Project description:Gastrointestinal microbes modulate peristalsis and stimulate the enteric nervous system (ENS), whose development, as in the central nervous system (CNS), continues into the murine postweaning period. Given that adult CNS function depends on stimuli received during critical periods of postnatal development, we hypothesized that adult ENS function, namely motility, depends on microbial stimuli during similar critical periods. We gave fecal microbiota transplantation (FMT) to germ-free mice at weaning or as adults and found that only the mice given FMT at weaning recovered normal transit, while those given FMT as adults showed limited improvements. RNAseq of colonic muscularis propria revealed enrichments in neuron developmental pathways in mice exposed to gut microbes earlier in life, while mice exposed later – or not at all – showed exaggerated expression of inflammatory pathways. These findings highlight a microbiota-dependent sensitive period in ENS development, pointing to potential roles of the early life microbiome in later life dysmotility.
2024-10-15 | GSE241697 | GEO
Project description:Microbiota-dependent early life programming of gastrointestinal motility
Project description:The search for factors beyond the radiotherapy dose that could identify patients more at risk of developing radio-induced toxicity is essential to establish personalised treatment protocols for improving the quality-of-life of survivors. To investigate the role of the intestinal microbiota in the development of radiotherapy-induced gastrointestinal toxicity, the MicroLearner observational cohort study characterised the intestinal microbiota of 136 (discovery) and 79 (validation) consecutive prostate cancer patients at baseline radiotherapy. Gastrointestinal toxicity was assessed weekly during RT using CTCAE. An average grade >1.3 over time points was used to identify patients suffering from persistent acute toxicity (endpoint). The intestinal microbiota of patients was quantified from the baseline faecal samples using 16S rRNA gene sequencing technology.
Project description:Study hypothesis: That minimal invasive laparoscopic surgery and/or multimodal patient care (fast-track) can prevent post-operative ileus and/or improve post-surgical gastrointestinal motility compared to open surgery and/or conventional patient care.
Primary outcome(s): Gastrointestinal transit
Project description:The gastrointestinal tract is covered by a single layer of epithelial cells that, together with the mucus layers, protect the underlying tissue from bacterial invasion. The epithelium has one of the highest turnover rates in the body, renewing every 4-5 days. Using stable isotope labelling, high-resolution mass spectrometry and computational analysis, we report here a comprehensive dataset of the turnover rate of 3041 and the expression of 5012 intestinal epithelial cell proteins, analyzed under conventional and germ-free conditions across five different segments in mouse intestine. The median protein half-life was shorter in small intestine compared to colon, ranging from 3.5 to 4.2 days. Differences in protein turnover rates along the intestinal tract can be explained by distinct physiological functions and site-specific immune responses between the small and large intestine. Absence of microflora resulted in increased protein half-life by approximately one day.
Project description:Developmental programming is the concept that environmental factors, particularly during foetal life, can alter development, metabolism and physiology of an organism and this can have consequences later in life. There is growing interest in developmental programming in livestock species, particularly effects of maternal pregnancy nutrition, which is easy to manipulate. Recent research, using a sheep model, has shown that milk production in ewe offspring may be susceptible to maternal nutritional programming, such that over nutrition (ad libitum) of the pregnant dam, compared with maintenance nutrition, may impair their first lactation performance and result in the weaning of lighter lambs. RNA-seq was performed to identify gene expression differences as a result of maternal nutrition in ewe offspring during their first parity. Samples were collected in late pregnancy and during lactation, allowing us to examine gene expression changes during maturation of the ovine mammary gland. Three biological replicates were sequenced for each of the treatment conditions (maternal nutrition: sub-maintenance, maintenance, and ad libitum) and time points (late pregnancy and lactation). Each biological replicate consisted of RNA from multiple individuals (late pregnancy n=3, lactation n=2).
Project description:Enteric glia are the predominant cell type in the enteric nervous system yet their identities and roles in gastrointestinal function are not well classified. Using our optimized single nucleus RNA-sequencing method, we identified distinct molecular classes of enteric glia and defined their morphological and spatial diversity. Our findings revealed a functionally specialized biosensor subtype of enteric glia that we call “hub cells.” Deletion of the mechanosensory ion channel PIEZO2 from adult enteric glial hub cells, but not other subtypes of enteric glia, led to defects in intestinal motility and gastric emptying in mice. These results provide insight into the multifaceted functions of different enteric glial cell subtypes in gut health and emphasize that therapies targeting enteric glia could advance the treatment of gastrointestinal diseases.