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Predicting probiotic success: lessons from Oxalobacter and oxalate metabolism. 预测益生菌的成功:草酸杆菌和草酸盐代谢的经验教训。
IF 9.2 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-06 DOI: 10.1038/s41522-025-00896-3
Mangesh Suryavanshi, Sromona D Mukherjee, Aaron W Miller

The gut microbiota influences host metabolism, immunity, and organ physiology, making it an attractive therapeutic target. However, clinical probiotic trials often produce inconsistent results, reflecting context-dependent effects shaped by metabolic, ecological, dietary, and host-specific factors. We critically synthesized the literature on hyperoxaluria, a condition of elevated urinary oxalate associated with kidney stones and chronic kidney disease, as a mechanistically tractable model for probiotic development. We examined evidence from clinical studies, microbiome analyses, and mechanistic experiments to identify factors influencing efficacy, with a focus on Oxalobacter formigenes, a specialist oxalate-degrading anaerobe. Across trials, probiotic success depended less on dose, strain identity, or persistence, and more on the ecological context - particularly the baseline abundance of oxalate-degrading genes (oxc, frc) in the native microbiota. Efficacy was highest when these metabolic niches were vacant. Diet, delivery format, and broader microbial community structure also shaped outcomes. A taxon-centric approach is insufficient for predicting probiotic efficacy. We propose a three-phase framework for rational design: (1) case-control microbiome studies to identify metabolically relevant deficits; (2) mechanistic in vivo and in vitro validation to establish causality; and (3) complex systems modeling to predict context-specific responses. This metabolism-first, ecology-grounded strategy is generalizable to other microbiota-linked conditions and supports precision microbial therapeutics.

肠道菌群影响宿主代谢、免疫和器官生理,使其成为一个有吸引力的治疗靶点。然而,临床益生菌试验经常产生不一致的结果,反映了代谢、生态、饮食和宿主特异性因素形成的环境依赖效应。我们批判性地综合了关于高草酸尿的文献,这是一种与肾结石和慢性肾脏疾病相关的尿草酸升高的情况,作为益生菌发育的机械模型。我们研究了临床研究、微生物组分析和机制实验的证据,以确定影响疗效的因素,重点研究了草酸降解厌氧菌——formigenes草酸杆菌。在所有试验中,益生菌的成功较少依赖于剂量、菌株特性或持久性,而更多地依赖于生态环境——特别是原生微生物群中草酸降解基因(oxc, frc)的基线丰度。当这些代谢生态位空缺时,疗效最高。饮食、分娩方式和更广泛的微生物群落结构也影响了结果。以分类群为中心的方法不足以预测益生菌的功效。我们提出了一个合理设计的三阶段框架:(1)病例对照微生物组研究,以确定代谢相关缺陷;(2)体内和体外机制验证,建立因果关系;(3)复杂系统建模,以预测情境特定的响应。这种以代谢为先、以生态为基础的策略可推广到其他与微生物群相关的疾病,并支持精确的微生物治疗。
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引用次数: 0
Biofertilizer induces soil disease suppression by activating pathogen suppressive protist taxa. 生物肥料通过激活病原抑制原生生物类群来抑制土壤病害。
IF 9.2 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-05 DOI: 10.1038/s41522-025-00897-2
Xin Pei, Na Zhang, Xuhui Deng, Ruochen Li, Yanjie Wang, Ying Wang, Wanting Huang, Yang Yue, Stefan Geisen, Zhilei Gao, Sai Guo, Donglan Tian, Qirong Shen, George A Kowalchuk, Rong Li

Given the increasing demand for sustainable agricultural solutions utilizing the microbiome, particularly the use of biofertilizer (BF), it is essential to understand the mode of action and the role of predatory protists, along with their interactions with biocontrol strains and resident community members. We therefore examined these interactions through a long-term field experiment and a series of greenhouse and pot experiments. In field and greenhouse studies, we observed that Bacillus significantly stimulated the growth of Cercomonas, a genus of predatory protists, in the soil. In turn, these protists promoted the growth of Bacillus, leading to increased detection of polyketide synthase (PKS) genes and the inhibition of bacterial wilt pathogen Ralstonia solanacearum. We here reveal a positive feedback loop between the biocontrol agent Bacillus and predatory protists, which explains the biofertilizer-induced reduction of plant pathogens. These findings highlight the significance of synergistic interactions between functional microbes and predatory protists in suppressing soil-borne diseases. Moreover, it underscores the potential of incorporating predator-prey interactions into agricultural practices to foster more sustainable ecosystem development.

