Preprints
Preprints of key researchers of our CoE – since 2024
Chen, Song-Can; Tanabe, Tomohisa; Sun, Chengliang; Yan, Jing-Ling; Ren, Xin-Yue; Loy, Alexander
Research Square, 2026.
@unpublished{Chen2026b,
title = {Global evolutionary pattern and distinct metabolic strategies of sulfur-cycling microorganisms across ecosystems},
author = {Song-Can Chen and Tomohisa Tanabe and Chengliang Sun and Jing-Ling Yan and Xin-Yue Ren and Alexander Loy},
url = {https://www.researchsquare.com/article/rs-10339560/v1},
doi = {10.21203/rs.3.rs-10339560/v1},
year = {2026},
date = {2026-07-16},
urldate = {2026-07-16},
publisher = {Springer Science and Business Media LLC},
abstract = {<title>Abstract</title>
<p>Microorganisms drive the global sulfur cycle, but the complexity of sulfur redox transformations complicates understanding of their evolution, metabolism, and ecology. We developed DiSuCy, a manually curated, phylogeny-aware knowledgebase of 116 dissimilatory sulfur metabolism genes to identify sulfur-cycling microorganisms in (meta)genomes/transcriptomes. Key sulfur metabolism genes showed varying evolutionary conservation and intermediate horizontal transfer rates, enabling taxonomically scaled predictions of sulfur metabolisms. Co-occurrence of sulfur metabolisms with other biochemical pathways was shaped by redox thermodynamics, defining metabolic niches and ecosystem specificity of sulfur-cycling microorganisms. We predicted previously unrecognized sulfur-cycling members across underexplored bacterial phyla, thiotrophs respiring nitrate/arsenate or utilizing light, and ocean and human gut microbiomes. Some non-canonical sulfur taxa abundantly transcribed pathways for methanethiol oxidation in the global ocean or reduced sulfur compound oxidation in the gut. These findings expand the toolkit for studying sulfur-cycling microorganisms and provide new insights into their evolutionary dynamics and ecology.</p>},
howpublished = {Research Square},
keywords = {},
pubstate = {published},
tppubtype = {unpublished}
}
<title>Abstract</title>
<p>Microorganisms drive the global sulfur cycle, but the complexity of sulfur redox transformations complicates understanding of their evolution, metabolism, and ecology. We developed DiSuCy, a manually curated, phylogeny-aware knowledgebase of 116 dissimilatory sulfur metabolism genes to identify sulfur-cycling microorganisms in (meta)genomes/transcriptomes. Key sulfur metabolism genes showed varying evolutionary conservation and intermediate horizontal transfer rates, enabling taxonomically scaled predictions of sulfur metabolisms. Co-occurrence of sulfur metabolisms with other biochemical pathways was shaped by redox thermodynamics, defining metabolic niches and ecosystem specificity of sulfur-cycling microorganisms. We predicted previously unrecognized sulfur-cycling members across underexplored bacterial phyla, thiotrophs respiring nitrate/arsenate or utilizing light, and ocean and human gut microbiomes. Some non-canonical sulfur taxa abundantly transcribed pathways for methanethiol oxidation in the global ocean or reduced sulfur compound oxidation in the gut. These findings expand the toolkit for studying sulfur-cycling microorganisms and provide new insights into their evolutionary dynamics and ecology.</p>
<p>Microorganisms drive the global sulfur cycle, but the complexity of sulfur redox transformations complicates understanding of their evolution, metabolism, and ecology. We developed DiSuCy, a manually curated, phylogeny-aware knowledgebase of 116 dissimilatory sulfur metabolism genes to identify sulfur-cycling microorganisms in (meta)genomes/transcriptomes. Key sulfur metabolism genes showed varying evolutionary conservation and intermediate horizontal transfer rates, enabling taxonomically scaled predictions of sulfur metabolisms. Co-occurrence of sulfur metabolisms with other biochemical pathways was shaped by redox thermodynamics, defining metabolic niches and ecosystem specificity of sulfur-cycling microorganisms. We predicted previously unrecognized sulfur-cycling members across underexplored bacterial phyla, thiotrophs respiring nitrate/arsenate or utilizing light, and ocean and human gut microbiomes. Some non-canonical sulfur taxa abundantly transcribed pathways for methanethiol oxidation in the global ocean or reduced sulfur compound oxidation in the gut. These findings expand the toolkit for studying sulfur-cycling microorganisms and provide new insights into their evolutionary dynamics and ecology.</p>
Colaço, Henrique G.; Gundacker, Anna; Burrett, Aubrey; Grozev, Christian; Hofmann, Anna; Séneca, Joana; Endler, Lukas; Wong, Joel; Sanchez, Juan; Baumgartner, Maximilian; Fell, Christopher W.; Lercher, Alexander; Siller, Magdalena; Keszei, Zsofia; Viczenczova, Csilla; Richter, Felix C.; Law, Yee Kwan; Antonio-Herrera, Laura; Dearlove, Bethany; Balcar, Lorenz; Kramer, Georg; Reiberger, Thomas; Pjevac, Petra; Campbell, Clarissa; Pollak, Daniela D.; Bergthaler, Andreas
Gut-derived ammonia modulates hypothalamic stress responses during viral infection Unpublished
bioRxiv, 2026.
