Early life antibiotics influence in vivo and in vitro mouse intestinal epithelium maturation and functioning
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PROVIDER: PRJNA721939 | ENA |
REPOSITORIES: ENA
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Project description:Background & Aims The use of antibiotics (AB) is a common practice during the first months of life. AB can perturb the intestinal microbiota, indirectly influencing the intestinal epithelial cells (IECs), but also directly affect IECs, independent of the microbiota. Previous studies in rodents have mostly focused on the impact of AB treatment during adulthood. However, the difference between the adult and neonatal intestine warrants careful investigation of the effects of AB in early life. Methods Neonatal mice were treated with a combination of amoxicillin, vancomycin, and metronidazole, from postnatal day 10 to 20. Intestinal permeability and whole intestine gene and protein expression were analyzed. IECs were FACS-sorted and their genome-wide gene expression analyzed. Mouse fetal intestinal organoids were treated with the same AB combination and their gene and protein expression, and metabolic capacity determined. Results We found that in vivo treatment of neonatal mice led to decreased intestinal permeability and reduced number of specialized vacuolated cells, characteristic of the neonatal period and necessary for absorption and digestion of milk macromolecules. Additionally, the expression of genes typically present in the neonatal intestinal epithelium was lower, whereas the adult gene expression signature was higher. Moreover, we found altered epithelial defense and transepithelial sensing capacity. In vitro treatment of intestinal fetal organoids with AB showed that part of the consequences observed in vivo is a result of a direct action of the AB on IECs. Lastly, AB reduced the metabolic capacity of intestinal fetal organoids. Conclusion Our results demonstrate that early life AB treatment induces direct and indirect effects on IECs, influencing their maturation and functioning.
2021-06-01 | GSE172061 | GEO
Project description:Background & aimsThe use of antibiotics (ABs) is a common practice during the first months of life. ABs can perturb the intestinal microbiota, indirectly influencing the intestinal epithelial cells (IECs), but can also directly affect IECs independent of the microbiota. Previous studies have focused mostly on the impact of AB treatment during adulthood. However, the difference between the adult and neonatal intestine warrants careful investigation of AB effects in early life.MethodsNeonatal mice were treated with a combination of amoxicillin, vancomycin, and metronidazole from postnatal day 10 to 20. Intestinal permeability and whole-intestine gene and protein expression were analyzed. IECs were sorted by a fluorescence-activated cell sorter and their genome-wide gene expression was analyzed. Mouse fetal intestinal organoids were treated with the same AB combination and their gene and protein expression and metabolic capacity were determined.ResultsWe found that in vivo treatment of neonatal mice led to decreased intestinal permeability and a reduced number of specialized vacuolated cells, characteristic of the neonatal period and necessary for absorption of milk macromolecules. In addition, the expression of genes typically present in the neonatal intestinal epithelium was lower, whereas the adult gene expression signature was higher. Moreover, we found altered epithelial defense and transepithelial-sensing capacity. In vitro treatment of intestinal fetal organoids with AB showed that part of the consequences observed in vivo is a result of the direct action of the ABs on IECs. Lastly, ABs reduced the metabolic capacity of intestinal fetal organoids.ConclusionsOur results show that early life AB treatment induces direct and indirect effects on IECs, influencing their maturation and functioning.
