Preprints
Preprints of key researchers of our CoE -2024
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Contribution of ammonia oxidizers to inorganic carbon fixation in the dark ocean Unpublished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@unpublished{Bayer2024,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tppubtype = {unpublished}
}
<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>
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}
}
<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>
Neumann, Charlotte Julia; Mohammadzadeh, Rokhsareh; Woh, Pei Yee; Kobal, Tanja; Pausan, Manuela-Raluca; Shinde, Tejus; Haid, Victoria; Mertelj, Polona; Mahnert, Alexander; Kumpitsch, Christina; Jantscher-Krenn, Evelyn; Moissl-Eichinger, Christine
First-Year Dynamics of the Anaerobic Microbiome and Archaeome in Infants Oral and Gastrointestinal Systems Unpublished
bioRxiv, 2024.
@unpublished{Neumann2024,
title = {First-Year Dynamics of the Anaerobic Microbiome and Archaeome in Infants Oral and Gastrointestinal Systems},
author = {Charlotte Julia Neumann and Rokhsareh Mohammadzadeh and Pei Yee Woh and Tanja Kobal and Manuela-Raluca Pausan and Tejus Shinde and Victoria Haid and Polona Mertelj and Alexander Mahnert and Christina Kumpitsch and Evelyn Jantscher-Krenn and Christine Moissl-Eichinger},
url = {http://biorxiv.org/lookup/doi/10.1101/2024.07.24.604926},
doi = {10.1101/2024.07.24.604926},
year = {2024},
date = {2024-07-24},
urldate = {2024-07-24},
publisher = {Cold Spring Harbor Laboratory},
abstract = {<jats:p>Recent research provides new insights into the early establishment of the infant gut microbiome, emphasizing the influence of breastfeeding on the development of gastrointestinal (GIT) microbiomes. In our study, we longitudinally examined the taxonomic and functional dynamics of the oral and GIT microbiomes of healthy infants (n=30) in their first year, focusing on the often over-looked aspects, the development of archaeal and anaerobic microbiomes. Breastfed (BF) infants exhibit a more defined transitional phase in their oral microbiome compared to non-breastfed (NBF) infants, marked by a decrease in Streptococcus and the emergence of anaerobic genera such as Granulicatella. This phase, characterized by increased alpha diversity and significant changes in beta diversity, occurs earlier in NBF infants (months 1-3) than in BF infants (months 4-6), suggesting that breastfeeding supports later, more defined microbiome maturation. We demonstrated the presence of archaea in the infant oral cavity and GIT microbiome from early infancy, with Methanobrevibacter being the predominant genus. Still, transient patterns show that no stable archaeome is formed. The GIT microbiome exhibited gradual development, with BF infants showing increased diversity and complexity between months 3 and 8, marked by anaerobic microbial networks. NBF infants displayed complex microbial cooccurrence patterns from the start. Those strong differences between BF and NBF infants GIT microbiomes are less pronounced on functional levels than on taxonomic level. Overall, the infant microbiome differentiates and stabilizes over the first year, with breastfeeding playing a crucial role in shaping anaerobic microbial networks and overall microbiome maturation.</jats:p>},
howpublished = {bioRxiv},
keywords = {},
pubstate = {published},
tppubtype = {unpublished}
}
<jats:p>Recent research provides new insights into the early establishment of the infant gut microbiome, emphasizing the influence of breastfeeding on the development of gastrointestinal (GIT) microbiomes. In our study, we longitudinally examined the taxonomic and functional dynamics of the oral and GIT microbiomes of healthy infants (n=30) in their first year, focusing on the often over-looked aspects, the development of archaeal and anaerobic microbiomes. Breastfed (BF) infants exhibit a more defined transitional phase in their oral microbiome compared to non-breastfed (NBF) infants, marked by a decrease in Streptococcus and the emergence of anaerobic genera such as Granulicatella. This phase, characterized by increased alpha diversity and significant changes in beta diversity, occurs earlier in NBF infants (months 1-3) than in BF infants (months 4-6), suggesting that breastfeeding supports later, more defined microbiome maturation. We demonstrated the presence of archaea in the infant oral cavity and GIT microbiome from early infancy, with Methanobrevibacter being the predominant genus. Still, transient patterns show that no stable archaeome is formed. The GIT microbiome exhibited gradual development, with BF infants showing increased diversity and complexity between months 3 and 8, marked by anaerobic microbial networks. NBF infants displayed complex microbial cooccurrence patterns from the start. Those strong differences between BF and NBF infants GIT microbiomes are less pronounced on functional levels than on taxonomic level. Overall, the infant microbiome differentiates and stabilizes over the first year, with breastfeeding playing a crucial role in shaping anaerobic microbial networks and overall microbiome maturation.</jats:p>
