|Year : 2020 | Volume
| Issue : 3 | Page : 159-165
Association of atopic dermatitis with inflammatory bowel disease: A systematic review and meta-analysis
Chi-Hui Wang1, Yun Fu2, Ching-Chi Chi3
1 Department of Dermatology, Chang Gung Memorial Hospital, Linkou, Taoyuan; Department of Dermatology, Chang Gung Memorial Hospital, Keelung, Taiwan
2 Department of Dermatology, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
3 Department of Dermatology, Chang Gung Memorial Hospital, Linkou; College of Medicine, Chang Gung University, Taoyuan, Taiwan
|Date of Submission||21-Apr-2020|
|Date of Decision||08-May-2020|
|Date of Acceptance||12-May-2020|
|Date of Web Publication||10-Sep-2020|
Prof. Ching-Chi Chi
Department of Dermatology, Chang Gung Memorial Hospital, Linkou, No. 5, Fuxing St., Guishan, Taoyuan 33305
Source of Support: None, Conflict of Interest: None
Background: Altered microbiota of the gastrointestinal tract have been implicated in both atopic dermatitis (AD) and inflammatory bowel disease (IBD). However, the relationship between AD and IBD has been unclear. Objectives: The objective of this study was to systemically assess the evidence on the association of AD with IBD. Methods: We conducted a systematic review and meta-analysis of observational studies on the association of AD with IBD. We searched MEDLINE, Embase, CENTRAL, Web of Science, and Airiti Library from inception to May 24, 2019, for relevant studies. The outcomes were the odds and risk of Crohn's disease (CD) and ulcerative colitis (UC) in patients with AD. Results: We included five case–control studies and one cohort study. We identified significant associations of AD with prevalent CD (odds ratio [OR]: 1.55, 95% confidence interval [CI]: 1.11–2.15) and UC (OR: 2.49, 95% CI: 1.04–5.98). One Danish cohort study found no increased risk for incident CD (hazard ratio [HR]: 0.69, 95% CI: 0.34–1.30) and UC (HR: 0.94, 95% CI: 0.61–1.43) in patients with AD. Conclusion: The current limited evidence supports an association of AD with prevalent IBD. Digestive symptoms in patients with AD, for example, chronic diarrhea and abdominal pain, shall not be overlooked, and gastroenterology counseling may be needed.
Keywords: Atopic dermatitis, Crohn's disease, inflammatory bowel disease, meta-analysis, ulcerative colitis
|How to cite this article:|
Wang CH, Fu Y, Chi CC. Association of atopic dermatitis with inflammatory bowel disease: A systematic review and meta-analysis. Dermatol Sin 2020;38:159-65
|How to cite this URL:|
Wang CH, Fu Y, Chi CC. Association of atopic dermatitis with inflammatory bowel disease: A systematic review and meta-analysis. Dermatol Sin [serial online] 2020 [cited 2021 Aug 3];38:159-65. Available from: https://www.dermsinica.org/text.asp?2020/38/3/159/294707
| Introduction|| |
Atopic dermatitis (AD) is the most common chronic inflammatory skin disease with a prevalence of up to 25% in children and 7% among adults., AD typically presents with pruritus and eczematous lesions starting within the first 5 years of life and follows a relapsing–remitting nature. According to the World Health Organization 2010 Global Burden of Disease Survey, AD ranked first among common skin diseases with respect to disability-adjusted life years and years lived with a disease. Nowadays, immunologic aberrations, interactions between genetic mutations, skin barrier dysfunction, and microbiota are considered as the major pathogenesis of AD. AD has been associated with activation of T-cell subsets inducing immune deviations. Mutation of filaggrin (FLG) gene for defect in FLG synthesis is found in patients with AD, with resultant skin barrier impairment.,, A growing body of evidence has accumulated that AD can be accompanied by a variety of systemic diseases including cardiovascular diseases, autoimmune disorders, sleep disturbance, and metabolic abnormalities.,,,,
Inflammatory bowel disease (IBD) is a group of chronic inflammatory conditions of the intestine including Crohn's disease (CD) and ulcerative colitis (UC). Over the past decade, IBD has emerged as a public health challenge worldwide. Clinically, CD is characterized by transmural granulomatous inflammation and may affect the entire gastrointestinal tract but sparing the rectum; by contrast, UC typically presents as mucosal inflammation involving the colon and rectum., The pathogenesis of IBD is thought to be mediated by the microbiota of the intestinal lumen and inappropriate immune responses in genetically susceptible individuals.
