Preprints
Preprints of key researchers of our CoE – since 2024
Lee, Ui-Ju; Gwak, Joo-Han; Abiola, Christiana; Lee, Seongjun; Yu, Jin-Sun; Si, Ok-Ja; Cho, Hyo Je; Quan, Zhe-Xue; Kitzinger, Katharina; Daims, Holger; Wagner, Michael; Jung, Man-Young; Rhee, Sung-Keun
Kinetic Plasticity of Nitrite-Oxidizing Bacteria Containing Cytoplasmic Nitrite Oxidoreductase Unpublished
bioRxiv, 2025.
@unpublished{Lee2025b,
title = {Kinetic Plasticity of Nitrite-Oxidizing Bacteria Containing Cytoplasmic Nitrite Oxidoreductase},
author = {Ui-Ju Lee and Joo-Han Gwak and Christiana Abiola and Seongjun Lee and Jin-Sun Yu and Ok-Ja Si and Hyo Je Cho and Zhe-Xue Quan and Katharina Kitzinger and Holger Daims and Michael Wagner and Man-Young Jung and Sung-Keun Rhee},
url = {http://biorxiv.org/lookup/doi/10.1101/2025.07.31.663499},
doi = {10.1101/2025.07.31.663499},
year = {2025},
date = {2025-07-31},
urldate = {2025-07-31},
publisher = {Cold Spring Harbor Laboratory},
abstract = {<jats:title>Abstract</jats:title>
<jats:p>Nitrite oxidation, the second step of nitrification, is essential to the global nitrogen cycle. Nitrite-oxidizing bacteria (NOB) are classified into two groups based on the cellular localization of their key enzyme nitrite oxidoreductase (NXR): periplasmic (pNXR) and cytoplasmic (cNXR). The use of a cNXR by NOB has been reported to be linked to a lower nitrite affinity and energy efficiency of nitrite oxidation, indicating adaptation to nitrogen-rich environments. In this study, cNXR NOB model strains demonstrated nitrite concentration-dependent shifts in optimal growth pH, a behavior not observed in pNXR NOB. <jats:italic>Nitrobacter winogradskyi</jats:italic> Nb-255 (cNXR NOB), grown at 1 mM nitrite (pH 7.5), exhibited a high nitrite affinity in terms of apparent <jats:italic>K</jats:italic>
<jats:sub>m</jats:sub> (25.9 μM) and a high specific affinity <jats:italic>a°</jats:italic> (440.5 l g cells<jats:sup>−1</jats:sup> h<jats:sup>−1</jats:sup>), both comparable to pNXR NOB in microrespirometry-based kinetic assays. Unexpectedly, cells pre-grown at 10 mM nitrite (pH 7.5) achieved a pNXR-like affinity at pH 5.5 without prior adaptation to acidic conditions. In contrast, pNXR NOB exhibited consistent kinetic behavior across different pH conditions. Kinetic inhibition in the presence of nitrate suggested that this plasticity is driven by a regulated interplay between nitrite uniport and nitrite/nitrate antiporter systems. Our findings indicate that <jats:italic>Nitrobacter</jats:italic> can dynamically modulate nitrite affinity in response to both nitrite concentration and pH, conferring a flexible adaptation strategy that features traits of both <jats:italic>r</jats:italic>-and <jats:italic>K</jats:italic>-strategists across a range of environmental conditions. This adaptive plasticity likely extends to other cNXR-containing NOB in response to fluctuating environmental conditions.</jats:p>},
howpublished = {bioRxiv},
keywords = {},
pubstate = {published},
tppubtype = {unpublished}
}
<jats:p>Nitrite oxidation, the second step of nitrification, is essential to the global nitrogen cycle. Nitrite-oxidizing bacteria (NOB) are classified into two groups based on the cellular localization of their key enzyme nitrite oxidoreductase (NXR): periplasmic (pNXR) and cytoplasmic (cNXR). The use of a cNXR by NOB has been reported to be linked to a lower nitrite affinity and energy efficiency of nitrite oxidation, indicating adaptation to nitrogen-rich environments. In this study, cNXR NOB model strains demonstrated nitrite concentration-dependent shifts in optimal growth pH, a behavior not observed in pNXR NOB. <jats:italic>Nitrobacter winogradskyi</jats:italic> Nb-255 (cNXR NOB), grown at 1 mM nitrite (pH 7.5), exhibited a high nitrite affinity in terms of apparent <jats:italic>K</jats:italic>