鉴于对利用微生物群的可持续农业解决方案的需求日益增加,特别是生物肥料(BF)的使用,有必要了解掠食性原生生物的作用模式和作用,以及它们与生物防治菌株和居民社区成员的相互作用。因此,我们通过长期的田间试验和一系列温室和盆栽试验来研究这些相互作用。在田间和温室研究中,我们观察到芽孢杆菌显著地促进了土壤中掠食性原生生物Cercomonas的生长。反过来,这些原生生物促进芽孢杆菌的生长,导致聚酮合成酶(PKS)基因的检测增加,并抑制青枯病病原菌Ralstonia solanacearum。我们在这里揭示了生物防治剂芽孢杆菌和掠夺性原生生物之间的正反馈回路,这解释了生物肥料诱导的植物病原体减少。这些发现强调了功能微生物和掠食性原生生物之间的协同相互作用在抑制土传疾病中的重要性。此外,它强调了将捕食者-猎物相互作用纳入农业实践以促进更可持续的生态系统发展的潜力。
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引用次数: 0
Conserved genotype-independent rhizobacteria promote maize growth. 保守的不依赖基因型的根瘤菌促进玉米生长。
IF 9.2 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-12-31 DOI: 10.1038/s41522-025-00895-4
Junnan Fang, Guoliang Wang, Chun Zhang, Guiming Liu, Jiacan Xu, Yuqian Gao, Yajie Guo, Xuming Wang, Tianlei Qiu

Rhizosphere microbiomes play an essential role in promoting plant growth and health. Although host genotype is known to shape rhizosphere microbial communities, it remains unclear whether core microbial taxa can persist across genetically diverse hosts and contribute to plant performance. Here, we conducted a large-scale analysis of 1005 rhizosphere samples from 335 maize populations to investigate the effects of host genetic variation on rhizosphere microbiota. We observed significant genotype-dependent variation in both bacterial and fungal community diversity and composition. However, community assembly was predominantly governed by stochastic processes, suggesting an evolutionary conservation of rhizosphere microbiota across genotypes. Based on the hypothesis that core microbes may consistently associate with maize independent of genotypes, we identified a core bacterial taxon, ASV245 (Pseudomonas sp.), which was consistently enriched across all maize genotypes. The corresponding strain, designated as WY16, was isolated from maize roots and significantly promoted both stem and root growth by activating maize hormone signaling pathways. These findings highlight the persistence and functional roles of genotype-independent core microbes, deepening our understanding of plant-microbiome interactions and providing new insights for microbiome-based strategies in sustainable agriculture.

根际微生物群在促进植物生长和健康方面发挥着重要作用。虽然已知寄主基因型可以塑造根际微生物群落,但核心微生物类群是否可以在遗传多样性寄主中持续存在并对植物性能做出贡献仍不清楚。本研究对335个玉米群体的1005份根际样品进行了大规模分析,探讨了寄主遗传变异对根际微生物群的影响。我们观察到细菌和真菌群落多样性和组成存在显著的基因型依赖性差异。然而,群落组装主要受随机过程控制,这表明根际微生物群在不同基因型中存在进化守恒。基于核心微生物可能独立于基因型与玉米一致关联的假设,我们鉴定了一个核心细菌分类群ASV245(假单胞菌sp.),它在所有玉米基因型中都一致富集。该菌株从玉米根中分离得到,命名为WY16,通过激活玉米激素信号通路,显著促进茎和根的生长。这些发现突出了基因型无关核心微生物的持久性和功能作用,加深了我们对植物-微生物组相互作用的理解,并为可持续农业中基于微生物组的策略提供了新的见解。
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引用次数: 0
Fecal microbial and metabolic signatures in children with very early onset inflammatory bowel disease. 非常早发性炎症性肠病儿童的粪便微生物和代谢特征
IF 9.2 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-12-31 DOI: 10.1038/s41522-025-00899-0
Kine Eide Kvitne, Simone Zuffa, Vincent Charron-Lamoureux, Ipsita Mohanty, Abubaker Patan, Helena Mannochio-Russo, Jasmine Zemlin, Lindsey A Burnett, Lisa S Zhang, Mia C Cecala, Ceylan Ersoz, James A Connelly, Natasha Halasa, Maribeth Nicholson, Pieter C Dorrestein, Shirley M Tsunoda, Janet Markle

