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Mahnert, A.

Publications and source records attributed to Mahnert, A..

15 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↗

Spatiotemporal Microbial Ecoevolutionary Dynamics on the International Space Station

This study presents the most comprehensive spatiotemporal analysis of the ISS microbiome to date. Over a seven-year period, 184 surface samples were collected for live/dead metagenomic profiling, phenotypic characterization of antimicrobial resistance (AMR) and virulence among 102 cultured isolates, and metagenome-assembled genome (MAG) analysis to evaluate evolutionary selection pressures. Despite ecological stability, comparative genomics revealed ongoing microevolution through lateral gene transfer and selection for traits (e.g., radiation resistance and biocide tolerance). Importantly, predictions of AMR and virulence frequently misaligned with experimental outcomes, underscoring the need for functional validation. This dataset highlights a stable core microbiome that persists across years, punctuated by localized adaptation and gene flow. The ISS microbiome exemplifies both ecological resilience and microevolutionary innovation that can inform risk management for long-duration spaceflight.

microbiology↗

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↗

Computational metabolic modeling unveils gut microbiomes role in metabolic shifts during murine cancer cachexia

Cancer cachexia is a multifactorial syndrome characterized by involuntary weight loss, muscle wasting, systemic inflammation, and metabolic alterations, affecting up to 87% of pancreatic and gastric cancer patients. Unlike simple starvation, cachexia is driven by metabolic disruption involving both host physiology and the gut microbiome. While microbiome changes in cachexia have been documented, a coherent understanding of how these changes translate into functional metabolic shifts remains elusive. In this study, we combined in vivo fecal and plasma metabolomic analyses with a novel computational microbiome simulation pipeline to identify cachexia-associated microbial metabolites. Using the murine MCA207 tumor line and its cachectic derivative CHX207, we differentiated microbiome changes driven by cachexia from those induced by tumor growth. Our computational tool, McMurGut, a murine-tailored extension of MICOM, enabled simulation of microbial metabolic interactions specific to the mouse microbiome, covering 91% of identified genera. We identified significant abundance changes in 35 microbial genera and corresponding shifts in metabolite production, including reductions in short-chain fatty acids (SCFAs) like acetate and butyrate, alongside increased production of galactose, formate, and propionate. Notably, decreases in SCFA production, particularly by genera such as Faecalibaculum and Dubosiella, correlated with exacerbated cachectic symptoms. Additionally, the elevated production of formate and galactose, primarily by Bacteroides and Lactobacillus, suggested altered fermentation pathways in cachexia, potentially linked to increased mucus degradation. Validation of our computational predictions via NMR metabolomics highlighted key congruencies between predicted and experimentally observed metabolites, supporting the role of microbiome-driven metabolic shifts in cachexia pathology. These findings provide crucial insights into the microbiomes involvement in cachexia and suggest future avenues for therapeutic interventions aimed at modulating microbial taxa and their metabolic outputs to improve patient outcomes.

microbiology↗

Molecular Tracking and Cultivation Reveal Ammonia Oxidizing Archaea as Integral Members of the Human Skin Microbiome

BackgroundAmmonia-oxidizing archaea (AOA) have repeatedly been detected on human skin, yet their persistence, physiological traits, and adaptations remain poorly understood. Here, we identify Nitrosocosmicus species as integral members of the healthy skin microbiome using two complementary approaches. ResultsThrough cultivation, we enriched two autotrophic strains, Candidatus Nitrosocosmicus epidermidis and Ca. Nitrosocosmicus unguis, from human skin samples. Genomic analyses revealed specific adaptations for skin colonization, including genomic islands and expanded gene families linked to interactions with host proteins and signaling pathways, distinguishing these AOA from their soil-dwelling relatives. Parallel molecular profiling in cross-sectional and longitudinal cohorts (n=47) consistently detected Nitrosocosmicus particularly in sebaceous areas. Co-occurrence patterns with specific bacterial taxa reinforce their role as stable components of the skin microbiome. ConclusionsThese findings indicate that Nitrosocosmicus species are emerging commensals, evolutionarily capable of transitioning from soil to human skin, where they likely play a critical role in the skin ecosystem.

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↗

Expanding the cultivable human archaeome: Methanobrevibacter intestini sp. nov. and strain Methanobrevibacter smithii GRAZ-2 from human feces

Two mesophilic, hydrogenotrophic methanogens, WWM1085 and M. smithii 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 Methanobrevibacter. M. smithii GRAZ-2 (= DSM 116045) was retrieved from fecal samples of a European, healthy female and represents a novel strain within this genus. Both Methanobrevibacter representatives form non-flagellated, short rods with variable morphologies and the capacity to form filaments. Both isolates showed the typical fluorescence of F420 and methane production. Compared to M. smithii GRAZ-2, WWM1085 did not accumulate formate when grown on H2 and CO2. The optimal growth conditions were at 37{degrees}C, and pH 7. Full genome sequencing revealed a genomic difference of WWM1085 to the type strain of M. smithii PS (type strain; DSM 861), with 93.55% ANI and major differences in the sequence of its mcrA 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. M. smithii GRAZ-2 was identified as a novel strain within the Methanobrevibacter genus (ANI 99.04 % to M. smithii PS). Due to the major differences of WWM1085 and M. smithii type strain PS in phenotypic, genomic and metabolic features, we propose M. intestini sp. nov. as a novel species with WWM1085 as the type strain (DSM 116060T = CECT 30992).