<jats:sub>m</jats:sub> (25.9 μM) and a high specific affinity <jats:italic>a°</jats:italic> (440.5 l g cells<jats:sup>−1</jats:sup> h<jats:sup>−1</jats:sup>), both comparable to pNXR NOB in microrespirometry-based kinetic assays. Unexpectedly, cells pre-grown at 10 mM nitrite (pH 7.5) achieved a pNXR-like affinity at pH 5.5 without prior adaptation to acidic conditions. In contrast, pNXR NOB exhibited consistent kinetic behavior across different pH conditions. Kinetic inhibition in the presence of nitrate suggested that this plasticity is driven by a regulated interplay between nitrite uniport and nitrite/nitrate antiporter systems. Our findings indicate that <jats:italic>Nitrobacter</jats:italic> can dynamically modulate nitrite affinity in response to both nitrite concentration and pH, conferring a flexible adaptation strategy that features traits of both <jats:italic>r</jats:italic>-and <jats:italic>K</jats:italic>-strategists across a range of environmental conditions. This adaptive plasticity likely extends to other cNXR-containing NOB in response to fluctuating environmental conditions.</jats:p>
Gwak, Joo-Han; Olabisi, Adebisi; Lee, Ui-Ju; Abiola, Christiana; Lee, Seongjun; Do, Hackwon; Choi, Yun Ji; Lee, Jay-Jung; Jung, Man-Young; Jehmlich, Nico; von Bergen, Martin; Wagner, Michael; Awala, Samuel Imisi; Quan, Zhe-Xue; Rhee, Sung-Keun
Hypoosmolarity inhibits archaeal ammonia oxidation Unpublished
bioRxiv, 2025.
@unpublished{Gwak2025,
title = {Hypoosmolarity inhibits archaeal ammonia oxidation},
author = {Joo-Han Gwak and Adebisi Olabisi and Ui-Ju Lee and Christiana Abiola and Seongjun Lee and Hackwon Do and Yun Ji Choi and Jay-Jung Lee and Man-Young Jung and Nico Jehmlich and Martin von Bergen and Michael Wagner and Samuel Imisi Awala and Zhe-Xue Quan and Sung-Keun Rhee},
url = {http://biorxiv.org/lookup/doi/10.1101/2025.07.07.663500},
doi = {10.1101/2025.07.07.663500},
year = {2025},
date = {2025-07-07},
urldate = {2025-07-07},
publisher = {Cold Spring Harbor Laboratory},
abstract = {<jats:title>Abstract</jats:title>
<jats:p>Salinity strongly influences the physiology and distribution of nitrifying microorganisms, yet the effects of low salinity on them remain understudied. This study investigates the impact of hypoosmolarity on different groups of ammonia oxidizers in soil and lake environments, as well as in pure culture isolates. In soil microcosms amended with ammonium, at low salinity levels (∼120 μS/cm), comparable to values commonly found in pristine terrestrial and aquatic environments, the abundance of ammonia-oxidizing bacteria (AOB), dominated by <jats:italic>Nitrosomonas oligotropha</jats:italic>, significantly increased. In contrast, the growth of ammonia-oxidizing archaea (AOA), dominated by “<jats:italic>Ca.</jats:italic> Nitrosotenuis” of the <jats:italic>Nitrosopumilaceae</jats:italic> family, was stimulated by high salinity (∼760 μS/cm). In ammonium-fed lake microcosms, the abundance of AOB, dominated by <jats:italic>N. oligotropha,</jats:italic> significantly increased under both low (∼170 μS/cm) and high salinity (∼850 μS/cm) conditions. In the presence of allylthiourea, a bacterial nitrification inhibitor, AOA were sensitive to low salinity in both soil and lake microcosms. Consistently, pure culture studies revealed marked growth inhibition of AOA, especially members of <jats:italic>Nitrosopumilaceae</jats:italic>, under hypoosmolarity, unlike AOB and complete ammonia oxidizer (comammox) strains. Comparative genomic analyses with AOB and comammox, along with transcriptomic studies, suggested that the sensitivity of AOA to hypoosmolarity stress was possibly due to a lack of sophisticated osmoregulatory transport systems and their S-layer cell wall structure. Overall, this study highlights hypoosmolarity as a key factor shaping the ecological niches and distribution of ammonia oxidizers, as well as nitrification activities, in terrestrial and aquatic environments that are increasingly affected by intensified water cycles due to climate change.</jats:p>},
howpublished = {bioRxiv},
keywords = {},
pubstate = {published},
tppubtype = {unpublished}
}