@unpublished{Colaço2026,
title = {Gut-derived ammonia modulates hypothalamic stress responses during viral infection},
author = {Henrique G. Colaço and Anna Gundacker and Aubrey Burrett and Christian Grozev and Anna Hofmann and Joana Séneca and Lukas Endler and Joel Wong and Juan Sanchez and Maximilian Baumgartner and Christopher W. Fell and Alexander Lercher and Magdalena Siller and Zsofia Keszei and Csilla Viczenczova and Felix C. Richter and Yee Kwan Law and Laura Antonio-Herrera and Bethany Dearlove and Lorenz Balcar and Georg Kramer and Thomas Reiberger and Petra Pjevac and Clarissa Campbell and Daniela D. Pollak and Andreas Bergthaler},
url = {http://biorxiv.org/lookup/doi/10.64898/2026.07.06.736796},
doi = {10.64898/2026.07.06.736796},
year = {2026},
date = {2026-07-09},
urldate = {2026-07-09},
publisher = {openRxiv},
abstract = {<jats:title>Abstract</jats:title>
<jats:p>The gut–brain axis integrates microbial and host metabolism to regulate systemic physiology, yet its role during viral infection remains poorly defined. Viral infection induces behavioral changes and neuroendocrine stress responses accompanied by profound alterations in gut microbial metabolism. Here, we show that chronic viral infection in mice increases systemic levels of microbiota-derived ammonia in a CD8⁺ T cell–dependent manner. Increased ammonia accumulates in the brain and selectively activates neurons within the paraventricular hypothalamus (PVH), driving corticosterone release into the circulation. Pharmacological inhibition of ammonia detoxification exacerbates these effects, leading to increased corticosterone levels, aggravated sickness behavior, and dampened antiviral responses. Together, these findings identify gut-derived ammonia as a previously unrecognized immunometabolic signal linking antiviral T cell responses to hypothalamic control of systemic stress during viral infection.</jats:p>
<jats:sec>
<jats:title>Graphical abstract</jats:title>
<jats:fig id="ufig1" position="float" orientation="portrait" fig-type="figure">
<jats:graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="736796v1_ufig1" position="float" orientation="portrait"/>
</jats:fig>
</jats:sec>},
howpublished = {bioRxiv},
keywords = {},
pubstate = {published},
tppubtype = {unpublished}
}
<jats:title>Abstract</jats:title>
<jats:p>The gut–brain axis integrates microbial and host metabolism to regulate systemic physiology, yet its role during viral infection remains poorly defined. Viral infection induces behavioral changes and neuroendocrine stress responses accompanied by profound alterations in gut microbial metabolism. Here, we show that chronic viral infection in mice increases systemic levels of microbiota-derived ammonia in a CD8⁺ T cell–dependent manner. Increased ammonia accumulates in the brain and selectively activates neurons within the paraventricular hypothalamus (PVH), driving corticosterone release into the circulation. Pharmacological inhibition of ammonia detoxification exacerbates these effects, leading to increased corticosterone levels, aggravated sickness behavior, and dampened antiviral responses. Together, these findings identify gut-derived ammonia as a previously unrecognized immunometabolic signal linking antiviral T cell responses to hypothalamic control of systemic stress during viral infection.</jats:p>
<jats:sec>
<jats:title>Graphical abstract</jats:title>
<jats:fig id="ufig1" position="float" orientation="portrait" fig-type="figure">
<jats:graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="736796v1_ufig1" position="float" orientation="portrait"/>
</jats:fig>
</jats:sec>
