Biology subjects

Mende, D.

Publications and source records attributed to Mende, D..

3 recordsLinked to original sources

bioRxiv2025

Microbiota-derived indole metabolites inhibit rotavirus infection in vitro and in vivo and in human infants

Rotavirus (RV) is the leading cause of life-threatening gastroenteritis in children under five despite effective RV vaccines availability, necessitating novel protective strategies for high-risk populations. Gut microbiota can modulate RV susceptibility and vaccine immunogenicity, yet underlying mechanisms are poorly characterized. Here, we demonstrate that microbiota-derived indole metabolites confer protection against RV infection. In healthy adults, higher fecal indole-3-acetic acid (IAA) and indole-3-propionic acid (IPA) levels associated with reduced fecal RV shedding following challenge. In human intestinal enteroids (HIEs), IAA pre-treatment inhibited human RV Wa G1P[8] replication via the aryl hydrocarbon receptor (AhR) pathway. In mice, treatment with AhR agonist indole-3-carbinol (I3C) significantly reduced fecal shedding of murine RV strain EDIM-Cambridge. Finally, Zambian infants with active RV infection exhibited lower fecal IAA and IPA levels than age-matched healthy controls. These findings demonstrate that microbiota-derived AhR ligands consistently inhibit RV infection across three experimental models and hold promise for protecting at-risk pediatric populations.

microbiology↗

bioRxiv2025

Unique ecology of co-occurring functionally and phylogenetically undescribed species in the infant oral microbiome

Early-life oral microbiome development is a complex community assembly process that influences long-term health outcomes. Nevertheless, microbial functions and interactions driving these ecological processes remain poorly understood. In this study, we analyze oral microbiomes from a longitudinal cohort of 24 mother-infant dyads at 1 and 6 months postpartum using shotgun metagenomics. We identify two previously undescribed Streptococcus and Rothia species to be among the most prevalent, abundant and strongly co-occurring members of the oral microbiome of six-month-old infants. To explore the underlying genomic traits enabling this unique lifestyle, we leveraged metagenome-assembled genomes (MAGs) and genome-scale metabolic models (GEMS). Comparative analyses revealed specific genomic and functional characteristics relative to other closely related species and highlighted unique functional features, including genes encoding adhesins and carbohydrate-active enzymes (CAZymes). The observed co-occurrence patterns were further supported by predicted metabolic interactions within a network of co-occurring oral taxa. Metabolic modeling identified potential exchange of key nutrients, particularly malate and lysine, between these species, suggesting metabolic cross-feeding interactions that may explain their co-occurrence across infant oral microbiomes. Overall, this study provides key insights into the functional adaptations and microbial interactions shaping early colonization in the oral cavity. Author SummaryWe investigated how infant oral bacterial communities develop during their first six months of life, with the aim to understand which microbes colonize, how they establish themselves and why they succeed together. Using high throughput DNA sequencing techniques, we analyzed oral samples from 24 mother-infant pairs at one and six months after birth. We found two abundant, but previously unknown bacterial species (one Streptococcus and one Rothia) at six months of age. These bacteria consistently appear together across different babies, suggesting they may depend on each other for survival and growth. By reconstructing the genomes of these bacteria directly from our samples, we discovered specific genetic features that help explain their success in the infant mouth. Streptococcus carries genes that allow it to break down nutrients from breast milk. Rothia has genes that help it rapidly build cell membranes and protect against harmful molecules, while producing nutrients that Streptococcus needs. We predict these bacteria exchange key nutrients like malate and lysine, creating a mutually beneficial partnership. The bacteria seem to cooperate and are predicted to exchange key nutrients like malate and lysine which may help maintain a healthy oral environment by regulating acidity levels, potentially protecting against tooth decay.

genomics↗

bioRxiv2021

Extended taxonomic profiling of diverse environments with mOTUs 2.6

BackgroundTaxonomic profiling is a fundamental task in microbiome research that aims to detect and quantify the relative abundance of microorganisms in biological samples. Available methods using shotgun metagenomic data generally depend on the availability of sequenced and taxonomically annotated reference genomes. However, the majority of microorganisms have not been cultured yet and lack such reference genomes. Thus, a substantial fraction of microbial community members remains unaccounted for during taxonomic profiling of metagenomes, particularly in samples from underexplored environments. To address this issue, we have developed the mOTU profiler, a tool that enables reference genome-independent species-level profiling of metagenomes. As such, it supports the identification and quantification of both "known" and "unknown" species based on a set of select marker genes. ResultsHere, we present mOTUs3, a command line tool that enables the profiling of metagenomes for >33,000 species-level operational taxonomic units. To achieve this, we leveraged the reconstruction and analysis of >600,000 draft genomes, most of which are metagenome assembled genomes (MAGs), from diverse microbiomes, including soil, freshwater systems, and the gastrointestinal tract of ruminants and other animals, which we found to be greatly underrepresented by reference genomes. Overall, two-thirds of all species-level taxa lacked a reference genome. The cumulative relative abundance of these newly included taxa was low in well-studied microbiomes, such as the human body sites (6-11%). By contrast, they accounted for substantial proportions (ocean, freshwater, soil: 43-63%) or even the vast majority (pig, fish, cattle: 60-80%) of the relative abundance across diverse non-human-associated microbiomes. Using community-developed benchmarks and datasets, we found mOTUs3 to be more accurate than other methods and to be more congruent with 16S rRNA gene-based methods for taxonomic profiling. Furthermore, we demonstrate that mOTUs3 greatly increases the resolution of well-known microbial groups into species-level taxa and helps identify new differentially abundant taxa in comparative metagenomic studies. ConclusionsWe developed mOTUs3 to enable accurate species-level profiling of metagenomes. Compared to other methods, it provides a more comprehensive view of prokaryotic community diversity, in particular for currently underexplored microbiomes. To facilitate comparative analyses by the research community, it is released with >11,000 precomputed profiles for publicly available metagenomes and is freely available at: https://github.com/motu-tool/mOTUs.

bioinformatics↗