<jats:p>Salinity strongly influences the physiology and distribution of nitrifying microorganisms, yet the effects of low salinity on them remain understudied. This study investigates the impact of hypoosmolarity on different groups of ammonia oxidizers in soil and lake environments, as well as in pure culture isolates. In soil microcosms amended with ammonium, at low salinity levels (∼120 μS/cm), comparable to values commonly found in pristine terrestrial and aquatic environments, the abundance of ammonia-oxidizing bacteria (AOB), dominated by <jats:italic>Nitrosomonas oligotropha</jats:italic>, significantly increased. In contrast, the growth of ammonia-oxidizing archaea (AOA), dominated by “<jats:italic>Ca.</jats:italic> Nitrosotenuis” of the <jats:italic>Nitrosopumilaceae</jats:italic> family, was stimulated by high salinity (∼760 μS/cm). In ammonium-fed lake microcosms, the abundance of AOB, dominated by <jats:italic>N. oligotropha,</jats:italic> significantly increased under both low (∼170 μS/cm) and high salinity (∼850 μS/cm) conditions. In the presence of allylthiourea, a bacterial nitrification inhibitor, AOA were sensitive to low salinity in both soil and lake microcosms. Consistently, pure culture studies revealed marked growth inhibition of AOA, especially members of <jats:italic>Nitrosopumilaceae</jats:italic>, under hypoosmolarity, unlike AOB and complete ammonia oxidizer (comammox) strains. Comparative genomic analyses with AOB and comammox, along with transcriptomic studies, suggested that the sensitivity of AOA to hypoosmolarity stress was possibly due to a lack of sophisticated osmoregulatory transport systems and their S-layer cell wall structure. Overall, this study highlights hypoosmolarity as a key factor shaping the ecological niches and distribution of ammonia oxidizers, as well as nitrification activities, in terrestrial and aquatic environments that are increasingly affected by intensified water cycles due to climate change.</jats:p>
Mohammadzadeh, Rokhsareh; Mahnert, Alexander; Zurabischvili, Tamara; Wink, Lisa; Kumpitsch, Christina; Habisch, Hansjoerg; Sprengel, Jannik; Filek, Klara; Mertelj, Polona; Pernitsch, Dominique; Hingerl, Kerstin; Gorkiewicz, Gregor; Diener, Christian; Loy, Alexander; Kolb, Dagmar; Trautwein, Christoph; Madl, Tobias; Moissl-Eichinger, Christine
Methanobrevibacter smithiiassociates with colorectal cancer through trophic control of the cancer bacteriome Unpublished
bioRxiv, 2025.
@unpublished{Mohammadzadeh2025b,
title = {\textit{Methanobrevibacter smithii}associates with colorectal cancer through trophic control of the cancer bacteriome},
author = {Rokhsareh Mohammadzadeh and Alexander Mahnert and Tamara Zurabischvili and Lisa Wink and Christina Kumpitsch and Hansjoerg Habisch and Jannik Sprengel and Klara Filek and Polona Mertelj and Dominique Pernitsch and Kerstin Hingerl and Gregor Gorkiewicz and Christian Diener and Alexander Loy and Dagmar Kolb and Christoph Trautwein and Tobias Madl and Christine Moissl-Eichinger},
url = {http://biorxiv.org/lookup/doi/10.1101/2025.06.12.659283},
doi = {10.1101/2025.06.12.659283},
year = {2025},
date = {2025-06-12},
urldate = {2025-06-12},
publisher = {Cold Spring Harbor Laboratory},
abstract = {<jats:title>Summary</jats:title><jats:p>The human gut is colonized by trillions of microbes that influence the health of their human host. Whereas many bacterial species have now been linked to a variety of different diseases, the involvement of Archaea in human disease remains elusive. Here we searched for gut archaeal signatures of disease by screening 19 cross-sectional clinical studies comprising more than 1,800 individuals. We found that associations between Archaea and medical disorders are common but highly variable and are dominated by a significant increase of<jats:italic>Methanobrevibacter smithii</jats:italic>in colorectal cancer (CRC) patients. Metabolic modelling and<jats:italic>in vitro</jats:italic>co-culture identified distinct mutualistic interactions of<jats:italic>M. smithii</jats:italic>with CRC-causing bacteria such as<jats:italic>Fusobacterium nucleatum</jats:italic>, including metabolic enhancement. Metabolomics further revealed archaeal-derived compounds with tumor-modulating properties. This provides the first mechanistic link between human gut archaeome and CRC and highlights its role in modulating health in humans through trophic control of the resident bacteriome.</jats:p>},
howpublished = {bioRxiv},
keywords = {},
pubstate = {published},
tppubtype = {unpublished}
}
Krasenbrink, Julia; Chen, Song-Can; Tanabe, Tomohisa Sebastian; Sarikece, Huseyin; Meurs, Pleun; Borusak, Sabrina; Samrat, Rahul; Osvatic, Jay; Seneca, Joana; Hausmann, Bela; Speth, Daan R; Selberherr, Evelyne; Wanek, Wolfgang; Schleheck, David; Mussmann, Marc; Loy, Alexander
Extensive richness and novel taxa of sulfoquinovose-degrading bacteria in the cow rumen Unpublished
bioRxiv, 2025.
