Genetic and environmental factors influencing Crohn’s disease

Table 1 The potential factors influencing Crohn’s disease

Pathogenesis	Factors	Description
Genetic factors	NOD2	NOD2 is involved in recognizing bacterial components and activating innate immune responses. Mutations in NOD2 are one of the most well-established genetic risk factors for CD, particularly influencing the response to intestinal bacteria
	ATG16 L1	ATG16 L1 is critical for autophagy, the process by which cells degrade and recycle components. Variants in this gene impair autophagy, which can increase susceptibility to CD by disrupting immune tolerance and promoting chronic inflammation
	TLRs	TLRs are part of the innate immune system, helping to recognize pathogens and initiate immune responses. Dysregulated TLR signaling can lead to an exaggerated immune response to gut microbiota, contributing to CD
Environmental factors	Smoking	Smoking is a well-established environmental risk factor for CD. It alters immune responses and microbiome composition, and is associated with more severe disease progression and complications, such as strictures and fistulas
	Diet	A diet high in processed foods, fats, and sugar, and low in fiber, can promote gut inflammation and dysbiosis, which may trigger or exacerbate CD. Diets rich in omega-3 fatty acids and fiber may have protective effects
	Vitamin D	Low levels of vitamin D have been associated with an increased risk of developing CD and may affect immune function. Vitamin D plays a role in regulating the immune system and maintaining the intestinal barrier
Gut microbiota	Bacteria	Dysbiosis, or an imbalance in gut bacterial composition, is linked to CD. Pathogenic bacteria like Escherichia coli may promote inflammation, while beneficial bacteria like Faecalibacterium prausnitzii have anti-inflammatory effects
	Fungi	The gut mycobiome (fungal microbiota) has been found to differ in CD patients compared to healthy controls. Dysregulated fungal populations may interact with bacteria, affecting immune responses and intestinal barrier function
	Virus	Viral infections, particularly those that affect the gut, may trigger or exacerbate CD in genetically susceptible individuals. Viruses like enteric adenoviruses and Epstein-Barr virus have been implicated in IBD pathogenesis
	Parasite	Parasitic infections may modulate immune responses, potentially either triggering or protecting against inflammation. Some studies suggest that exposure to certain parasites may be protective against CD
Immune factors	Innate immunity	Innate immunity involves the body's first line of defense, including pattern recognition receptors. Dysregulation in innate immunity leads to an inappropriate immune response to normal gut bacteria, contributing to chronic inflammation in CD
	Acquired immunity	The acquired immune response involves T cells and antibodies. In CD, an imbalance of Th1 and Th17 responses can drive inflammation, while Tregs may be insufficient to control it. Abnormal cytokine production is a key feature of CD
Non-coding RNA	miRNA	miRNAs are small RNA molecules that regulate gene expression post-transcriptionally. In CD, altered miRNA expression can affect immune cell differentiation and response, potentially contributing to inflammation and disease progression
	lncRNA	lncRNAs are involved in the regulation of gene expression, chromatin remodeling, and immune cell differentiation. Their dysregulation in CD may impact immune function and contribute to intestinal inflammation
	siRNA	siRNAs regulate gene silencing and play a role in modulating immune responses. They have been explored as potential therapeutic agents for targeting specific genes involved in CD pathogenesis
	circRNA	circRNAs are a type of non-coding RNA that form closed loops. They are involved in regulating gene expression and protein activity. In CD, altered circRNA expression may influence immune responses and gut barrier integrity

NOD2: Nucleotide-binding oligomerization domain-2; ATG16 L1: Autophagy related 16 like 1; TLRs: Toll-like receptors; CD: Crohn’s disease; Tregs: Regulatory T cells; IBD: Inflammatory bowel disease.