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Löber, U.

Publications and source records attributed to Löber, U..

3 recordsLinked to original sources

The elusive resistome: a global comparison reveals large discrepancies among detection pipelines

Identifying antibiotic resistance genes (ARGs) from metagenomic data is critical for studying antimicrobial resistance across microbial communities and pathogens. However, there is no standardized methodology for ARG annotation. Here, we compare ten commonly used ARG detection pipelines by analysing over 270 million prokaryotic genes from the Global Microbial Gene Catalogue across 13 distinct habitats. We observed up to a 45-fold difference in the number of reported ARGs, with a mean Jaccard index of only 16% between pipelines. Pipeline selection profoundly impacted downstream biological interpretations, with drastic changes to estimates of ARG relative abundance and richness, to the characterization of pan- and core-resistomes, and to the class-level composition of the inferred resistome. ARG detection pipelines make different, defensible trade-offs, and no single approach should be treated as authoritative. Therefore, users should justify and communicate choices carefully, as our analyses show that, taken uncritically, the same data can support conflicting biological and ecological interpretations.

bioinformatics↗

Similar Fecal SCFA Patterns Despite Diverse Gut Microbiota in Polish and Japanese Children During the First Two Years of Life. The longitudinal, comparative, validated study.

BackgroundEarly-life gut microbiome assembly is shaped by environment, diet, and perinatal exposures. Whether population context shifts taxonomic trajectories and functional outputs similarly remains unclear. MethodsWe re-analyzed longitudinal infant cohorts from Poland (PL) and Japan (JP) across five time points (1 week, 1 month, 6 months, 1 year, 2 years). Amplicon sequence variants (ASVs) were processed uniformly. Cross-sectional alpha diversity (richness, evenness, Shannon, Simpson) was modeled with covariate adjustment (sex, antibiotics, diet). Beta diversity used Bray-Curtis distances (PCoA) and PERMANOVA (unadjusted/adjusted). Confounder-aware genus-level differential abundance identified features not reducible to covariates. Longitudinal genus trajectories and genus-SCFA (acetate, propionate, butyrate, isobutyrate) associations were tested using mixed-effects models. SCFAs were z-score-normalized to harmonize units across cohorts. Sensitivity analyses restricted PL to vaginally delivered infants. Finnish (FIN) and United States (US) cohorts were included for taxonomic validation. ResultsEvenness, Shannon, and Simpson were similar between PL and JP at most time points; richness was higher in PL at 1 week with trends at 6 months. Beta diversity showed a significant country effect at every time point except 1 month, robust to covariate adjustment and to restriction to 74 genera shared between PL and JP. Genus-level differential abundance yielded 33 features (26 enriched in PL, 7 in JP) without consistent cross-time recurrence. Longitudinally, most genus trajectories were cohort-specific; genus-SCFA associations were largely population-specific (few overlaps for butyrate/isobutyrate, none for acetate/propionate). Despite taxonomic and association differences, SCFA trajectories did not differ between cohorts after harmonization and adjustment. FIN/US validation supported the robustness of temporal taxonomic signals with few discordances. ConclusionsTaxonomic profiles and genus-SCFA relationships diverge across populations, whereas core metabolic outputs (fecal SCFAs) follow a conserved, resilient trajectory in early life. This "divergent taxa, convergent function" pattern suggests early-life interventions should prioritize functional maturation over targeting specific taxa. Broader multi-omic studies integrating growth, immune, and neurodevelopmental outcomes are warranted.

microbiology↗

Gut microbiota dysbiosis is associated with altered tryptophan metabolism and dysregulated inflammatory response in severe COVID-19

The clinical course of the 2019 coronavirus disease (COVID-19) is variable and to a substantial degree still unpredictable, especially in persons who have neither been vaccinated nor recovered from previous infection. We hypothesized that disease progression and inflammatory responses were associated with alterations in the microbiome and metabolome. To test this, we integrated metagenome, metabolome, cytokine, and transcriptome profiles of longitudinally collected samples from hospitalized COVID-19 patients at the beginning of the pandemic (before vaccines or variants of concern) and non-infected controls, and leveraged detailed clinical information and post-hoc confounder analysis to identify robust within- and cross-omics associations. Severe COVID-19 was directly associated with a depletion of potentially beneficial intestinal microbes mainly belonging to Clostridiales, whereas oropharyngeal microbiota disturbance appeared to be mainly driven by antibiotic use. COVID-19 severity was also associated with enhanced plasma concentrations of kynurenine, and reduced levels of various other tryptophan metabolites, lysophosphatidylcholines, and secondary bile acids. Decreased abundance of Clostridiales potentially mediated the observed reduction in 5-hydroxytryptophan levels. Moreover, altered plasma levels of various tryptophan metabolites and lower abundances of Clostridiales explained significant increases in the production of IL-6, IFN{gamma} and/or TNF. Collectively, our study identifies correlated microbiome and metabolome alterations as a potential contributor to inflammatory dysregulation in severe COVID-19. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=150 HEIGHT=200 SRC="FIGDIR/small/518860v1_ufig1.gif" ALT="Figure 1"> View larger version (48K): org.highwire.dtl.DTLVardef@afc4edorg.highwire.dtl.DTLVardef@1a9ac2aorg.highwire.dtl.DTLVardef@65fb46org.highwire.dtl.DTLVardef@153ee6a_HPS_FORMAT_FIGEXP M_FIG C_FIG

systems biology↗