Table 1.
Factors involved in the gut/microbiota/brain interplay in inflammatory bowel disease (IBD) development.
| Factor | Type of study | N | Intervention/Methodology | Outcome | Author(s) | Reference |
|---|---|---|---|---|---|---|
| Genetics | Clinical study | 637 | Questionnaire | First-degree relatives have 10-fold increased risk of IBD development | Orholm, M. et al. | 37 |
| Meta-analysis | >75,000 cases & controls | GWAS | Identified 30 gene loci for CD and 23 for UC | Jostins, L. et al. | 39 | |
| Trans-ancestry association studies | 238,401 | GWAS | Identified 38 susceptibility loci for IBD | Liu, J.Z. et al. | 40 | |
| Genetic association study | 6228 | Association studies | Identified UPS and CYLD gene are important in IBD pathogenesis | Cleynen, I. et al. | 41 | |
| Genotype association study | 34,819 | Association studies | Insights into genetic heterogeneity between ileal and colonic CD | Cleynen, I. et al. | 42 | |
| Clinical study | 323 | Array-based transcriptome data | Identified 99 strong positional candidate genes in 63 risk loci | Momozawa, Y. et al. | 43 | |
| Clinical study | 189 twin pairs | Questionnaire | Results highlight the importance of environmental triggers | Spehlmann, ME. et al. | 45 | |
| Clinical study | 80 twin pairs | Questionnaire | Genetic influence is stronger in CD than in UC | Halfvarson, J. et al. | 46 | |
| Diet | Interventional, open-label, pilot study | 16 | Vitamin D3 supplementation | Vitamin D3 modulates the gut microbiome | Bashir, M. et al. | 48 |
| In-vivo mouse study | 4–8 mice per group | Oral antibiotics | Increased levels of intracellular zinc led to bacterial clearance | Lahiri, A. et al. | 49 | |
| In-vivo mouse study | 4–5 mice per group | High-fat diet and oral antibiotics | High-fat diet alters gut microbiome composition | Hildebrandt, MA. | 55 | |
| In-vivo mouse study | >100 inbred mouse strains | High-fat/high-sucrose diet | High-fat/high-sucrose diet influences gut microbiota composition | Parks, BW. et al. | 56 | |
| Case-control study | 86 | Dietary intake | Mono- and polyunsaturated fats consumption is a risk factor for IBD | Geerling, BJ. et al. | 57 | |
| In-vivo mouse study | 4–5 mice per group | Diet enriched with phytosterols | Phytosterols are protective against IBD | Aldini, R. et al. | 58 | |
| Environment | Population-based case-control study | 1382 | Questionnaire on 25 different topics | Altered intestinal microbiota may modulate risk of IBD | Ng, SC. et al. | 62 |
| Retrospective case study | 1194 | Clinical history and questionnaire | Higher prevalence of CD in urban areas and UC in inland areas | Carpio, D. et al. | 68 | |
| Smoking | Meta-analysis | 245 articles | Smoking | Smoking is a risk factor for IBD | Mahid, SS. et al. | 51 |
| Prospective case-control study | 160 | Transdermal nicotine or placebo patches | Smoking effects gut microbiota composition | Richardson, CE. et al. | 52 | |
| Medication | Meta-analysis | 11 observational studies | Antibiotic exposure | Antibiotics increases the risk of new-onset CD than UC | Ungaro, R. et al. | 70 |
| Meta-analysis | 20 studies | OCP | Increased risk for development of CD and UC | Ortizo, R. et al. | 71 | |
| Case-control study | 122 | NSAIDs | Provoked disease activity in IBD | Felder, JB. et al. | 72 | |
| Exercise | In-vivo mouse study | 4 mice per group | Exercise training | Alleviated symptoms of acute colitis | Saxena, A. et al. | 60 |
| Prospective cohort study | 194,711 | Physical activity | Inversely associated with risk of CD | Khalili, H. | 61 | |
| Uncontrolled pilot study | 12 | 12-week walking program | Beneficial for IBD patients | Loudon, CP. et al. | 63 | |
| Sleep disturbances | Longitudinal,internet-based cohort data | 3173 | Questionnaire | Increased risk of disease flares in CD but not UC | Ananthakrishnan, AN. et al. | 75 |
| Clinical study | 10 | Disturbances in sleep-wake cycle | Sleep disturbances led to immunologic alterations | Born, J. et al. | 76 | |
| Clinical study | 47 | Questionnaire assessing sleep quality | Impaired sleep quality is associated with pediatric IBD | Mahlmann, L. et al. | 77 | |
| Clinical study | 32 | Questionnaire assessing sleep quality | Impaired quality of life in IBD | Keefer, L. et al. | 78 | |
| Prospective observational cohort study | 41 | Pittsburgh sleep quality index (PSQI) | Strong association between poor sleep quality and IBD | Ali, T. et al. | 79 | |
| In-vivo mouse study | 33 | Diet and sleep disturbances | Circadian disorganization impacts intestinal microbiota | Voigt, RM. et al. | 80 |
CD = Crohn’s disease; GWAS = genome-wide association studies; NSAIDs = nonsteroidal anti-inflammatory drugs; OCP = oral contraceptive pill; SNP = single nucleotide polymorphism; UC = ulcerative colitis; UPS = ubiquitin protease system.