Sergio Andreu-Sánchez, Shahzad Ahmad, Alexander Kurilshikov, Marian Beekman, Mohsen Ghanbari, Martijn van Faassen, Inge C. L. van den Munckhof, Marinka Steur, Amy Harms, Thomas Hankemeier, M. Arfan Ikram, Maryam Kavousi, Trudy Voortman, Robert Kraaij, Mihai G. Netea, Joost H. W. Rutten, Niels P. Riksen, Alexandra Zhernakova, Folkert Kuipers, P. Eline Slagboom, Cornelia M. van Duijn, Jingyuan Fu, Dina Vojinovic
Trimethylamine N-oxide (TMAO) is a circulating microbiome-derived metabolite implicated in the development of atherosclerosis and cardiovascular disease (CVD). We investigated whether plasma levels of TMAO, its precursors (betaine, carnitine, deoxycarnitine, choline), and TMAO-to-precursor ratios are associated with clinical outcomes, including CVD and mortality. This was followed by an in-depth analysis of their genetic, gut microbial, and dietary determinants. The analyses were conducted in five Dutch prospective cohort studies including 7834 individuals. To further investigate association results, Mendelian Randomization (MR) was also explored. We found only plasma choline levels (hazard ratio [HR] 1.17, [95% CI 1.07; 1.28]) and not TMAO to be associated with CVD risk. Our association analyses uncovered 10 genome-wide significant loci, including novel genomic regions for betaine (6p21.1, 6q25.3), choline (2q34, 5q31.1), and deoxycarnitine (10q21.2, 11p14.2) comprising several metabolic gene associations, for example, CPS1 or PEMT. Furthermore, our analyses uncovered 68 gut microbiota associations, mainly related to TMAO-to-precursors ratios and the Ruminococcaceae family, and 16 associations of food groups and metabolites including fish-TMAO, meat-carnitine, and plant-based food-betaine associations. No significant association was identified by the MR approach. Our analyses provide novel insights into the TMAO pathway, its determinants, and pathophysiological impact on the general population.
{"title":"Unraveling interindividual variation of trimethylamine N-oxide and its precursors at the population level","authors":"Sergio Andreu-Sánchez, Shahzad Ahmad, Alexander Kurilshikov, Marian Beekman, Mohsen Ghanbari, Martijn van Faassen, Inge C. L. van den Munckhof, Marinka Steur, Amy Harms, Thomas Hankemeier, M. Arfan Ikram, Maryam Kavousi, Trudy Voortman, Robert Kraaij, Mihai G. Netea, Joost H. W. Rutten, Niels P. Riksen, Alexandra Zhernakova, Folkert Kuipers, P. Eline Slagboom, Cornelia M. van Duijn, Jingyuan Fu, Dina Vojinovic","doi":"10.1002/imt2.183","DOIUrl":"10.1002/imt2.183","url":null,"abstract":"<p>Trimethylamine <i>N</i>-oxide (TMAO) is a circulating microbiome-derived metabolite implicated in the development of atherosclerosis and cardiovascular disease (CVD). We investigated whether plasma levels of TMAO, its precursors (betaine, carnitine, deoxycarnitine, choline), and TMAO-to-precursor ratios are associated with clinical outcomes, including CVD and mortality. This was followed by an in-depth analysis of their genetic, gut microbial, and dietary determinants. The analyses were conducted in five Dutch prospective cohort studies including 7834 individuals. To further investigate association results, Mendelian Randomization (MR) was also explored. We found only plasma choline levels (hazard ratio [HR] 1.17, [95% CI 1.07; 1.28]) and not TMAO to be associated with CVD risk. Our association analyses uncovered 10 genome-wide significant loci, including novel genomic regions for betaine (6p21.1, 6q25.3), choline (2q34, 5q31.1), and deoxycarnitine (10q21.2, 11p14.2) comprising several metabolic gene associations, for example, <i>CPS1</i> or <i>PEMT</i>. Furthermore, our analyses uncovered 68 gut microbiota associations, mainly related to TMAO-to-precursors ratios and the Ruminococcaceae family, and 16 associations of food groups and metabolites including fish-TMAO, meat-carnitine, and plant-based food-betaine associations. No significant association was identified by the MR approach. Our analyses provide novel insights into the TMAO pathway, its determinants, and pathophysiological impact on the general population.</p>","PeriodicalId":73342,"journal":{"name":"iMeta","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/imt2.183","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140364255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiayu Zhang, Aixi Tang, Tao Jin, Deshou Sun, Fangliang Guo, Huaxin Lei, Lin Lin, Wensheng Shu, Pingfeng Yu, Xiaoyan Li, Bing Li