Weinberger, Viktoria; Darnhofer, Barbara; Mertelj, Polona; Stentz, Regis; Thapa, Himadri B; Jones, Emily; Grabmann, Gerlinde; Mohammadzadeh, Rokhsareh; Shinde, Tejus; Juodeikis, Rokas; Pernitsch, Dominique; Hingerl, Kerstin; Zurabishvili, Tamara; Kumpitsch, Christina; Kuehnast, Torben; Kolb, Dagmar; Gotts, Kathryn; Weichhart, Thomas; Köcher, Thomas; Köfeler, Harald; Carding, Simon R.; Schild, Stefan; Moissl-Eichinger, Christine
Proteomic and Metabolomic Profiling of Archaeal Extracellular Vesicles from the Human Gut Unpublished
bioRxiv, 2024.
@unpublished{Weinberger2024,
title = {Proteomic and Metabolomic Profiling of Archaeal Extracellular Vesicles from the Human Gut},
author = {Viktoria Weinberger and Barbara Darnhofer and Polona Mertelj and Regis Stentz and Himadri B Thapa and Emily Jones and Gerlinde Grabmann and Rokhsareh Mohammadzadeh and Tejus Shinde and Rokas Juodeikis and Dominique Pernitsch and Kerstin Hingerl and Tamara Zurabishvili and Christina Kumpitsch and Torben Kuehnast and Dagmar Kolb and Kathryn Gotts and Thomas Weichhart and Thomas Köcher and Harald Köfeler and Simon R. Carding and Stefan Schild and Christine Moissl-Eichinger},
url = {http://biorxiv.org/lookup/doi/10.1101/2024.06.22.600174},
doi = {10.1101/2024.06.22.600174},
year = {2024},
date = {2024-06-22},
urldate = {2024-06-22},
publisher = {Cold Spring Harbor Laboratory},
abstract = {<jats:title>Abstract</jats:title><jats:p>One potential mechanism for microbiome-host, and microbiome constituents’ interaction and communication involves extracellular vesicles (EVs). Here, for the first time, we report the capability of two M. smithii strains (ALI and GRAZ-2), Candidatus M. intestini, and Methanosphaera stadtmanae, as underrepresented components of the gut microbiome, to produce EVs. Interesting, size, morphology, and composition of AEVs were comparable to bacterial EVs, as indicated by ultrastructure, composition, proteomic and metabolomic analyses; however, EVs were substantially less prevalent in the studied Archaea. When looking at the proteomics more precisely, although AEVs from M. smithii ALI and M. intestini were found to be carrying unique proteins (n=135 and n=30, respectively), the shared proteins in AEVs within this genus (n=229), were mostly adhesins(/like) proteins, or proteins with IG-like domains. One remarkable observation was the uptake of AEVs obtained from Methanosphaera stadtmanae and the studied Methanobrevibacter species by human monocytes and the subsequent IL-8 secretion.</jats:p>},
howpublished = {bioRxiv},
keywords = {},
pubstate = {published},
tppubtype = {unpublished}
}
<jats:title>Abstract</jats:title><jats:p>One potential mechanism for microbiome-host, and microbiome constituents’ interaction and communication involves extracellular vesicles (EVs). Here, for the first time, we report the capability of two M. smithii strains (ALI and GRAZ-2), Candidatus M. intestini, and Methanosphaera stadtmanae, as underrepresented components of the gut microbiome, to produce EVs. Interesting, size, morphology, and composition of AEVs were comparable to bacterial EVs, as indicated by ultrastructure, composition, proteomic and metabolomic analyses; however, EVs were substantially less prevalent in the studied Archaea. When looking at the proteomics more precisely, although AEVs from M. smithii ALI and M. intestini were found to be carrying unique proteins (n=135 and n=30, respectively), the shared proteins in AEVs within this genus (n=229), were mostly adhesins(/like) proteins, or proteins with IG-like domains. One remarkable observation was the uptake of AEVs obtained from Methanosphaera stadtmanae and the studied Methanobrevibacter species by human monocytes and the subsequent IL-8 secretion.</jats:p>
Birner-Gruenberger, Ruth; Tomin, Tamara; Honeder, Sophie; Liesinger, Laura; Gremel, Daniela; Retzl, Bermhard; Lindenmann, Joerg; Brcic, Luka; Schittmayer, Matthias
Research Square, 2024.
