Project description:Intestinal microorganisms impact on health maintaining gut homeostasis and shaping the host immunity, while gut dysbiosis associates with many conditions including autism, a complex neurodevelopmental disorder with multifactorial aetiology. In autism, gut dysbiosis correlates with symptom severity and is characterized by a reduced bacterial variability and a diminished beneficial commensal relationship. Microbiota can influence the expression of host microRNAs that, in turn, regulate the growth of intestinal bacteria by means of bidirectional host-gut micro-biota cross-talk. We investigated possible interactions among intestinal microbes and between them and host transcriptional modulators in autism. To this purpose, we analysed, by “omics” technologies, faecal microbiome, mycobiome and small non-coding-RNAs (particularly miRNAs and piRNAs) of children with autism and neurotypical development. Patients displayed gut dysbiosis, related to a reduction of healthy gut micro- and mycobiota, and up-regulated tran-scriptional modulators. The targets of dysregulated non-coding-RNAs are involved in intestinal permeability, inflammation and autism. Furthermore, microbial families, underrepresented in patients, participate to the production of human essential metabolites negatively influencing the health condition. Here, we propose a novel approach to analyse faeces as a whole and, for the first time, we detected miRNAs and piRNAs in faecal samples of patients with autism.
Project description:Metagenomic and targeted meta-proteomics were used to investigate the mycobiome profile of the infant gut to identify proteins involved during atopic dermatitis manifestation in a Thai population-based birth cohort.
2021-09-14 | PXD027687 | JPOST Repository
Project description:Gut mycobiome and habitat enviromental mycobiome
Project description:Female genital tract (FGT) diseases such as bacterial vaginosis (BV) and sexually transmitted infections are prevalent in South Africa, with young women being at an increased risk. Since imbalances in the FGT microbiome are associated with FGT diseases, it is vital to investigate the factors that influence FGT health. The mycobiome plays an important role in regulating mucosal health, especially when the bacterial component is disturbed. However, we have a limited understanding of the FGT mycobiome since many studies have focused on bacterial communities and have neglected low abundance taxonomic groups, such as fungi. To reduce this knowledge deficit, we present the first large-scale metaproteomic study to define the taxonomic composition and potential functional processes of the FGT mycobiome in South African reproductive-age women. We examined FGT fungal communities present in 123 women by collecting lateral vaginal wall swabs for liquid chromatography-tandem mass spectrometry.
Project description:TH2 and innate lymphoid cells 2 (ILC2) can stimulate tumor growth by secreting pro-tumorigenic cytokines such as IL4, IL5 and IL13. However, the mechanisms by which type 2 immune cells traffic to the tumor microenvironment (TME) are unknown. Here, in pancreatic ductal adenocarcinoma (PDAC), we show that oncogenic KrasG12D (Kras*) increases the expression of IL33 in cancer cells, which upon secretion recruits and activates the TH2 and ILC2. Correspondingly, cancer cell-specific deletion of IL33 reduces TH2 and ILC2 recruitment and promotes tumor regression. Unexpectedly, we discovered that the cellular release of IL33 into the TME is dependent on the intratumoral fungal mycobiome. Genetic deletion of IL33 or anti-fungal treatment decreases TH2 and ILC2 infiltration and increases survival. Consistent with these murine data, high IL33 expression is observed in approximately 20% of human PDAC, and expression is mainly restricted to cancer cells. These data expand our knowledge of the mechanisms driving PDAC tumor progression and identifies therapeutically targetable pathways involving intratumoral mycobiome-driven secretion of IL33.