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Keynote talk
Methane, Microbes, and More: Archaea in the Human Microbiome
By Prof. Christine Moissl-Eichinger
Archaea, a distinct domain of life, play critical yet often overlooked roles in the human microbiome. Despite their recognition as members of the human microbiota since the 1970s, archaea remain understudied due to their non-pathogenic nature and technical challenges. In this talk, I will explore the multifaceted contributions of archaea to human health, focusing on their role in fiber digestion, methane production, and interactions with the host.
Recent advances from my research have unveiled more than 1,000 archaeal genomes from the human gut, encoding 1.8 million genes, half of which have unknown functions. These findings highlight the untapped potential of archaea in shaping microbiome and human physiology. Through a combination of metagenomics, comparative genomics, and laboratory-based studies such as targeted cultivation, we aim to understand the functional and ecological roles of archaea across diverse human microbiomes, including the gut, respiratory tract, and skin.
Selected Talks
Genomic, functional, and metabolic enhancements in multidrug-resistant Enterobacter bugandensis facilitating its persistence and succession in the International Space Station
By Pratyay Sengupta, Indian Institute of Technology Madras, India
The International Space Station (ISS) stands as a testament to human achievement in space exploration. Despite its highly controlled environment, characterised by microgravity, increased CO2 levels, and elevated solar radiation, microorganisms occupy a unique niche. These microbial inhabitants play a significant role in influencing the health and well-being of astronauts on board. One microorganism of particular interest in our study is Enterobacter bugandensis, primarily found in clinical specimens including the human gastrointestinal tract, and also reported to possess pathogenic traits, leading to a plethora of infections. During the 2-year Microbial Tracking 1 mission, 13 strains of multidrug-resistant E. bugandensis were isolated from various locations within the ISS. We have carried out a comprehensive study to understand the genomic intricacies of ISS-derived E. bugandensis in comparison to terrestrial strains, with a keen focus on those associated with clinical infections. We unravel the evolutionary trajectories of pivotal genes, especially those contributing to functional adaptations and potential antimicrobial resistance. A hypothesis central to our study was that the singular nature of the stresses of the space environment, distinct from any on Earth, could be driving these genomic adaptations. Extending our investigation, we meticulously mapped the prevalence and distribution of E. bugandensis across the ISS over time. This temporal analysis provided insights into the persistence, succession, and potential patterns of colonisation of E. bugandensis in space. Furthermore, by leveraging advanced metabolic modelling, we delved into the coexisting microbial communities alongside E. bugandensis in the ISS across multiple missions and spatial locations. This exploration revealed intricate microbial interactions, offering a window into the microbial ecosystem dynamics within the ISS. Our comprehensive analysis illuminated not only the ways these interactions sculpt microbial diversity but also the factors that might contribute to the potential dominance and succession of E. bugandensis within the environment. The implications of these findings are twofold. Firstly, they shed light on microbial behaviour, adaptation, and evolution in extreme, isolated environments. Secondly, they underscore the need for robust preventive measures, ensuring the health and safety of astronauts by mitigating risks associated with potential pathogenic threats.
Off-target effects of nervous system drugs on the human gut microbiome
By Fatima C Pereira, University of Southampton, UK
Many human-targeted drugs alter the gut microbiome, leading to implications for host health. However, the mechanisms underlying these effects are not well known. Here we combined quantitative microbiome profiling, long-read metagenomics, stable isotope probing and single-cell chemical imaging to investigate the impact of two widely prescribed drugs on the gut microbiome. Physiologically relevant concentrations of entacapone, a treatment for Parkinson’s disease, or loxapine succinate, used to treat schizophrenia, were incubated ex vivo with human faecal samples. Both drugs significantly impact microbial activity, more so than microbial abundance. Mechanistically, entacapone can complex and deplete available iron resulting in gut microbiome composition and function changes. Microbial growth can be rescued by replenishing levels of microbiota-accessible iron. Further, entacapone-induced iron starvation selected for iron-scavenging gut microbiome members encoding antimicrobial resistance and virulence genes. These findings reveal the impact of two under-investigated drugs on whole microbiomes and identify metal sequestration as a mechanism of drug-induced microbiome disturbance.
Link to OA paper: https://www.nature.com/articles/s41564-024-01853-0
Fecal microbiota transplantation alters the proteomic landscape of inflammation in HIV: identifying bacterial drivers
By Claudio Díaz García, Hospital Universitario Ramón y Cajal, Spain
BACKGROUND. Despite effective antiretroviral therapy, people with HIV (PWH) experience persistent systemic inflammation and increased morbidity and mortality. Modulating the gut microbiome through fecal microbiota transplantation (FMT) represents a novel therapeutic strategy. We aimed to evaluate proteomic changes in inflammatory pathways following repeated, low-dose FMT versus placebo.