<jats:p>The gut–brain axis integrates microbial and host metabolism to regulate systemic physiology, yet its role during viral infection remains poorly defined. Viral infection induces behavioral changes and neuroendocrine stress responses accompanied by profound alterations in gut microbial metabolism. Here, we show that chronic viral infection in mice increases systemic levels of microbiota-derived ammonia in a CD8⁺ T cell–dependent manner. Increased ammonia accumulates in the brain and selectively activates neurons within the paraventricular hypothalamus (PVH), driving corticosterone release into the circulation. Pharmacological inhibition of ammonia detoxification exacerbates these effects, leading to increased corticosterone levels, aggravated sickness behavior, and dampened antiviral responses. Together, these findings identify gut-derived ammonia as a previously unrecognized immunometabolic signal linking antiviral T cell responses to hypothalamic control of systemic stress during viral infection.</jats:p>
<jats:sec>
<jats:title>Graphical abstract</jats:title>
<jats:fig id="ufig1" position="float" orientation="portrait" fig-type="figure">
<jats:graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="736796v1_ufig1" position="float" orientation="portrait"/>
</jats:fig>
</jats:sec>
Baumgartner, Maximilian; Schnaufer, Franziska; Duquesnoy, Maeva; Asatsuma, Takahiro; Chakrabarty, Adrija; Frick, Adrian; Fuchs, Claudia; Gerstorfer, Michael; Hains, Patrik; Köcher, Thomas; Schimmel, Patrick; Lichtenstein, Mauriz A.; Leistl, Sofia; Pinter, Felix; Krstevska, Elena; Nyein, Thet Khaing; Högenauer, Christoph; Makristathis, Athanasios; Gasche, Christoph; Primas, Christian; Reinisch, Walter; Winter, Georg E.; Trauner, Michael; Günther, Claudia; Busslinger, Georg; Gorkiewicz, Gregor; Chassaing, Benoit; Campbell, Clarissa
bioRxiv, 2026.
@unpublished{Baumgartner2026,
title = {Host-derived bile acids drive dysbiosis by selecting bile-resistant epimerizing bacteria in inflammatory bowel disease},
author = {Maximilian Baumgartner and Franziska Schnaufer and Maeva Duquesnoy and Takahiro Asatsuma and Adrija Chakrabarty and Adrian Frick and Claudia Fuchs and Michael Gerstorfer and Patrik Hains and Thomas Köcher and Patrick Schimmel and Mauriz A. Lichtenstein and Sofia Leistl and Felix Pinter and Elena Krstevska and Thet Khaing Nyein and Christoph Högenauer and Athanasios Makristathis and Christoph Gasche and Christian Primas and Walter Reinisch and Georg E. Winter and Michael Trauner and Claudia Günther and Georg Busslinger and Gregor Gorkiewicz and Benoit Chassaing and Clarissa Campbell},
url = {http://biorxiv.org/lookup/doi/10.64898/2026.06.18.733240},
doi = {10.64898/2026.06.18.733240},
year = {2026},
date = {2026-06-19},
urldate = {2026-06-19},
publisher = {openRxiv},
abstract = {<jats:title>Abstract</jats:title>
<jats:p>Microbial dysbiosis is a hallmark of inflammatory bowel diseases (IBD); however, its drivers and impact on disease pathophysiology are poorly understood. Applying neural network-based feature attribution to metabolomics and metagenomics datasets from >5000 individuals, we identified epimerized host derived bile acids (BAs) produced by microbial hydroxysteroid dehydrogenases (HSDHs) as a novel hallmark of IBD-associated dysbiosis. Epimerized BAs reduce FXR activity in intestinal epithelial cells and dampen their production of FGF19, a negative feedback regulator of host-derived bile acid (HBA) production in the liver. Increased HBA levels drive colonic epithelial remodeling by impacting goblet cell maturation and select for HSDH-carrying bacteria that transform bactericidal HBA into less toxic, epimerized forms. Confirming the translational relevance of these findings, we demonstrated that high HBA levels limit fecal microbiota transplant engraftment and show that BA sequestering drugs support microbiome recovery in patients with high HBA levels. Together, we discover that elevated HBAs deplete BA-sensitive commensals and favor the growth of HSDH-encoding pathobionts that disrupt host BA feedback signaling, establishing a causal link between changes in microbial ecology and IBD pathophysiology.