Very early onset inflammatory bowel disease (VEO-IBD) is a clinically distinct form of IBD manifesting in children before the age of six years. Disease in these children is especially severe and often refractory to treatment. While previous studies have investigated changes in the fecal microbiome and metabolome in adult and pediatric IBD, insights in VEO-IBD remain limited. This multi-omics analysis reveals changes in the fecal microbiome and metabolome in children diagnosed with VEO-IBD compared with age- and sexmatched healthy controls. Untargeted metabolomics analysis identified a depletion of short-chain N-acyl lipids and an enrichment of dipeptides, tripeptides, and oxo bile acids in children with VEO-IBD. Differential abundance analysis of 16S rRNA sequencing data showed lower abundance of beneficial bacteria such as Bifidobacterium and Blautia, and higher abundance of Lachnospira, Veillonella, and Bacteroides in VEO-IBD. Multi-omics integration revealed associations between the altered gut microbiome composition and metabolic dysregulation, specifically for the N-acyl lipids. This study offers unique insight into fecal microbial and metabolic signatures in VEO-IBD, paving the way for a better understanding of disease patterns and thereby more effective treatment strategies.

极早发性炎症性肠病(VEO-IBD)是一种临床独特的IBD形式,表现在6岁前的儿童中。这些儿童的疾病特别严重,而且往往难以治疗。虽然以前的研究已经调查了成人和儿童IBD中粪便微生物组和代谢组的变化,但对VEO-IBD的见解仍然有限。这项多组学分析揭示了诊断为VEO-IBD的儿童与年龄和性别匹配的健康对照组相比,粪便微生物组和代谢组的变化。非靶向代谢组学分析发现,VEO-IBD患儿的短链n -酰基脂质减少,二肽、三肽和氧胆汁酸富集。16S rRNA测序数据的差异丰度分析显示,VEO-IBD中有益菌如双歧杆菌和Blautia丰度较低,而Lachnospira、Veillonella和Bacteroides丰度较高。多组学整合揭示了肠道微生物组成改变与代谢失调之间的关联,特别是n -酰基脂质。这项研究为VEO-IBD的粪便微生物和代谢特征提供了独特的见解,为更好地了解疾病模式铺平了道路,从而制定了更有效的治疗策略。
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引用次数: 0
Microbiota-derived indole-3-acetic acid alleviates rumen epithelial barrier dysfunction during the peripartum period through AhR signaling. 微生物源性吲哚-3-乙酸通过AhR信号通路缓解围产期瘤胃上皮屏障功能障碍。
IF 9.2 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-12-30 DOI: 10.1038/s41522-025-00898-1
Moli Li, Shiquan Zhu, Yihui Huo, Qiqi Cao, Zhaoju Deng, Kui Li, Yue Li, Juan J Loor, Jiangchun Wan, Jiangjiao Qi, Chuang Xu

Peripartum dairy cows are highly susceptible to metabolic disorders, with ketosis being the most prevalent postpartum disease associated with rumen microbial dysbiosis and systemic inflammation. However, the mechanisms by which microbial alterations compromise rumen epithelial integrity remain poorly understood. Using peripartum cows with ketosis as a model, we demonstrated that perturbations of rumen microbiota disrupt tryptophan metabolism, resulting in pronounced depletion of indole-3-acetic acid (IAA). The loss of IAA-producing taxa (Lactobacillus and Bifidobacterium) contributed to reduced IAA levels and epithelial barrier dysfunction, whereas enrichment of proinflammatory taxa (Candidatus Saccharimonas and Mycoplasma) was associated with exacerbated epithelial inflammation. In vitro, IAA supplementation activated the AhR/IL-22 signaling pathway, promoting bovine rumen epithelial cells (BRECs) regeneration and restoring barrier integrity. These findings identify the microbiota-IAA-AhR/IL-22 axis as a key regulator of rumen epithelial homeostasis and suggest that targeting this pathway represents a promising strategy to prevent metabolic disorders in dairy cows.

围产期奶牛易患代谢紊乱,酮症是与瘤胃微生物生态失调和全身性炎症相关的最普遍的产后疾病。然而,微生物改变损害瘤胃上皮完整性的机制仍然知之甚少。以围产期奶牛酮症为模型,我们证明了瘤胃微生物群的扰动会破坏色氨酸的代谢,导致吲哚-3-乙酸(IAA)的明显消耗。产生IAA的分类群(乳酸杆菌和双歧杆菌)的缺失导致IAA水平降低和上皮屏障功能障碍,而促炎分类群(糖假酵母菌和支原体)的富集与上皮炎症加剧有关。在体外,补充IAA激活AhR/IL-22信号通路,促进牛瘤胃上皮细胞(BRECs)再生,恢复屏障完整性。这些发现确定了微生物群- iaa - ahr /IL-22轴是瘤胃上皮稳态的关键调节因子,并表明靶向这一途径是预防奶牛代谢紊乱的有希望的策略。
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引用次数: 0
DPO production by gut commensals suggests a broader role in bacterial communication and host-microbiome interactions. 肠道共生体产生DPO表明在细菌交流和宿主-微生物相互作用中具有更广泛的作用。
IF 9.2 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-12-28 DOI: 10.1038/s41522-025-00886-5
Michael Moraskie, Sara Li, Josep-Ramon Codina, Md Harun Or Roshid, Kevin Núño, Gregory O'Connor, Emre Dikici, Sapna Deo, Eleonore Beurel, Sylvia Daunert