Wastewater biotreatment systems harbor a rich diversity of microorganisms, and the effectiveness of biotreatment systems largely depends on the activity of these microorganisms. Specifically, viruses play a crucial role in altering microbial behavior and metabolic processes throughout their infection phases, an aspect that has recently attracted considerable interest. Two metagenomic approaches, viral-like particle-concentrated (VPC, representing free viral-like particles) and non-concentrated (NC, representing the cellular fraction), were employed to assess their efficacy in revealing virome characteristics, including taxonomy, diversity, host interactions, lifestyle, dynamics, and functional genes across processing units of three wastewater treatment plants (WWTPs). Our findings indicate that each approach offers unique insights into the viral community and functional composition. Their combined use proved effective in elucidating WWTP viromes. We identified nearly 50,000 viral contigs, with Cressdnaviricota and Uroviricota being the predominant phyla in the VPC and NC fractions, respectively. Notably, two pathogenic viral families, Asfarviridae and Adenoviridae, were commonly found in these WWTPs. We also observed significant differences in the viromes of WWTPs processing different types of wastewater. Additionally, various phage-derived auxiliary metabolic genes (AMGs) were active at the RNA level, contributing to the metabolism of the microbial community, particularly in carbon, sulfur, and phosphorus cycling. Moreover, we identified 29 virus-carried antibiotic resistance genes (ARGs) with potential for host transfer, highlighting the role of viruses in spreading ARGs in the environment. Overall, this study provides a detailed and integrated view of the virosphere in three WWTPs through the application of VPC and NC metagenomic approaches. Our findings enhance the understanding of viral communities, offering valuable insights for optimizing the operation and regulation of wastewater treatment systems.
{"title":"A panoramic view of the virosphere in three wastewater treatment plants by integrating viral-like particle-concentrated and traditional non-concentrated metagenomic approaches","authors":"Jiayu Zhang, Aixi Tang, Tao Jin, Deshou Sun, Fangliang Guo, Huaxin Lei, Lin Lin, Wensheng Shu, Pingfeng Yu, Xiaoyan Li, Bing Li","doi":"10.1002/imt2.188","DOIUrl":"10.1002/imt2.188","url":null,"abstract":"<p>Wastewater biotreatment systems harbor a rich diversity of microorganisms, and the effectiveness of biotreatment systems largely depends on the activity of these microorganisms. Specifically, viruses play a crucial role in altering microbial behavior and metabolic processes throughout their infection phases, an aspect that has recently attracted considerable interest. Two metagenomic approaches, viral-like particle-concentrated (VPC, representing free viral-like particles) and non-concentrated (NC, representing the cellular fraction), were employed to assess their efficacy in revealing virome characteristics, including taxonomy, diversity, host interactions, lifestyle, dynamics, and functional genes across processing units of three wastewater treatment plants (WWTPs). Our findings indicate that each approach offers unique insights into the viral community and functional composition. Their combined use proved effective in elucidating WWTP viromes. We identified nearly 50,000 viral contigs, with Cressdnaviricota and Uroviricota being the predominant phyla in the VPC and NC fractions, respectively. Notably, two pathogenic viral families, Asfarviridae and Adenoviridae, were commonly found in these WWTPs. We also observed significant differences in the viromes of WWTPs processing different types of wastewater. Additionally, various phage-derived auxiliary metabolic genes (AMGs) were active at the RNA level, contributing to the metabolism of the microbial community, particularly in carbon, sulfur, and phosphorus cycling. Moreover, we identified 29 virus-carried antibiotic resistance genes (ARGs) with potential for host transfer, highlighting the role of viruses in spreading ARGs in the environment. Overall, this study provides a detailed and integrated view of the virosphere in three WWTPs through the application of VPC and NC metagenomic approaches. Our findings enhance the understanding of viral communities, offering valuable insights for optimizing the operation and regulation of wastewater treatment systems.