@unpublished{Krasenbrink2025b,
title = {Extensive richness and novel taxa of sulfoquinovose-degrading bacteria in the cow rumen},
author = {Julia Krasenbrink and Song-Can Chen and Tomohisa Sebastian Tanabe and Huseyin Sarikece and Pleun Meurs and Sabrina Borusak and Rahul Samrat and Jay Osvatic and Joana Seneca and Bela Hausmann and Daan R Speth and Evelyne Selberherr and Wolfgang Wanek and David Schleheck and Marc Mussmann and Alexander Loy},
url = {http://biorxiv.org/lookup/doi/10.1101/2025.05.20.655074},
doi = {10.1101/2025.05.20.655074},
year = {2025},
date = {2025-05-20},
urldate = {2025-05-20},
publisher = {Cold Spring Harbor Laboratory},
abstract = {<jats:p>Sulfoquinovose (SQ), a sulfonated sugar derived from the thylakoid membrane lipid sulfoquinovosyl diacylglycerol (SQDG), is abundant in photosynthetic organisms and plays a key role in global sulfur cycling. Its degradation in nature is mediated by specialized bacteria, many of which rely on the enzyme sulfoquinovosidase (YihQ) to release SQ from SQDG. Despite its ecological importance, the diversity and functional roles of SQ-degrading microorganisms remain poorly characterized in natural environments. Here, we developed a yihQ-targeted amplicon sequencing approach to investigate the richness and distribution of SQ-degrading bacteria across selected environments, including marine sediments and the mammalian gut. We revealed particularly high richness of yihQ-containing microorganisms in cow rumen, far exceeding that observed in human and mouse gut microbiomes, suggesting an important role of SQ metabolism in ruminant digestion. Anaerobic microcosm experiments with SQ-amended rumen fluid revealed cooperative microbial degradation of SQ to sulfide via isethionate cross-feeding. Amplicon sequencing and genome-resolved metagenomics identified novel uncultured SQ-degrading taxa, including members of Caproiciproducens (Acutalibacteraceae), Limivicinus (Oscillospiraceae), and Sphaerochaetaceae, which encode the sulfo-transketolase pathway, along with Mailhella (Desulfovibrionaceae), a likely isethionate-respiring bacterium. This study presents the first functional gene-based assay for tracking environmental yihQ diversity, highlights SQ degradation as a central metabolic process in the cow rumen, describes novel SQ-metabolizing bacteria, and advances understanding of sulfur physiology in complex microbial communities.</jats:p>},
howpublished = {bioRxiv},
keywords = {},
pubstate = {published},
tppubtype = {unpublished}
}
Ye, Huimin; Šlipogor, Vedrana; Hanson, Buck T.; Séneca, Joana; Hausmann, Bela; Herbold, Craig W.; Pjevac, Petra; Bugnyar, Thomas; Loy, Alexander
bioRxiv, 2025.
