Cystic fibrosis transmembrane conductance regulator knockout mice exhibit aberrant gastrointestinal microbiota.

The composition of the gastrointestinal microbiome is increasingly recognized as a crucial contributor to immune and metabolic homeostasis-deficiencies in which are characteristic of cystic fibrosis (CF) patients. The murine model (CFTR (-/-) , CF), has, in previous studies, demonstrated characteristic CF gastrointestinal (GI) manifestations including slowed transit and significant upregulation of genes associated with inflammation. To determine if characteristics of the microbiome are associated with these phenotypes we used a phylogenetic microarray to compare small intestine bacterial communities of wild type and congenic CF mice. Loss of functional CFTR is associated with significant decreases in GI bacterial community richness, evenness and diversity and reduced relative abundance of putative protective species such as Acinetobacter lwoffii and a multitude of Lactobacilliales members. CF mice exhibited significant enrichment of Mycobacteria species and Bacteroides fragilis, previously associated with GI infection and immunomodulation. Antibiotic administration to WT and CF animals resulted in convergence of their microbiome composition and significant increases in community diversity in CF mice. These communities were characterized by enrichment of members of the Lactobacillaceae and Bifidobacteriaceae and reduced abundance of Enterobacteriaceae and Clostridiaceae. These data suggest that Enterobacteria and Clostridia species, long associated with small intestinal overgrowth and inflammatory bowel disease, may suppress both ileal bacterial diversity and the particular species which maintain motility and immune homeostasis in this niche. Thus, these data provide the first indications that GI bacterial colonization is strongly impacted by the loss of functional CFTR and opens up avenues for alternative therapeutic approaches to improve CF disease management.

Gastroesophageal reflux is not associated with dental erosion in children.

BACKGROUND & AIMS: Dental erosion is a complication of gastroesophageal reflux (GER) in adults; in children, it is not clear if GER has a role in dental pathologic conditions. Dietary intake, oral hygiene, high bacterial load, and decreased salivary flow might contribute independently to GER development or dental erosion, but their potential involvement in dental erosion from GER is not understood. We investigated the prevalence of dental erosion among children with and without GER symptoms, and whether salivary flow rate or bacterial load contribute to location-specific dental erosion. METHODS: We performed a cross-sectional study of 59 children (ages, 9-17 y) with symptoms of GER and 20 asymptomatic children (controls); all completed a questionnaire on dietary exposure. Permanent teeth were examined for erosion into dentin, erosion locations, and affected surfaces. The dentist was not aware of GER status, and the gastroenterologist was not aware of dental status. Stimulated salivary flow was measured and salivary bacterial load was calculated for total bacteria, Streptococcus mutans, and Lactobacilli. RESULTS: Controlling for age, dietary intake, and oral hygiene, there was no association between GER symptoms and dental erosion by tooth location or affected surface. Salivary flow did not correlate with GER symptoms or erosion. Erosion location and surface were independent of total bacteria and levels of Streptococcus mutans and Lactobacilli. CONCLUSIONS: Location-specific dental erosion is not associated with GER, salivary flow, or bacterial load. Prospective studies are required to determine the pathogenesis of GER-associated dental erosion and the relationship between dental caries to GER and dental erosion.

Abnormal parathyroid cell proliferation precedes biochemical abnormalities in a mouse model of primary hyperparathyroidism.

The properties of neoplastic proliferation and hormonal dysregulation are tightly linked in primary hyperparathyroidism (HPT). However, whether abnormal parathyroid proliferation is the cause or result of a shift in calcium-sensitive parathyroid hormonal regulation has been controversial. We addressed this issue by analyzing the temporal sequence of these fundamental abnormalities in a mouse model of primary HPT. These transgenic mice (PTH-D1) harbor a transgene that targets overexpression of the cyclin D1 oncogene to parathyroid cells, resulting in parathyroid hypercellularity with a phenotype of chronic biochemical HPT and, notably, an abnormal in vivo PTH-calcium set point. We examined parathyroid cell proliferation and biochemical alterations in PTH-D1 and control wild-type mice from ages 1-14 months. Strikingly, abnormal parathyroid proliferation regularly preceded dysregulation of the calcium-PTH axis, supporting the concept that disturbed parathyroid proliferation is the crucial primary initiator leading to the development of the biochemical phenotype of HPT. Furthermore, we observed that decreased expression of the calcium-sensing receptor in the parathyroid glands occurs several months before development of biochemical HPT, suggesting that decreased calcium-sensing receptor may not be sufficient to cause PTH dysregulation in this animal model of primary HPT.