As AD and IBD both involve chronic inflammation and alterations in microbiota, there may be a link between the two diseases. The objective of this study was to systemically assess the evidence on the association of AD with IBD.
| Materials and Methods|| |
We conducted a systematic review and meta-analysis of observational studies, including cross-sectional, case–control, and cohort studies, on the association of AD with IBD. This study was done following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology guidelines. We have registered the protocol with PROSPERO (CRD42018106852; see https://www.crd.york.ac.uk/PROSPERO/display_record.php&?RecordID = 106852).
Two authors (CW and CC) performed a literature search of electronic databases (MEDLINE, Embase, CENTRAL, Web of Science, and Airiti Library) from inception to May 24, 2019, for relevant studies. The search strategy is shown in [Table 1]. In addition, relevant published conference abstracts were tracked for full publications. No restrictions on language, publication status, or geographic regions were imposed.
Study selection and eligibility criteria
The eligibility criteria for articles to be included in this study were as follows: (1) observational studies investigating the association of AD with IBD, including case–control or cohort studies; (2) research of human subjects; and (3) the case group consisting of adults with AD and the control group consisting of adults without AD. We only included studies on adults because the peak incidence of CD and UC is in the 20–29-year and 20–39-year age group, respectively.
Review articles, case reports, case series, and comments were excluded. Titles, abstracts of citations, and contexts were independently screened and assessed by two authors (CH Wang and Y Fu). All three authors examined the full text of potentially eligible studies and determined which studies met the eligibility criteria.
Data extraction and risk of bias assessment
The relevant information extracted from the included studies was as follows: first author, year of publication, country of study, study design, sex of individuals, number of patients with AD and controls, and quantitative measures including odds ratio (OR) and hazard ratio (HR) with 95% confidence intervals (CIs) on the association of AD with IBD.
The risk of bias of included studies was assessed with the Newcastle–Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in systematic review and meta-analysis. Three broad perspectives were evaluated for included case–control studies: the selection of study groups, the comparability of study groups, and the ascertainment of study groups. Comparably, enrolled cohort studies were judged on three domains: the selection of study participants, the comparability of cohort, and the outcome of cohort. The details of NOS for assessing the quality are shown in [Table 2]. Data extraction and risks of bias were independently screened and assessed by two authors (CH Wang and Y Fu). Discrepancies during data extraction were resolved by consensus meetings of the authors.
|Table 2: Newcastle-Ottawa Quality Assessment Scale for case-control and cohort Studies|
Click here to view
The Review Manager version 5.3 (Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014) was used for conducting the meta-analysis. The most fully adjusted OR and HR were used whenever provided. In case–control studies, if OR estimates were not available in the studies, crude ORs were calculated in accordance with the reported raw data. We calculated the pooled OR with 95% CI for included case–control studies, while HR with 95% CI was estimated for cohort studies. The statistical heterogeneity across the included studies was assessed using the I2 statistic. An I2 > 50% represents substantial heterogeneity. We performed a random-effects model meta-analysis due to the anticipated clinical variations of included studies.
| Results|| |
The PRISMA flowchart of study selection is shown in [Figure 1]. Our systematic literature search identified 3,842 records after removing duplicates, with 3,833 excluded after screening the titles and abstracts. For one relevant conference abstract, the full journal article was later obtained. After examining the full text, one study was excluded for duplicate data of study participants. Another study did not include adults and was thus excluded. We also excluded one study because the study participants were mainly children and adolescents. Eventually, 5 case–control studies,,,, and 1 cohort study with a total of 76,019,448 study participants were included in our study. The main characteristics of the included studies are summarized, respectively, in [Table 3]. Two case–control studies did not provide the respective data for CD and UC,, while one cohort study did not report the number of all IBD patients.
