Biology subjects

Clavel, T.

Publications and source records attributed to Clavel, T..

24 records · Page 2Linked to original sources

bioRxiv2022

Enhanced cultured diversity of the mouse gut microbiota enables custom-made synthetic communities

Microbiome research is hampered by the fact that many bacteria are still unknown and by the lack of publicly available isolates. Fundamental and clinical research is in need of comprehensive and well-curated repositories of cultured bacteria from the intestine of mammalian hosts. In this work, we expanded the mouse intestinal bacterial collection (www.dsmz.de/miBC) to 212 strains, all publicly available and taxonomically described. This includes the study of strain-level diversity, small-sized bacteria, and the isolation and characterization of the first cultured members of one novel family, 10 novel genera, and 39 novel species. We demonstrate the value of this collection by performing two studies. First, metagenome-educated design allowed establishing custom synthetic communities (SYNs) that reflect different susceptibilities to DSS-induced colitis. Second, nine phylogenetically and functionally diverse species were used to amend the Oligo-Mouse Microbiota (OMM)12 model [Brugiroux et al. 2016 Nat Microbiol]. These strains compensated for differences observed between gnotobiotic OMM12 and specific pathogen-free (SPF) mice at multiple levels, including body composition and immune cell populations (e.g., T-cell subtypes) in the intestine and associated lymphoid tissues. Ready-to-use OMM stocks are available to the community for use in future studies. In conclusion, this work improves our knowledge of gut microbiota diversity in mice and enables functional studies via the modular use of isolates.

microbiology↗

bioRxiv2022

Neonatal Peyer's patch cDC activation as a pacemaker of postnatal immune maturation

Marked differences exist between the mucosal immune system of the neonate and adult host. The pronounced influence of the enteric microbiota in adults suggests a causal relationship between postnatal colonization and immune maturation. However, using metagenomic, metaproteomic, and functional immunological analyses we demonstrate an early presence of bacteria and immunogenic microbial antigens preceding immune maturation in the small intestine, the primary inductive site of intestinal immunity. Instead, transcriptomic, flow cytometric and histological analysis indicated neonatal Peyers patch (PP) mononuclear phagocytes (MNP) as rate limiting factor of postnatal immune maturation. Despite the early presence of MNPs, conventional dendritic cells (cDC) of type 1, 2a and 2b exhibited significant age-dependent differences in tissue distribution and cellular composition. Single cell transcriptional profiling and functional assays revealed decreased antimicrobial and antigen processing/presentation capacity, an overall retarded cell maturation and reduced antigen uptake. In cDC2a this resulted in a reduced proportion of CCR7+ migratory cells and a consequent defect in CD4 T cell priming. Interestingly, transcriptional profiling of neonatal DC subsets identified reduced expression of type I interferon (IFN)-stimulated genes (ISG). Type I IFN induction by oral administration of the TLR7 agonist R848 accelerated MNP maturation and enhanced cognate antigen CD4 T cell priming. However, humoral responses to oral vaccination in the presence of R848 were significantly reduced. Together, our results identify PP MNP maturation as pacemaker of postnatal mucosal immune priming, indicate the biological role of delayed maturation and demonstrate that targeted interventional strategies allow manipulation of mucosal responses in early life.

immunology↗

bioRxiv2020

Diversity and function of microbial lipases within the mammalian gut

Triglycerides are a major dietary component and excessive intake has been linked to many health conditions. While the impact of host lipases on fat degradation and absorption have been well documented, bacterial lipases have been largely ignored. Here, we identified the landscape of microbial lipases within the gut of mice, pigs, and humans. In total, 373 microbial lipases were identified and formed two major clusters based on protein sequences, with the sequences containing highly conserved motifs. Metagenomic and cultivation approaches identified lipase-positive bacteria as diverse, occurring within seven phyla, and abundant within the human gut (9.1% {+/-} 4.6%). Pathway analysis in lipase-positive species identified a low prevalence of fatty acid utilisation and a higher frequency of glycerol metabolism. In vitro testing with stable isotopes confirmed that human gut bacteria can utilise the released glycerol. Overall, this study highlights the role of bacterial lipolytic activity in triglycerides metabolism within the gut.