@unpublished{Ye2025,
title = {Associations between gut microbiota and personality traits: insights from a captive common marmoset (\textit{Callithrix jacchus}) colony},
author = {Huimin Ye and Vedrana Šlipogor and Buck T. Hanson and Joana Séneca and Bela Hausmann and Craig W. Herbold and Petra Pjevac and Thomas Bugnyar and Alexander Loy},
url = {http://biorxiv.org/lookup/doi/10.1101/2025.02.12.637913},
doi = {10.1101/2025.02.12.637913},
year = {2025},
date = {2025-02-13},
urldate = {2025-02-13},
publisher = {Cold Spring Harbor Laboratory},
abstract = {<jats:title>Abstract</jats:title><jats:p>Recent studies have suggested the link between inter-individual behavioural variation (i.e., animal personality) and gut microbiota. Non-human primates living under controlled conditions are valuable models to investigate diet-independent microbiome-host interactions. In this study, we investigated links between specific gut microbiota members and personality traits, as well as group membership, sex, age class, breeding status and relatedness of 26 captive common marmosets (<jats:italic>Callithrix jacchus</jats:italic>), maintained under the same diet and housing conditions. Personality was assessed using an established testing battery in repeated tests. Then, we collected a total of 225 fecal samples during the summers of 2017 and 2019 from five marmoset social groups for 16S rRNA gene amplicon sequencing. Within-individual microbiota variance was smaller than that between group members. Group members also exhibited more similar gut microbiota than individuals from different groups in each sampling year. Beta diversity of the gut microbiota was linked with personality traits, age class, sex, and breeding status, but not with genetic relatedness. We identified specific bacterial taxa associated with personality traits. In particular, members of the sulfite-reducing genera<jats:italic>Desulfovibrio</jats:italic>were enriched in more avoidant marmosets. Amplicon sequencing of the dissimilatory sulfite reductase gene<jats:italic>dsrB</jats:italic>confirmed this pattern, yet additionally revealed an unknown uncultured bacterium that was the predominant sulfite-reducing bacterium in the fecal samples and was linked to more explorative individuals. These findings highlight specific association patterns between selected microbial taxa and personality traits in captive common marmosets.</jats:p><jats:sec><jats:title>Importance</jats:title><jats:p>This study provides valuable insights into the intricate relationship between gut microbiota and host personality traits, using captive common marmosets as a model. By controlling for diet and housing conditions, it probes key host factors such as personality, age, sex, and social group membership, offering a robust framework for understanding microbiome-host interactions. The discovery of specific microbial taxa associated with personality traits, particularly the enrichment of sulfite-reducing genera in more avoidant individuals, underscores the potential role of the gut microbiome in shaping or reflecting personality. These findings advance our understanding of microbiome-host dynamics and pave the way for future research on the mechanistic links between behavior and gut microbiota in other animal models and across broader ecological contexts.</jats:p></jats:sec>},
howpublished = {bioRxiv},
keywords = {},
pubstate = {published},
tppubtype = {unpublished}
}
Bayer, Barbara; Kitzinger, Katharina; Paul, Nicola L; Albers, Justine B; Saito, Mak A; Wagner, Michael; Carlson, Craig A; Santoro, Alyson E
Contribution of ammonia oxidizers to inorganic carbon fixation in the dark ocean Unpublished
bioRxiv, 2024.
