Environmental risk factors for inflammatory bowel diseases: Evidence based literature review

Table 4 Effect of environmental factors on ulcerative colitis and impact of interventional studies to modify specific environmental factors

Ref.	Disease onset (incident UC)	Disease Activity	Study population and design	Intervention and comparison group	Outcome
Lifestyle
Smoking[11,20,24] (LOE 2b, 3b, 2a)	Current smoking ↓	↓	Mild-moderate UC Systematic review (n = 233)[205] (LOE 1a) (n = 81)[205] (LOE 1a)	Nicotine or placebo	No evidence for efficacy for nicotine preparations in inducing remission in UC
	Smoking cessation ↑			Nicotine or corticosteroids
Sleep[176,179] (LOE 2b)	No data	↑	None	None	No data
Stress[158,159] (LOE 5, 2b)	No data	↑?	Adult and adolescent patients with IBD	Multi-modality psychotherapy	No evidence for efficacy of psychological therapy in adult patients with IBD
			Systematic review of RCTs and quasi-RCTs (n = 1745)[162] (LOE 1a)		In adolescents, psychological interventions may be beneficial, but the evidence is limited
Diet
Dietary fat[118] (LOE 3a)	n-3 PUFA ↓	n-3 PUFA ↓	UC in remission Systematic review of RCTs (n = 148)[208] (LOE 1a)	fish oil (n-3 PUFA) or placebo	No difference in risk of relapse between n-3 PUFA compared with placebo
	n-6 PUFA ↑
Dietary milk[116,117] (LOE 5)	↑	No data	Active UC	Milk-free diet or sham diet	Fewer relapses on milk-free diet than on sham diet
			RCT (n = 77)[209] (LOE 2b)
Dietary protein[118] (LOE 3a)	↑	↑	None	None	No data
Dietary fiber[118,120] (LOE 2b)	↔	↔	UC in remission Open label RCT (n = 59)[200](LOE 2b)	Germinated barley food stuff (GBF) + conventional therapy or conventional therapy	Prolonged maintenance of remission in GBF group[200]
			UC in remission Open label RCT (n = 105)[122] (LOE 2b)	Plantago ovata or Mesalamine	Plantago ovata as effective as Mesalamine in maintenance of remission[122]
Food antigens[128] (LOE 4)	↑?	No data	None	None	No data
Food additives[131,132] (LOE 5)	↑?	No data	None	None	No data
Breastfeeding[187,189] (LOE 3a, 3b, 2b)	↔	No data	None	None	No data
Medication
Nsaids[139,140] (LOE 2b)	↑?	↑	Quiescent to mild	Rofecoxib 25 mg or 12.5 mg × 20 d	41% responded with reduction in arthralgia scores. P < 0.05. No IBD flares 9% developed GI side effects
			UC and CD with arthralgia
			Prospective Open label trial (n = 32)
Oral contraceptives[150,151,153,155] (LOE 3a, 2b)	↑	↔	None	None	No data
Antibiotics[145,147] (LOE 3b, 3a)	Early exposure ↔	↓	Active UC Systematic review of RCTs (n = 9 studies)[71] (LOE 1a)	Antibiotic or placebo	Antibiotics superior to placebo at inducing remission
Vaccination[183] (LOE 3a)	No effect	No data	None	None	No data
Gut microbiome
Dysbiosis[80,83,84] (LOE 4)	↑	↑	Mild-moderate UC Systematic review of RCTs (n = 650)[199] (LOE 1a)	Probiotics + conventional treatment or placebo	Probiotics effective for induction and maintenance of remission in UC and pouchitis[199]
			Active UC RCT (n = 70)[204] (LOE 1b)	Fecal microbiota transplant (FMT) or Placebo	FMT induced remission in a significantly greater percentage of patients with active UC than placebo (24% vs 5%)[204]
			Active UC, RCT (n = 100)[206] (LOE1b)	Ciprofloxacin + E-coli Nissle or placebo + E-coli Nissle	No benefit in the use of E. coli Nissle as an add-on treatment to conventional therapies for active UC
Ecological (Abiotic)
Air pollution[33,34] (LOE 2c, 3b)	↑	↑	None	None	No data
Water pollution[36-38] (LOE 5)	↑	↑	None	None	No data
Low Vitamin D[44,57] (LOE 2a, 2b)	↑	↑	Active UC Cohort study (n = 368)[59] (LOE 2b)	Vitamin D3 or No treatment	Reduction in health-care utilization in the vitamin D treatment group
Surgery
Appendectomy[195-196] (LOE 2b, 3b)	↓	No data	None	None	No data

↑ : Increased risk; ↔ : Equivocal risk; ↓ : Decreased risk; ? : Questionable risk. LoE: Levels of Evidence; CD: Crohn's disease; IBD: Inflammatory bowel diseases; PUFA: Polyunsaturated fatty acid; UC: Ulcerative colitis.