Alterations of oral microbiota and impact on the gut microbiome in type 1 diabetes mellitus revealed by integrated multi-omic analyses

in Microbiome (2022)

Background: Alterations to the gut microbiome have been linked to multiple chronic diseases. However, the drivers of such changes remain largely unknown. The oral cavity acts as a major route of exposure ... [more ▼]

Background: Alterations to the gut microbiome have been linked to multiple chronic diseases. However, the drivers of such changes remain largely unknown. The oral cavity acts as a major route of exposure to exogenous factors including pathogens, and processes therein may affect the communities in the subsequent compartments of the gastrointestinal tract. Here, we perform strain‑resolved, integrated meta‑genomic, transcriptomic, and proteomic analyses of paired saliva and stool samples collected from 35 individuals from eight families with multiple cases of type 1 diabetes mellitus (T1DM). Results: We identified distinct oral microbiota mostly reflecting competition between streptococcal species. More specifically, we found a decreased abundance of the commensal Streptococcus salivarius in the oral cavity of T1DM individuals, which is linked to its apparent competition with the pathobiont Streptococcus mutans. The decrease in S. salivarius in the oral cavity was also associated with its decrease in the gut as well as higher abundances in facultative anaerobes including Enterobacteria. In addition, we found evidence of gut inflammation in T1DM as reflected in the expression profiles of the Enterobacteria as well as in the human gut proteome. Finally, we were able to follow transmitted strain‑variants from the oral cavity to the gut at the individual omic levels, highlighting not only the transfer, but also the activity of the transmitted taxa along the gastrointestinal tract. Conclusions: Alterations of the oral microbiome in the context of T1DM impact the microbial communities in the lower gut, in particular through the reduction of “mouth‑to‑gut” transfer of Streptococcus salivarius. Our results indicate that the observed oral‑cavity‑driven gut microbiome changes may contribute towards the inflammatory processes involved in T1DM. Through the integration of multi‑omic analyses, we resolve strain‑variant “mouth‑to‑gut” transfer in a disease context. [less ▲]

Bioremediation of 27 Micropollutants by Symbiotic Microorganisms of Wetland Macrophytes

in Sustainability (2022), 14(7), 3944

Background: Micropollutants in bodies of water represent many challenges. We addressedthese challenges by the application of constructed wetlands, which represent advanced treatmenttechnology for the ... [more ▼]

Background: Micropollutants in bodies of water represent many challenges. We addressedthese challenges by the application of constructed wetlands, which represent advanced treatmenttechnology for the removal of micropollutants from water. However, which mechanisms specificallycontribute to the removal efficiency often remains unclear. Methods: Here, we focus on the removalof 27 micropollutants by bioremediation. For this, macrophytesPhragmites australis,Iris pseudacorusandLythrum salicariawere taken from established wetlands, and a special experimental set-up wasdesigned. In order to better understand the impact of the rhizosphere microbiome, we determinedthe microbial composition using 16S rRNA gene sequencing and investigated the role of identifiedgenera in the micropollutant removal of micropollutants. Moreover, we studied the colonizationof macrophyte roots by arbuscular mycorrhizal fungi, which are known for their symbiotic rela-tionship with plants. This symbiosis could result in increased removal of present micropollutants.Results: We foundIris pseudacorusto be the most successful bioremediative system, as it removed22 compounds, including persistent ones, with more than 80% efficiency. The most abundant generathat contributed to the removal of micropollutants werePseudomonas, Flavobacterium, Variovorax,Methylotenera, Reyranella, AmaricoccusandHydrogenophaga.Iris pseudacorusexhibited the highest colo-nization rate (56%). Conclusions: Our experiments demonstrate the positive impact of rhizospheremicroorganisms on the removal of micropollutants. [less ▲]

Roles of bacteriophages, plasmids and CRISPR immunity in microbial community dynamics revealed using time-series integrated meta-omics

in Nature Microbiology (2021), 6(1), 123--135

Viruses and plasmids (invasive mobile genetic elements (iMGEs)) have important roles in shaping microbial communities, but their dynamic interactions with CRISPR-based immunity remain unresolved. We ... [more ▼]

Viruses and plasmids (invasive mobile genetic elements (iMGEs)) have important roles in shaping microbial communities, but their dynamic interactions with CRISPR-based immunity remain unresolved. We analysed generation-resolved iMGE–host dynamics spanning one and a half years in a microbial consortium from a biological wastewater treatment plant using integrated meta-omics. We identified 31 bacterial metagenome-assembled genomes encoding complete CRISPR–Cas systems and their corresponding iMGEs. CRISPR-targeted plasmids outnumbered their bacteriophage counterparts by at least fivefold, highlighting the importance of CRISPR-mediated defence against plasmids. Linear modelling of our time-series data revealed that the variation in plasmid abundance over time explained more of the observed community dynamics than phages. Community-scale CRISPR-based plasmid–host and phage–host interaction networks revealed an increase in CRISPR-mediated interactions coinciding with a decrease in the dominant ‘Candidatus Microthrix parvicella’ population. Protospacers were enriched in sequences targeting genes involved in the transmission of iMGEs. Understanding the factors shaping the fitness of specific populations is necessary to devise control strategies for undesirable species and to predict or explain community-wide phenotypes. [less ▲]

Integration of time-series meta-omics data reveals how microbial ecosystems respond to disturbance

in Nature Communications (2020)

The development of reliable, mixed-culture biotechnological processes hinges on understanding how microbial ecosystems respond to disturbances. Here we reveal extensive phenotypic plasticity and niche ... [more ▼]