@unpublished{Birner-Gruenberger2024,
title = {Active Oxidative Metabolism and Impaired Glyoxalase System Under Increased Intracellular Oxidative Stress in Non-Small Cell Lung Cancer},
author = {Ruth Birner-Gruenberger and Tamara Tomin and Sophie Honeder and Laura Liesinger and Daniela Gremel and Bermhard Retzl and Joerg Lindenmann and Luka Brcic and Matthias Schittmayer},
url = {https://www.researchsquare.com/article/rs-4535848/v1},
doi = {10.21203/rs.3.rs-4535848/v1},
year = {2024},
date = {2024-06-19},
urldate = {2024-06-19},
publisher = {Research Square Platform LLC},
abstract = {<title>Abstract</title>
<p>Reactive oxygen species can oxidatively modify enzymes to reroute metabolic pathways according to tumor needs but we lack overview of all potential targets. Thiol groups are most susceptible to oxidative modifications but rarely analyzed in clinical settings due to their reactivity. To accurately address the cross-talk between redox signaling and metabolism we collected tumor and healthy tissue from 70 individuals with non-small cell lung cancer right after surgery into a thiol-quenching solution, then carried out redox-proteomics. As a result of such an unbiased approach, we for the first time show evidence of higher oxidation of a number of key metabolic enzymes in tumor (especially glucose-related); we demonstrate that cancer strives to maintain oxidative metabolism amid the rise of intracellular oxidative stress; and report both redox and protein level deactivation of the glyoxalase system, which might be compensated by higher excretion or lower production of toxic methylglyoxal, aiding cancer progression.</p>},
howpublished = {Research Square},
keywords = {},
pubstate = {published},
tppubtype = {unpublished}
}
<title>Abstract</title>
<p>Reactive oxygen species can oxidatively modify enzymes to reroute metabolic pathways according to tumor needs but we lack overview of all potential targets. Thiol groups are most susceptible to oxidative modifications but rarely analyzed in clinical settings due to their reactivity. To accurately address the cross-talk between redox signaling and metabolism we collected tumor and healthy tissue from 70 individuals with non-small cell lung cancer right after surgery into a thiol-quenching solution, then carried out redox-proteomics. As a result of such an unbiased approach, we for the first time show evidence of higher oxidation of a number of key metabolic enzymes in tumor (especially glucose-related); we demonstrate that cancer strives to maintain oxidative metabolism amid the rise of intracellular oxidative stress; and report both redox and protein level deactivation of the glyoxalase system, which might be compensated by higher excretion or lower production of toxic methylglyoxal, aiding cancer progression.</p>
<p>Reactive oxygen species can oxidatively modify enzymes to reroute metabolic pathways according to tumor needs but we lack overview of all potential targets. Thiol groups are most susceptible to oxidative modifications but rarely analyzed in clinical settings due to their reactivity. To accurately address the cross-talk between redox signaling and metabolism we collected tumor and healthy tissue from 70 individuals with non-small cell lung cancer right after surgery into a thiol-quenching solution, then carried out redox-proteomics. As a result of such an unbiased approach, we for the first time show evidence of higher oxidation of a number of key metabolic enzymes in tumor (especially glucose-related); we demonstrate that cancer strives to maintain oxidative metabolism amid the rise of intracellular oxidative stress; and report both redox and protein level deactivation of the glyoxalase system, which might be compensated by higher excretion or lower production of toxic methylglyoxal, aiding cancer progression.</p>
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}
}
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.
