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 ▲]

binny: an automated binning algorithm to recover high-quality genomes from complex metagenomic datasets

in Briefings in Bioinformatics (2022)

The reconstruction of genomes is a critical step in genome-resolved metagenomics and for multi-omic data integration from microbial communities. Here, we present binny, a binning tool that produces high ... [more ▼]

The reconstruction of genomes is a critical step in genome-resolved metagenomics and for multi-omic data integration from microbial communities. Here, we present binny, a binning tool that produces high-quality metagenome-assembled genomes (MAG) from both contiguous and highly fragmented genomes. Based on established metrics, binny outperforms or is highly competitive with commonly used and state-of-the-art binning methods and finds unique genomes that could not be detected by other methods. binny uses k-mer-composition and coverage by metagenomic reads for iterative, nonlinear dimension reduction of genomic signatures as well as subsequent automated contig clustering with cluster assessment using lineage-specific marker gene sets. When compared with seven widely used binning algorithms, binny provides substantial amounts of uniquely identified MAGs and almost always recovers the most near-complete (⁠>95% pure, >90% complete) and high-quality (⁠>90% pure, >70% complete) genomes from simulated datasets from the Critical Assessment of Metagenome Interpretation initiative, as well as substantially more high-quality draft genomes, as defined by the Minimum Information about a Metagenome-Assembled Genome standard, from a real-world benchmark comprised of metagenomes from various environments than any other tested method. [less ▲]

SnapShot: The Expobiome Map

in Cell Host and Microbe (2022), 30(9), 1340

The human gut microbiome is intricately connected to health and disease. Microbiome-derived molecules are implicated in many chronic diseases involving inflammation. Herein, we summarize the diverse ... [more ▼]

The human gut microbiome is intricately connected to health and disease. Microbiome-derived molecules are implicated in many chronic diseases involving inflammation. Herein, we summarize the diverse complex of such immunogenic molecules, including nucleic acids, (poly)peptides, structural molecules, and metabolites. The interactions between this “expobiome” and human immune pathways are specifically illustrated in the context of chronic diseases. [less ▲]

Studying the Parkinson's disease metabolome and exposome in biological samples through different analytical and cheminformatics approaches: a pilot study

in Analytical and Bioanalytical Chemistry (2022)

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease, with an increasing incidence in recent years due to the ageing population. Genetic mutations alone only explain <10% of PD ... [more ▼]

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease, with an increasing incidence in recent years due to the ageing population. Genetic mutations alone only explain <10% of PD cases, while environmental factors, including small molecules, may play a significant role in PD. In the present work, 22 plasma (11 PD, 11 control) and 19 feces samples (10 PD, 9 control) were analyzed by non-target high resolution mass spectrometry (NT-HRMS) coupled to two liquid chromatography (LC) methods (reversed phase (RP) and hydrophilic interaction liquid chromatography (HILIC)). A cheminformatics workflow was optimized using open software (MS-DIAL and patRoon) and open databases (all public MSP-formatted spectral libraries for MS-DIAL, PubChemLite for Exposomics and the LITMINEDNEURO list for patRoon). Furthermore, five disease-specific databases and three suspect lists (on PD and related disorders) were developed, using PubChem functionality to identifying relevant unknown chemicals. The results showed that non-target screening with the larger databases generally provided better results compared with smaller suspect lists. However, two suspect screening approaches with patRoon were also good options to study specific chemicals in PD. The combination of chromatographic methods (RP and HILIC) as well as two ionization modes (positive and negative) enhanced the coverage of chemicals in the biological samples. While most metabolomics studies in PD have focused on blood and cerebrospinal fluid, we found a higher number of relevant features in feces, such as alanine betaine or nicotinamide, which can be directly metabolized by gut microbiota. This highlights the potential role of gut dysbiosis in PD development. [less ▲]

Individual factors and beliefs determining COVID-19 vaccination willingness

Poster (2022, April)

Background: High vaccination coverage rates are necessary to reduce infections and transmissions of the SARS-CoV-2 virus causing COVID-19 and to allow successful mitigation of the current pandemic. To ... [more ▼]

Background: High vaccination coverage rates are necessary to reduce infections and transmissions of the SARS-CoV-2 virus causing COVID-19 and to allow successful mitigation of the current pandemic. To date, we are still lacking information to explain the hesitancy in Luxembourg towards uptake of the available COVID-19 vaccines. The present study explored motivations for and against vaccination in a population-representative sample of residents across Luxembourg to identify hesitant groups and develop strategies to increase population immunity against SARS-CoV-2. Methods: In the framework of the nationwide, representative longitudinal CON-VINCE study, a sample of 1589 respondents (49.6% women, 84.3% Luxembourg nationality) ranging from 18-84 years, participated in the survey in spring 2021. The protocol of the CON-VINCE study has been described in detail elsewhere (Snoeck et al. 2020). Results: 52% of the respondents had at least partial vaccination at time of assessment between April to June 2021. The most common reasons for vaccination of those willing to be vaccinated (81.2%) were altruistic motivations. Prevalent reasons against vaccination for those undecided (8.7%) or reluctant (10.2%) to be vaccinated were that the vaccine had not been tested sufficiently and the fear of long-term vaccine side effects. Only very few of the vaccination-hesitant or -reluctant respondents reported that they did not believe in vaccination in general. Conclusion: The present study identified motivations for and against COVID-19 vaccination and determined demographic and socio-economic factors associated with vaccination willingness. To increase vaccination rates, public health communication needs to target those unsure or unwilling to be vaccinated. We will continue to study the vaccination uptake in the Luxembourg population, as CON-VINCE is now part of the H2020-funded international ORCHESTRA project (https://orchestra-cohort.eu), research into comparing these results on a Pan-European level. [less ▲]

