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Kumpitsch, C.

Publications and source records attributed to Kumpitsch, C..

9 recordsLinked to original sources

Functional profiling of spacecraft cleanroom microbiomes through genome-wide phenotype predictions

Current planetary protection approaches rely heavily on spore-based tests developed for Mars missions and may not adequately assess contamination risks for icy ocean worlds such as Europa. We developed a genome-based framework combining deep shotgun metagenomics and supervised machine learning to predict survival-relevant microbial traits in ESA JUICE launch-site cleanrooms. From 183 genome bins, 25 representative genomes were analyzed for traits including cryotolerance, desiccation tolerance, salt resilience, anaerobic metabolism, autotrophy, and sporulation. Several skin-associated microbes carried multiple relevant traits, and some appeared actively replicating. A broader meta-analysis of 1,868 genomes showed that trait profiles vary strongly within taxa, demonstrating that taxonomy alone is insufficient for risk assessment. This framework complements current planetary protection assays, helps to predict how microbes would survive in a new biotope, and supports functional, risk-informed contamination monitoring for future space missions.

microbiology↗

Enhanced environmental complexity worsens experimental colitis and dysregulates microbiota-gut-brain axis signalling in female mice

Ulcerative colitis (UC) is a chronic inflammatory disease characterized by colonic inflammation and bloody diarrhoea. Accumulating evidence suggests that UC not only affects the intestinal tract, but also distant organs including the brain. Environmental factors are key determinants of the disease course, yet the impact and potential disease modifying effects of living environment complexity on microbiota-gut-brain axis signalling during colitis remain unclear. To address this gap, we investigated how enhanced environmental complexity (EC) affects the disease course and gut-brain axis signalling during experimental colitis in mice. Our results show that EC exacerbates dextran sulphate sodium (DSS)-induced colitis in female mice, but not in male mice, as evidenced by greater weight loss and higher disease activity. Immune cell profiling across the gut-brain axis reveals strong effects of DSS treatment on colonic, circulating and brain immune cell populations and a restriction of central nervous system (CNS) T cell infiltration due to EC. In addition, female EC/DSS mice have higher circulating corticosterone levels than controls indicating chronic stress. Metabolomics across the gut-brain axis revealed that EC exacerbates colitis-induced metabolite perturbations in plasma, brain tissue, brain interstitial and cerebrospinal fluid. Notably, microbiota-derived metabolites, including deoxycholic acid and trimethylamine-N-oxide (TMAO), are increased in EC/DSS mice, concordant with EC-associated microbiome changes and anxiety-like behaviour. Overall, this study indicates that EC worsens experimental colitis in female mice and directs microbiota-gut-brain axis signalling during colitis towards a less favourable state. From a translational perspective, this study highlights the importance of environmental factors for a sex-specific disease course of UC and associated neurobehavioral comorbidities. HighlightsO_LIEnhanced environmental complexity (EC) exacerbates experimental colitis C_LIO_LIColitis and EC have compartment-specific effects on immune cells C_LIO_LIEC augments colitis-induced metabolic shifts in plasma, brain and CSF C_LIO_LIMicrobiota-derived metabolites are important players for the effects of EC C_LI

neuroscience↗

Pan-microbiome analysis along the human respiratory axis reveals an ecological continuum in health and collapse in disease

The human respiratory tract (RT) harbors complex microbial communities whose functions are critical to health and disease. Yet, current insights remain fragmented across anatomical sites, populations, and clinical states, limiting the fields ability to define common patterns in health and disease. Here, we present the first global respiratory pan-microbiome atlas, a resource integrating over 4,000 metagenomes across upper, intermediate, and lower RT from diverse cohorts encompassing health, pneumonia, COVID-19, and cystic fibrosis. Standardized taxonomic profiling reveals marked biogeographic structure: in health, lower RT communities largely represent filtered subsets of upper RT microbiota. Respiratory disease disrupts this organization, with reproducible depletion of core taxa at specific locations such as Rothia mucilaginosa and Fusobacterium pseudoperiodonticum, the latter being present in 88% of healthy sputum samples. Source-tracking analyses further support the collapse of inter-compartmental connectivity in disease and show the emergence of invasive taxa of unclear origin. Finally, prevalence-based models outperform abundance-based models in detecting disease-associated disruptions, providing greater sensitivity to shifts in community stability. Altogether, this atlas defines the healthy RT microbiome as a spatially structured ecosystem and provides a foundational reference for advancing personalized care and systems-level models of respiratory disease.