Risk of bias of included studies
The risk of bias assessment for included case–control and cohort studies are summarized in [Figure 2]a and [Figure 2]b, respectively. Three of five included case–control studies,, were rated as unclear risk in the “adequacy of case definition” taking account that these studies defined the case group according to the International Classification of Diseases (ICD) diagnosis codes. In addition, most of the case–control studies,,, were rated as uncertain risk for “ascertainment of exposure” because they used ICD diagnosis codes or medical records as the independent sources for assessing exposure ascertainment. In contrast, the 2004 study by Niwa et al. was rated as low risk of bias in adequate definition of the case group with established diagnosis of AD by fulfilling the Hanifin and Rajka criteria confirmed by one or more dermatologists and was rated as low risk for exposure ascertainment that the diagnosis of CD and UC was confirmed by colonoscopy examination and biopsy. We rated the Narla and Silverberg 2018 study at high risk in the “representativeness of cases” and “selection of controls” because of including only inpatients from the National Inpatient Sample database, which might have included a population with high disease severity.
|Figure 2:Risk of bias in included (a) case–control and (b) cohort studies|
Click here to view
Odds of Crohn's disease in patients with atopic dermatitis in case–control studies
A total of three case–control studies provided data for this outcome. Exclusive of the 2004 study by Niwa et al., the other two case–control studies denoted an increased odds of CD associated with AD., As shown in [Figure 3], the meta-analysis of three studies identified significant associations of AD with prevalent CD (pooled OR: 1.55, 95% CI: 1.11–2.15), and the substantial statistical heterogeneity across the included studies was demonstrated (I2 = 69%).
|Figure 3:Associations of atopic dermatitis with inflammatory bowel disease in case–control studies|
Click here to view
Odds of ulcerative colitis in patients with atopic dermatitis in case–control studies
Three included case–control studies,, illustrated an increased odds of UC in AD patients. A meta-analysis of these studies revealed a twofold increase of UC in AD patients (pooled OR: 2.49, 95% CI: 1.04–5.98), as shown in
[Figure 3]. There was high statistical heterogeneity across the included studies (I2 = 99%).
Odds of inflammatory bowel disease in patients with atopic dermatitis in case–control studies
Five case–control studies with a total of 72,424,442 individuals provided data for this outcome.,,,, As shown in [Figure 3], the meta-analysis illustrated an increased odds for prevalent IBD in relation to AD though not statistically significant (pooled OR: 1.46, 95% CI: 0.97–2.19). We identified substantial statistical heterogeneity across these five studies (I2 = 85%).
Risk of Crohn's disease and ulcerative colitis in patients with atopic dermatitis in a Cohort study
Only one Danish cohort study provided data for this outcome and demonstrated an adjusted overall HR of 0.69 (95% CI: 0.34–1.30) for incident CD and 0.94 (95% CI: 0.61–1.43) for incident UC in patients with AD.
| Discussion|| |
We identified evidence showing that AD patients are more likely to have prevalent IBD. The denotation of meta-analysis indicates that AD patients are associated with 1.55-fold odds to have prevalent CD and 2.49-fold odds to have prevalent UC compared to controls. In parallel, we found an increased odds for prevalent IBD in relation to AD though not statistically significant. Meanwhile, one cohort study did not detect an increase in the risk of incident IBD in AD patients; a causal link between AD and IBD needs further clarification.
The statistical heterogeneity found in the association of AD with CD in case–control studies may be attributed to the low number of events in the 2004 study by Niwa et al. Although we detected considerable statistical heterogeneity in the association of AD with UC in case–control studies, the overall association was consistent and thus did not affect our conclusion. The Wu 2014 study resulted in statistical heterogeneity found in the association of AD with IBD in case–control studies, which may be explained by the different roles of T helper (Th) 17 discussed below.
The potential explanations for the association of AD with IBD include immune dysfunction with activated systemic inflammation, shared genetic mutations, and dysregulation of microbiota.
Immunologically, both AD and IBD have been linked to dysregulation of Th2-mediated response., Imbalance of Th2 response promotes pro-infflammatory cytokines causing impaired epidermal integrity and activates keratinocytes to release pruritogenic mediators in AD; meanwhile, upregulation of Th2-mediated pathway leads to disruption of epithelial tight junctions and resultant chronic inflammation in UC., The latter phenomenon may explain the stronger association between AD and UC found in our meta-analysis.
AD shows heterogeneity in immune circuits across different phenotypes. Except for Japanese population, the activation of Th17 axis is involved in Asian AD patients.
