Publications

Publications in peer reviewed journals

15 Publications found
  • Connecting structure to function with the recovery of over 1000 high-quality activated sludge metagenome-assembled genomes encoding full-length rRNA genes using long-read sequencing

    Singleton CM, Petriglieri F, Kristensen JM, Kirkegaard RH, Michaelsen TY, Andersen MH, Kondrotaite Z, Karst SM, Dueholm MS, Nielsen PH, Albertsen M.
    2021 - bioRxiv, 2020.05.12.088096

    Abstract: 

    Microorganisms are critical to water recycling, pollution removal and resource recovery processes in the wastewater industry. While the structure of this complex community is increasingly understood based on 16S rRNA gene studies, this structure cannot currently be linked to functional potential due to the absence of high-quality metagenome-assembled genomes (MAGs) with full-length rRNA genes for nearly all species. Here, we sequence 23 Danish full-scale wastewater treatment plant metagenomes, producing >1 Tbp of long-read and >0.9 Tbp of short-read data. We recovered 1083 high-quality MAGs, including 57 closed circular genomes. The MAGs accounted for ~30% of the community, and meet the stringent MIMAG high-quality draft requirements including full-length rRNA genes. We show how novel high-quality MAGs in combination with >13 years of amplicon data, Raman microspectroscopy and fluorescence in situ hybridisation can be used to uncover abundant undescribed lineages belonging to important functional groups.

  • Reduced alpha diversity of the oral microbiome correlates with short progression‐free survival in patients with relapsed/refractory multiple myeloma treated with ixazomib‐based therapy (AGMT MM 1, phase II trial)

    Ludwig H, Hausmann B, Schreder M, Pönisch W, Zojer N, Knop S, Gunsilius E, Egle A, Petzer A, Einsele H, Hajek R, Weisel K, Krenosz KJ, Lang A, Lechner D, Greil R, Berry D
    2021 - eJHaem, 2: 102–106

    Abstract: 

    Alterations in the human microbiome have been linked to several malignant diseases. Here, we investigated the oral microbiome of 79 patients with relapsed/refractory multiple myeloma (MM) treated with ixazomib‐thalidomide‐dexamethasone. Increased alpha diversity (Shannon index) at the phylum level was associated with longer progression‐free survival (PFS) (10.2 vs 8.5 months, P = .04), particularly in patients with very long (>75% quartile) PFS . Additionally, alpha diversity was lower in patients with progressive disease (P < .05). These findings suggest an interrelationship between the oral microbiome and outcome in patients with MM and encourage a novel direction for diagnostic and/or therapeutic strategies.

  • Aberrant gut-microbiota-immune-brain axis development in premature neonates with brain damage.

    Seki D, Mayer M, Hausmann B, Pjevac P, Giordano V, Goeral K, Unterasinger L, Klebermaß-Schrehof K, De Paepe K, Van de Wiele T, Spittler A, Kasprian G, Warth B, Berger A, Berry D, Wisgrill L
    2021 - Cell Host Microbe, in press

    Abstract: 

    Premature infants are at substantial risk for suffering from perinatal white matter injury. Though the gut microbiota has been implicated in early-life development, a detailed understanding of the gut-microbiota-immune-brain axis in premature neonates is lacking. Here, we profiled the gut microbiota, immunological, and neurophysiological development of 60 extremely premature infants, which received standard hospital care including antibiotics and probiotics. We found that maturation of electrocortical activity is suppressed in infants with severe brain damage. This is accompanied by elevated γδ T cell levels and increased T cell secretion of vascular endothelial growth factor and reduced secretion of neuroprotectants. Notably, Klebsiella overgrowth in the gut is highly predictive for brain damage and is associated with a pro-inflammatory immunological tone. These results suggest that aberrant development of the gut-microbiota-immune-brain axis may drive or exacerbate brain injury in extremely premature neonates and represents a promising target for novel intervention strategies.

  • Global biogeography of chemosynthetic symbionts reveals both localized and globally distributed symbiont groups.

