Nature metabolismPub Date : 2025-05-23DOI: 10.1038/s42255-025-01302-0
Zhiming Wei, Ning Jiang, Yiwei Zhang, Qilong Li, Ziwei Su, Yanxin Zhang, Kunying Lv, Yixin Yang, Tong Liu, Lu Sun, Kexin Zheng, Ang Li, Anni Feng, Xiaoyu Sang, Ying Feng, Ran Chen, Qijun Chen
{"title":"β-hydroxybutyrate inhibits Plasmodium falciparum development and confers protection against malaria in mice","authors":"Zhiming Wei, Ning Jiang, Yiwei Zhang, Qilong Li, Ziwei Su, Yanxin Zhang, Kunying Lv, Yixin Yang, Tong Liu, Lu Sun, Kexin Zheng, Ang Li, Anni Feng, Xiaoyu Sang, Ying Feng, Ran Chen, Qijun Chen","doi":"10.1038/s42255-025-01302-0","DOIUrl":"https://doi.org/10.1038/s42255-025-01302-0","url":null,"abstract":"<p>Environmental factors restrict malaria parasite development, but the influence of host metabolic variations on the infectivity of the blood stage parasite is not fully understood. Here we show that mice on a ketogenic diet are completely protected from infection with the malaria parasite <i>Plasmodium berghei</i>. We further show that administration of the ketone body β-hydroxybutyrate (βOHB), but not of acetoacetate, increases survival of infected mice and inhibits proliferation of both <i>P.</i> <i>berghei</i> and <i>Plasmodium falciparum</i> in vitro. Administration of either a ketogenic diet or βOHB induces metabolic reprogramming in parasites, including reduced levels of nicotinamide adenine dinucleotide, which is associated with the downregulation of genes controlling parasite development, erythrocyte invasion and pathogenicity. Our data indicate that a ketogenic diet and the ketone body βOHB confer resistance to malaria in mice by causing developmental arrest of <i>Plasmodium</i> parasites, highlighting the potential of dietary and metabolic strategies to fight malarial infection.</p>","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"89 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144122945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nature metabolismPub Date : 2025-05-23DOI: 10.1038/s42255-025-01310-0
Temitope W. Ademolue, Lena Pernas
{"title":"A ketogenic diet halts malaria parasite growth","authors":"Temitope W. Ademolue, Lena Pernas","doi":"10.1038/s42255-025-01310-0","DOIUrl":"https://doi.org/10.1038/s42255-025-01310-0","url":null,"abstract":"A new study reveals that the host-derived ketone body, β-hydroxybutyrate, protects against malaria in mice by inhibiting Plasmodium development. These findings highlight the anti-microbial potential of metabolic interventions.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"4 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144122944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nuclear SREBP2 condensates regulate the transcriptional activation of lipogenic genes and cholesterol homeostasis","authors":"Mengqiang Xu, Shi-You Jiang, Shuocheng Tang, Meimei Zhu, Yueer Hu, Juewan Li, Jizhi Yan, Chenyang Qin, Dongxia Tan, Yang An, Yuxiu Qu, Bao-Liang Song, Hanhui Ma, Wei Qi","doi":"10.1038/s42255-025-01291-0","DOIUrl":"https://doi.org/10.1038/s42255-025-01291-0","url":null,"abstract":"<p>The precursor of sterol regulatory element-binding protein-2 (SREBP2) is a membrane-bound transcription factor regulating cholesterol biosynthesis. Under cholesterol-deficient conditions, mature SREBP2 is released from membrane-bound precursors through proteolytic cleavage and enters the nucleus. However, regulation of the transcriptional activity of nuclear SREBP2 (nSREBP2) is poorly understood. In the present study, we reported that nSREBP2 forms nuclear condensates through its amino-terminal, intrinsically disordered region (IDR) and works together with transcription coactivators, partly on superenhancers, for the transcriptional activation of SREBP2 target genes. Substitution of a conserved phenylalanine by alanine within the IDR abolishes the formation of nSREBP2 condensates and reduces its transcriptional activity. This can be effectively rescued by fusion with a phase separation driving FUS-IDR. Knock-in of the phenylalanine-to-alanine substitution in male mice compromises feeding-induced nSREBP2 activity and lowers hepatic and circulating cholesterol levels, underscoring the functional significance of nSREBP2 condensates. Together, the present study reveals that nuclear condensates driven by nSREBP2 N-terminal IDR facilitate the efficient activation of lipogenic genes and play an important role in cholesterol homeostasis.