Towards hypothesis-driven, personalized microbiome screening

in Cell Reports Methods (2022), 2(1),

Combinatorial analysis reveals highly coordinated early-stage immune reactions that predict later antiviral immunity in mild COVID-19 patients

in Cell Reports Medicine (2022), 3(4), 100600

While immunopathology has been widely studied in patients with severe COVID-19, immune responses in non-hospitalized patients have remained largely elusive. We systematically analyze 484 peripheral ... [more ▼]

While immunopathology has been widely studied in patients with severe COVID-19, immune responses in non-hospitalized patients have remained largely elusive. We systematically analyze 484 peripheral cellular or soluble immune features in a longitudinal cohort of 63 mild and 15 hospitalized patients versus 14 asymptomatic and 26 household controls. We observe a transient increase of IP10/CXCL10 and interferon-β levels, coordinated responses of dominant SARS-CoV-2-specific CD4 and fewer CD8 T cells, and various antigen-presenting and antibody-secreting cells in mild patients within 3 days of PCR diagnosis. The frequency of key innate immune cells and their functional marker expression are impaired in hospitalized patients at day 1 of inclusion. T cell and dendritic cell responses at day 1 are highly predictive for SARS-CoV-2-specific antibody responses after 3 weeks in mild but not hospitalized patients. Our systematic analysis reveals a combinatorial picture and trajectory of various arms of the highly coordinated early-stage immune responses in mild COVID-19 patients. [less ▲]

Gastrische Interozeption und gastrische myoelektrische Aktivität bei chronisch-entzündlichen Darmerkrankungen und Reizdarmsyndrom

in Heinrichs, Markus; Schönauer, Monika (Eds.) 47. Jahrestagung Psychologie und Gehirn (2022)

Viszerale Hypersensitivität wird als zentraler Mechanismus bei chronisch-entzündlichen Darmerkrankungen (CED) und Reizdarmsyndrom (RDS) diskutiert, welche beide mit einer erheblichen Einschränkung der ... [more ▼]

Viszerale Hypersensitivität wird als zentraler Mechanismus bei chronisch-entzündlichen Darmerkrankungen (CED) und Reizdarmsyndrom (RDS) diskutiert, welche beide mit einer erheblichen Einschränkung der Lebensqualität einhergehen. Bisherige Studien verwenden zumeist invasive Verfahren, die jedoch typischerweise mit der Messung viszeraler Wahrnehmung interferieren. Diese Studie untersucht daher, ob CED und RDS mit einer veränderten Wahrnehmung „natürlicher“ (nicht-invasiver) gastrischer Dehnungen assoziiert sind („Interozeption“). Zwanzig CED-Patienten in Remission (13 Morbus Crohn, 7 Colitis Ulcerosa), 12 RDS-Patienten, sowie 20/12 parallelisierte gesunde Kontrollprobanden absolvierten den 2-stufigen Water-Load-Test, bei dem eine beliebige Menge Wasser getrunken wird, bis die subjektiven Schwelle der Sättigung (Stufe 1) und des Völlegefühls (Stufe 2) erreicht sind. Gastrische Motilität wurde mittels Elektrogastrographie untersucht. CED-Patienten tranken signifikant mehr Wasser bis zur Sättigungsschwelle als RDS-Patienten, während es keine Unterschiede zu den Kontrollgruppen gab. Die getrunkene Wassermenge bis zur Schwelle des Völlegefühls unterschied sich nicht zwischen den Gruppen. Die elektrogastrographischen Muster zeigten ebenfalls keine Gruppenunterschiede, was impliziert, dass es keine Pathologien in der gastrischen Motilität gab. Die getrunkene Wassermenge bis zur Sättigung korrelierte negativ mit darmbezogener Lebensqualität bei CED-Patienten, aber positiv mit emotionalem Wohlbefinden bei RDS-Patienten. Diese Ergebnisse legen eine relative gastrische Hypersensitivität bei RDS und eine relative gastrische Hyposensitivität bei CED nahe, was jeweils mit spezifischen Facetten der wahrgenommenen Lebensqualität assoziiert ist. [less ▲]

binny: an automated binning algorithm to recover high-quality genomes from complex metagenomic datasets 2021.12.22.473795

E-print/Working paper (2021)

The reconstruction of genomes is a critical step in genome-resolved metagenomics as well as for multi-omic data integration from microbial communities. Here, we present binny, a binning tool that produces ... [more ▼]

The reconstruction of genomes is a critical step in genome-resolved metagenomics as well as for multi-omic data integration from microbial communities. Here, we present binny, a binning tool that produces high-quality metagenome-assembled genomes from both contiguous and highly fragmented genomes. Based on established metrics, binny outperforms existing state-of-the-art binning methods and finds unique genomes that could not be detected by other methods.binny uses k-mer-composition and coverage by metagenomic reads for iterative, non-linear dimension reduction of genomic signatures as well as subsequent automated contig clustering with cluster assessment using lineage-specific marker gene sets.When compared to five widely used binning algorithms, binny recovers the most near-complete (\>95 pure, \>90 complete) and high-quality (\>90 pure, \>70 complete) genomes from simulated data sets from the Critical Assessment of Metagenome Interpretation (CAMI) initiative, as well as from a real-world benchmark comprised of metagenomes from various environments. binny is implemented as Snakemake workflow and available from https://github.com/a-h-b/binny.Competing Interest StatementThe authors have declared no competing interest. [less ▲]

The Metaproteomics Initiative: a coordinated approach for propelling the functional characterization of microbiomes

in Microbiome (2021), 9(1), 243