    Osvatic JT, Wilkins LGE, Leibrecht L, Leray M, Zauner S, Polzin J, Camacho Y, Gros O, van Gils JA, Eisen JA, Petersen JM, Yuen B
    2021 - Proc Natl Acad Sci U S A, 29: in press

    Abstract: 

    In the ocean, most hosts acquire their symbionts from the environment. Due to the immense spatial scales involved, our understanding of the biogeography of hosts and symbionts in marine systems is patchy, although this knowledge is essential for understanding fundamental aspects of symbiosis such as host-symbiont specificity and evolution. Lucinidae is the most species-rich and widely distributed family of marine bivalves hosting autotrophic bacterial endosymbionts. Previous molecular surveys identified location-specific symbiont types that "promiscuously" form associations with multiple divergent cooccurring host species. This flexibility of host-microbe pairings is thought to underpin their global success, as it allows hosts to form associations with locally adapted symbionts. We used metagenomics to investigate the biodiversity, functional variability, and genetic exchange among the endosymbionts of 12 lucinid host species from across the globe. We report a cosmopolitan symbiont species, Thiodiazotropha taylori, associated with multiple lucinid host species. T. taylori has achieved more success at dispersal and establishing symbioses with lucinids than any other symbiont described thus far. This discovery challenges our understanding of symbiont dispersal and location-specific colonization and suggests both symbiont and host flexibility underpin the ecological and evolutionary success of the lucinid symbiosis.

  • Mucosal Biofilms Are an Endoscopic Feature of Irritable Bowel Syndrome and Ulcerative Colitis.

    Baumgartner M, Lang M, Holley H, Crepaz D, Hausmann B, Pjevac P, Moser D, Haller F, Hof F, Beer A, Orgler E, Frick A, Khare V, Evstatiev R, Strohmaier S, Primas C, Dolak W, Köcher T, Klavins K, Rath T, Neurath MF, Berry D, Makristathis A, Muttenthaler M, Gasche C
    2021 - Gastroenterology, 4: 1245-1256.e20

    Abstract: 

    Irritable bowel syndrome (IBS) and inflammatory bowel diseases result in a substantial reduction in quality of life and a considerable socioeconomic impact. In IBS, diagnosis and treatment options are limited, but evidence for involvement of the gut microbiome in disease pathophysiology is emerging. Here we analyzed the prevalence of endoscopically visible mucosal biofilms in gastrointestinal disease and associated changes in microbiome composition and metabolism.
    The presence of mucosal biofilms was assessed in 1426 patients at 2 European university-based endoscopy centers. One-hundred and seventeen patients were selected for in-depth molecular and microscopic analysis using 16S ribosomal RNA gene amplicon-sequencing of colonic biopsies and fecal samples, confocal microscopy with deep learning-based image analysis, scanning electron microscopy, metabolomics, and in vitro biofilm formation assays.
    Biofilms were present in 57% of patients with IBS and 34% of patients with ulcerative colitis compared with 6% of controls (P < .001). These yellow-green adherent layers of the ileum and right-sided colon were microscopically confirmed to be dense bacterial biofilms. 16S-sequencing links the presence of biofilms to a dysbiotic gut microbiome, including overgrowth of Escherichia coli and Ruminococcus gnavus. R. gnavus isolates cultivated from patient biofilms also formed biofilms in vitro. Metabolomic analysis found an accumulation of bile acids within biofilms that correlated with fecal bile acid excretion, linking this phenotype with a mechanism of diarrhea.
    The presence of mucosal biofilms is an endoscopic feature in a subgroup of IBS and ulcerative colitis with disrupted bile acid metabolism and bacterial dysbiosis. They provide novel insight into the pathophysiology of IBS and ulcerative colitis, illustrating that biofilm can be seen as a tipping point in the development of dysbiosis and disease.

  • Microbial community structure in hadal sediments: high similarity along trench axes and strong changes along redox gradients.

    Schauberger C, Glud RN, Hausmann B, Trouche B, Maignien L, Poulain J, Wincker P, Arnaud-Haond S, Wenzhöfer F, Thamdrup B
    2021 - ISME J, in press

    Abstract: 

    Hadal trench sediments are hotspots of biogeochemical activity in the deep sea, but the biogeochemical and ecological factors that shape benthic hadal microbial communities remain unknown. Here, we sampled ten hadal sites from two trench regions with a vertical resolution of down to 1 cm. We sequenced 16S rRNA gene amplicons using universal and archaea-specific primer sets and compared the results to biogeochemical parameters. Despite bathymetric and depositional heterogeneity we found a high similarity of microbial communities within each of the two trench axes, while composition at the phylum level varied strongly with sediment depth in conjunction with the redox stratification into oxic, nitrogenous, and ferruginous zones. As a result, communities of a given sediment horizon were more similar to each other across a distance of hundreds of kilometers within each trench, than to those of adjacent horizons from the same sites separated only by centimeters. Total organic carbon content statistically only explained a small part of the variation within and between trenches, and did not explain the community differences observed between the hadal and adjacent shallower sites. Anaerobic taxa increased in abundance at the top of the ferruginous zone, seeded by organisms deposited at the sediment surface and surviving burial through the upper redox zones. While an influence of other potential factors such as geographic isolation, hydrostatic pressure, and non-steady state depositional regimes could not be discerned, redox stratification and diagenesis appear to be the main selective forces that structure community composition in hadal sediments.