METHODS. This double-masked, placebo-controlled pilot study assessed the proteomic impacts of weekly FMT versus placebo treatment over 8 weeks on systemic inflammation in 29 PWH receiving stable antiretroviral therapy (ART). Three stool donors with high Faecalibacterium and butyrate profiles were selected, and their individual stools were used for FMT capsule preparation. Proteomic changes in 345 inflammatory proteins in plasma were quantified using the proximity extension assay, with samples collected at baseline and at weeks 1, 8, and 24. Concurrently, we characterized shifts in the gut microbiota composition and annotated functions through shotgun metagenomics. We fitted generalized additive models to evaluate the dynamics of protein expression. We selected the most relevant proteins to explore their correlations with microbiome composition and functionality over time using linear mixed models.
RESULTS. FMT significantly reduced the plasma levels of 45 inflammatory proteins, including established mortality predictors such as IL6 and TNF-α. We found notable reductions persisting up to 16 weeks after the final FMT procedure, including in the expression of proteins such as CCL20 and CD22. We identified changes in 46 proteins, including decreases in FT3LG, IL6, IL10RB, IL12B, and IL17A, which correlated with multiple bacterial species. We found that specific bacterial species within the Ruminococcaceae, Succinivibrionaceae, Prevotellaceae families, and the Clostridium genus, in addition to their associated genes and functions, were significantly correlated with changes in inflammatory markers.
CONCLUSIONS. Targeting the gut microbiome through FMT effectively decreased inflammatory proteins in PWH, with sustained effects. These findings suggest the potential of the microbiome as a therapeutic target to mitigate inflammation-related complications in this population, encouraging further research and development of microbiome-based interventions.
Link to OA paper: https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-024-01919-5
MicroTalks
Just A Gut Feeling: Faecal Microbiota Transplant For Treatment Of Depression
By Minna Chang, Epsom and St Helier University Hospitals NHS Trust, UK
The microbiota-gut-brain-axis allows bidirectional crosstalk between the brain and the gut microbiota (GM) and is believed to play a central role in the regulation of mood, cognition, behaviour, as well as metabolism, health, biological processes and homeostasis. Manipulation of the GM through faecal microbiota transplant (FMT) is a new, exciting and promising treatment for major depressive disorder (MDD). Studies have demonstrated significant gut dysbiosis in depressed patients compared to healthy cohorts, with an overgrowth of pro-inflammatory microbiota, a reduction in anti-inflammatory species and reduced overall stability and taxonomic richness. FMT allows healthy microbiota to be introduced into the gastrointestinal tract (GIT) and this ultimately leads to a restoration of eubiosis.
This presentation provides an overview of the current research into the GM and the FMT as a therapy for depression. We first summarise the current data on the GM and depression. We then discuss the communication through the microbiota-gut-brain-axis and how antidepressant treatment and the GM interact through this. We then review the composition of the dysbiosis found in depressed patients, focusing on how this can be treated by FMT and the future directions in the treatment of depression.
microbetag: simplifying microbial network interpretation through annotation, enrichment tests and metabolic complementarity analysis
By Haris Zafeiropoulos, KU Leuven, Belgium
Microbial co-occurrence network inference is often hindered by low accuracy and tool dependency. Building on the reverse-ecology paradigm, we applied data integration and metabolic modeling methods to address these challenges.
We introduce microbetag (https://hariszaf.github.io/microbetag/), a comprehensive software ecosystem designed to enhance network annotation. Nodes (taxa) are enriched with phenotypic traits, based on genome and literature knowledge, while edges represent two types of metabolic complementarities, highlighting potential cross-feeding relationships. Pathway complementarities are inferred from genome annotations, based on a donor species' ability to complete a missing step in a beneficiary's KEGG module. Seed complementarities, on the other hand, are derived from the metabolites a species requires exogenously, as determined by its metabolic model, and the donor's ability to produce these metabolites.
microbetag’s online version relies on microbetagDB, a database of 34,608 high-quality genomes with detailed annotations. It effectively identified known metabolic interactions on previously published data. A preprocessing module allows the analysis of large data sets, while a stand-alone version allows users to apply microbetag to custom reference genomes/bins/MAGs. Ultimately, MGG, a CytoscapeApp we developed, offers a streamlined, user-friendly interface for retrieving and visualizing microbetag-annotated networks.
Combined with network clustering and enrichment analysis, microbetag serves as a robust hypothesis-generating tool.