microbiology↗

bioRxiv2019

Arrhythmic gut microbiome signatures for risk profiling of Type-2 Diabetes

To combat the epidemic increase in Type-2-Diabetes (T2D), risk factors need to be identified. Diet, lifestyle and the gut microbiome are among the most important factors affecting metabolic health. We demonstrate in 1,976 subjects of a prospective population cohort that specific gut microbiota members show diurnal oscillations in their relative abundance and we identified 13 taxa with disrupted rhythmicity in T2D. Prediction models based on this signature classified T2D with an area under the curve of 73%. BMI as microbiota-independent risk marker further improved diagnostic classification of T2D. The validity of this arrhythmic risk signature to predict T2D was confirmed in 699 KORA subjects five years after initial sampling. Shotgun metagenomic analysis linked 26 pathways associated with xenobiotic, amino acid, fatty acid, and taurine metabolism to the diurnal oscillation of gut bacteria. In summary, we determined a cohort-specific risk pattern of arrhythmic taxa which significantly contributes to the classification and prediction of T2D, highlighting the importance of circadian rhythmicity of the microbiome in targeting metabolic human diseases.

microbiology↗

bioRxiv2019

Sporaefaciens musculi gen. nov., sp. nov., a novel bacterium isolated from the caecum of an obese mouse

A bacterial strain, designated WCA-9-b2, was isolated from the caecal content of an 18-week-old obese C57BL/6NTac male mouse. According to phenotypic analyses, the isolate is rod-shaped, Gram-positive, strictly anaerobic, spore-forming and non-motile under the conditions tested. Bacterial colonies were irregular and non-pigmented. Analysis of the 16S rRNA gene indicated that the isolate belonged to the family Lachnospiraceae with Clostridium scindens ATTC 35704 (94.9% sequence identity) and Dorea formicigenerans ATCC 27755 (94.8%) being the closest relatives. Whole genome sequencing showed average nucleotide identity (ANI) ranging from 69.80-74.23% and percentage of conserved proteins (POCP) values < 50% against the nine closest relatives. The genome-based G+C content of genomic DNA was 44.4%. The predominant metabolic end products of glucose fermentation were acetate and succinate. Based on these data, we propose that strain WCA-9-b2 represents a novel species within a novel genus, for which the name Sporaefaciens musculi gen. nov., sp. nov. is proposed. The type strain is WCA-9-b2T (=DSM 106039T = CCUG pending IDT). RepositoriesThe GenBank accession number for the 16S rRNA gene sequence of strain WCA-9-b2T is MN756014, and the accession number for the genome assembly is PRJNA592877. Raw sequencing Illumina NextSeq (PRJEB35655) and ONT MinION (PRJEB35656) data can be accessed at EMBL-EBI.

microbiology↗

bioRxiv2019

An integrated metagenome catalog reveals novel insights into the murine gut microbiome

The vast complexity of host-associated microbial ecosystems requires generation of host-specific gene catalogs to survey the functions and diversity of these communities. We generated a comprehensive resource, the integrated mouse gut metagenome catalog (iMGMC), comprising 4.6 million unique genes and 660 high-quality metagenome-assembled genomes (MAGs) linked to reconstructed full-length 16S rRNA gene sequences. iMGMC enables unprecedented coverage and taxonomic resolution, i.e. more than 89% of the identified taxa are not represented in any other databases. The tool (github.com/tillrobin/iMGMC) allowed characterizing the diversity and functions of prevalent and previously unknown microbial community members along the gastrointestinal tract. Moreover, we show that integration of MAGs and 16S rRNA gene data allows a more accurate prediction of functional profiles of communities than based on 16S rRNA amplicons alone. Integrated gene catalogs such as iMGMC are needed to enhance the resolution of numerous existing and future sequencing-based studies.

microbiology↗