Fecal Dysbiosis and Inflammation in Intestinal-Specific Cftr Knockout Mice on Regimens Preventing Intestinal Obstruction Article Swipe
Sarah M. Young
,
Rowena A. Woode
,
Estela Williams
,
Aaron C. Ericsson
,
Lane L. Clarke
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1101/2023.07.24.550378
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1101/2023.07.24.550378
Chronic intestinal inflammation is a poorly understood manifestation of Cystic Fibrosis (CF), which may be refractory to ion channel CFTR modulator therapy. People with CF exhibit intestinal dysbiosis which has potential for stimulating intestinal and systemic inflammation. CFTR is expressed in organ epithelia and in the leukocyte population. Here, we investigate the contribution of intestinal epithelial-specific loss of Cftr (iCftr KO) to dysbiosis and inflammation in mice treated with either of two anti-obstructive dietary regimens necessary to maintain CF mouse models (PEG laxative or a liquid diet, LiqD). Feces collected from iCftr KO mice and their wildtype (WT) sex-matched littermates were used to measure fecal calprotectin and to perform 16S rRNA sequencing to characterize the gut microbiome. Fecal calprotectin was elevated in iCftr KO relative to WT samples of mice consuming either PEG or LiqD. PEG iCftr KO mice did not show a change in α-diversity versus WT but demonstrated a significant difference in microbial composition (β-diversity) with increases in phylum Proteobacteria , family Peptostreptococcaceae , four genera of Clostridia including C. innocuum , and mucolytic genus Akkermansia . Fecal microbiome analysis of LiqD iCftr KO mice showed both decreased α-diversity and differences in microbial composition with increases in Proteobacteria family Enterobacteriaceae , Firmicutes families Clostridiaceae and Peptostreptococcaceae , and enrichment of Clostridium perfringens , C. innocuum , C. difficile , mucolytic Ruminococcus gnavus , and reduction of Akkermansia . It was concluded that epithelial-specific loss of Cftr is a major driver of CF intestinal dysbiosis and inflammation with significant similarities to previous studies of global Cftr KO mice. New and noteworthy Chronic intestinal inflammation is a manifestation of cystic fibrosis (CF), a disease caused by loss of the anion channel CFTR that is expressed in many tissues. This study shows that intestinal epithelial cell-specific loss of CFTR (iCftr KO) in mice is sufficient to induce intestinal dysbiosis and inflammation. Studies were performed on mice consuming either dietary regimen (PEG laxative or liquid diet) routinely used to prevent obstruction in CF mice.
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Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2023.07.24.550378
- https://www.biorxiv.org/content/biorxiv/early/2023/07/26/2023.07.24.550378.full.pdf
- OA Status
- green
- References
- 67
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4385285529
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4385285529Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/2023.07.24.550378Digital Object Identifier
- Title
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Fecal Dysbiosis and Inflammation in Intestinal-Specific Cftr Knockout Mice on Regimens Preventing Intestinal ObstructionWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2023Year of publication
- Publication date
-
2023-07-26Full publication date if available
- Authors
-
Sarah M. Young, Rowena A. Woode, Estela Williams, Aaron C. Ericsson, Lane L. ClarkeList of authors in order
- Landing page
-
https://doi.org/10.1101/2023.07.24.550378Publisher landing page
- PDF URL
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https://www.biorxiv.org/content/biorxiv/early/2023/07/26/2023.07.24.550378.full.pdfDirect link to full text PDF
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YesWhether a free full text is available
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greenOpen access status per OpenAlex
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https://www.biorxiv.org/content/biorxiv/early/2023/07/26/2023.07.24.550378.full.pdfDirect OA link when available
- Concepts
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Dysbiosis, Inflammation, Gastroenterology, Knockout mouse, Medicine, Mucosal inflammation, Feces, Internal medicine, Biology, Microbiology, Disease, ReceptorTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
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67Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| primary_location.license | |
| primary_location.pdf_url | https://www.biorxiv.org/content/biorxiv/early/2023/07/26/2023.07.24.550378.full.pdf |
| primary_location.version | acceptedVersion |
| primary_location.raw_type | posted-content |
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| publication_year | 2023 |
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