Previous studies have demonstrated that Th17 cells and their related cytokines are crucial mediators in IBD; however, both pro-inflammatory and anti-inflammatory responses of intestinal Th17 cells have emerged under various situations. Notably, Th17-type cytokines including interleukin (IL)-17A and IL-22 have been reported to possess tissue-protective effects in the intestinal mucosa., The different actions of Th17 pathway activation may explain the decreasing trend of IBD in Taiwanese AD patients in the study by Wu et al.
Interestingly, as an important pro-inflammatory signaling, the Janus kinase and signal transducer and activator of transcription (JAK-STAT) pathway has been identified in the pathogenesis of both AD and IBD., The JAK-STAT pathway drives Th2 immunity and leads to increased downstream cytokines such as IL-4 and IL-13 in AD and contributes to dysregulated immune system and overexpression of multiple inflammatory cytokines including IL-6 and IL-12/IL-23 in IBD., Recently, the JAK inhibitor tofacitinib has been reported to have potential benefit in the treatment of recalcitrant AD and IBD.,,
The association between AD and IBD may be explained in part by shared common genetic abnormalities. A susceptibility locus for eczema has been identified on chromosome 11q13.5 with risk allele A of single-nucleotide polymorphism (SNP) rs7927894. In childhood AD, the significant association of rs7927894 was found to be independent of the well-established risk alleles of FLG and may be multiplicative in its effect. Furthermore, SNP rs7927894 has been identified as a susceptibility factor for CD. This common gene carrying susceptibility to epithelial infflammation may have analogous functions affecting both skin barrier in AD and intestinal mucosal epithelium in IBD.
It is noteworthy that the skin and gut have similarities including rich vascular supply, diverse microbial communities, and vital interfaces between the internal human body and the external environment. Gut microbiome alternation and low diversity of gut microbiota contribute to the development of allergic diseases such as AD. Intestinal microbial dysbiosis is also strongly associated with IBD. The gut-skin axis involves interactions between bacterial antigens and pattern recognition receptors expressed by host cells, with consequent triggering of cascades of innate and adaptive immune systems which participate in the pathophysiology of both AD and IBD.
Recently, Shi et al. published a similar systemic review on the association between IBD and AD and included three case–control studies and one cohort study. By contrast, our study included five case–control studies and one cohort study. Moreover, we have registered our protocol with PROSPERO.
There are a few limitations of our study. First, the majority of included studies were case–control and only one cohort study met our inclusion criteria. More cohort studies are warranted to clarify the risk of incident IBD in AD patients. Second, we rated two included studies with high risk of bias because of lacking adjustment for variables including sex, age, body mass index, and smoking habit, as well as study participants from a particular inpatient population. However, the direction of associations remained the same if we excluded the two studies with high risk of bias (data not shown). Third, considerable statistical heterogeneity was detected, as discussed previously.
| Conclusion|| |
The current limited evidence to date supports an association of AD with prevalent IBD. Prolonged digestive symptoms in AD patients, for example, chronic diarrhea and abdominal pain, shall not be overlooked, and gastroenterology counseling may be needed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Darlenski R, Kazandjieva J, Hristakieva E, Fluhr JW. Atopic dermatitis as a systemic disease. Clin Dermatol 2014;32:409-13.
Flohr C, Mann J. New insights into the epidemiology of childhood atopic dermatitis. Allergy 2014;69:3-16.
Brunner PM, Guttman-Yassky E, Leung DY. The immunology of atopic dermatitis and its reversibility with broad-spectrum and targeted therapies. J Allergy Clin Immunol 2017;139:S65-76.
Weidinger S, Novak N. Atopic dermatitis. Lancet 2016;387:1109-22.
Bieber T. Atopic dermatitis. N
Engl J Med 2008;358:1483-94.
Werfel T, Allam JP, Biedermann T, Eyerich K, Gilles S, Guttman-Yassky E, et al
. Cellular and molecular immunologic mechanisms in patients with atopic dermatitis. J Allergy Clin Immunol 2016;138:336-49.
Palmer CN, Irvine AD, Terron-Kwiatkowski A, Zhao Y, Liao H, Lee SP, et al
. Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet 2006;38:441-6.
Cork MJ, Danby SG, Vasilopoulos Y, Hadgraft J, Lane ME, Moustafa M, et al
. Epidermal barrier dysfunction in atopic dermatitis. J Invest Dermatol 2009;129:1892-908.
