 O2 水平升高对微生物甲烷(CH4)和二氧化碳(CO2)排放的影响。研究结果揭示了该群落对 SO42- 和 O2 可用性变化的适应性反应,并确定了驱动 CH4 和 CO2 排放的微生物行会和代谢过程的改变。SO42-的升高减少了CH4的排放,而养氢型甲烷生成的抑制作用要大于乙酰甲烷生成的抑制作用。O2 升高使温室气体排放从 CH4 转向 CO2。联合暴露于 SO42- 和 O2 对 CH4 和 CO2 排放的代谢影响与单独暴露于 O2 的影响相似。增加 SO42- 和 O2 所减少的 CH4 排放量远远大于同时增加的 CO2 排放量。因此,湿地中更多的 SO42- 和 O2 暴露预计会减少 CH4 和 CO2 的总体变暖效应。元蛋白质组学和化学计量学模型揭示了一个涉及碳代谢的独特子网络,当 SO42- 在缺氧条件下升高时,该子网络将乳酸和 SO42- 转化为乙酸、H2S 和 CO2。这项研究为预测未来气候情景下湿地的甲烷和二氧化碳排放提供了更高的关键代谢过程定量分辨率。
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引用次数: 0
Metaproteomic portrait of the healthy human gut microbiota. 健康人体肠道微生物群的元蛋白质组图谱。
IF 7.8 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-06-28 DOI: 10.1038/s41522-024-00526-4
Alessandro Tanca, Antonio Palomba, Giovanni Fiorito, Marcello Abbondio, Daniela Pagnozzi, Sergio Uzzau

Gut metaproteomics can provide direct evidence of microbial functions actively expressed in the colonic environments, contributing to clarify the role of the gut microbiota in human physiology. In this study, we re-analyzed 10 fecal metaproteomics datasets of healthy individuals from different continents and countries, with the aim of identifying stable and variable gut microbial functions and defining the contribution of specific bacterial taxa to the main metabolic pathways. The "core" metaproteome included 182 microbial functions and 83 pathways that were identified in all individuals analyzed. Several enzymes involved in glucose and pyruvate metabolism, along with glutamate dehydrogenase, acetate kinase, elongation factors G and Tu and DnaK, were the proteins with the lowest abundance variability in the cohorts under study. On the contrary, proteins involved in chemotaxis, response to stress and cell adhesion were among the most variable functions. Random-effect meta-analysis of correlation trends between taxa, functions and pathways revealed key ecological and molecular associations within the gut microbiota. The contribution of specific bacterial taxa to the main biological processes was also investigated, finding that Faecalibacterium is the most stable genus and the top contributor to anti-inflammatory butyrate production in the healthy gut microbiota. Active production of other mucosal immunomodulators facilitating host tolerance was observed, including Roseburia flagellin and lipopolysaccharide biosynthetic enzymes expressed by members of Bacteroidota. Our study provides a detailed picture of the healthy human gut microbiota, contributing to unveil its functional mechanisms and its relationship with nutrition, immunity, and environmental stressors.

肠道元蛋白质组学可以提供结肠环境中积极表达的微生物功能的直接证据,有助于阐明肠道微生物群在人类生理学中的作用。在这项研究中,我们重新分析了来自不同大洲和国家的 10 个健康人的粪便元蛋白质组数据集,目的是确定稳定和可变的肠道微生物功能,并定义特定细菌类群对主要代谢途径的贡献。核心 "元蛋白质组包括 182 种微生物功能和 83 条通路,这些功能和通路在所有分析对象中都得到了确定。参与葡萄糖和丙酮酸代谢的几种酶,以及谷氨酸脱氢酶、乙酸激酶、伸长因子 G 和 Tu 以及 DnaK,是所研究群体中丰度变化最小的蛋白质。相反,参与趋化、应激反应和细胞粘附的蛋白质的功能变化最大。对分类群、功能和途径之间相关趋势的随机效应荟萃分析揭示了肠道微生物群中的关键生态和分子关联。研究还调查了特定细菌类群对主要生物过程的贡献,发现粪杆菌是最稳定的菌属,也是健康肠道微生物群中产生抗炎丁酸盐的最大贡献者。研究还观察到了其他促进宿主耐受性的粘膜免疫调节剂的活性生产,包括由类菌群成员表达的蔷薇鞭毛菌素和脂多糖生物合成酶。我们的研究提供了健康人体肠道微生物群的详细情况,有助于揭示其功能机制及其与营养、免疫和环境压力因素的关系。
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引用次数: 0
Carbon source competition within the wound microenvironment can significantly influence infection progression. 伤口微环境中的碳源竞争会极大地影响感染的进展。
IF 7.8 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-06-25 DOI: 10.1038/s41522-024-00518-4
Evgenia Maslova, Lara EisaianKhongi, Petra Rigole, Tom Coenye, Ronan R McCarthy