The quorum-sensing molecule 3,5-dimethylpyrazine-2-ol (DPO), known for regulating biofilm formation in Vibrio cholerae, has unknown distribution among commensal bacteria. We screened 37 bacterial strains using a validated biosensor and found widespread production. Inoculating mice with high producers elevated gut DPO levels, highlighting DPO's potential influence on gut microbiota. These findings expand DPO's ecological relevance and underscore quorum sensing as a potentially critical influence on microbiome function and host-microbe interactions.

群体感应分子3,5-二甲基吡嗪-2-醇(DPO)以调节霍乱弧菌的生物膜形成而闻名,但在共生菌中的分布未知。我们使用经过验证的生物传感器筛选了37株细菌菌株,发现其广泛生产。给高产量的小鼠接种DPO后,肠道DPO水平升高,凸显了DPO对肠道微生物群的潜在影响。这些发现扩展了DPO的生态学相关性,并强调了群体感应对微生物组功能和宿主-微生物相互作用的潜在关键影响。
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引用次数: 0
Directed evolution of a staphylophage under biofilm and planktonic conditions. 生物膜和浮游条件下葡萄噬细胞的定向进化。
IF 9.2 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-12-25 DOI: 10.1038/s41522-025-00893-6
Carlos Valdivia, Pilar Domingo-Calap

The rise of multidrug-resistant bacteria, particularly biofilm-forming pathogens such as Staphylococcus epidermidis, highlights the urgent need for alternative antimicrobial strategies. Phage therapy, which uses phages to selectively infect and lyse bacterial cells, offers a promising solution. In this study, we evolved the lytic phage vB_Sep_Steph1 under both biofilm and planktonic conditions, using varying initial phage inoculum titers. Whole-genome sequencing of evolved populations revealed recurrent condition-dependent mutations in holins and structural genes with putative depolymerase activity-critical for host recognition and biofilm degradation. Phenotypic improvements in traits such as antibacterial efficacy and replicative fitness were observed to be highly dependent on both the presence of biofilm and the initial phage titer during evolution. Furthermore, some evolved phage lineages could delay bacterial resistance better than the ancestral strain. These findings support the utility of directed phage evolution to improve therapeutic efficacy and robustness, particularly against biofilm-associated infections.

耐多药细菌的增加,特别是表皮葡萄球菌等生物膜形成病原体的增加,突出表明迫切需要其他抗微生物策略。噬菌体疗法,利用噬菌体选择性地感染和溶解细菌细胞,提供了一个很有前途的解决方案。在本研究中,我们利用不同的初始噬菌体接种滴度,在生物膜和浮游条件下进化出了裂解噬菌体vB_Sep_Steph1。进化种群的全基因组测序揭示了holins和结构基因中反复出现的条件依赖性突变,这些基因具有假定的解聚合酶活性,这对宿主识别和生物膜降解至关重要。在进化过程中,抗菌功效和复制适应性等性状的表型改善高度依赖于生物膜的存在和初始噬菌体滴度。此外,一些进化的噬菌体谱系可以比祖先菌株更好地延缓细菌的耐药性。这些发现支持定向噬菌体进化的效用,以提高治疗效果和稳健性,特别是针对生物膜相关感染。
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引用次数: 0
Microplastic biofilm as hotspots of antibiotic resistance genes and potential pathogens. 微塑料生物膜是抗生素耐药基因和潜在病原体的热点。
IF 9.2 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-12-22 DOI: 10.1038/s41522-025-00890-9
Xu Zhang, Zheng Dong, Shuping Zhang, Juan Ma, Sijin Liu

Microplastic biofilms, known as the "plastisphere", harbor diverse microbial communities and serve as reservoirs for antibiotic resistance genes (ARGs). This review discussed the mechanisms driving bacterial community alteration on microplastics and delineated the pathways through which ARGs transfer within microplastic biofilms. We expected to provide a comprehensive understanding of the ecological and human health impacts associated with microplastic biofilms and ARGs, thereby informing strategies to mitigate plastic pollution and its risks.

