Biology subjects

Hoegenauer, C.

Publications and source records attributed to Hoegenauer, C..

4 recordsLinked to original sources

bioRxiv2026

Host-derived bile acids drive dysbiosis by selecting bile-resistant epimerizing bacteria in inflammatory bowel disease

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.

microbiology↗

bioRxiv2024

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↗

bioRxiv2020

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↗

bioRxiv2018

Measuring the archaeome: detection and quantification of archaea signatures in the human body

Due to their fundamentally different biology, archaea are consistently overlooked in conventional 16S rRNA gene amplicon surveys. Herein, we evaluate different methodological set-ups to detect and quantify archaea signatures in human samples (nose, oral, appendix, stool, and skin) using amplicon sequencing and quantitative PCR.\n\nWith our optimized protocol, we were able to increase the detection of archaeal RSVs from one (using a so-called \"universal\" approach) to 81 RSVs in a representative sample set. Moreover, we confirmed the presence of about 5% archaeal signatures in the human gut, but found, unexpectedly, an almost 1:1 ratio of archaeal to bacterial 16S rRNA genes in appendix and nose samples. This finding indicates a high prevalence of archaeal signatures in body regions thus far not analyzed for the presence of archaea using appropriate methods.\n\nIn order to assess the archaeome diversity and archaeal abundance, a specific archaea-targeting methodology is required, for which we propose two standard procedures. These methodologies might not only prove useful for analyzing the human archaeome in more detail, but could also be used for other holobionts samples.

microbiology↗