</p>","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"38 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nature metabolismPub Date : 2025-05-19DOI: 10.1038/s42255-025-01293-y
Anastasia Tsyben, Andreas Dannhorn, Gregory Hamm, Manthos Pitoulias, Dominique-Laurent Couturier, Ashley Sawle, Mayen Briggs, Alan J. Wright, Cara Brodie, Lee Mendil, Jodi L. Miller, Eleanor C. Williams, Lovisa Franzén, Grand De Jong, Tannia Gracia, Fani Memi, Omer Ali Bayraktar, Ram Adapa, Jyotsna Rao, Ariadna González-Fernández, Josephine Bunch, Zoltan Takats, Simon T. Barry, Richard J. A. Goodwin, Richard Mair, Kevin M. Brindle
{"title":"Cell-intrinsic metabolic phenotypes identified in patients with glioblastoma, using mass spectrometry imaging of 13C-labelled glucose metabolism","authors":"Anastasia Tsyben, Andreas Dannhorn, Gregory Hamm, Manthos Pitoulias, Dominique-Laurent Couturier, Ashley Sawle, Mayen Briggs, Alan J. Wright, Cara Brodie, Lee Mendil, Jodi L. Miller, Eleanor C. Williams, Lovisa Franzén, Grand De Jong, Tannia Gracia, Fani Memi, Omer Ali Bayraktar, Ram Adapa, Jyotsna Rao, Ariadna González-Fernández, Josephine Bunch, Zoltan Takats, Simon T. Barry, Richard J. A. Goodwin, Richard Mair, Kevin M. Brindle","doi":"10.1038/s42255-025-01293-y","DOIUrl":"https://doi.org/10.1038/s42255-025-01293-y","url":null,"abstract":"<p>Transcriptomic studies have attempted to classify glioblastoma (GB) into subtypes that predict survival and have different therapeutic vulnerabilities<sup>1,2,3</sup>. Here we identified three metabolic subtypes: glycolytic, oxidative and a mix of glycolytic and oxidative, using mass spectrometry imaging of rapidly excised tumour sections from two patients with GB who were infused with [U-<sup>13</sup>C]glucose and from spatial transcriptomic analysis of contiguous sections. The phenotypes are not correlated with microenvironmental features, including proliferation rate, immune cell infiltration and vascularization, are retained when patient-derived cells are grown in vitro or as orthotopically implanted xenografts and are robust to changes in oxygen concentration, demonstrating their cell-intrinsic nature. The spatial extent of the regions occupied by cells displaying these distinct metabolic phenotypes is large enough to be detected using clinically applicable metabolic imaging techniques. A limitation of the study is that it is based on only two patient tumours, albeit on multiple sections, and therefore represents a proof-of-concept study.</p>","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"131 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nature metabolismPub Date : 2025-05-15DOI: 10.1038/s42255-025-01303-z
Sue C. Bodine, Craig A. Goodman
{"title":"Mechanically sensitive MAPK signalling mediates resistance exercise-induced muscle growth","authors":"Sue C. Bodine, Craig A. Goodman","doi":"10.1038/s42255-025-01303-z","DOIUrl":"https://doi.org/10.1038/s42255-025-01303-z","url":null,"abstract":"Understanding the molecular regulators of skeletal muscle mass is essential for the future development of therapies that promote muscle growth and/or inhibit muscle wasting. A new study shows that muscle-building resistance exercise in humans and mice activates a MAPK signalling pathway to increase protein synthesis and stimulate muscle hypertrophy.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"39 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nature metabolismPub Date : 2025-05-15DOI: 10.1038/s42255-025-01298-7
