(497) Cystic fibrosis epithelial defect and immune defect influence intestinal microbiota differentially

Thursday, November 3, 2022

12:45 PM – 1:25 PM ET

Presenting Author(s)

Callie E. Scull

Graduate Student
LSUHSC NOLA, Louisiana, United States

Co-Author(s)

ML

Meng Luo

Instructor
LSUHSC NOLA
New Orleans, Louisiana, United States
Scott R. Jennings, MS (he/him/his)

Research Associate
LSU Health Sciences Center NO
New Orleans, Louisiana, United States
CT

Christopher Taylor

Associate Professor
LSUHSC, United States
GW

Guoshun Wang

Professor
LSU Health Sciences Center, United States

Background: Cystic fibrosis (CF) is a life-threatening genetic disorder, caused by mutations in the CF transmembrane-conductance regulator gene (cftr). Clinically, CF gastrointestinal illness claims the early morbidity and mortality, manifesting as small intestinal bacterial overgrowth, large intestinal microbial dysbiosis, intestinal inflammation and obstruction. As CF is widely accepted as an epithelial disease, it is unknown whether its immune defect contributes to these clinical outcomes.

Methods: Whole-body CF (Pan-CF), myeloid CF (Mye-CF), macrophage CF (Mac-CF), and neutrophil CF (Neu-CF) mice were established and co-housed with wild-type (WT) mice. Microbiota in feces and intestinal contents were interrogated by 16S rRNA gene sequencing. Alpha and beta diversities as well as prediction of metagenome functions were evaluated to compare the microbiota within each genotype and across the genotypes. Moreover, CF and WT mice with bone marrow replacement were similarly investigated for their changes in intestinal microbiota.

Results: Data demonstrate that both epithelial defect and immune defect in CF collectively influence the intestinal microbiota. However, the immune defect is the major factor determining the microbiome in the small intestine, while the epithelial defect the major factor in the large intestine.

Conclusions: This finding revises the current concept by suggesting that CF epithelial defect and immune defect play differential roles in CF intestinal disease.

Acknowledgements: Funding was provided to GW by NIH (HL150370) and the Cystic Fibrosis Foundation (WANG18I0).

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