微塑料生物膜,被称为“塑料球”,拥有多种微生物群落,并作为抗生素耐药基因(ARGs)的储存库。本文讨论了微塑料细菌群落改变的机制,并描述了微塑料生物膜中ARGs转移的途径。我们希望全面了解与微塑料生物膜和ARGs相关的生态和人类健康影响,从而为减轻塑料污染及其风险的策略提供信息。
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引用次数: 0
Microbiome dysbiosis and chemotherapy resistance in acute myeloid leukemia (AML). 急性髓性白血病(AML)的微生物群落失调和化疗耐药。
IF 9.2 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-12-22 DOI: 10.1038/s41522-025-00891-8
Maojin Tian, Hamed Soleimani Samarkhazan, Seyed Shahabedin Alemohammad, Milad Fakhraei Manesh, Farzaneh Tavakoli, Ali Shams, Amirhossein Zeynalabadi

AML often relapses due to chemotherapy resistance, increasingly linked to gut microbiome dysbiosis. Microbial drug modification, immune modulation, and metabolite-driven survival/epigenetic changes (e.g., SCFAs, kynurenine) promote resistance. Clinical data associate reduced diversity, loss of Faecalibacterium, and Enterococcus overgrowth with poorer outcomes. Microbiome interventions (FMT, probiotics, diet) show promise; priorities are standardizing methods and defining microbe-metabolite mechanisms to guide trials.

AML经常因化疗耐药而复发,与肠道微生物群失调的关系日益密切。微生物药物修饰、免疫调节和代谢物驱动的生存/表观遗传变化(例如,SCFAs、犬尿氨酸)促进耐药性。临床数据表明,粪杆菌多样性减少、粪杆菌丧失和肠球菌过度生长与预后较差有关。微生物组干预(FMT、益生菌、饮食)显示出希望;重点是标准化方法和确定微生物代谢机制,以指导试验。
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引用次数: 0
Gut microbiome profiling of a migratory Anser serrirostris population reveals two groups with distinct pathogen and ARG contents. 一个迁徙的serrirostris种群的肠道微生物组分析显示两组具有不同的病原体和ARG含量。
IF 9.2 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-12-20 DOI: 10.1038/s41522-025-00888-3
Yu Wang, Jin Xu, Guixin Liang, Shenglong Liang, Meicun Hou, Lin Sun, Jing Wang, Hao Chen, Yongqiang Zhao, Weihua Chen, Entao Wang, Jinlin Huang, Xin'an Jiao, Yunzeng Zhang

Migratory birds are key vectors of pathogens and antibiotic-resistance genes (ARGs), yet intrapopulation variation and its microbiome-mediated basis remain poorly understood. Here, we characterized the gut microbiome of 70 individuals from a migratory Anser serrirostris population using full-length 16S rDNA sequencing, followed by metagenomic analysis of 25 representative samples. Both approaches consistently identified two distinct groups (E1 and E2). Network analysis revealed impaired microbial interactions in E1 compared to E2. E1 exhibited higher abundances of opportunistic pathogens (e.g., Pseudomonas, Erwinia) and enriched functions related to pathogenicity and ARGs, predominantly driven by these taxa. Conversely, E2 showed function enrichment in short-chain fatty acid biosynthesis and plant metabolite degradation, mediated mainly by Bradyrhizobium and Ligilactobacillus. Genome-centric analysis identified several pathogenic genomes (e.g., Salmonella, Vibrio parahaemolyticus) harboring critical virulence factors and ARGs predominantly in E1. These results provide valuable insights into microbiome-driven variation in pathogen/ARG loads within migratory bird populations.

候鸟是病原体和抗生素耐药基因(ARGs)的主要传播媒介,但种群内变异及其微生物组介导的基础仍然知之甚少。在这里,我们使用全长16S rDNA测序对来自一个迁徙的serrirostris种群的70个个体的肠道微生物组进行了表征,然后对25个代表性样本进行了宏基因组分析。两种方法一致地确定了两个不同的组(E1和E2)。网络分析显示,与E2相比,E1中的微生物相互作用受损。E1具有较高的条件致病菌丰度(如假单胞菌、欧文菌),并具有丰富的致病性和ARGs相关功能,主要由这些类群驱动。相反,E2在短链脂肪酸生物合成和植物代谢物降解中表现出功能富集,主要由慢生根瘤菌和脂乳杆菌介导。以基因组为中心的分析发现了几个致病基因组(如沙门氏菌、副溶血性弧菌),其中含有关键毒力因子和ARGs,主要在E1中。这些结果为候鸟种群中微生物组驱动的病原体/ARG负荷变化提供了有价值的见解。
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引用次数: 0
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npj Biofilms and Microbiomes
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