Wenyuan G. Zhu, Aaron C. Q. Thomas, Gary M. Wilson, Chris McGlory, Jamie E. Hibbert, Corey GK. Flynn, Ramy K. A. Sayed, Hector G. Paez, Marius Meinhold, Kent W. Jorgenson, Jae-Sung You, Nathaniel D. Steinert, Kuan-Hung Lin, Martin J. MacInnis, Joshua J. Coon, Stuart M. Phillips, Troy A. Hornberger
{"title":"Identification of a resistance-exercise-specific signalling pathway that drives skeletal muscle growth","authors":"Wenyuan G. Zhu, Aaron C. Q. Thomas, Gary M. Wilson, Chris McGlory, Jamie E. Hibbert, Corey GK. Flynn, Ramy K. A. Sayed, Hector G. Paez, Marius Meinhold, Kent W. Jorgenson, Jae-Sung You, Nathaniel D. Steinert, Kuan-Hung Lin, Martin J. MacInnis, Joshua J. Coon, Stuart M. Phillips, Troy A. Hornberger","doi":"10.1038/s42255-025-01298-7","DOIUrl":"https://doi.org/10.1038/s42255-025-01298-7","url":null,"abstract":"<p>Endurance and resistance exercise lead to distinct functional adaptations: the former increases aerobic capacity and the latter increases muscle mass. However, the signalling pathways that drive these adaptations are not well understood. Here we identify phosphorylation events that are differentially regulated by endurance and resistance exercise. Using a model of unilateral exercise in male participants and deep phosphoproteomic analyses, we find that a prolonged activation of a signalling pathway involving MKK3b/6, p38, MK2 and mTORC1 occurs specifically in response to resistance exercise. Follow-up studies in both male and female participants reveal that the resistance-exercise-induced activation of MKK3b is highly correlated with the induction of protein synthesis (<i>R</i> = 0.87). Additionally, we show that in mice, genetic activation of MKK3b is sufficient to induce signalling through p38, MK2 and mTORC1, along with an increase in protein synthesis and muscle fibre size. Overall, we identify core components of a signalling pathway that drives the growth-promoting effects of resistance exercise.</p>","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"115 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nature metabolismPub Date : 2025-05-13DOI: 10.1038/s42255-025-01296-9
Anne Loft, Margo P. Emont, Ada Weinstock, Adeline Divoux, Adhideb Ghosh, Allon Wagner, Ann V. Hertzel, Babukrishna Maniyadath, Bart Deplancke, Boxiang Liu, Camilla Scheele, Carey Lumeng, Changhai Ding, Chenkai Ma, Christian Wolfrum, Clarissa Strieder-Barboza, Congru Li, Danh D. Truong, David A. Bernlohr, Elisabet Stener-Victorin, Erin E. Kershaw, Esti Yeger-Lotem, Farnaz Shamsi, Hannah X. Hui, Henrique Camara, Jiawei Zhong, Joanna Kalucka, Joseph A. Ludwig, Julie A. Semon, Jutta Jalkanen, Katie L. Whytock, Kyle D. Dumont, Lauren M. Sparks, Lindsey A. Muir, Lingzhao Fang, Lucas Massier, Luis R. Saraiva, Marc D. Beyer, Marc G. Jeschke, Marcelo A. Mori, Mariana Boroni, Martin J. Walsh, Mary-Elizabeth Patti, Matthew D. Lynes, Matthias Blüher, Mikael Rydén, Natnael Hamda, Nicole L. Solimini, Niklas Mejhert, Peng Gao, Rana K. Gupta, Rinki Murphy, Saeed Pirouzpanah, Silvia Corvera, Su’an Tang, Swapan K. Das, Søren F. Schmidt, Tao Zhang, Theodore M. Nelson, Timothy E. O’Sullivan, Vissarion Efthymiou, Wenjing Wang, Yihan Tong, Yu-Hua Tseng, Susanne Mandrup, Evan D. Rosen
{"title":"Towards a consensus atlas of human and mouse adipose tissue at single-cell resolution","authors":"Anne Loft, Margo P. Emont, Ada Weinstock, Adeline Divoux, Adhideb Ghosh, Allon Wagner, Ann V. Hertzel, Babukrishna Maniyadath, Bart Deplancke, Boxiang Liu, Camilla Scheele, Carey Lumeng, Changhai Ding, Chenkai Ma, Christian Wolfrum, Clarissa Strieder-Barboza, Congru Li, Danh D. Truong, David A. Bernlohr, Elisabet Stener-Victorin, Erin E. Kershaw, Esti Yeger-Lotem, Farnaz Shamsi, Hannah X. Hui, Henrique Camara, Jiawei Zhong, Joanna Kalucka, Joseph A. Ludwig, Julie A. Semon, Jutta Jalkanen, Katie L. Whytock, Kyle D. Dumont, Lauren M. Sparks, Lindsey A. Muir, Lingzhao Fang, Lucas Massier, Luis R. Saraiva, Marc D. Beyer, Marc G. Jeschke, Marcelo A. Mori, Mariana Boroni, Martin