</jats:p>},
howpublished = {bioRxiv},
keywords = {},
pubstate = {published},
tppubtype = {unpublished}
}
<jats:title>Abstract</jats:title>
<jats:p>Microbial dysbiosis is a hallmark of inflammatory bowel diseases (IBD); however, its drivers and impact on disease pathophysiology are poorly understood. Applying neural network-based feature attribution to metabolomics and metagenomics datasets from >5000 individuals, we identified epimerized host derived bile acids (BAs) produced by microbial hydroxysteroid dehydrogenases (HSDHs) as a novel hallmark of IBD-associated dysbiosis. Epimerized BAs reduce FXR activity in intestinal epithelial cells and dampen their production of FGF19, a negative feedback regulator of host-derived bile acid (HBA) production in the liver. Increased HBA levels drive colonic epithelial remodeling by impacting goblet cell maturation and select for HSDH-carrying bacteria that transform bactericidal HBA into less toxic, epimerized forms. Confirming the translational relevance of these findings, we demonstrated that high HBA levels limit fecal microbiota transplant engraftment and show that BA sequestering drugs support microbiome recovery in patients with high HBA levels. Together, we discover that elevated HBAs deplete BA-sensitive commensals and favor the growth of HSDH-encoding pathobionts that disrupt host BA feedback signaling, establishing a causal link between changes in microbial ecology and IBD pathophysiology.</jats:p>
<jats:p>Microbial dysbiosis is a hallmark of inflammatory bowel diseases (IBD); however, its drivers and impact on disease pathophysiology are poorly understood. Applying neural network-based feature attribution to metabolomics and metagenomics datasets from >5000 individuals, we identified epimerized host derived bile acids (BAs) produced by microbial hydroxysteroid dehydrogenases (HSDHs) as a novel hallmark of IBD-associated dysbiosis. Epimerized BAs reduce FXR activity in intestinal epithelial cells and dampen their production of FGF19, a negative feedback regulator of host-derived bile acid (HBA) production in the liver. Increased HBA levels drive colonic epithelial remodeling by impacting goblet cell maturation and select for HSDH-carrying bacteria that transform bactericidal HBA into less toxic, epimerized forms. Confirming the translational relevance of these findings, we demonstrated that high HBA levels limit fecal microbiota transplant engraftment and show that BA sequestering drugs support microbiome recovery in patients with high HBA levels. Together, we discover that elevated HBAs deplete BA-sensitive commensals and favor the growth of HSDH-encoding pathobionts that disrupt host BA feedback signaling, establishing a causal link between changes in microbial ecology and IBD pathophysiology.</jats:p>
Jelusic, Barbara; Boerno, Stefan; Schimmel, Patrick; Wurm, Philipp; Przysiecki, Nicole; Watschinger, Christina; Wolfgruber, Stella; Hardt, Melina; Anthofer, Margit; Ehmann, Sandra; Klages, Sven; Zatloukal, Kurt; Timmermann, Bernd; Moschen, Alexander; Gorkiewicz, Gregor
Research Square, 2025.