@unpublished{Bayer2024,
title = {Contribution of ammonia oxidizers to inorganic carbon fixation in the dark ocean},
author = {Barbara Bayer and Katharina Kitzinger and Nicola L Paul and Justine B Albers and Mak A Saito and Michael Wagner and Craig A Carlson and Alyson E Santoro},
url = {http://biorxiv.org/lookup/doi/10.1101/2024.11.16.623942},
doi = {10.1101/2024.11.16.623942},
year = {2024},
date = {2024-11-16},
urldate = {2024-11-16},
publisher = {Cold Spring Harbor Laboratory},
abstract = {<jats:p>Ammonia-oxidizing archaea are the most abundant chemolithoautotrophs in the ocean, comprising up to 40% of microbial cells in deep waters, and are assumed to dominate dissolved inorganic carbon (DIC) fixation below the sunlit surface layer. Yet, the supply of reduced nitrogen from particulate organic matter flux from the surface is insufficient to support the amount of nitrification required to sustain measured DIC fixation rates in the dark ocean. The aim of this study was to quantify the contribution of ammonia oxidizers to DIC fixation in the dark ocean. We used phenylacetylene - a specific inhibitor of the ammonia monooxygenase enzyme - to selectively inhibit ammonia oxidizers during two oceanographic expeditions in the eastern tropical and subtropical Pacific Ocean spanning 35° N to 10° S. We show that ammonia oxidizers contribute only a small fraction to dark DIC fixation, accounting for 2 to 22% of the depth-integrated rates in the eastern tropical Pacific, challenging the current view that dark DIC fixation is primarily sustained by nitrification. The highest contributions were observed at the depth of the nitrification maximum, where ammonia oxidation could account for up to 50% of dark DIC fixation. Our results help to reconcile the observed discrepancies between nitrogen supply and DIC fixation at depth, and provide a new perspective on global ocean chemolithoautotrophy, revealing that the majority of DIC fixation within the lower euphotic zone and below 200 m depth is not fueled by ammonia oxidation.</jats:p>},
howpublished = {bioRxiv},
keywords = {},
pubstate = {published},
tppubtype = {unpublished}
}
Mahnert, Alexander; Dreer, Maximilian; Perier, Uelkue; Melcher, Michael; Duller, Stefanie; Lehnen, Adina; Goessler, Theodora; Brunner, Daniela; Graier, Thomas; Wolf, Peter; Ponce-Toledo, Rafael Isaac; Hodgskiss, Logan; Kerou, Melina; Moissl-Eichinger, Christine; Schleper, Christa
bioRxiv, 2024.
@unpublished{Mahnert2024b,
title = {Molecular Tracking and Cultivation Reveal Ammonia Oxidizing Archaea as Integral Members of the Human Skin Microbiome},
author = {Alexander Mahnert and Maximilian Dreer and Uelkue Perier and Michael Melcher and Stefanie Duller and Adina Lehnen and Theodora Goessler and Daniela Brunner and Thomas Graier and Peter Wolf and Rafael Isaac Ponce-Toledo and Logan Hodgskiss and Melina Kerou and Christine Moissl-Eichinger and Christa Schleper},
url = {http://biorxiv.org/lookup/doi/10.1101/2024.08.05.606590},
doi = {10.1101/2024.08.05.606590},
year = {2024},
date = {2024-08-05},
urldate = {2024-08-05},
publisher = {Cold Spring Harbor Laboratory},
abstract = {<jats:p>Ammonia oxidizing archaea (AOA) have been repeatedly detected in the human skin microbiome through molecular and biochemical analyses, yet their persistence, physiology, and adaptations remain poorly understood. Here, we describe two cultivated strains, Candidatus Nitrosocosmicus epidermidis and Ca. Nitrosocosmicus unguis, enriched from human skin samples. These autotrophic strains grow on ammonia and urea as sole energy sources. Genomic islands and expanded gene families in their genomes testify to the capacity of colonizing skin, including specific interactions with host proteins and signaling cascades that distinguish these AOA from their close relatives from soil. Molecular signatures of Nitrosocosmicus ssp. were consistently identified on individuals in cross-sectional and longitudinal cohorts (n=47) with a higher prevalence in sebaceous areas. Co-occurrence network patterns with specific bacteria reinforce the observation that AOA of the genus Nitrosocosmicus form a stable component of the healthy skin and represent emerging commensals in the human microbiome.</jats:p>},
howpublished = {bioRxiv},
keywords = {},
pubstate = {published},
tppubtype = {unpublished}
}
Kane, Alice E; Chellappa, Karthikeyani; Schultz, Michael B; Arnold, Matthew; Li, Jien; Amorim, Joao; Diener, Christian; Zhu, Dantong; Mitchell, Sarah J; Griffin, Patrick; Tian, Xiao; Petty, Christopher; Conway, Ryan; Walsh, Katie; Shelerud, Lukas; Duesing, Charlotte; Mueller, Amber; Li, Karlin; McNamara, Maeve; Shima, Rafaella T; Mitchell, James; Bonkowski, Michael S; de Cabo, Rafael; Gibbons, Sean M; Wu, Lindsay E; Ikeno, Yuji; Baur, Joseph A; Rajman, Luis; Sinclair, David A
Long-term NMN treatment increases lifespan and healthspan in mice in a sex dependent manner Journal Article
In: bioRxiv, 2024, ISSN: 2692-8205.