J. Walsh, Mary-Elizabeth Patti, Matthew D. Lynes, Matthias Blüher, Mikael Rydén, Natnael Hamda, Nicole L. Solimini, Niklas Mejhert, Peng Gao, Rana K. Gupta, Rinki Murphy, Saeed Pirouzpanah, Silvia Corvera, Su’an Tang, Swapan K. Das, Søren F. Schmidt, Tao Zhang, Theodore M. Nelson, Timothy E. O’Sullivan, Vissarion Efthymiou, Wenjing Wang, Yihan Tong, Yu-Hua Tseng, Susanne Mandrup, Evan D. Rosen","doi":"10.1038/s42255-025-01296-9","DOIUrl":"https://doi.org/10.1038/s42255-025-01296-9","url":null,"abstract":"<p>Adipose tissue (AT) is a complex connective tissue with a high relative proportion of adipocytes, which are specialized cells with the ability to store lipids in large droplets. AT is found in multiple discrete depots throughout the body, where it serves as the primary repository for excess calories. In addition, AT has an important role in functions as diverse as insulation, immunity and regulation of metabolic homeostasis. The Human Cell Atlas Adipose Bionetwork was established to support the generation of single-cell atlases of human AT as well as the development of unified approaches and consensus for cell annotation. Here, we provide a first roadmap from this bionetwork, including our suggested cell annotations for humans and mice, with the aim of describing the state of the field and providing guidelines for the production, analysis, interpretation and presentation of AT single-cell data.</p>","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"12 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143940087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nature metabolismPub Date : 2025-05-13DOI: 10.1038/s42255-025-01276-z
Yu-San Kao, Mario Lauterbach, Aleksandra Lopez Krol, Ute Distler, Gloria Janet Godoy, Matthias Klein, Rafael Jose Argüello, Fatima Boukhallouk, Sara Vallejo Fuente, Kathrin Luise Braband, Assel Nurbekova, Monica Romero, Panagiota Mamareli, Luana Silva, Luis Eduardo Alves Damasceno, Francesca Rampoldi, Luciana Berod, Lydia Lynch, Karsten Hiller, Tim Sparwasser
{"title":"Metabolic reprogramming of interleukin-17-producing γδ T cells promotes ACC1-mediated de novo lipogenesis under psoriatic conditions","authors":"Yu-San Kao, Mario Lauterbach, Aleksandra Lopez Krol, Ute Distler, Gloria Janet Godoy, Matthias Klein, Rafael Jose Argüello, Fatima Boukhallouk, Sara Vallejo Fuente, Kathrin Luise Braband, Assel Nurbekova, Monica Romero, Panagiota Mamareli, Luana Silva, Luis Eduardo Alves Damasceno, Francesca Rampoldi, Luciana Berod, Lydia Lynch, Karsten Hiller, Tim Sparwasser","doi":"10.1038/s42255-025-01276-z","DOIUrl":"https://doi.org/10.1038/s42255-025-01276-z","url":null,"abstract":"<p>Metabolic reprogramming determines γδ T cell fate during thymic development; however, the metabolic requirements of interleukin (IL)-17A-producing γδ T cells (γδT17 cells) under psoriatic conditions are unclear. Combining high-throughput techniques, including RNA sequencing, SCENITH, proteomics and stable isotope tracing, we demonstrated that psoriatic inflammation caused γδT17 cells to switch toward aerobic glycolysis. Under psoriatic conditions, γδT17 cells upregulated ATP-citrate synthase to convert citrate to acetyl-CoA, linking carbohydrate metabolism and fatty acid synthesis (FAS). Accordingly, we used a pharmacological inhibitor, Soraphen A, which blocks acetyl-CoA carboxylase (ACC), to impair FAS in γδT17 cells, reducing their intracellular lipid stores and ability to produce IL-17A under psoriatic conditions in vitro. We pinpointed the pathogenic role of ACC1 in γδT17 cells in vivo by genetic ablation, ameliorating inflammation in a psoriatic mouse model. Furthermore, ACC inhibition limited human IL-17A-producing γδT17 cells. Targeting ACC1 to attenuate pathogenic γδT17 cell function has important implications for psoriasis management.</p>","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"55 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143940088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nature metabolismPub Date : 2025-05-13DOI: 10.1038/s42255-025-01308-8