Weinberger, Viktoria; Mohammadzadeh, Rokhsareh; Blohs, Marcus; Kalt, Kerstin; Mahnert, Alexander; Moser, Sarah; Cecovini, Marina; Mertelj, Polona; Zurabishvili, Tamara; Wolf, Jacqueline; Shinde, Tejus; Madl, Tobias; Habisch, Hansjörg; Kolb, Dagmar; Pernitsch, Dominique; Hingerl, Kerstin; Metcalf, William; Moissl-Eichinger, Christine
bioRxiv, 2024.
@unpublished{Weinberger2024b,
title = {Expanding the cultivable human archaeome: Methanobrevibacter intestini sp. nov. and strain Methanobrevibacter smithii “GRAZ-2” from human feces},
author = {Viktoria Weinberger and Rokhsareh Mohammadzadeh and Marcus Blohs and Kerstin Kalt and Alexander Mahnert and Sarah Moser and Marina Cecovini and Polona Mertelj and Tamara Zurabishvili and Jacqueline Wolf and Tejus Shinde and Tobias Madl and Hansjörg Habisch and Dagmar Kolb and Dominique Pernitsch and Kerstin Hingerl and William Metcalf and Christine Moissl-Eichinger},
url = {http://biorxiv.org/lookup/doi/10.1101/2024.05.15.594450},
doi = {10.1101/2024.05.15.594450},
year = {2024},
date = {2024-05-16},
urldate = {2024-05-16},
publisher = {Cold Spring Harbor Laboratory},
abstract = {<jats:title>Abstract</jats:title><jats:p>Two mesophilic, hydrogenotrophic methanogens, WWM1085 and<jats:italic>M. smithii</jats:italic>GRAZ-2 were isolated from human fecal samples. WWM1085 was isolated from an individual in the USA, and represents a novel species with in the genus<jats:italic>Methanobrevibacter</jats:italic>.<jats:italic>M. smithii</jats:italic>GRAZ-2 (= DSM 116045) was retrieved from fecal samples of a European, healthy female and represents a novel strain within this genus. Both<jats:italic>Methanobrevibacter</jats:italic>representatives form non-flagellated, short rods with variable morphologies and the capacity to form filaments. Both isolates showed the typical fluorescence of F<jats:sub>420</jats:sub>and methane production.</jats:p><jats:p>Compared to<jats:italic>M. smithii</jats:italic>GRAZ-2, WWM1085 did not accumulate formate when grown on H<jats:sub>2</jats:sub>and CO<jats:sub>2</jats:sub>. The optimal growth conditions were at 37°C, and pH 7. Full genome sequencing revealed a genomic difference of WWM1085 to the type strain of<jats:italic>M. smithii</jats:italic>PS (type strain; DSM 861), with 93.55% ANI and major differences in the sequence of its<jats:italic>mcrA</jats:italic>gene (3.3% difference in nucleotide sequence). Differences in the 16S rRNA gene were very minor and thus distinction based on this sequence might not be possible.<jats:italic>M. smithii</jats:italic>GRAZ-2 was identified as a novel strain within the<jats:italic>Methanobrevibacter</jats:italic>genus (ANI 99.04 % to<jats:italic>M. smithii</jats:italic>PS).</jats:p><jats:p>Due to the major differences of WWM1085 and<jats:italic>M. smithii</jats:italic>type strain PS in phenotypic, genomic and metabolic features, we propose<jats:italic>M. intestini</jats:italic>sp. nov. as a novel species with WWM1085 as the type strain (DSM 116060T = CECT 30992).</jats:p>},
howpublished = {bioRxiv},
keywords = {},
pubstate = {published},
tppubtype = {unpublished}
}