The development of reliable, mixed-culture biotechnological processes hinges on understanding how microbial ecosystems respond to disturbances. Here we reveal extensive phenotypic plasticity and niche complementarity in oleaginous microbial populations from a biological wastewater treatment plant. We perform meta-omics analyses (metagenomics, metatranscriptomics, metaproteomics and metabolomics) on in situ samples over 14 months at weekly intervals. Based on 1,364 de novo metagenome-assembled genomes, we uncover four distinct fundamental niche types. Throughout the time-series, we observe a major, transient shift in community structure, coinciding with substrate availability changes. Functional omics data reveals extensive variation in gene expression and substrate usage amongst community members. Ex situ bioreactor experiments confirm that responses occur within five hours of a pulse disturbance, demonstrating rapid adaptation by specific populations. Our results show that community resistance and resilience are a function of phenotypic plasticity and niche complementarity, and set the foundation for future ecological engineering efforts. [less ▲]

Microbiome-derived Multi-omicBiomarkers for Early-stage Detection and Stratification of Parkinson's Disease

Poster (2018, October)

Integrated time-resolved multi-omics for understanding microbial niche ecology

Poster (2018, August)

Microbial communities are strongly shaped by the niche breadths of their constituent populations. However, a detailed understanding of microbial niche ecology is typically lacking. Integrated multi-omic ... [more ▼]

Microbial communities are strongly shaped by the niche breadths of their constituent populations. However, a detailed understanding of microbial niche ecology is typically lacking. Integrated multi-omic analyses of host- or environment-derived samples offer the prospect of resolving fundamental and realised niches in situ. In turn, this is considered a prerequisite for niche engineering in order to drive an individual population or a community towards a specific phenotype, e.g., improvement of a biotechnological process. Here, we sampled floating islets on the surface of an activated sludge tank in a time-series spanning 51 time-points over 14 months. Multi-omics datasets (metagenomics, metatranscriptomics, metaproteomics, and (meta-)metabolomics) were generated for all time-points. Leveraging nucleotide sequencing data, we analyzed the community structure and reconstructed genomes for specific populations of interest. Moreover, based on their metabolic potential, three major groups emerged, serving as proxies for their respective fundamental niches . Time-resolved linkage of the proteomic and transcriptomic data to the reconstructed genomes revealed a fine-grained picture of niche realization. In particular, environmental factors (temperature, metabolites, oxygen) were significantly associated with gene expression of individual populations. Furthermore, we subjected the community to controlled oxygen conditions (stable or dynamic) in a bioreactor experiment and measured the transcriptomic response. Our results suggest short-term adaptations of populations of interest with respect to lipid metabolism, among other pathways. In conclusion, our work demonstrates how longitudinal multi-omic datasets can be integrated in order to further our understanding of microbial niche ecology within a biotechnological process with potential applications beyond waste water treatment. [less ▲]

Sequential Isolation of DNA, RNA, Protein, and Metabolite Fractions from Murine Organs and Intestinal Contents for Integrated Omics of Host-Microbiota Interactions.

in Microbial Proteomics (2018)

The gastrointestinal microbiome plays a central role in health and disease. Imbalances in the microbiome, also referred to as dysbiosis, have recently been associated with a number of human idiopathic ... [more ▼]

The gastrointestinal microbiome plays a central role in health and disease. Imbalances in the microbiome, also referred to as dysbiosis, have recently been associated with a number of human idiopathic diseases ranging from metabolic to neurodegenerative. However, to causally link specific microorganisms or dysbiotic communities with tissue-specific and/or systemic disease-associated phenotypes, systematic in vivo studies are fundamental. Gnotobiotic mouse models have proven to be particularly useful for the elucidation of microbiota-associated characteristics as they provide a means to conduct targeted perturbations followed by analyses of induced localized and systemic effects. Here, we describe a methodology in the framework of systems biology which allows the comprehensive isolation of high quality biomolecular fractions (DNA, RNA, proteins and metabolites) from limited and/or heterogeneous sample material derived from murine brain, liver, and colon tissues, as well as from intestinal contents (fecal pellets and fecal masses). The obtained biomolecular fractions are compatible with current high-throughput genomic, transcriptomic, proteomic, and metabolomic analyses. The resulting data fulfills the premise of systematic measurements and allows the detailed study of tissue-specific and/or systemic effects of host-microbiota interactions in relation to health and disease. [less ▲]

Erratum: Integrated multi-omics of the human gut microbiome in a case study of familial type 1 diabetes.

in Nature Microbiology (2016), 2

Integrated multi-omics of the human gut microbiome in a case study of familial type 1 diabetes.

in Nature Microbiology (2016), 2

The gastrointestinal microbiome is a complex ecosystem with functions that shape human health. Studying the relationship between taxonomic alterations and functional repercussions linked to disease ... [more ▼]

The gastrointestinal microbiome is a complex ecosystem with functions that shape human health. Studying the relationship between taxonomic alterations and functional repercussions linked to disease remains challenging. Here, we present an integrative approach to resolve the taxonomic and functional attributes of gastrointestinal microbiota at the metagenomic, metatranscriptomic and metaproteomic levels. We apply our methods to samples from four families with multiple cases of type 1 diabetes mellitus (T1DM). Analysis of intra- and inter-individual variation demonstrates that family membership has a pronounced effect on the structural and functional composition of the gastrointestinal microbiome. In the context of T1DM, consistent taxonomic differences were absent across families, but certain human exocrine pancreatic proteins were found at lower levels. The associated microbial functional signatures were linked to metabolic traits in distinct taxa. The methodologies and results provide a foundation for future large-scale integrated multi-omic analyses of the gastrointestinal microbiome in the context of host-microbe interactions in human health and disease. [less ▲]

Changes in the human gastrointestinal microbiome during cancer treatments

Poster (2015, March)