Project description:Interventions: healthy people, intestinal polyp group and intestinal cancer group.:Nil
Primary outcome(s): bacteria;fungi;phages
Study Design: Factorial
Project description:Microbial consortia consist of a multitude of prokaryotic and eukaryotic microorganisms. Their interaction is critical for the functioning of ecosystems. Until now, there is limited knowledge about the communication signals determining the interaction between bacteria and fungi and how they influence microbial consortia. Here, we discovered that bacterial low molecular weight arginine-derived polyketides trigger the production of distinct natural products in fungi. These compounds are produced by actinomycetes found on all continents except Antarctica and are characterized by an arginine-derived positively charged group linked to a linear or cyclic polyene moiety. Producer bacteria can be readily isolated from soil as well as fungi that decode the signal and respond with the biosynthesis of natural products. Both arginine-derived polyketides and the compounds produced by fungi in response shape microbial interactions.
Project description:Fermented foods are microbial ecosystems in which bacteria and fungi convert raw ingredients into stable, nutritious, and health-promoting products. The composition and activity of these microorganisms determine the biochemical and nutritional profile of the final food. We analyzed 17 fermented foods, each in triplicate, using metaproteomics. This analysis revealed that microbial proteins contribute up to 11% of total protein and 60% of identified proteins. Detailed information on file-naming conventions (database files, MS raw files, and output files), as well as food source suppliers, fermenting microorganisms, peptide loading volumes, and LC-MS gradient lengths, is provided in the table FileAndSampleDescription_PRIDE_submission.csv.
Project description:We sequenced the transcriptome of a host (Caenorhabditis elegans) following its interaction with a non-native bacterium (Enterococcus faecalis) that has protective traits against the pathogen, Staphylococcus aureus. We also investigated the impact that the evolutionary history of the protective bacterium has on the transcriptional history of the host. We tested protective bacteria that had either coevolved against the pathogen within C. elegans, or had evolved on its own within C. elegans.
Project description:Neutrophils are essential innate immune cells with unusual anti-microbial properties while dysfunctions of neutrophils lead to severe health problems such as lethal infections. Generation of neutrophils from human induced pluripotent stem cells (hiPSCs) is highly promising to produce off-the-shelf neutrophils for transfusion therapies. However, the anti-microbial potencies of hiPSCs derived neutrophils (iNEUs) remain less documented. Here, we develop a scalable approach to generate iNEUs in a chemical defined condition. iNEUs display typical neutrophil characters in terms of phagocytosis, migration, formation of neutrophil extracellular traps (NETs), etc. Importantly, iNEUs display a strong killing potency against various bacteria such as K.pneumoniae, P.aeruginosa, E.coli and S.aureus. Moreover, transfusions of iNEUs in mice with neutrophil dysfunction largely enhance their survival in lethal infection of different bacteria. Together, our data show that hiPSCs derived neutrophils hold strong anti-microbial potencies to protect severe infections under neutrophil dysfunction conditions.
Project description:The gut-brain axis allows gut microbes to influence host social behavior, yet the specific role of microbial genetic variation in this process and its potential transgenerational effects remains poorly understood. Using C. elegans as a model, we identified 77 E. coli strains among 3,983 mutants that markedly enhanced C. elegans aggregation behavior. Our findings reveal that mutant bacteria modulate C. elegans social behavior through distinct neurobehavioral pathways, demonstrating a synergistic regulatory mechanism between microbial genetics and host heredity. Mechanistically, ycgJ mutant bacteria were found to impact C. elegans social behavior via the mitochondrial pathway. Additionally, even F2 offspring of parent C. elegans exposed to these mutant bacteria exhibited enhanced social behavior within their populations. These insights underscore the significance of investigating microbial genetic variation in relation to host behavior, particularly for the development of genetically engineered probiotics, aimed at promoting well-being across generations.
Project description:Coculturing experiments involving three microbial species: Aspergillus (A), Trichoderma (T), and Bacillus (B), representing fungi (A, T) and bacteria (B), respectively. These experiments encompassed various interaction levels, including dual cultures (AB, AT, TB) and triple cultures (ATB). Metabolic profiling by LC-QTOFMS revealed the effect of interaction level on the productivity and diversity of microbial specialized metabolites.
Project description:Altered gut microbial composition observed in Alzheimer’s disease patients drive microbial metabolome changes associated with AD pathogenesis; however, key microbial metabolites involved in this process and their functional roles are unknown. Here, we screened library of 352 gut metabolites in AD patient iPSC derived neurons for their ability to reduce phosphorylation of tau. We identified 4-methylcatechol, menaquinone-4 and agmatine as candidate metabolites associated with decreased tau phosphorylation and chose agmatine for further validatory studies. We demonstrated that Agmatine significantly reduce tau hyperphosphorylations (pTau181, pTau205 and pTau231) in AD patient iPSC-derived neurons and cerebral organoids. We also observed that agmatine treatment enhances learning and memory, reduces amyloid burden and neuroinflammation in a 5xFAD mouse model. Transcriptomics analysis from patient iPSC derived brain organoids suggested decreased expression of complement system pathway genes (e.g. C1S, C2, C3AR1, C5AR1) by agmatine treatment. The study also highlights agmatine as an important modulator of AD pathology via regulating C3aR-STAT3 axis and implicates it as a novel therapeutic target for AD.