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↗

The Dynamics of the Female Microbiome: Unveiling Abrupt Changes of Microbial Domains across Body Sites from Preconception to Perinatal Phase

The microbial ecosystem of women undergoes enormous changes during pregnancy and the perinatal period. Little is known about the extent of changes in the maternal microbiome beyond the vaginal cavity and its recovery after birth. In this study, we followed pregnant women (mpre, n = 30) into the postpartum period (1 month postpartum, mpost, n = 30). We profiled their oral, urinary, and vaginal microbiome, archaeome, mycobiome and urinary metabolome and compared them with nonpregnant women (np, n = 29). Overall, pregnancy status (np, mpre, mpost) had a smaller effect on the microbiomes than body site, but massive transitions were observed for the oral and urogenital (vaginal and urinary) microbiomes. While the oral microbiome fluctuates during pregnancy but stabilizes rapidly within the first month postpartum, the urogenital microbiome is characterized by a major remodeling caused by a massive loss of Lactobacillus and thus a shift from vaginal community state type (CST) I (40% of women) to CST IV (85% of women). The urinary metabolome rapidly reached an np-like composition after delivery, apart from lactose and oxaloacetic acid, which were elevated during active lactation. Fungal and archaeal profiles were indicative of pregnancy status. Methanobacterium signatures were found exclusively in np women, and Methanobrevibacter showed opposite behavior in oral cavity (increased) and vagina (decreased) during pregnancy. Our findings suggest that the massive remodeling of the maternal microbiome and metabolome needs more attention and that potential interventions could be envisioned to optimize recovery and avoid long-term effects on maternal health and subsequent pregnancies.

microbiology↗

Acute appendicitis manifests as two microbiome state types with oral pathogens influencing severity

Mounting evidence suggests that acute appendicitis (AA) is not one but two diseases: complicated appendicitis, which is associated with necrosis leading to perforation or periappendicular abscess, and uncomplicated appendicitis, which does not necessarily result in perforation. Even though AA is the most frequent cause of surgery from abdominal pain, little is known about the origins and etiopathogenesis of this disease, much less regarding the different disease types. In this study, we investigated the microbiome of samples from the appendix, rectum and peritoneum of 60 children and adolescents with AA to assess the composition and potential function of bacteria, archaea and fungi. The analysis of the appendix microbial community revealed a shift depending on the severity of the AA. This shift was reflected by two major community state types that represented the complicated and uncomplicated cases. We could demonstrate that complicated, but not uncomplicated, appendicitis is associated with a significant local expansion of oral, bacterial pathogens in the appendix, most strongly influenced by necrotizing Fusobacterium spp., Porphyromonas and Parvimonas. Uncomplicated appendicitis, however, was characterised by gut-associated microbiomes. Our findings support the hypothesis that two disease types exist in AA, which cannot be distinguished beyond doubt using standard clinical characterization methods or by analysis of the patients rectal microbiome. An advanced microbiome diagnosis, however, could improve non-surgical treatment of uncomplicated AA. ImportanceWith a lifetime risk of up to 17%, acute appendicitis is one of the most frequent causes of emergency abdominal surgery in westernized countries. Latest literature reports suggests that appendicitis manifests in two disease types: complicated and uncomplicated appendicitis with different, yet unknown, etiopathogenesis. In this study, we investigated the microbial composition (bacteria, archaea and fungi) from 60 children and adolescents that were diagnosed with acute appendicitis. Appendix, rectal and peritoneal samples were analysed using amplicon and metagenomic sequencing. Our results suggest that acute appendicitis manifests in three microbial state types that reflect complicated and uncomplicated appendicitis as well as special cases that are caused by bacterial overgrowth. Strikingly, uncomplicated appendicitis appears to be caused by gut-associated pathogens while complicated appendicitis is driven by oral-associated microbes such as Fusobacterium sp. or Porphyromonas sp. The findings provided in our study are of special interest to understand the etiopathogenesis of both complicated and uncomplicated appendicitis.