  • An Economical and Flexible Dual Barcoding, Two-Step PCR Approach for Highly Multiplexed Amplicon Sequencing.

    2021 - Front Microbiol, 669776

    Abstract: 

    In microbiome research, phylogenetic and functional marker gene amplicon sequencing is the most commonly-used community profiling approach. Consequently, a plethora of protocols for the preparation and multiplexing of samples for amplicon sequencing have been developed. Here, we present two economical high-throughput gene amplification and sequencing workflows that are implemented as standard operating procedures at the Joint Microbiome Facility of the Medical University of Vienna and the University of Vienna. These workflows are based on a previously-published two-step PCR approach, but have been updated to either increase the accuracy of results, or alternatively to achieve orders of magnitude higher numbers of samples to be multiplexed in a single sequencing run. The high-accuracy workflow relies on unique dual sample barcoding. It allows the same level of sample multiplexing as the previously-published two-step PCR approach, but effectively eliminates residual read missasignments between samples (crosstalk) which are inherent to single barcoding approaches. The high-multiplexing workflow is based on combinatorial dual sample barcoding, which theoretically allows for multiplexing up to 299,756 amplicon libraries of the same target gene in a single massively-parallelized amplicon sequencing run. Both workflows presented here are highly economical, easy to implement, and can, without significant modifications or cost, be applied to any target gene of interest.

  • Functional iron-deficiency in women with allergic rhinitis is associated with symptoms after nasal provocation and lack of iron-sequestering microbes.

    Petje LM, Jensen SA, Szikora S, Sulzbacher M, Bartosik T, Pjevac P, Hausmann B, Hufnagl K, Untersmayr E, Fischer L, Vyskocil E, Eckl-Dorna J, Jensen-Jarolim E, Hofstetter G, Afify SM, Krenn CG, Roth GA, Rivelles E, Hann S, Roth-Walter F
    2021 - Allergy, 9: 2882-2886
  • Multiplexed detection of SARS-CoV-2 and other respiratory infections in high throughput by SARSeq.

    Yelagandula R, Bykov A, Vogt A, Heinen R, Özkan E, Strobl MM, Baar JC, Uzunova K, Hajdusits B, Kordic D, Suljic E, Kurtovic-Kozaric A, Izetbegovic S, Schaeffer J, Hufnagl P, Zoufaly A, Seitz T, Födinger M, Allerberger F, Stark A, Cochella L, Elling U
    2021 - Nat Commun, 1: 3132

    Abstract: 

    The COVID-19 pandemic has demonstrated the need for massively-parallel, cost-effective tests monitoring viral spread. Here we present SARSeq, saliva analysis by RNA sequencing, a method to detect SARS-CoV-2 and other respiratory viruses on tens of thousands of samples in parallel. SARSeq relies on next generation sequencing of multiple amplicons generated in a multiplexed RT-PCR reaction. Two-dimensional, unique dual indexing, using four indices per sample, enables unambiguous and scalable assignment of reads to individual samples. We calibrate SARSeq on SARS-CoV-2 synthetic RNA, virions, and hundreds of human samples of various types. Robustness and sensitivity were virtually identical to quantitative RT-PCR. Double-blinded benchmarking to gold standard quantitative-RT-PCR performed by human diagnostics laboratories confirms this high sensitivity. SARSeq can be used to detect Influenza A and B viruses and human rhinovirus in parallel, and can be expanded for detection of other pathogens. Thus, SARSeq is ideally suited for differential diagnostic of infections during a pandemic.

  • Novel taxa of Acidobacteriota implicated in seafloor sulfur cycling.

    Flieder M, Buongiorno J, Herbold CW, Hausmann B, Rattei T, Lloyd KG, Loy A, Wasmund K
    2021 - ISME J, in press

    Abstract: 