Robert M Gutgesell, Ahmed Khalil, Arkadiusz Liskiewicz, Gandhari Maity-Kumar, Aaron Novikoff, Gerald Grandl, Daniela Liskiewicz, Callum Coupland, Ezgi Karaoglu, Seun Akindehin, Russell Castelino, Fabiola Curion, Xue Liu, Cristina Garcia-Caceres, Alberto Cebrian-Serrano, Jonathan D Douros, Patrick J Knerr, Brian Finan, Richard D DiMarchi, Kyle W Sloop, Ricardo J Samms, Fabian J Theis, Matthias H Tschöp, Timo D Müller
{"title":"Publisher Correction: GIPR agonism and antagonism decrease body weight and food intake via different mechanisms in male mice.","authors":"Robert M Gutgesell, Ahmed Khalil, Arkadiusz Liskiewicz, Gandhari Maity-Kumar, Aaron Novikoff, Gerald Grandl, Daniela Liskiewicz, Callum Coupland, Ezgi Karaoglu, Seun Akindehin, Russell Castelino, Fabiola Curion, Xue Liu, Cristina Garcia-Caceres, Alberto Cebrian-Serrano, Jonathan D Douros, Patrick J Knerr, Brian Finan, Richard D DiMarchi, Kyle W Sloop, Ricardo J Samms, Fabian J Theis, Matthias H Tschöp, Timo D Müller","doi":"10.1038/s42255-025-01308-8","DOIUrl":"10.1038/s42255-025-01308-8","url":null,"abstract":"","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":" ","pages":""},"PeriodicalIF":18.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nature metabolismPub Date : 2025-05-12DOI: 10.1038/s42255-025-01290-1
Stefan Schreiber, Georg H. Waetzig, Víctor A. López-Agudelo, Corinna Geisler, Kristina Schlicht, Sina Franzenburg, Romina di Giuseppe, Daniel Pape, Thomas Bahmer, Michael Krawczak, Elisabeth Kokott, Josef M. Penninger, Oliver Harzer, Jan Kramer, Tammo von Schrenck, Felix Sommer, Helena U. Zacharias, Belén Millet Pascual-Leone, Sofia K. Forslund, Jan Heyckendorf, Konrad Aden, Regina Hollweck, Matthias Laudes, Philip Rosenstiel
{"title":"Nicotinamide modulates gut microbial metabolic potential and accelerates recovery in mild-to-moderate COVID-19","authors":"Stefan Schreiber, Georg H. Waetzig, Víctor A. López-Agudelo, Corinna Geisler, Kristina Schlicht, Sina Franzenburg, Romina di Giuseppe, Daniel Pape, Thomas Bahmer, Michael Krawczak, Elisabeth Kokott, Josef M. Penninger, Oliver Harzer, Jan Kramer, Tammo von Schrenck, Felix Sommer, Helena U. Zacharias, Belén Millet Pascual-Leone, Sofia K. Forslund, Jan Heyckendorf, Konrad Aden, Regina Hollweck, Matthias Laudes, Philip Rosenstiel","doi":"10.1038/s42255-025-01290-1","DOIUrl":"https://doi.org/10.1038/s42255-025-01290-1","url":null,"abstract":"<p>Cellular NAD<sup>+</sup> depletion, altered tryptophan metabolism and gut microbiome dysbiosis are associated with disease progression and unfavourable clinical outcomes in COVID-19. Here, we show that supplementing tryptophan metabolism with nicotinamide alleviates COVID-19 symptoms. We evaluate a 4-week intervention with a novel nicotinamide formulation (1,000 mg) in a prospective, double-blind, randomized, placebo-controlled trial in 900 symptomatic outpatients with PCR-proven COVID-19. In the primary analysis population of participants at risk for severe COVID-19, 57.6% of those receiving nicotinamide and 42.6% receiving placebo recover from their performance drop at week 2 (<i>P</i> = 0.004). Nicotinamide is also beneficial for returning to normal activities (<i>P</i> = 0.009). Effects on gut metagenomic signatures parallel clinical efficacy, suggesting that nicotinamide influences COVID-19-associated faecal microbiome changes. After 6 months, responders to nicotinamide in acute COVID-19 show fewer post-COVID symptoms than placebo responders (<i>P</i> = 0.010). No relevant safety signals are observed. Overall, our results show that nicotinamide leads to faster recovery of physical performance and modulates COVID-19-associated faecal microbiome changes.</p>","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"137 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143933440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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