Cipriani F, Marzatico A, Ricci G. Autoimmune diseases involving skin and intestinal mucosa are more frequent in adolescents and young adults suffering from atopic dermatitis. J Dermatol 2017;44:1341-8.
Yamanaka K, Mizutani H. “Inflammatory skin march”: IL-1-mediated skin inflammation, atopic dermatitis, and psoriasis to cardiovascular events. J Allergy Clin Immunol 2015;136:823-4.
Fishbein AB, Vitaterna O, Haugh IM, Bavishi AA, Zee PC, Turek FW, et al
. Nocturnal eczema: Review of sleep and circadian rhythms in children with atopic dermatitis and future research directions. J Allergy Clin Immunol 2015;136:1170-7.
Silverberg JI, Greenland P. Eczema and cardiovascular risk factors in 2 US adult population studies. J Allergy Clin Immunol 2015;135:721-8.
Li LJ, Gong C, Zhao MH, Feng BS. Role of interleukin-22 in inflammatory bowel disease. World J Gastroenterol 2014;20:18177-88.
Kaplan GG. The global burden of IBD: From 2015 to 2025. Nat Rev Gastroenterol Hepatol 2015;12:720-7.
Clarke K, Chintanaboina J. Allergic and immunologic perspectives of inflammatory bowel disease. Clin Rev Allergy Immunol 2019;57:179-93.
Baumgart DC, Sandborn WJ. Inflammatory bowel disease: Clinical aspects and established and evolving therapies. Lancet 2007;369:1641-57.
Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Med 2009;6:e1000097.
Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, et al
. Meta-analysis of observational studies in epidemiology: A proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 2000;283:2008-12.
Johnston RD, Logan RF. What is the peak age for onset of IBD&? Inflamm Bowel Dis 2008;14 Suppl 2:S4-5.
Review Manager (RevMan). Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration; 2014.
Narla S, Silverberg JI. Association between atopic dermatitis and autoimmune disorders in US adults and children: A cross-sectional study. J Am Acad Dermatol 2019;80:382-9.
Egeberg A, Andersen YM, Gislason GH, Skov L, Thyssen JP. Prevalence of comorbidity and associated risk factors in adults with atopic dermatitis. Allergy 2017;72:783-91.
Augustin M, Radtke MA, Glaeske G, Reich K, Christophers E, Schaefer I, et al
. Epidemiology and comorbidity in children with psoriasis and atopic eczema. Dermatology 2015;231:35-40.
Schmitt J, Schwarz K, Baurecht H, Hotze M, Fölster-Holst R, Rodríguez E, et al
. Atopic dermatitis is associated with an increased risk for rheumatoid arthritis and inflammatory bowel disease, and a decreased risk for type 1 diabetes. J Allergy Clin Immunol 2016;137:130-6.
Niwa Y, Sumi H, Akamatsu H. An association between ulcerative colitis and atopic dermatitis, diseases of impaired superficial barriers. J Invest Dermatol 2004;123:999-1000.
Andersen YM, Egeberg A, Gislason GH, Skov L, Thyssen JP. Autoimmune diseases in adults with atopic dermatitis. J Am Acad Dermatol 2017;76:274-80.e1.
Treudler R, Walther F, Zeynalova S, Engel C, Simon J. Atopic dermatitis is not independently associated with cardiovascular or autoimmune comorbidities in the general population: Results from the LIFE-adult-study. Allergy Eur J Allergy Clin Immunol 2017;72:53-4.
Wu LC, Hwang CY, Chung PI, Hua TC, Chen YD, Chu SY, et al
. Autoimmune disease comorbidities in patients with atopic dermatitis: A nationwide case-control study in Taiwan. Pediatr Allergy Immunol 2014;25:586-92.
Egeberg A, Wienholtz N, Gislason GH, Skov L, Thyssen JP. New-onset inflammatory bowel disease in adults with atopic dermatitis. J Eur Acad Dermatol Venereol 2017;31:e363-5.
Hanifin, J.M. and Rajka, G. Diagnostic features of atopic dermatitis. Acta Derm Venereol Suppl (Stockh) 1980;92:44-7.
Abraham C, Cho JH. Inflammatory bowel disease. N
Engl J Med 2009;361:2066-78.