    Acidobacteriota are widespread and often abundant in marine sediments, yet their metabolic and ecological properties are poorly understood. Here, we examined metabolisms and distributions of Acidobacteriota in marine sediments of Svalbard by functional predictions from metagenome-assembled genomes (MAGs), amplicon sequencing of 16S rRNA and dissimilatory sulfite reductase (dsrB) genes and transcripts, and gene expression analyses of tetrathionate-amended microcosms. Acidobacteriota were the second most abundant dsrB-harboring (averaging 13%) phylum after Desulfobacterota in Svalbard sediments, and represented 4% of dsrB transcripts on average. Meta-analysis of dsrAB datasets also showed Acidobacteriota dsrAB sequences are prominent in marine sediments worldwide, averaging 15% of all sequences analysed, and represent most of the previously unclassified dsrAB in marine sediments. We propose two new Acidobacteriota genera, Candidatus Sulfomarinibacter (class Thermoanaerobaculia, "subdivision 23") and Ca. Polarisedimenticola ("subdivision 22"), with distinct genetic properties that may explain their distributions in biogeochemically distinct sediments. Ca. Sulfomarinibacter encode flexible respiratory routes, with potential for oxygen, nitrous oxide, metal-oxide, tetrathionate, sulfur and sulfite/sulfate respiration, and possibly sulfur disproportionation. Potential nutrients and energy include cellulose, proteins, cyanophycin, hydrogen, and acetate. A Ca. Polarisedimenticola MAG encodes various enzymes to degrade proteins, and to reduce oxygen, nitrate, sulfur/polysulfide and metal-oxides. 16S rRNA gene and transcript profiling of Svalbard sediments showed Ca. Sulfomarinibacter members were relatively abundant and transcriptionally active in sulfidic fjord sediments, while Ca. Polarisedimenticola members were more relatively abundant in metal-rich fjord sediments. Overall, we reveal various physiological features of uncultured marine Acidobacteriota that indicate fundamental roles in seafloor biogeochemical cycling.

  • Combined hormonal contraceptives are associated with minor changes in composition and diversity in gut microbiota of healthy women.

    Mihajlovic J, Leutner M, Hausmann B, Kohl G, Schwarz J, Röver H, Stimakovits N, Wolf P, Maruszczak K, Bastian M, Kautzky-Willer A, Berry D
    2021 - Environ Microbiol, 6: 3037-3047

    Abstract: 

    Recent human and animal studies have found associations between gut microbiota composition and serum levels of sex hormones, indicating that they could be an important factor in shaping the microbiota. However, little is known about the effect of regular hormonal fluctuations over the menstrual cycle or CHC-related changes of hormone levels on gut microbiota structure, diversity and dynamics. The aim of this study was to investigate the effect of CHCs on human gut microbiota composition. The effect of CHC pill intake on gut microbiota composition was studied in a group of seven healthy pre-menopausal women using the CHC pill, compared to the control group of nine age-matched healthy women that have not used hormonal contraceptives in the 6 months prior to the start of the study. By analysing the gut microbiota composition in both groups during one menstrual cycle, we found that CHC usage is associated with a minor decrease in gut microbiota diversity and differences in the abundance of several bacterial taxa. These results call for further investigation of the mechanisms underlying hormonal and hormonal contraceptive-related changes of the gut microbiota and the potential implications of these changes for women's health.

  • In vitro interactions of Alternaria mycotoxins, an emerging class of food contaminants, with the gut microbiota: a bidirectional relationship.

    Crudo F, Aichinger G, Mihajlovic J, Varga E, Dellafiora L, Warth B, Dall'Asta C, Berry D, Marko D
    2021 - Arch Toxicol, .

    Abstract: 

    The human gut microbiota plays an important role in the maintenance of human health. Factors able to modify its composition might predispose the host to the development of pathologies. Among the various xenobiotics introduced through the diet, Alternaria mycotoxins are speculated to represent a threat for human health. However, limited data are currently available about the bidirectional relation between gut microbiota and Alternaria mycotoxins. In the present work, we investigated the in vitro effects of different concentrations of a complex extract of Alternaria mycotoxins (CE; containing eleven mycotoxins; e.g. 0.153 µM alternariol and 2.3 µM altersetin, at the maximum CE concentration tested) on human gut bacterial strains, as well as the ability of the latter to metabolize or adsorb these compounds. Results from the minimum inhibitory concentration assay showed the scarce ability of CE to inhibit the growth of the tested strains. However, the growth kinetics of most of the strains were negatively affected by exposure to the various CE concentrations, mainly at the highest dose (50 µg/mL). The CE was also found to antagonize the formation of biofilms, already at concentrations of 0.5 µg/mL. LC-MS/MS data analysis of the mycotoxin concentrations found in bacterial pellets and supernatants after 24 h incubation showed the ability of bacterial strains to adsorb some Alternaria mycotoxins, especially the key toxins alternariol, alternariol monomethyl ether, and altersetin. The tendency of these mycotoxins to accumulate within bacterial pellets, especially in those of Gram-negative strains, was found to be directly related to their lipophilicity.