@unpublished{Jelusic2025,
title = {Reduced SARS-CoV-2 infection levels and pathotype specific altered antiviral transcriptional response in IBD intestinal organoids},
author = {Barbara Jelusic and Stefan Boerno and Patrick Schimmel and Philipp Wurm and Nicole Przysiecki and Christina Watschinger and Stella Wolfgruber and Melina Hardt and Margit Anthofer and Sandra Ehmann and Sven Klages and Kurt Zatloukal and Bernd Timmermann and Alexander Moschen and Gregor Gorkiewicz},
url = {https://www.researchsquare.com/article/rs-8029502/v1},
doi = {10.21203/rs.3.rs-8029502/v1},
year = {2025},
date = {2025-11-26},
urldate = {2025-11-26},
publisher = {Springer Science and Business Media LLC},
abstract = {<title>Abstract</title>
<p>
Background
IBD is characterized by altered immune reactions and infections are thought to trigger chronic inflammation in IBD. The gut represents a productive reservoir for SARS-CoV-2 and the aforementioned factors together with immunosuppression used to treat IBD are likely influencing the outcomes of IBD patients with COVID-19.
Methods
We used large and small intestinal organoids from ulcerative colitis and Crohn's disease patients and controls to comparatively assess infection levels and transcriptional response of the gut epithelium during SARS-CoV-2 infection.
Results
Our analysis showed that IBD epithelia exhibit reduced viral loads compared to controls associated with a reduced expression of SARS-CoV-2 entry factors including the host receptor ACE2. Moreover, several genes implicated in the epithelial response to viral infection are intrinsically altered in IBD potentially counteracting viral propagation. Notably, differences between IBD phenotypes exist wherein ulcerative colitis represents with induced cell death pathways and increased
<italic>IL1B</italic>
expression despite lower viral loads suggestive of increased epithelial stress.
Conclusions
Altogether our analysis shows that the IBD epithelium is not more prone to SARS-CoV-2 infection and that several antiviral response genes are intrinsically activated in IBD. Moreover, ulcerative colitis and Crohn's disease exhibit specific transcriptional differences which might explain the differing COVID-19 outcomes between IBD phenotypes.
</p>},
howpublished = {Research Square},
keywords = {},
pubstate = {published},
tppubtype = {unpublished}
}
<title>Abstract</title>
<p>
Background
IBD is characterized by altered immune reactions and infections are thought to trigger chronic inflammation in IBD. The gut represents a productive reservoir for SARS-CoV-2 and the aforementioned factors together with immunosuppression used to treat IBD are likely influencing the outcomes of IBD patients with COVID-19.
Methods
We used large and small intestinal organoids from ulcerative colitis and Crohn's disease patients and controls to comparatively assess infection levels and transcriptional response of the gut epithelium during SARS-CoV-2 infection.
Results
Our analysis showed that IBD epithelia exhibit reduced viral loads compared to controls associated with a reduced expression of SARS-CoV-2 entry factors including the host receptor ACE2. Moreover, several genes implicated in the epithelial response to viral infection are intrinsically altered in IBD potentially counteracting viral propagation. Notably, differences between IBD phenotypes exist wherein ulcerative colitis represents with induced cell death pathways and increased
<italic>IL1B</italic>
expression despite lower viral loads suggestive of increased epithelial stress.
Conclusions
Altogether our analysis shows that the IBD epithelium is not more prone to SARS-CoV-2 infection and that several antiviral response genes are intrinsically activated in IBD. Moreover, ulcerative colitis and Crohn's disease exhibit specific transcriptional differences which might explain the differing COVID-19 outcomes between IBD phenotypes.
</p>
<p>
Background
IBD is characterized by altered immune reactions and infections are thought to trigger chronic inflammation in IBD. The gut represents a productive reservoir for SARS-CoV-2 and the aforementioned factors together with immunosuppression used to treat IBD are likely influencing the outcomes of IBD patients with COVID-19.
Methods
We used large and small intestinal organoids from ulcerative colitis and Crohn's disease patients and controls to comparatively assess infection levels and transcriptional response of the gut epithelium during SARS-CoV-2 infection.
Results
Our analysis showed that IBD epithelia exhibit reduced viral loads compared to controls associated with a reduced expression of SARS-CoV-2 entry factors including the host receptor ACE2. Moreover, several genes implicated in the epithelial response to viral infection are intrinsically altered in IBD potentially counteracting viral propagation. Notably, differences between IBD phenotypes exist wherein ulcerative colitis represents with induced cell death pathways and increased
<italic>IL1B</italic>
expression despite lower viral loads suggestive of increased epithelial stress.