<jats:title>Abstract</jats:title><jats:p>Two mesophilic, hydrogenotrophic methanogens, WWM1085 and<jats:italic>M. smithii</jats:italic>GRAZ-2 were isolated from human fecal samples. WWM1085 was isolated from an individual in the USA, and represents a novel species with in the genus<jats:italic>Methanobrevibacter</jats:italic>.<jats:italic>M. smithii</jats:italic>GRAZ-2 (= DSM 116045) was retrieved from fecal samples of a European, healthy female and represents a novel strain within this genus. Both<jats:italic>Methanobrevibacter</jats:italic>representatives form non-flagellated, short rods with variable morphologies and the capacity to form filaments. Both isolates showed the typical fluorescence of F<jats:sub>420</jats:sub>and methane production.</jats:p><jats:p>Compared to<jats:italic>M. smithii</jats:italic>GRAZ-2, WWM1085 did not accumulate formate when grown on H<jats:sub>2</jats:sub>and CO<jats:sub>2</jats:sub>. The optimal growth conditions were at 37°C, and pH 7. Full genome sequencing revealed a genomic difference of WWM1085 to the type strain of<jats:italic>M. smithii</jats:italic>PS (type strain; DSM 861), with 93.55% ANI and major differences in the sequence of its<jats:italic>mcrA</jats:italic>gene (3.3% difference in nucleotide sequence). Differences in the 16S rRNA gene were very minor and thus distinction based on this sequence might not be possible.<jats:italic>M. smithii</jats:italic>GRAZ-2 was identified as a novel strain within the<jats:italic>Methanobrevibacter</jats:italic>genus (ANI 99.04 % to<jats:italic>M. smithii</jats:italic>PS).</jats:p><jats:p>Due to the major differences of WWM1085 and<jats:italic>M. smithii</jats:italic>type strain PS in phenotypic, genomic and metabolic features, we propose<jats:italic>M. intestini</jats:italic>sp. nov. as a novel species with WWM1085 as the type strain (DSM 116060T = CECT 30992).</jats:p>
Duller, Stefanie; Vrbancic, Simone; Szydłowski, Lukasz; Mahnert, Alexander; Blohs, Marcus; Predl, Michael; Kumpitsch, Christina; Zrim, Verena; Högenauer, Christoph; Kosciolek, Tomasz; Schmitz, Ruth A.; Eberhard, Anna; Dragovan, Melanie; Schmidberger, Laura; Zurabischvili, Tamara; Weinberger, Viktoria; Moser, Adrian Mathias; Kolb, Dagmar; Pernitsch, Dominique; Mohammadzadeh, Rokhsareh; Kühnast, Torben; Rattei, Thomas; Moissl-Eichinger, Christine
bioRxiv, 2024.
@unpublished{Duller2024,
title = {Expanding the cultivated human archaeome by targeted isolation of novel Methanobrevibacter strains from fecal samples},
author = {Stefanie Duller and Simone Vrbancic and Lukasz Szydłowski and Alexander Mahnert and Marcus Blohs and Michael Predl and Christina Kumpitsch and Verena Zrim and Christoph Högenauer and Tomasz Kosciolek and Ruth A. Schmitz and Anna Eberhard and Melanie Dragovan and Laura Schmidberger and Tamara Zurabischvili and Viktoria Weinberger and Adrian Mathias Moser and Dagmar Kolb and Dominique Pernitsch and Rokhsareh Mohammadzadeh and Torben Kühnast and Thomas Rattei and Christine Moissl-Eichinger},
url = {http://biorxiv.org/lookup/doi/10.1101/2024.04.10.588852},
doi = {10.1101/2024.04.10.588852},
year = {2024},
date = {2024-04-11},
urldate = {2024-04-11},
publisher = {Cold Spring Harbor Laboratory},
abstract = {<jats:title>Abstract</jats:title><jats:p>Archaea are integral components of the human microbiome but persist as understudied entities within the gastrointestinal tract (GIT), primarily due to the lack of cultured representatives for comprehensive mechanistic investigations. With only four<jats:italic>Methanobrevibacter smithii</jats:italic>isolates from humans available according to the Global Catalogue of Microorganisms (GCM), the existing cultures fail to adequately represent the observed diversity, as underscored by recent findings.</jats:p><jats:p>This study introduces a targeted cultivation method for enriching methanogenic archaea from human fecal samples. Applied to 16 stool samples from healthy and diseased donors, the method aimed to genomically characterize the archaeal cultures and establish correlations with gastrointestinal disorders. The procedure combines methane breath testing,<jats:italic>in silico</jats:italic>metabolic modelling, media optimization, FACS, dilution series, and genomic sequencing through Nanopore technology. Additional analyses include co-cultured bacteriome, comparative genomics of archaeal genomes, functional comparisons, and structure-based protein function prediction of unknown differential traits.