Indigenous gut microbes modulate neural cell state and neurodegenerative disease susceptibility [mono-colonized_RNA-seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE289591 | GEO | 2026/02/03
REPOSITORIES: GEO
Similar Datasets
Project description:The mammalian gastrointestinal tract contains a diverse ecosystem of microbial species collectively making up the gut microbiome. Emerging evidence highlights a critical relationship between gut microbiota and neurocognitive development. Consumption of unhealthy yet palatable dietary factors associated with obesity and metabolic dysfunction (e.g., saturated fat, added sugar) produces microbiota dysbiosis and negatively impacts neurocognitive function, particularly when consumed during early life developmental periods. Here we explore whether excessive early life consumption of added sugars negatively impacts neurocognitive development via the gut microbiome. Using a rodent model of habitual sugar-sweetened beverage (SSB) consumption during the adolescent stage of development, we first show that excessive early life sugar intake impairs hippocampal-dependent memory function when tested during adulthood while preserving other neurocognitive domains. Gut microbiome genomic sequencing analyses reveal that early life SSB consumption alters the abundance of various bacterial populations, including elevations in operational taxonomic units within the genus Parabacteroides (P. distasonis and P. johnsonii) whose abundance negatively correlated with memory task performance. Additional results reveal that in vivo Parabacteroides enrichment of cultured P. distasonis and P. johnsonii bacterial species in adolescent rats severely impairs memory function during adulthood. Hippocampus transcriptome analyses identify gene expression alterations in neurotransmitter synaptic signaling, intracellular kinase signaling, metabolic function, neurodegenerative disease, and dopaminergic synaptic signaling-associated pathways as potential mechanisms linking microbiome outcomes with memory impairment. Collectively these results identify microbiota dysbiosis as a mechanism through which early life unhealthy dietary patterns negatively impact neurocognitive outcomes.
2021-02-25 | GSE150091 | GEO
Project description:The gut microbiome shapes local and systemic immunity. The liver is presumed to be a protected sterile site. As such, a hepatic microbiome has not been examined. Here, we show that the liver hosts a robust microbiome in mice and humans that is distinct from the gut and is enriched in Proteobacteria. It undergoes dynamic alterations with age and is influenced by the environment and host physiology. Fecal microbial transfer experiments revealed that the liver microbiome is populated from the gut in a highly selective manner. Hepatic immunity is dependent on the microbiome, specifically Bacteroidetes species. Targeting Bacteroidetes with oral antibiotics reduced the hepatic immune cell infiltrate by ~90%, prevented APC maturation, and mitigated adaptive immunity. Mechanistically, presentation of Bacteroidetes-derived glycosphingolipids to NKT cells promotes CCL5 signaling, which drives hepatic leukocyte expansion and maturation. Collectively, we reveal a microbial – glycosphingolipid – NKT – CCL5 axis that underlies hepatic immunity.
2022-05-17 | GSE161876 | GEO
Project description:The native microbiome influences a plethora of host processes, including neurological function. We have shown that colonization by Escherichia coli induces a distinct adaptive immune and neurogenerative disease-associated cell state in wildtype mice, suggesting increased disease susceptibility. Further, E. coli exposure in the 5xFAD mouse model results in exacerbated cognitive decline and amyloid pathology, demonstrating its sufficiency to worsen Alzheimer’s disease-relevant outcomes. Here, we performed bulk RNA-seq of CD11b+ brain myeloid cells from E. coli or vehicle treated 5xFAD mice to understand how E. coli modulates neuroimmune responses in the context of amyloid pathology. We demonstrate that E. coli exposed animals have a subtle decrease in genes associated with the disease associated microglia phenotype after 1 month of enrichment, perhaps helping to explain why these animals displayed worsened outcomes.
2026-02-03 | GSE289590 | GEO
Project description:The native microbiome influences a plethora of host processes, including neurological function. However, its impacts on diverse brain cell types remains poorly understood. Here, we performed single nucleus RNA sequencing on hippocampi from wildtype, germ-free mice and reveal the microbiome-dependent transcriptional landscape across all major neural cell types. We found conserved impacts on key adaptive immune and neurodegenerative transcriptional pathways, underscoring the microbiome’s contributions to disease-relevant processes. In addition, mono-colonization with Escherichia coli was found to induce a distinct adaptive immune and neurogenerative disease-associated cell state, suggesting increased disease susceptibility.