  • Sulfoquinovose is a select nutrient of prominent bacteria and a source of hydrogen sulfide in the human gut.

    Hanson BT, Dimitri Kits K, Löffler J, Burrichter AG, Fiedler A, Denger K, Frommeyer B, Herbold CW, Rattei T, Karcher N, Segata N, Schleheck D, Loy A
    2021 - ISME J, In press

    Abstract: 

    Responses of the microbiota to diet are highly personalized but mechanistically not well understood because many metabolic capabilities and interactions of human gut microorganisms are unknown. Here we show that sulfoquinovose (SQ), a sulfonated monosaccharide omnipresent in green vegetables, is a selective yet relevant substrate for few but ubiquitous bacteria in the human gut. In human feces and in defined co-culture, Eubacterium rectale and Bilophila wadsworthia used recently identified pathways to cooperatively catabolize SQ with 2,3-dihydroxypropane-1-sulfonate as a transient intermediate to hydrogen sulfide (HS), a key intestinal metabolite with disparate effects on host health. SQ-degradation capability is encoded in almost half of E. rectale genomes but otherwise sparsely distributed among microbial species in the human intestine. However, re-analysis of fecal metatranscriptome datasets of four human cohorts showed that SQ degradation (mostly from E. rectale and Faecalibacterium prausnitzii) and HS production (mostly from B. wadsworthia) pathways were expressed abundantly across various health states, demonstrating that these microbial functions are core attributes of the human gut. The discovery of green-diet-derived SQ as an exclusive microbial nutrient and an additional source of HS in the human gut highlights the role of individual dietary compounds and organosulfur metabolism on microbial activity and has implications for precision editing of the gut microbiota by dietary and prebiotic interventions.

  • High-accuracy long-read amplicon sequences using unique molecular identifiers with Nanopore or PacBio sequencing.

    Karst SM, Ziels RM, Kirkegaard RH, Sørensen EA, McDonald D, Zhu Q, Knight R, Albertsen M
    2021 - Nat Methods, 2: 165-169

    Abstract: 

    High-throughput amplicon sequencing of large genomic regions remains challenging for short-read technologies. Here, we report a high-throughput amplicon sequencing approach combining unique molecular identifiers (UMIs) with Oxford Nanopore Technologies (ONT) or Pacific Biosciences circular consensus sequencing, yielding high-accuracy single-molecule consensus sequences of large genomic regions. We applied our approach to sequence ribosomal RNA operon amplicons (~4,500 bp) and genomic sequences (>10,000 bp) of reference microbial communities in which we observed a chimera rate <0.02%. To reach a mean UMI consensus error rate <0.01%, a UMI read coverage of 15× (ONT R10.3), 25× (ONT R9.4.1) and 3× (Pacific Biosciences circular consensus sequencing) is needed, which provides a mean error rate of 0.0042%, 0.0041% and 0.0007%, respectively.

  • Anaerobic bacterial degradation of protein and lipid macromolecules in subarctic marine sediment.

    Pelikan C, Wasmund K, Glombitza C, Hausmann B, Herbold CW, Flieder M, Loy A
    2021 - ISME J, 3: 833-847

    Abstract: 

    Microorganisms in marine sediments play major roles in marine biogeochemical cycles by mineralizing substantial quantities of organic matter from decaying cells. Proteins and lipids are abundant components of necromass, yet the taxonomic identities of microorganisms that actively degrade them remain poorly resolved. Here, we revealed identities, trophic interactions, and genomic features of bacteria that degraded C-labeled proteins and lipids in cold anoxic microcosms containing sulfidic subarctic marine sediment. Supplemented proteins and lipids were rapidly fermented to various volatile fatty acids within 5 days. DNA-stable isotope probing (SIP) suggested Psychrilyobacter atlanticus was an important primary degrader of proteins, and Psychromonas members were important primary degraders of both proteins and lipids. Closely related Psychromonas populations, as represented by distinct 16S rRNA gene variants, differentially utilized either proteins or lipids. DNA-SIP also showed C-labeling of various Deltaproteobacteria within 10 days, indicating trophic transfer of carbon to putative sulfate-reducers. Metagenome-assembled genomes revealed the primary hydrolyzers encoded secreted peptidases or lipases, and enzymes for catabolism of protein or lipid degradation products. Psychromonas species are prevalent in diverse marine sediments, suggesting they are important players in organic carbon processing in situ. Together, this study provides new insights into the identities, functions, and genomes of bacteria that actively degrade abundant necromass macromolecules in the seafloor.

Book chapters and other publications

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