</p>","PeriodicalId":73342,"journal":{"name":"iMeta","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/imt2.188","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140366829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lactobacillus rhamnosus GG (LGG), the well-characterized human-derived probiotic strain, possesses excellent properties in the maintenance of intestinal homeostasis, immunoregulation and defense against gastrointestinal pathogens in mammals. Here, we demonstrate that the SpaC pilin of LGG causes intestinal epithelium injury by inducing cell pyroptosis and gut microbial dysbiosis in zebrafish. Dietary SpaC activates Caspase-3−GSDMEa pathways in the intestinal epithelium, promotes intestinal pyroptosis and increases lipopolysaccharide (LPS)-producing gut microbes in zebrafish. The increased LPS subsequently activates Gaspy2−GSDMEb pyroptosis pathway. Further analysis reveals the Caspase-3−GSDMEa pyroptosis is initiated by the species-specific recognition of SpaC by TLR4ba, which accounts for the species-specificity of the SpaC-inducing intestinal pyroptosis in zebrafish. The observed pyroptosis-driven gut injury and microbial dysbiosis by LGG in zebrafish suggest that host-specific beneficial/harmful mechanisms are critical safety issues when applying probiotics derived from other host species and need more attention.
{"title":"Lactobacillus rhamnosus GG triggers intestinal epithelium injury in zebrafish revealing host dependent beneficial effects","authors":"Zhen Zhang, Hong-Ling Zhang, Da-Hai Yang, Qiang Hao, Hong-Wei Yang, De-Long Meng, Willem Meindert de Vos, Le-Luo Guan, Shu-Bin Liu, Tsegay Teame, Chen-Chen Gao, Chao Ran, Ya-Lin Yang, Yuan-Yuan Yao, Qian-Wen Ding, Zhi-Gang Zhou","doi":"10.1002/imt2.181","DOIUrl":"10.1002/imt2.181","url":null,"abstract":"<p><i>Lactobacillus rhamnosus</i> GG (LGG), the well-characterized human-derived probiotic strain, possesses excellent properties in the maintenance of intestinal homeostasis, immunoregulation and defense against gastrointestinal pathogens in mammals. Here, we demonstrate that the SpaC pilin of LGG causes intestinal epithelium injury by inducing cell pyroptosis and gut microbial dysbiosis in zebrafish. Dietary SpaC activates Caspase-3−GSDMEa pathways in the intestinal epithelium, promotes intestinal pyroptosis and increases lipopolysaccharide (LPS)-producing gut microbes in zebrafish. The increased LPS subsequently activates Gaspy2−GSDMEb pyroptosis pathway. Further analysis reveals the Caspase-3−GSDMEa pyroptosis is initiated by the species-specific recognition of SpaC by TLR4ba, which accounts for the species-specificity of the SpaC-inducing intestinal pyroptosis in zebrafish. The observed pyroptosis-driven gut injury and microbial dysbiosis by LGG in zebrafish suggest that host-specific beneficial/harmful mechanisms are critical safety issues when applying probiotics derived from other host species and need more attention.</p>","PeriodicalId":73342,"journal":{"name":"iMeta","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/imt2.181","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140383030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The role of diverse soil microbiota in restoring erosion-induced degraded lands is well recognized. Yet, the facilitative interactions among symbiotic arbuscular mycorrhizal (AM) fungi, rhizobia, and heterotrophic bacteria, which underpin multiple functions in eroded ecosystems, remain unclear. Here, we utilized quantitative microbiota profiling and ecological network analyses to explore the interplay between the diversity and biotic associations of root-associated microbiota and multifunctionality across an eroded slope of a Robinia pseudoacacia plantation on the Loess Plateau. We found explicit variations in slope multifunctionality across different slope positions, associated with shifts in limiting resources, including soil phosphorus (P) and moisture. To cope with P limitation, AM fungi were recruited by R. pseudoacacia, assuming pivotal roles as keystones and connectors within cross-kingdom networks. Furthermore, AM fungi facilitated the assembly and composition of bacterial and rhizobial communities, collectively driving slope multifunctionality. The symbiotic association among R. pseudoacacia, AM fungi, and rhizobia promoted slope multifunctionality through enhanced decomposition of recalcitrant compounds, improved P mineralization potential, and optimized microbial metabolism. Overall, our findings highlight the crucial role of AM fungal-centered microbiota associated with R. pseudoacacia in functional delivery within eroded landscapes, providing valuable insights for the sustainable restoration of degraded ecosystems in erosion-prone regions.