2026-02-03 | GSE289589 | GEO
Project description:Exposure to dogs in early infancy has been shown to reduce the risk of childhood allergic disease development and dog-ownership is associated with a distinct house dust microbial exposure. Here we demonstrate, using murine models, that exposure of mice toM-BM- dog-associated house dust protects against ovalbumin or cockroach allergen mediated airway pathology. Protected animals exhibited significant reductions in the total number of airway T cells, down-regulation of Th2-related airway responses as well as mucin secretion. Following house dust exposure, the cecal microbiome of protected animals was extensively restructured with significant enrichment of, amongst others, Lactobacillus johnsonii. Supplementation of wild type animals with L. johnsonii protected them against both airway allergen challenge or infection with respiratory syncytial virus. L. johnsonii mediated protection wasM-BM- associated with significant reductions in the total number and proportion of activated CD11c+/CD11b+ and CD11c+/CD8+ cells, as well as significantly reduced airway Th2 cytokine expression. Our results reveal that exposure to dog-associated household dust results in protection against airway allergen challenge and a distinct GI microbiome composition. Moreover the study identifies L. johnsonii as a pivotal species within the gastrointestinal tract capable of influencing adaptive immunity at remote mucosal surfaces in a manner that is protective against a variety of respiratory insults. The G2 PhyloChip microarray platform (commercially available from Second Genome, Inc.) was used to profile cecal gut bacteria from 29 mice: 7 controls, 5 gavaged with dust from homes with pets, 5 gavaged with dust from homes with no pets, 4 CRA-challenged, 4 gavaged with L. johnsonii, and 4 gavaged with L. johnsonii prior to CRA challenge. The PhyloChip was also used to profile 1 house dust sample collected from a home with dogs
2013-12-20 | E-GEOD-52907 | biostudies-arrayexpress
Project description:Exposure to dogs in early infancy has been shown to reduce the risk of childhood allergic disease development and dog-ownership is associated with a distinct house dust microbial exposure. Here we demonstrate, using murine models, that exposure of mice toM-BM- dog-associated house dust protects against ovalbumin or cockroach allergen mediated airway pathology. Protected animals exhibited significant reductions in the total number of airway T cells, down-regulation of Th2-related airway responses as well as mucin secretion. Following house dust exposure, the cecal microbiome of protected animals was extensively restructured with significant enrichment of, amongst others, Lactobacillus johnsonii. Supplementation of wild type animals with L. johnsonii protected them against both airway allergen challenge or infection with respiratory syncytial virus. L. johnsonii mediated protection wasM-BM- associated with significant reductions in the total number and proportion of activated CD11c+/CD11b+ and CD11c+/CD8+ cells, as well as significantly reduced airway Th2 cytokine expression. Our results reveal that exposure to dog-associated household dust results in protection against airway allergen challenge and a distinct GI microbiome composition. Moreover the study identifies L. johnsonii as a pivotal species within the gastrointestinal tract capable of influencing adaptive immunity at remote mucosal surfaces in a manner that is protective against a variety of respiratory insults. The G2 PhyloChip microarray platform (commercially available from Second Genome, Inc.) was used to profile cecal gut bacteria from 29 mice: 7 controls, 5 gavaged with dust from homes with pets, 5 gavaged with dust from homes with no pets, 4 CRA-challenged, 4 gavaged with L. johnsonii, and 4 gavaged with L. johnsonii prior to CRA challenge. The PhyloChip was also used to profile 1 house dust sample collected from a home with dogs
2013-12-20 | E-GEOD-52906 | biostudies-arrayexpress
Project description:Exposure to dogs in early infancy has been shown to reduce the risk of childhood allergic disease development and dog-ownership is associated with a distinct house dust microbial exposure. Here we demonstrate, using murine models, that exposure of mice toM-BM- dog-associated house dust protects against ovalbumin or cockroach allergen mediated airway pathology. Protected animals exhibited significant reductions in the total number of airway T cells, down-regulation of Th2-related airway responses as well as mucin secretion. Following house dust exposure, the cecal microbiome of protected animals was extensively restructured with significant enrichment of, amongst others, Lactobacillus johnsonii. Supplementation of wild type animals with L. johnsonii protected them against both airway allergen challenge or infection with respiratory syncytial virus. L. johnsonii mediated protection wasM-BM- associated with significant reductions in the total number and proportion of activated CD11c+/CD11b+ and CD11c+/CD8+ cells, as well as significantly reduced airway Th2 cytokine expression. Our results reveal that exposure to dog-associated household dust results in protection against airway allergen challenge and a distinct GI microbiome composition. Moreover the study identifies L. johnsonii as a pivotal species within the gastrointestinal tract capable of influencing adaptive immunity at remote mucosal surfaces in a manner that is protective against a variety of respiratory insults. The G2 PhyloChip microarray platform (commercially available from Second Genome, Inc.) was used to profile cecal gut bacteria from 29 mice: 7 controls, 5 gavaged with dust from homes with pets, 5 gavaged with dust from homes with no pets, 4 CRA-challenged, 4 gavaged with L. johnsonii, and 4 gavaged with L. johnsonii prior to CRA challenge. The PhyloChip was also used to profile 1 house dust sample collected from a home with dogs
2013-12-20 | E-GEOD-52908 | biostudies-arrayexpress
Project description:The human gut microbiota impacts host metabolism and has been implicated in the pathophysiology of obesity and metabolic syndromes. However, defining the roles of specific microbial activities and metabolites on host phenotypes has proven challenging due to the complexity of the microbiome-host ecosystem. Here, we identify strains from the abundant gut bacterial phylum Bacteroidetes that display selective bile salt hydrolase (BSH) activity. Using isogenic strains of wild-type and BSH-deleted Bacteroides thetaiotaomicron, we selectively modulated the levels of the bile acid tauro-b-muricholic acid in monocolonized gnotobiotic mice. B. thetaiotaomicron BSH mutant-colonized mice displayed altered metabolism, including reduced weight gain and respiratory exchange ratios, as well as transcriptional changes in metabolic, circadian rhythm, and immune pathways in the gut and liver. Our results demonstrate that metabolites generated by a single microbial gene and enzymatic activity can profoundly alter host metabolism and gene expression at local and organism-level scales.