It is becoming increasingly apparent that commensal skin bacteria have an important role in wound healing and infection progression. However, the precise mechanisms underpinning many of these probiotic interactions remain to be fully uncovered. In this work, we demonstrate that the common skin commensal Cutibacterium acnes can limit the pathogenicity of the prevalent wound pathogen Pseudomonas aeruginosa in vivo. We show that this impact on pathogenicity is independent of any effect on growth, but occurs through a significant downregulation of the Type Three Secretion System (T3SS), the primary toxin secretion system utilised by P. aeruginosa in eukaryotic infection. We also show a downregulation in glucose acquisition systems, a known regulator of the T3SS, suggesting that glucose availability in a wound can influence infection progression. C. acnes is well known as a glucose fermenting organism, and we demonstrate that topically supplementing a wound with glucose reverses the probiotic effects of C. acnes. This suggests that introducing carbon source competition within the wound microenvironment may be an effective way to prevent or limit wound infection.

人们越来越清楚地认识到,皮肤共生细菌在伤口愈合和感染进展中发挥着重要作用。然而,许多益生菌相互作用的确切机制仍有待全面揭示。在这项研究中,我们证明了常见的皮肤共生菌痤疮棒状杆菌能在体内限制伤口致病菌铜绿假单胞菌的致病性。我们表明,这种致病性影响与对生长的任何影响无关,而是通过显著下调三型分泌系统(T3SS)来实现的,三型分泌系统是铜绿假单胞菌在真核感染中使用的主要毒素分泌系统。我们还发现葡萄糖获取系统(T3SS 的一个已知调节因子)也出现了下调,这表明伤口中葡萄糖的可用性会影响感染的进展。痤疮丙酸杆菌是众所周知的葡萄糖发酵生物,我们证明在伤口局部补充葡萄糖能逆转痤疮丙酸杆菌的益生作用。这表明,在伤口微环境中引入碳源竞争可能是预防或限制伤口感染的有效方法。
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引用次数: 0
Fasting-mimicking diet remodels gut microbiota and suppresses colorectal cancer progression. 模拟空腹饮食可重塑肠道微生物群并抑制结直肠癌的发展。
IF 7.8 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-06-25 DOI: 10.1038/s41522-024-00520-w
Man Luo, Qingyi Wang, Yong Sun, Yao Jiang, Qiwen Wang, Yanrou Gu, Zhefang Hu, Qianyi Chen, Jilei Xu, Shujie Chen, Tongyao Hou, Lijun Feng

The progression of colorectal cancer is closely associated with diet. Fasting-mimicking diet (FMD) is a promising type of dietary intervention that have beneficial effects in the prevention and treatment of various cancers. We investigated the therapeutic effect of 4-day FMD against colorectal cancer in mice through immune cell analysis, microbiota composition analysis and anti-PD-1 treatment. These FMD cycles effectively suppressed colorectal cancer growth, reduced cell proliferation and angiogenesis, increased tumor-infiltration lymphocytes especially CD8+T cells. FMD stimulated protective gut microbiota, especially Lactobacillus. Supplementation of Lactobacillus johnsonii induced similar results as FMD intervention, which also suppressed tumor growth and increased CD45+ and CD8+ T cells. Additionally, FMD synthesizing with anti-PD-1 therapy effectively inhibited CRC progression. These findings suggest that Lactobacillus. johnsonii is necessary for the anticancer process of FMD in CRC. FMD through its effects on both gut microbiota and immune system, effectively suppressed colorectal cancer progression in mouse model.

大肠癌的进展与饮食密切相关。空腹模拟饮食(FMD)是一种很有前景的饮食干预方法,对预防和治疗各种癌症有好处。我们通过免疫细胞分析、微生物群组成分析和抗 PD-1 治疗,研究了 4 天 FMD 对小鼠结直肠癌的治疗效果。这些 FMD 循环有效抑制了结直肠癌的生长,减少了细胞增殖和血管生成,增加了肿瘤浸润淋巴细胞,尤其是 CD8+T 细胞。FMD 可刺激保护性肠道微生物群,尤其是乳酸杆菌。补充约翰逊乳杆菌与 FMD 的干预效果相似,也能抑制肿瘤生长,增加 CD45+ 和 CD8+ T 细胞。此外,FMD与抗PD-1疗法的合成能有效抑制CRC的进展。这些研究结果表明,约翰逊乳杆菌对 FMD 在 CRC 中的抗癌过程是必要的。FMD通过对肠道微生物群和免疫系统的影响,有效抑制了小鼠模型中结直肠癌的进展。
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npj Biofilms and Microbiomes
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