The effect of NOD2 on the microbiota in Crohn's disease

Abstract

Recent advancements toward the treatment of Crohn’s disease (CD) indicate great promise for long-term remission. CD patients suffer from a complex host of dysregulated interactions between their innate immune system and microbiome. The most predominant link to the onset of CD is a genetic mutation in the innate immune receptor nucleotide-binding oligomerization domain-containing 2 (NOD2). NOD2 responds to the presence of bacteria and stimulates the immune response. Mutations to NOD2 promote low diversity and dysbiosis in the microbiome, leading to impaired mucosal barrier function. Current treatments suppress the immune response rather than enhancing the function of this critical protein. New progress towards stabilizing NOD2 signaling through its interactions with chaperone proteins holds potential in the development of novel CD therapeutics.

Curcumin, the golden nutraceutical: multitargeting for multiple chronic diseases

“…Crohn's disease is an immune‐mediated IBD, which has become increasingly prevalent throughout the past decade (Lauro et al , ; Manuc et al , ). A pilot study was conducted with Crohn's disease to determine the effect of curcumin, as an addition to the existing treatments, in decreasing inflammation.…”

Inflammatory Bowel Diseases: Host-Microbial-Environmental Interactions in Dysbiosis

“…The α-defensins HD5 and HD6 are depleted in Crohn’s Disease but up-regulated in Ulcerative Colitis, as are hBD2 and LL-37/hCAP18. However, BPI and CCL20 increase and hBD1 diminishes in CD and UC [ 132 , 133 , 134 ].…”

“…Moreover, functional disruption of endosomal stress protein XBP1, Toll-like receptor 9, calcium-mediated potassium channel KCNN4, immunity-related GTPase family M protein IRGM, and cytosolic protein kinase LRRK2 can be evident. The overall effect is to attenuate production or release of anti-microbial factors, such as HD5, HD6, and lysozyme by ileal Paneth cells [ 134 , 189 , 197 ]. In contrast, while absent in the healthy colon, HD5 and HD6 are found in the distal colon of CD patients.…”

Updated review on immune factors in pathogenesis of Crohn’s disease

“…However, the innate immune system is also important, especially in the stage of disease induction; the congenital immune system cells is an important generator of cytokines, such as IL-1, TNF-α, IL-6, and other cytokines, and these factors play an important role in intestinal mucosal inflammation. The CD susceptibility genes encoding intracellular proteins (such as NOD2/CARD15) were found first in the innate immune system, which can activate certain cytokines dependent on NF-kappa B to cause intestinal bacteria to break the immune tolerance of the intestinal mucosa[ 47 ]. By using monoclonal antibodies against cell factors, fusion proteins, and receptor antagonists for cytokine blocking, immunomodulation of CD can be done effectively.…”