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↗

The indoor environment - a potent source for intact human-associated anaerobes

BackgroundPeople in westernised countries spend most of their time indoors. A healthy human microbiome relies on the interaction with and exchange of microbes that takes place between the human body and its environment. For this reason, the built environment might represent a potent source of commensal microbes. Anaerobic microbes are of particular interest, as researchers have not yet sufficiently clarified how the human microbiome acquires oxygen-sensitive microbes, such as obligate or facultative anaerobes. MethodsWe sampled ten households and used propidium monoazide to assess the viability of the collected prokaryotes. We compared the microbiome profiles based on 16S rRNA gene sequencing and confirmed our results by genetic and cultivation-based analyses. ResultsQuantitative and qualitative analysis revealed that most of the microbial taxa are of human origin. Less than 25% of the prokaryotic signatures found in built environment (BE) samples originate from intact - and thus potentially living - cells, indicating that aerobic and stress resistant taxa display an apparent survival advantage. Although the dominant microbial fraction identified on the bathroom floors is composed of aerobes, we confirmed the presence of strictly anaerobic taxa, including methanogenic archaea, in PMA-treated samples. As methanogens are regarded as highly sensitive to aerobic conditions, oxygen-tolerance experiments were performed with human-associated isolates to validate their survival. These results show that these taxa have a limited but substantial ability to survive in the BE. We determined that human-associated methanogens can survive oxic conditions for at least 6 h. ConclusionsThis study enabled us to collect strong evidence that supports the hypothesis that obligate anaerobic taxa can survive in the BE for a limited amount of time. This suggests that the BE serves as a potential source of anaerobic human commensals.

microbiology↗

A comprehensive analysis of the global human gut archaeome from a thousand genome catalogue

The human gut microbiome plays an important role in health and disease, but the archaeal diversity therein remains largely unexplored. Here we report the pioneering analysis of 1,167 non-redundant archaeal genomes recovered from human gastrointestinal tract microbiomes across countries and populations. We identified three novel genera and 15 novel species including 52 previously unknown archaeal strains. Based on distinct genomic features, we warrant the split of the Methanobrevibacter smithii clade into two separate species, with one represented by the novel Candidatus M. intestini. Patterns derived from 1.8 million proteins and 28,851 protein clusters coded in these genomes showed substantial correlation with socio-demographic characteristics such as age and lifestyle. We infer that archaea are actively replicating in the human gastrointestinal tract and are characterized by specific genomic and functional adaptations to the host. We further demonstrate that the human gut archaeome carries a complex virome, with some viral species showing unexpected host flexibility. Our work furthers our current understanding of the human archaeome, and provides a large genome catalogue for future analyses to decipher its role and impact on human physiology. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=81 SRC="FIGDIR/small/392621v1_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@3e0060org.highwire.dtl.DTLVardef@8adb45org.highwire.dtl.DTLVardef@41c087org.highwire.dtl.DTLVardef@c6fdf9_HPS_FORMAT_FIGEXP M_FIG GRAPHICAL ABSTRACT C_FIG HIGHLIGHTSO_LIThe human gut archaeome analysis reveals a previously unseen active diversity C_LIO_LIThe most abundant methanogen, Methanobrevibacter smithii, splits into two species C_LIO_LIArchaeal protein catalogue can predict geography, demographics and health aspects C_LIO_LIHost-associated and environmental archaea show distinct genomic & functional traits C_LI

bioinformatics↗

The International Space Station selects for microorganisms adapted to the extreme environment, but does not induce genomic and physiological changes relevant for human health

The International Space Station (ISS) is a unique, completely confined habitat for the human crew and co-inhabiting microorganisms. Here, we report on the results of the ISS experiment "EXTREMOPHILES". We aimed to exploit the microbial information obtained from three surface and air sampling events aboard the International Space Station during increments 51 and 52 (2017) with respect to: i) microbial sources, diversity and distribution within the ISS, ii) functional capacity of microbiome and microbial isolates, iii) extremotolerance and antibiotics-resistance (compared to ground controls), and iv) microbial behavior towards ISS-relevant materials such as biofilm formation, or potential for degradation. We used wipe samples and analyzed them by amplicon and metagenomics sequencing, cultivation, comparative physiological studies, antibiotic resistance tests, genome analysis of isolates and co-incubation experiments with ISS-relevant materials. The major findings were: i) the ISS microbiome profile is highly similar to ground-based confined indoor environments, ii) the ISS microbiome is subject to fluctuations and indicative for the (functional) location, although a core microbiome was present over time and independent from location, iii) the ISS selects for microorganisms adapted to the extreme environment, but does not necessarily induce genomic and physiological changes which might be relevant for human health, iv) cleanrooms and cargo seems to be a minor source of microbial contamination aboard, and v) microorganisms can attach to and grow on ISS-relevant materials. Biofilm formation might be a threat for spacecraft materials with the potential to induce instrument malfunctioning with consequences for mission success. We conclude that our data do not raise direct reason for concern with respect to crew health, but indicate a potential threat towards biofilm formation and material integrity in moist areas.

microbiology↗