Ordás I, Eckmann L, Talamini M, Baumgart DC, Sandborn WJ. Ulcerative colitis. Lancet 2012;380:1606-19.
Guttman-Yassky E, Krueger JG. IL-17C: A unique epithelial cytokine with potential for targeting across the spectrum of atopic dermatitis and psoriasis. J Invest Dermatol 2018;138:1467-9.
Shibata S, Saeki H, Tsunemi Y, Kato T, Nakamura K, Kakinuma T, et al
. IL-17F single nucleotide polymorphism is not associated with psoriasis vulgaris or atopic dermatitis in the Japanese population. J Dermatol Sci 2009;53:163-5.
Noda S, Suárez-Fariñas M, Ungar B, Kim SJ, de Guzman Strong C, Xu H, et al
. The Asian atopic dermatitis phenotype combines features of atopic dermatitis and psoriasis with increased TH17 polarization. J Allergy Clin Immunol 2015;136:1254-64.
Wu W, Chen F, Liu Z, Cong Y. Microbiota-specific Th17 Cells: Yin and yang in regulation of inflammatory bowel disease. Inflamm Bowel Dis 2016;22:1473-82.
Kinugasa T, Sakaguchi T, Gu X, Reinecker HC. Claudins regulate the intestinal barrier in response to immune mediators. Gastroenterology 2000;118:1001-11.
Bao L, Zhang H, Chan LS. The involvement of the JAK-STAT signaling pathway in chronic inflammatory skin disease atopic dermatitis. JAKSTAT 2013;2:e24137.
Coskun M, Salem M, Pedersen J, Nielsen OH. Involvement of JAK/STAT signaling in the pathogenesis of inflammatory bowel disease. Pharmacol Res 2013;76:1-8.
Leung DY, Guttman-Yassky E. Deciphering the complexities of atopic dermatitis: Shifting paradigms in treatment approaches. J Allergy Clin Immunol 2014;134:769-79.
Danese S, Grisham M, Hodge J, Telliez JB. JAK inhibition using tofacitinib for inflammatory bowel disease treatment: A hub for multiple inflammatory cytokines. Am J Physiol Gastrointest Liver Physiol 2016;310:G155-62.
Levy LL, Urban J, King BA. Treatment of recalcitrant atopic dermatitis with the oral Janus kinase inhibitor tofacitinib citrate. J Am Acad Dermatol 2015;73:395-9.
Damsky W, King BA. JAK inhibitors in dermatology: The promise of a new drug class. J Am Acad Dermatol 2017;76:736-44.
Esparza-Gordillo J, Weidinger S, Fölster-Holst R, Bauerfeind A, Ruschendorf F, Patone G, et al
. A common variant on chromosome 11q13 is associated with atopic dermatitis. Nat Genet 2009;41:596-601.
O'Regan GM, Campbell LE, Cordell HJ, Irvine AD, McLean WH, Brown SJ. Chromosome 11q13.5 variant associated with childhood eczema: An effect supplementary to filaggrin mutations. J Allergy Clin Immunol 2010;125:170-40.
Barrett JC, Hansoul S, Nicolae DL, Cho JH, Duerr RH, Rioux JD, et al
. Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease. Nat Genet 2008;40:955-62.
Vaughn AR, Notay M, Clark AK, Sivamani RK. Skin-gut axis: The relationship between intestinal bacteria and skin health. World J Dermatol 2017;6:52-8.
Melli LC, do Carmo-Rodrigues MS, Araújo-Filho HB, Solé D, de Morais MB. Intestinal microbiota and allergic diseases: A systematic review. Allergol Immunopathol (Madr) 2016;44:177-88.
Hold GL, Smith M, Grange C, Watt ER, El-Omar EM, Mukhopadhya I. Role of the gut microbiota in inflammatory bowel disease pathogenesis: What have we learnt in the past 10 years&? World J Gastroenterol 2014;20:1192-210.
Salem I, Ramser A, Isham N, Ghannoum MA. The gut microbiome as a major regulator of the gut-skin axis. Front Microbiol 2018;9:1459.
Shi X, Chen Q, Wang F. The Bidirectional Association between Inflammatory Bowel Disease and Atopic Dermatitis: A Systematic Review and Meta-Analysis [published online ahead of print, 2020 Jan 17]. Dermatology. 2020;1-8. doi:10.1159/000505290.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3]