多样化的土壤微生物群在恢复侵蚀引起的退化土地中的作用已得到广泛认可。然而,共生的丛枝菌根(AM)真菌、根瘤菌和异养菌之间的促进性相互作用仍不清楚,而这种相互作用支撑着侵蚀生态系统的多种功能。在这里,我们利用定量微生物区系剖析和生态网络分析,探讨了黄土高原刺槐种植园侵蚀斜坡上根系相关微生物区系的多样性和生物关联与多功能性之间的相互作用。我们发现,不同坡位的坡面多功能性存在明显差异,这与土壤磷和水分等限制性资源的变化有关。为了应对磷的限制,R. pseudoacacia 吸收了 AM 真菌,并在跨领域网络中扮演了关键的基石和连接者的角色。此外,AM 真菌促进了细菌和根瘤菌群落的组装和组成,共同推动了斜坡的多功能性。R.pseudoacacia、AM 真菌和根瘤菌之间的共生关系通过加强对难分解化合物的分解、提高钾矿化潜力和优化微生物新陈代谢促进了斜坡的多功能性。总之,我们的研究结果凸显了以AM真菌为中心、与假巴西杉相关的微生物群在侵蚀地貌的功能传递中的关键作用,为易受侵蚀地区退化生态系统的可持续恢复提供了宝贵的见解。
{"title":"Arbuscular mycorrhizal fungal interactions bridge the support of root-associated microbiota for slope multifunctionality in an erosion-prone ecosystem","authors":"Tianyi Qiu, Josep Peñuelas, Yinglong Chen, Jordi Sardans, Jialuo Yu, Zhiyuan Xu, Qingliang Cui, Ji Liu, Yongxing Cui, Shuling Zhao, Jing Chen, Yunqiang Wang, Linchuan Fang","doi":"10.1002/imt2.187","DOIUrl":"10.1002/imt2.187","url":null,"abstract":"<p>The role of diverse soil microbiota in restoring erosion-induced degraded lands is well recognized. Yet, the facilitative interactions among symbiotic arbuscular mycorrhizal (AM) fungi, rhizobia, and heterotrophic bacteria, which underpin multiple functions in eroded ecosystems, remain unclear. Here, we utilized quantitative microbiota profiling and ecological network analyses to explore the interplay between the diversity and biotic associations of root-associated microbiota and multifunctionality across an eroded slope of a <i>Robinia pseudoacacia</i> plantation on the Loess Plateau. We found explicit variations in slope multifunctionality across different slope positions, associated with shifts in limiting resources, including soil phosphorus (P) and moisture. To cope with P limitation, AM fungi were recruited by <i>R. pseudoacacia</i>, assuming pivotal roles as keystones and connectors within cross-kingdom networks. Furthermore, AM fungi facilitated the assembly and composition of bacterial and rhizobial communities, collectively driving slope multifunctionality. The symbiotic association among <i>R. pseudoacacia</i>, AM fungi, and rhizobia promoted slope multifunctionality through enhanced decomposition of recalcitrant compounds, improved P mineralization potential, and optimized microbial metabolism. Overall, our findings highlight the crucial role of AM fungal-centered microbiota associated with <i>R. pseudoacacia</i> in functional delivery within eroded landscapes, providing valuable insights for the sustainable restoration of degraded ecosystems in erosion-prone regions.</p>","PeriodicalId":73342,"journal":{"name":"iMeta","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/imt2.187","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140384789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The Microbiome Protocols eBook (MPB) serves as a crucial bridge, filling gaps in microbiome protocols for both wet experiments and data analysis. The first edition, launched in 2020, featured 152 meticulously curated protocols, garnering widespread acclaim. We now extend a sincere invitation to researchers to participate in the upcoming 2nd version of MPB, contributing their valuable protocols to advance microbiome research.