Transcriptional Profiling of the Small Intestine and the Colon Reveals Modulation of Gut Infection with Citrobacter rodentium According to the Vitamin A Status

Abstract

Vitamin A (VA) deficiency and diarrheal diseases are both serious public health issues worldwide. VA deficiency is associated with impaired intestinal barrier function and increased risk of mucosal infection-related mortality. The bioactive form of VA, retinoic acid, is a well-known regulator of mucosal integrity. Using Citrobacter rodentium-infected mice as a model for diarrheal diseases in humans, previous studies showed that VA-deficient (VAD) mice failed to clear C. rodentium as compared to their VA-sufficient (VAS) counterparts. However, the distinct intestinal gene responses that are dependent on the host’s VA status still need to be discovered. The mRNAs extracted from the small intestine (SI) and the colon were sequenced and analyzed on three levels: differential gene expression, enrichment, and co-expression. C. rodentium infection interacted differentially with VA status to alter colon gene expression. Novel functional categories downregulated by this pathogen were identified, highlighted by genes related to the metabolism of VA, vitamin D, and ion transport, including improper upregulation of Cl– secretion and disrupted HCO3– metabolism. Our results suggest that derangement of micronutrient metabolism and ion transport, together with the compromised immune responses in VAD hosts, may be responsible for the higher mortality to C. rodentium under conditions of inadequate VA.

Vitamin A- and D-Deficient Diets Disrupt Intestinal Antimicrobial Peptide Defense Involving Wnt and STAT5 Signaling Pathways in Mice

“…Deficiency of VA or VD has been associated with gastrointestinal infections, severe diarrhea, and intestinal barrier dysfunction [ 3 , 4 , 8 , 9 , 10 ], which is in turn considered to be a key determinant in the pathogenesis of a variety of diseases such as inflammatory bowel disease (IBD) [ 9 , 11 , 12 ], irritable bowel syndrome (IBS) [ 13 , 14 ], and metabolic diseases, e.g., diabetes and nonalcoholic fatty liver disease (NAFLD) [ 15 , 16 ]. Consistent with this, the absence of VD receptor (VDR) increased the risk for these diseases [ 17 ].…”