Project description:This study examined the functional response of a host (zebrafish) to implantation of a conspecific or allospecific (goldfish) gastrointestinal (GIT) microbiome followed by diet manipulation and the repercussions of these manipulations on host GIT physiology. Implantation of a native zebrafish biome successfully reintroduced wildtype (WT) communities with the exception of several rare, phylogenetically distant species. Implantation of a foreign goldfish biome created communities that were distinct from WT, suggesting that the seeding community created substantial differences from the native host communities. A mismatched ?natural? diet and an implanted allospecific biome enriched for rarer and more phylogenetically diverse bacteria. Transcriptional changes within the GIT clustered in relationship to biome treatments, mirroring clustering of biome implants. Implantation of an allospecific biome along with an altered diet markedly down-regulated approximately 70% of the transcripts involved in cholesterol biosynthesis, while tissue content analysis revealed an increase in total tissue cholesterol. Furthermore, transcripts involved in lipogenesis pathways were significantly downregulated and correlated with a striking decrease in intestinal lipase activity driven by both biome and diet. Glucose-6P dehydrogenase (G6PD) activities increased during dietary manipulations regardless of biome, while the allospecific biome down-regulated transcripts involved in gluconeogenesis and altered glucokinase (GK) and hexokinase (HK) activities regardless of diet. However, growth rates did not reveal an impact of these responses. Adult zebrafish are unable to reform proportional representation within bacterial communities following transplantation of an allospecific biome resulting in transcriptional and enzymatic alterations for lipid and carbohydrate metabolism that did not affect overall animal homeostasis.
Project description:Piezo1 is a stretch-gated ion channel required for mechanosensation in many organ systems. Recent provocative findings describe a new role for Piezo1 in the gut, suggesting that it is a sensor of microbial single-stranded RNA (ssRNA) rather than mechanical force. If true, this would redefine the scope of Piezo biology. Here, we sought to replicate the central finding that fecal ssRNA is a natural agonist of Piezo1. While we observed that fecal extracts and ssRNA stimulate calcium influx in certain cell lines, this response was independent of Piezo1. Additionally, sterilized dietary extracts devoid of gut biome RNA showed similar cell line-specific stimulatory activity to fecal extracts. Together, our data highlight potential confounds inherent to gut-derived extracts, exclude Piezo1 as a receptor for ssRNA in the gut, and support a dedicated role for Piezo channels in mechanosensing.
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:CS Baby Biome randomized control trial aims to investigate if the timing of intrapartum antibiotics given to mother influences the infant gut microbiome composition. The study was performed in women delivering via elective CS, who received antibiotics prior to skin incision, or after umbilical cord clamping.