@article{pmid38979132,
title = {Long-term NMN treatment increases lifespan and healthspan in mice in a sex dependent manner},
author = {Alice E Kane and Karthikeyani Chellappa and Michael B Schultz and Matthew Arnold and Jien Li and Joao Amorim and Christian Diener and Dantong Zhu and Sarah J Mitchell and Patrick Griffin and Xiao Tian and Christopher Petty and Ryan Conway and Katie Walsh and Lukas Shelerud and Charlotte Duesing and Amber Mueller and Karlin Li and Maeve McNamara and Rafaella T Shima and James Mitchell and Michael S Bonkowski and Rafael de Cabo and Sean M Gibbons and Lindsay E Wu and Yuji Ikeno and Joseph A Baur and Luis Rajman and David A Sinclair},
doi = {10.1101/2024.06.21.599604},
issn = {2692-8205},
year = {2024},
date = {2024-06-01},
urldate = {2024-06-01},
journal = {bioRxiv},
abstract = {Nicotinamide adenine dinucleotide (NAD) is essential for many enzymatic reactions, including those involved in energy metabolism, DNA repair and the activity of sirtuins, a family of defensive deacylases. During aging, levels of NAD can decrease by up to 50% in some tissues, the repletion of which provides a range of health benefits in both mice and humans. Whether or not the NAD precursor nicotinamide mononucleotide (NMN) extends lifespan in mammals is not known. Here we investigate the effect of long-term administration of NMN on the health, cancer burden, frailty and lifespan of male and female mice. Without increasing tumor counts or severity in any tissue, NMN treatment of males and females increased activity, maintained more youthful gene expression patterns, and reduced overall frailty. Reduced frailty with NMN treatment was associated with increases in levels of a gut bacterium associated with lower inflammation in mice and increased longevity in humans. NMN slowed the accumulation of adipose tissue later in life and improved metabolic health in male but not female mice, while in females but not males, NMN increased median lifespan by 8.5%, possible due to sex-specific effects of NMN on NAD metabolism. Together, these data show that chronic NMN treatment delays frailty, alters the microbiome, improves male metabolic health, and increases female mouse lifespan, without increasing cancer burden. These results highlight the potential of NAD boosters for treating age-related conditions and the importance of using both sexes for interventional lifespan studies.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Carr, Alex; Baliga, Nitin S; Diener, Christian; Gibbons, Sean M
Personalized Clostridioides difficile engraftment risk prediction and probiotic therapy assessment in the human gut Miscellaneous
2024, ISSN: 2692-8205.
@misc{pmid37162960,
title = {Personalized Clostridioides difficile engraftment risk prediction and probiotic therapy assessment in the human gut},
author = {Alex Carr and Nitin S Baliga and Christian Diener and Sean M Gibbons},
doi = {10.1101/2023.04.28.538771},
issn = {2692-8205},
year = {2024},
date = {2024-01-01},
urldate = {2024-01-01},
journal = {bioRxiv},
abstract = { colonizes up to 30-40% of community-dwelling adults without causing disease. infections (CDIs) are the leading cause of antibiotic-associated diarrhea in the U.S. and typically develop in individuals following disruption of the gut microbiota due to antibiotic or chemotherapy treatments. Further treatment of CDI with antibiotics is not always effective and can lead to antibiotic resistance and recurrent infections (rCDI). The most effective treatment for rCDI is the reestablishment of an intact microbiota via fecal microbiota transplants (FMTs). However, the success of FMTs has been difficult to generalize because the microbial interactions that prevent engraftment and facilitate the successful clearance of are still only partially understood. Here we show how microbial community-scale metabolic models (MCMMs) accurately predicted known instances of colonization susceptibility or resistance and . MCMMs provide detailed mechanistic insights into the ecological interactions that govern engraftment, like cross-feeding or competition involving metabolites like succinate, trehalose, and ornithine, which differ from person to person. Indeed, three distinct metabolic niches emerge from our MCMMs, two associated with positive growth rates and one that represents non-growth, which are consistently observed across 15,204 individuals from five independent cohorts. Finally, we show how MCMMs can predict personalized engraftment and growth suppression for a probiotic cocktail (VE303) designed to replace FMTs for the treatment rCDI. Overall, this powerful modeling approach predicts personalized engraftment risk and can be leveraged to assess probiotic treatment efficacy. MCMMs could be extended to understand the mechanistic underpinnings of personalized engraftment of other opportunistic bacterial pathogens, beneficial probiotic organisms, or more complex microbial consortia.},
keywords = {},
pubstate = {published},
tppubtype = {misc}
}