From genes to environment: A life-course approach to prevent pediatric autoimmune diseases

Table 2 Environmental triggers of autoimmune disorders and preventive strategies

Environmental trigger	Associated autoimmune risk	Proposed mechanism	Prevention strategy
Tobacco smoke	JIA, T1DM, multiple sclerosis, rheumatoid arthritis, SLE	Induces oxidative stress, promotes pro-inflammatory cytokines, impairs T-cell function, and alters epigenetic markers	Complete avoidance of prenatal and second-hand smoke exposure
Endocrine disruptors (e.g., BPA, phthalates, pesticides)	Increased autoantibody production, immune dysregulation	Mimic or block hormones critical for immune regulation; can alter gut microbiome and promote inflammation	Use glass/stainless steel containers, avoid microwaving in plastic, buy organic produce, and use non-toxic household products
Infections (viruses and bacteria)	T1DM (enteroviruses), lupus (EBV), myocarditis (coxsackievirus)	Molecular mimicry (pathogen antigens resemble self-antigens), bystander activation (inflammation damages tissues and releases self-antigens)	Adhere to vaccination schedules for preventable diseases
Nutrient deficiencies (vitamin D)	T1DM, SLE, multiple sclerosis, rheumatoid arthritis	Impairs regulatory T-cell function and promotes pro-inflammatory Th1 and Th17 pathways	Ensure adequate vitamin D intake through sunlight exposure, fortified foods, or supplementation as recommended by a physician
Diet (high sugar/fat, low fiber)	IBD, T1DM, rheumatoid arthritis	Promotes gut dysbiosis, “leaky gut” (increased intestinal permeability), and systemic inflammation	Emphasize a diet rich in fiber, fruits, vegetables, and whole grains; limit processed foods, sugar, and unhealthy fats
Stress (physical/psychological)	IBD, psoriasis, rheumatoid arthritis, SLE	Activates the hypothalamic-pituitary-adrenal axis, leading to the release of stress hormones (e.g., cortisol) and pro-inflammatory cytokines that can exacerbate autoimmunity	Promote stress-reduction techniques such as mindfulness, adequate sleep, and physical activity
Overly sterile environment	Impaired immune tolerance (hygiene hypothesis)	Lack of exposure to diverse microbes and parasites in early life impairs the maturation of regulatory T-cells and other immune-modulating pathways	Encourage balanced microbial exposure through outdoor play, pets, and safe interaction with natural environments

The table outlines key environmental triggers implicated in the development of pediatric autoimmune disorders and summarizes the proposed biological mechanisms linking these exposures to immune dysregulation. The table also provides practical, evidence-informed prevention strategies to reduce risk during critical developmental windows. Environmental triggers include tobacco smoke, endocrine-disrupting chemicals, infectious agents, nutritional deficiencies, dietary patterns, psychosocial stress, and reduced early-life microbial exposure. These factors can influence immune maturation through oxidative stress, hormonal disruption, microbiome alterations, molecular mimicry, impaired gut barrier function, and dysregulation of both innate and adaptive immunity. Preventive recommendations emphasize modifiable behaviors and early-life interventions that may lower autoimmune susceptibility in genetically predisposed children. T1DM: Type 1 diabetes mellitus; JIA: Juvenile idiopathic arthritis; SLE: Systemic lupus erythematosus; BPA: Bisphenol A; EBV: Epstein-Barr virus; IBD: Inflammatory bowel disease.