</jats:p><jats:p>Successful establishment of stable archaeal cultures from 14 out of 16 fecal samples yielded nine previously uncultivated strains, eight of which were absent from a recent archaeome genome catalog. Comparative genomic and functional assessments of<jats:italic>Methanobrevibacter smithii</jats:italic>and<jats:italic>Candidatus</jats:italic>Methanobrevibacter intestini strains from diverse participant cohorts revealed features potentially associated with gastrointestinal diseases.</jats:p><jats:p>This work substantially broadens the scope of available archaeal representatives for functional and mechanistic studies in the human GIT. The established protocol facilitates the cultivation of methanogenic archaea from nearly every human fecal sample, offering insights into the adaptability of<jats:italic>Candidatus</jats:italic>Methanobrevibacter intestini genomes in critical microbiome situations.</jats:p>},
howpublished = {bioRxiv},
keywords = {},
pubstate = {published},
tppubtype = {unpublished}
}
<jats:title>Abstract</jats:title><jats:p>Archaea are integral components of the human microbiome but persist as understudied entities within the gastrointestinal tract (GIT), primarily due to the lack of cultured representatives for comprehensive mechanistic investigations. With only four<jats:italic>Methanobrevibacter smithii</jats:italic>isolates from humans available according to the Global Catalogue of Microorganisms (GCM), the existing cultures fail to adequately represent the observed diversity, as underscored by recent findings.</jats:p><jats:p>This study introduces a targeted cultivation method for enriching methanogenic archaea from human fecal samples. Applied to 16 stool samples from healthy and diseased donors, the method aimed to genomically characterize the archaeal cultures and establish correlations with gastrointestinal disorders. The procedure combines methane breath testing,<jats:italic>in silico</jats:italic>metabolic modelling, media optimization, FACS, dilution series, and genomic sequencing through Nanopore technology. Additional analyses include co-cultured bacteriome, comparative genomics of archaeal genomes, functional comparisons, and structure-based protein function prediction of unknown differential traits.</jats:p><jats:p>Successful establishment of stable archaeal cultures from 14 out of 16 fecal samples yielded nine previously uncultivated strains, eight of which were absent from a recent archaeome genome catalog. Comparative genomic and functional assessments of<jats:italic>Methanobrevibacter smithii</jats:italic>and<jats:italic>Candidatus</jats:italic>Methanobrevibacter intestini strains from diverse participant cohorts revealed features potentially associated with gastrointestinal diseases.</jats:p><jats:p>This work substantially broadens the scope of available archaeal representatives for functional and mechanistic studies in the human GIT. The established protocol facilitates the cultivation of methanogenic archaea from nearly every human fecal sample, offering insights into the adaptability of<jats:italic>Candidatus</jats:italic>Methanobrevibacter intestini genomes in critical microbiome situations.</jats:p>
Mohammadzadeh, Rokhsareh; Mahnert, Alexander; Shinde, Tejus; Kumpitsch, Christina; Weinberger, Viktoria; Schmidt, Helena; Moissl-Eichinger, Christine
bioRxiv, 2024.