2018-07-19 | GSE112571 | GEO
Project description:The gut microbiome is significantly altered in inflammatory bowel diseases, but the basis of these changes is not well understood. We have combined metagenomic and metatranscriptomic profiling of the gut microbiome to assess changes to both bacterial community structure and transcriptional activity in a mouse model of colitis. Gene families involved in microbial resistance to oxidative stress, including Dps/ferritin, Fe-dependent peroxidase and glutathione S-transferase, were transcriptionally up-regulated in colitis, implicating a role for increased oxygen tension in gut microbiota modulation. Transcriptional profiling of the host gut tissue and host RNA in the gut lumen revealed a marked increase in the transcription of genes with an activated macrophage and granulocyte signature, suggesting the involvement of these cell types in influencing microbial gene expression. Down-regulation of host glycosylation genes further supports a role for inflammation-driven changes to the gut niche that may impact the microbiome. We propose that members of the bacterial community react to inflammation-associated increased oxygen tension by inducing genes involved in oxidative stress resistance. Furthermore, correlated transcriptional responses between host glycosylation and bacterial glycan utilisation support a role for altered usage of host-derived carbohydrates in colitis. Complementary RNA-seq and DNA-seq data sets of the microbiome from this study have also been deposited at ArrayExpress under accession number E-MTAB-3562 ( http://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-3562/ ).
2015-05-22 | E-MTAB-3590 | biostudies-arrayexpress
Project description:Genome scale metabolic model of Drosophila gut microbe Acetobacter fabarum
Abstract -
An important goal for many nutrition-based microbiome studies is to identify the metabolic function of microbes in complex microbial communities and their impact on host physiology. This research can be confounded by poorly understood effects of community composition and host diet on the metabolic traits of individual taxa. Here, we investigated these multiway interactions by constructing and analyzing metabolic models comprising every combination of five bacterial members of the Drosophila gut microbiome (from single taxa to the five-member community of Acetobacter and Lactobacillus species) under three nutrient regimes. We show that the metabolic function of Drosophila gut bacteria is dynamic, influenced by community composition, and responsive to dietary modulation. Furthermore, we show that ecological interactions such as competition and mutualism identified from the growth patterns of gut bacteria are underlain by a diversity of metabolic interactions, and show that the bacteria tend to compete for amino acids and B vitamins more frequently than for carbon sources. Our results reveal that, in addition to fermentation products such as acetate, intermediates of the tricarboxylic acid (TCA) cycle, including 2-oxoglutarate and succinate, are produced at high flux and cross-fed between bacterial taxa, suggesting important roles for TCA cycle intermediates in modulating Drosophila gut microbe interactions and the potential to influence host traits. These metabolic models provide specific predictions of the patterns of ecological and metabolic interactions among gut bacteria under different nutrient regimes, with potentially important consequences for overall community metabolic function and nutritional interactions with the host.IMPORTANCE Drosophila is an important model for microbiome research partly because of the low complexity of its mostly culturable gut microbiota. Our current understanding of how Drosophila interacts with its gut microbes and how these interactions influence host traits derives almost entirely from empirical studies that focus on individual microbial taxa or classes of metabolites. These studies have failed to capture fully the complexity of metabolic interactions that occur between host and microbe. To overcome this limitation, we reconstructed and analyzed 31 metabolic models for every combination of the five principal bacterial taxa in the gut microbiome of Drosophila This revealed that metabolic interactions between Drosophila gut bacterial taxa are highly dynamic and influenced by cooccurring bacteria and nutrient availability. Our results generate testable hypotheses about among-microbe ecological interactions in the Drosophila gut and the diversity of metabolites available to influence host traits.
2021-07-01 | MODEL2002040002 | BioModels