| S-EPMC8346670 | biostudies-literature
Project description:Impact of antibiotics (T2) or antibiotics in combination with stress (T3) in early life on intestinal functioning in pigs on 8, 55, 176 days in jejunum and ileum (blood only day 8) and control pigs (T1)
2014-09-01 | GSE53170 | GEO
Project description:Impact of antibiotics (T2) or antibiotics in combination with stress (T3) in early life on intestinal functioning in pigs on 8, 55, 176 days in jejunum and ileum (blood only day 8) and control pigs (T1) 4 pools consisting of 16 animals were generated per time-point (day 8, 55, 176 after birth) per treatment (T1;control, T2; antibiotics, T3; antibiotics+stress)
2014-09-01 | E-GEOD-53170 | biostudies-arrayexpress
Project description:To assess the role of LSD1 in mouse small intestinal epithelium, we isolated small intestinal crypts and villus from wild type (WT) (Villin-Cre -; Lsd1f/f) and intestinal-epithelial-specific knock-out (cKO) (Villin-Cre+; Lsd1f/f) mice. This experiment uses a new Cre strain with 100% recombination efficiency. RNA was directly isolated from the crypt and villus, and this was used for RNAseq. Gene expression analysis of cKO derived crypt and villus provides a spatially restricted outlook on the maturation status of the intestinal epithelium in the villi and the absence of Paneth cells in the crypt. Additionally, these mice were treated with antibiotics to study epithelium intrinsic changes related to LSD1 deletion but independent of the bacterial microbiome.
2023-08-02 | E-MTAB-10499 | biostudies-arrayexpress
Project description:Transcriptional changes associated with functioning and non-functioning Pituitary adenomas.
| PRJNA831798 | ENA
Project description:Early life exposure to antibiotics alters the gut microbiome. These alterations lead to changes in metabolic homeostasis and an increase in host adiposity. We used microarrays to identify metabolic genes that may be up- or down-regulated secondary to antibiotic exposure. Low dose antibiotics have been widely used as growth promoters in the agricultural industry since the 1950’s, yet the mechanisms for this effect are unclear. Because antimicrobial agents of different classes and varying activity are effective across several vertebrate species, we hypothesized that such subtherapeutic administration alters the population structure of the gut microbiome as well as its metabolic capabilities. We generated a model of adiposity by giving subtherapeutic antibiotic therapy (STAT) to young mice and evaluated changes in the composition and capabilities of the gut microbiome. STAT administration increased adiposity in young mice and altered hormones related to metabolism. We observed substantial taxonomic changes in the microbiome, changes in copies of key genes involved in the metabolism of carbohydrates to short-chain fatty acids (SCFA), increases in colonic SCFA levels, and alterations in the regulation of hepatic metabolism of lipids and cholesterol. In this model, we demonstrate the alteration of early life murine metabolic homeostasis through antibiotic manipulation. C57BL6 mice were divided into low-dose penicillin or control groups. Given antibiotics via drinking water after weaning. Sacrificed and liver sections collected for RNA extraction.
2012-06-30 | E-GEOD-38880 | biostudies-arrayexpress
Project description:Early life exposure to antibiotics alters the gut microbiome. These alterations lead to changes in metabolic homeostasis and an increase in host adiposity. We used microarrays to identify metabolic genes that may be up- or down-regulated secondary to antibiotic exposure. Low dose antibiotics have been widely used as growth promoters in the agricultural industry since the 1950’s, yet the mechanisms for this effect are unclear. Because antimicrobial agents of different classes and varying activity are effective across several vertebrate species, we hypothesized that such subtherapeutic administration alters the population structure of the gut microbiome as well as its metabolic capabilities. We generated a model of adiposity by giving subtherapeutic antibiotic therapy (STAT) to young mice and evaluated changes in the composition and capabilities of the gut microbiome. STAT administration increased adiposity in young mice and altered hormones related to metabolism. We observed substantial taxonomic changes in the microbiome, changes in copies of key genes involved in the metabolism of carbohydrates to short-chain fatty acids (SCFA), increases in colonic SCFA levels, and alterations in the regulation of hepatic metabolism of lipids and cholesterol. In this model, we demonstrate the alteration of early life murine metabolic homeostasis through antibiotic manipulation.
2012-07-01 | GSE38880 | GEO
Project description:Soy protein nanofiber scaffolds for uniform maturation of hiPSC-derived retinal pigment epithelium
| PRJNA643537 | ENA
Project description:Non-functioning pituitary adenomas AmpliSeq data
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