@unpublished{Mohammadzadeh2024,
title = {Age-Related Dynamics of Methanogenic Archaea in the Human Gut Microbiome: Implications for Longevity and Health},
author = {Rokhsareh Mohammadzadeh and Alexander Mahnert and Tejus Shinde and Christina Kumpitsch and Viktoria Weinberger and Helena Schmidt and Christine Moissl-Eichinger},
url = {http://biorxiv.org/lookup/doi/10.1101/2024.02.09.579604},
doi = {10.1101/2024.02.09.579604},
year = {2024},
date = {2024-02-12},
urldate = {2024-02-12},
publisher = {Cold Spring Harbor Laboratory},
abstract = {<jats:title>Abstract</jats:title><jats:p>The reciprocal relationship between aging and alterations in the gut microbiota is a subject of ongoing research. While the role of bacteria in the gut microbiome is well-documented, specific changes in the composition of methanogens during extreme aging and the impact of high methane production in general on health remain unclear. To address these questions, we analyzed metagenomic data from the stool samples of young adults (n=127, Age: 19-59 y), older adults (n=86), and centenarians (n=34, age: 100-109 years).</jats:p><jats:p>Our findings reveal a compelling link between age and the prevalence of high methanogen phenotype, while overall archaeal diversity diminishes. Surprisingly, the archaeal composition of methanogens in the microbiome of centenarians appears more akin to that of younger adults, showing an increase in<jats:italic>Methanobrevibacter smithii</jats:italic>, rather than<jats:italic>Ca.</jats:italic>M. intestini. Remarkably,<jats:italic>Ca.</jats:italic>M. intestini emerged as a central player in the network stability of adults, paving the way for<jats:italic>M. smithii</jats:italic>in older adults and centenarians. Notably, centenarians exhibit a highly complex and stable network of these two methanogens with other bacteria. Furthermore, the mutual exclusion between Lachnospiraceae and these methanogens throughout all age groups suggests that these archaeal communities may compensate for the age-related drop in Lachnospiraceae by co-occurring with butyrate-producing Oscillospiraceae.</jats:p><jats:p>This study underscores the crucial role of the archaeal microbiome in human physiology and aging. It highlights age-related shifts in methanogen composition, emphasizing the significance of<jats:italic>Ca.</jats:italic>M. intestini and the partnership between methanogens and specific butyrate-producing bacteria for enhanced health and potential longevity.</jats:p>},
howpublished = {bioRxiv},
keywords = {},
pubstate = {published},
tppubtype = {unpublished}
}
<jats:title>Abstract</jats:title><jats:p>The reciprocal relationship between aging and alterations in the gut microbiota is a subject of ongoing research. While the role of bacteria in the gut microbiome is well-documented, specific changes in the composition of methanogens during extreme aging and the impact of high methane production in general on health remain unclear. To address these questions, we analyzed metagenomic data from the stool samples of young adults (n=127, Age: 19-59 y), older adults (n=86), and centenarians (n=34, age: 100-109 years).</jats:p><jats:p>Our findings reveal a compelling link between age and the prevalence of high methanogen phenotype, while overall archaeal diversity diminishes. Surprisingly, the archaeal composition of methanogens in the microbiome of centenarians appears more akin to that of younger adults, showing an increase in<jats:italic>Methanobrevibacter smithii</jats:italic>, rather than<jats:italic>Ca.</jats:italic>M. intestini. Remarkably,<jats:italic>Ca.</jats:italic>M. intestini emerged as a central player in the network stability of adults, paving the way for<jats:italic>M. smithii</jats:italic>in older adults and centenarians. Notably, centenarians exhibit a highly complex and stable network of these two methanogens with other bacteria. Furthermore, the mutual exclusion between Lachnospiraceae and these methanogens throughout all age groups suggests that these archaeal communities may compensate for the age-related drop in Lachnospiraceae by co-occurring with butyrate-producing Oscillospiraceae.</jats:p><jats:p>This study underscores the crucial role of the archaeal microbiome in human physiology and aging. It highlights age-related shifts in methanogen composition, emphasizing the significance of<jats:italic>Ca.</jats:italic>M. intestini and the partnership between methanogens and specific butyrate-producing bacteria for enhanced health and potential longevity.</jats:p>
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}
}
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.
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