bioinformatics↗

Methanobrevibacter smithii associates with colorectal cancer through trophic control of the cancer bacteriome

The human gut is colonized by trillions of microbes that influence the health of their human host. Whereas many bacterial species have now been linked to a variety of different diseases, the involvement of Archaea in human disease remains elusive. Here we searched for gut archaeal signatures of disease by screening 19 cross-sectional clinical studies comprising more than 1,800 individuals. We found that associations between Archaea and medical disorders are common but highly variable and are dominated by a significant increase of Methanobrevibacter smithii in colorectal cancer (CRC) patients. Metabolic modelling and in vitro co-culture identified distinct mutualistic interactions of M. smithii with CRC-causing bacteria such as Fusobacterium nucleatum, including metabolic enhancement. Metabolomics further revealed archaeal-derived compounds with tumor-modulating properties. This provides the first mechanistic link between human gut archaeome and CRC and highlights its role in modulating health in humans through trophic control of the resident bacteriome.

microbiology↗

First-Year Dynamics of the Anaerobic Microbiome and Archaeome in Infants Oral and Gastrointestinal Systems

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 co-occurrence 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.

microbiology↗

Proteomic and Metabolomic Profiling of Archaeal Extracellular Vesicles from the Human Gut

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.

microbiology↗

Expanding the cultivated human archaeome by targeted isolation of novel Methanobrevibacter strains from fecal samples

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 Methanobrevibacter smithii 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. 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, in silico 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. 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 Methanobrevibacter smithii and Candidatus Methanobrevibacter intestini strains from diverse participant cohorts revealed features potentially associated with gastrointestinal diseases. 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 Candidatus Methanobrevibacter intestini genomes in critical microbiome situations.

microbiology↗

Age-Related Dynamics of Methanogenic Archaea in the Human Gut Microbiome: Implications for Longevity and Health

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). 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 Methanobrevibacter smithii, rather than Ca. M. intestini. Remarkably, Ca. M. intestini emerged as a central player in the network stability of adults, paving the way for M. smithii 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. 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 Ca. M. intestini and the partnership between methanogens and specific butyrate-producing bacteria for enhanced health and potential longevity.

microbiology↗

Methane emission of humans is explained by dietary habits, host genetics, local formate availability and a uniform archaeome

Archaea are responsible for methane production in the human gastrointestinal tract. Twenty percent of the Western populations exhale substantial amounts of this gas. The underlying principle determining high or low methane emission and its effect on human health was still not sufficiently understood. In this study, we analysed the gastrointestinal microbiome, archaeome, metagenome, metabolome, and eating behaviour of 100 healthy young adults. We correlated high levels of human methane emission (5-75 ppm) with a 1000-fold increase in Methanobrevibacter smithii. This archaeon co-occurred with a bacterial community specialised on dietary fibre degradation, which included members of the Ruminococcaceae and Christensenellaceae. Methane production was negatively affected by high vitamin B12 and fat intake of the subjects, and was positively associated with increased formate concentrations in the gut. Overall, methane emission is explained by dietary habits, host genetics, local metabolite availability and microbiome/archaeome composition, emphasizing the unique biology of high methane-emitters which has potentially positive impact on human health. O_FIG O_LINKSMALLFIG WIDTH=171 HEIGHT=200 SRC="FIGDIR/small/423794v1_ufig1.gif" ALT="Figure 1"> View larger version (79K): org.highwire.dtl.DTLVardef@16eb91org.highwire.dtl.DTLVardef@c3b928org.highwire.dtl.DTLVardef@1b11fa5org.highwire.dtl.DTLVardef@194bed2_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical abstract:C_FLOATNO C_FIG

microbiology↗