Virginia Research Day 2022

Graduate Student Research Biomedical

10 NLRX1 Is Critical For Maintaining Gut Microbiome Symbiosis Following Adherence To A Gluten-Free Diet

Holly A. Morrison a ; Yang Liub; Kristin Eden a ; Margaret A. Nagai-Singer a ; Paul Wade b ; Irving C. Allen a,c Corresponding author: Hamorrison18@vt.edu

a Virginia-Maryland College of Veterinary Medicine b National Institute of Environmental Health Sciences, Research Triangle Park, NC c Virginia Tech Carilion School of Medicine

significantly decreased NLRX1 . Microbiome assessments comparing NLR-knockout mice indicate that NLRX1-deficient mice have a genetically inherent microbiome unique from NLRP12-deficient mice and mice with intact NLR signaling. Regardless of genetic status, adherence to GFD demonstrated a significant shift in the microbial community structure and metabolic activity of the gut microbiome. Holistically evaluating the implications of GFD, our data also demonstrates the negative impact that gluten exclusionary diets can have on gastrointestinal health and microbiome homeostasis regardless of NLR status. This research was funded by a VCOM One Health Seed Grant

have been well-documented in dampening overzealous inflammatory responses. It has been postulated that their regulatory nature reciprocally shapes the microbiome by preventing inflammation-induced dysbiosis by preventing the expansion of opportunistic/ pathogenic bacteria. The only existing treatment for patients with gluten sensitivities is strict adherence to a gluten-free diet (GFD). However, such strict adherence further shifts the gut microbiome towards dysbiosis. Here, we demonstrate that deficiency of NLRX1 poises the gut towards dysbiosis prior to GFD by promoting the expansion of opportunistic bacteria. Our preliminary data demonstrates in a metadata analysis of human clinical gene expression data that active CeD patients have

Patients with gluten sensitivity present with dysbiosis of the gut microbiome. Patients are genetically susceptible to Celiac Disease (CeD) if they are carriers of the HLA DR3/DQ2 or HLA DR4/DQ8 haplotypes. Between 85-95% of all CeD patients carry HLA DQ2, yet only between 25-50% of the world population carry this haplotype with only a minority developing CeD. This suggests that CeD is mediated by factors beyond genetics. As innate immune signaling has been overlooked in the context of CeD pathology, we further examined the role of nucleotide-binding domain and leucine-rich repeat-containing proteins (NLRs), a subtype of pattern recognition receptors, in maintaining the gut microbiome composition. The negative regulatory NLRs, NLRX1 and NLRP12,

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