Publications by authors named "Stephanie Grunberg"

Background: Oral manifestations are common in Crohn's disease (CD). Here we characterized the subgingival microbiota in pediatric patients with CD initiating therapy and after 8 weeks to identify microbial community features associated with CD and therapy.

Methods: Pediatric patients with CD were recruited from The Children's Hospital of Pennsylvania.

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Background: Inflammatory bowel disease (IBD) involves dysregulation of mucosal immunity in response to environmental factors such as the gut microbiota. The bacterial microbiota is often altered in IBD, but the connection to disease is not fully clarified and gut fungi have recently been suggested to play a role as well. In this study, we compared microbes from all 3 domains of life-bacteria, archaea, and eukaryota-in pediatric patients with IBD and healthy controls.

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Background & Aims: The gut microbiota is a complex and densely populated community in a dynamic environment determined by host physiology. We investigated how intestinal oxygen levels affect the composition of the fecal and mucosally adherent microbiota.

Methods: We used the phosphorescence quenching method and a specially designed intraluminal oxygen probe to dynamically quantify gut luminal oxygen levels in mice.

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The development and severity of inflammatory bowel diseases and other chronic inflammatory conditions can be influenced by host genetic and environmental factors, including signals derived from commensal bacteria. However, the mechanisms that integrate these diverse cues remain undefined. Here we demonstrate that mice with an intestinal epithelial cell (IEC)-specific deletion of the epigenome-modifying enzyme histone deacetylase 3 (HDAC3(ΔIEC) mice) exhibited extensive dysregulation of IEC-intrinsic gene expression, including decreased basal expression of genes associated with antimicrobial defence.

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Antibiotic use in humans has been associated with outgrowth of fungi. Here we used a murine model to investigate the gut microbiome over 76 days of treatment with vancomycin, ampicillin, neomycin, and metronidazole and subsequent recovery. Mouse stool was studied as a surrogate for the microbiota of the lower gastrointestinal tract.

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Diet influences health as a source of nutrients and toxins, and by shaping the composition of resident microbial populations. Previous studies have begun to map out associations between diet and the bacteria and viruses of the human gut microbiome. Here we investigate associations of diet with fungal and archaeal populations, taking advantage of samples from 98 well-characterized individuals.

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Article Synopsis
  • Innate lymphoid cells (ILCs) play a vital role in maintaining the integrity of the intestinal barrier and are linked to chronic diseases like inflammatory bowel disease.
  • Research on ILCs has mainly occurred in mice without adaptive immune cells, leading to uncertainty about their function in the presence of an active immune system.
  • The study found that RORγt(+) ILCs help regulate adaptive immune responses to bacteria without promoting inflammation, indicating their crucial role in maintaining intestinal health through interactions with CD4(+) T cells.
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Eukaryotic microorganisms are important but understudied components of the human microbiome. Here we present a pipeline for analysis of deep sequencing data on single cell eukaryotes. We designed a new 18S rRNA gene-specific PCR primer set and compared a published rRNA gene internal transcribed spacer (ITS) gene primer set.

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Article Synopsis
  • The mammalian gut is home to many beneficial bacteria that are normally restricted to specific areas, but how this restriction is maintained is not well understood.
  • Research found that interleukin-22 (IL-22)-producing innate lymphoid cells (ILCs) play a crucial role in keeping these bacteria contained; without ILCs, harmful bacteria can spread and cause inflammation.
  • Specifically, Alcaligenes species bacteria can trigger systemic inflammation when ILCs are depleted, and links were found between these bacteria and diseases like Crohn's and hepatitis C in humans.
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Genetic variation is critical in microbial immune evasion and drug resistance, but variation has rarely been studied in complex heterogeneous communities such as the human microbiome. To begin to study natural variation, we analyzed DNA viruses present in the lower gastrointestinal tract of 12 human volunteers by determining 48 billion bases of viral DNA sequence. Viral genomes mostly showed low variation, but 51 loci of ∼100 bp showed extremely high variation, so that up to 96% of the viral genomes encoded unique amino acid sequences.

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