Conclusions
Altogether our analysis shows that the IBD epithelium is not more prone to SARS-CoV-2 infection and that several antiviral response genes are intrinsically activated in IBD. Moreover, ulcerative colitis and Crohn's disease exhibit specific transcriptional differences which might explain the differing COVID-19 outcomes between IBD phenotypes.
</p>
Glasl, Bettina; Kitzinger, Katharina; Luter, Heidi M.; Legin, Anton; Salas, Erika; Heldwein, Nathalie; Damjanovic, Katarina; Schuster, Stefan; Rutsch, Marie; Vekeman, Bram; Speth, Daan R; Geerlings, Nicole MJ; Pjevac, Petra; Séneca, Joana; Watzka, Margarete; Wanek, Wolfgang; Wagner, Michael
Branched-chain amino acid assimilation promotes mixotrophy of ammonia-oxidizing archaeal sponge symbionts Unpublished
bioRxiv, 2025.
@unpublished{Glasl2025,
title = {Branched-chain amino acid assimilation promotes mixotrophy of ammonia-oxidizing archaeal sponge symbionts},
author = {Bettina Glasl and Katharina Kitzinger and Heidi M. Luter and Anton Legin and Erika Salas and Nathalie Heldwein and Katarina Damjanovic and Stefan Schuster and Marie Rutsch and Bram Vekeman and Daan R Speth and Nicole MJ Geerlings and Petra Pjevac and Joana Séneca and Margarete Watzka and Wolfgang Wanek and Michael Wagner},
url = {http://biorxiv.org/lookup/doi/10.1101/2025.09.09.672702},
doi = {10.1101/2025.09.09.672702},
year = {2025},
date = {2025-09-09},
urldate = {2025-09-09},
publisher = {Cold Spring Harbor Laboratory},
abstract = {<jats:p>Ammonia-oxidizing archaea (AOA) frequently form symbiotic associations with marine sponges. While free-living AOA are generally considered metabolically constrained chemolithoautotrophs, sponge-associated AOA encode for a branched-chain amino acid (BCAA) transporter, suggesting mixotrophic potential. Here, we test the unusual mixotrophic lifestyle of sponge-associated AOA by tracing the assimilation of <jats:sup>13</jats:sup>C- and <jats:sup>15</jats:sup>N-labeled BCAA in the sponge holobiont Ianthella basta. We demonstrate that BCAA degradation fuels ammonia oxidation and quantify BCAA uptake at the single-cell level by combining stable isotope probing, catalyzed reporter deposition fluorescence <jats:italic>in situ</jats:italic> hybridization, and nanoscale secondary ion mass spectrometry. Our results reveal that sponge-associated AOA are mixotrophic, assimilating BCAA as an additional carbon and nitrogen source. This metabolic adaptation may modulate BCAA availability in the holobiont, potentially regulating the host's mTOR pathway. Collectively, our study reveals a novel nutritional interaction in sponge holobionts and challenges the perception of constrained metabolic capacities of AOA.</jats:p>},
howpublished = {bioRxiv},
keywords = {},
pubstate = {published},
tppubtype = {unpublished}
}
<jats:p>Ammonia-oxidizing archaea (AOA) frequently form symbiotic associations with marine sponges. While free-living AOA are generally considered metabolically constrained chemolithoautotrophs, sponge-associated AOA encode for a branched-chain amino acid (BCAA) transporter, suggesting mixotrophic potential. Here, we test the unusual mixotrophic lifestyle of sponge-associated AOA by tracing the assimilation of <jats:sup>13</jats:sup>C- and <jats:sup>15</jats:sup>N-labeled BCAA in the sponge holobiont Ianthella basta. We demonstrate that BCAA degradation fuels ammonia oxidation and quantify BCAA uptake at the single-cell level by combining stable isotope probing, catalyzed reporter deposition fluorescence <jats:italic>in situ</jats:italic> hybridization, and nanoscale secondary ion mass spectrometry. Our results reveal that sponge-associated AOA are mixotrophic, assimilating BCAA as an additional carbon and nitrogen source. This metabolic adaptation may modulate BCAA availability in the holobiont, potentially regulating the host's mTOR pathway. Collectively, our study reveals a novel nutritional interaction in sponge holobionts and challenges the perception of constrained metabolic capacities of AOA.</jats:p>
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