Oxidative Stress in the Pathogenesis of Crohn’s Disease and the Interconnection with Immunological Response, Microbiota, External Environmental Factors, and Epigenetics
Abstract
:1. Introduction
2. Oxidative Stress in Crohn’s Disease
2.1. Oxidative Stress and the Impaired Immunological Response
2.2. Oxidative Stress as a Key Effector Mechanism in CD Pathogenesis
3. The Role of the Environment in Crohn’s Disease
3.1. The “In-Vironment”: The Microbiota
3.2. External and Environmental Factors
3.2.1. Western Diet Versus the Mediterranean Diet and Their Impact on Crohn’s Disease
3.2.2. Other Lifestyle Factors and Health Conditions Relevant to the Pathogenesis
3.3. Epigenetics as a Transducer of Environmental Factors in Crohn’s Disease
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Study | Type of Study | Methodology | Main Findings |
---|---|---|---|
Agus et al. (2016) [81] | In vivo study | WT and CEABAC10 mice 1 were fed with a high-fat/high-sugar diet (HF/HS) (N = 6) vs. a conventional diet (N = 5) over a period of 18 weeks. Germ-Free (GF) mice were transplanted with fecal pellets of HF/HS donor mice (N = 5) or conventional donor mice (N = 5), followed by an infection with an adherent-invasive E. coli (AEIC) LF82 strain isolated from a CD patient | Western diet causes an inflammatory environment in the digestive tract associated with microbiome perturbations; favors the emergence of E. coli associated with the ileal, cecal, and colonic mucosa; and decreases the level of SCFA produced by intestinal microbiota modulating immune response. Transplantation of feces from HF/HS treated mice to GF mice increases susceptibility to AIEC infection |
Martinez-Medina, M. et al. (2014) [82] | In vivo study | WT and CEABAC10 mice 1 were fed with a HF/HS diet vs. conventional diet for 12 weeks 2, and orally infected with AIEC strain LF82 | Western diet induces changes in gut microbiota composition with an increase in the mucin-degrading bacterium Ruminococcus torques and the group Bacteroides/Prevotella; alters intestinal permeability, decreases barrier function, and affects the host homeostasis promoting AEIC gut colonization in genetically susceptible mice |
Geirnaert et al. (2017) [94] | Clinical research—In vitro study | Butyrate-producing bacteria supplemented to the fecal microbial communities of CD patients (N = 10) in an in vitro system simulating the mucus- and lumen-associated microbiota, and an in vitro study of the resulting microbiota influence on epithelial barrier integrity with a Caco-2 model | In vitro supplementation of microbiota of CD patients with butyrate-producing bacteria results in a higher butyrate production, with and enhanced epithelial barrier integrity in a Caco-2 model. Supports the preclinical development of a probiotic product containing butyrate-producing species |
Desai et al. (2016) [95] | In vivo study | Assembled synthetic gut microbiota from fully sequenced human gut bacteria in gnotobiotic mice were fed with fiber-rich vs. fiber-free diets 2 | In the chronic or intermittent absence of dietary fiber mucolytic bacteria become the predominant species within the gut microbiota with the consequent degradation of the colonic mucus layer and increased pathogen susceptibility |
Chassaing et al. (2015) [101] | In vivo study | WT mice and two engineered strains of mice, namely IL10−/− and TLR5−/− (prone to develop shifts in microbiota composition and inflammation) exposed to emulsifiers in the drinking water or to water alone (control group) for 12 weeks 2 | Relatively low concentrations of commonly used dietary emulsifiers (carboxymethylcellulose and polysorbate-80) can disturb the host-microbiota relationship, induce low-grade inflammation and obesity/metabolic syndrome in WT hosts and promote robust colitis in mice predisposed to this disorder |
Mu et al. (2019) [102] | In vivo study | WT mice and DSS-induced colitis mice treated with titanium dioxide nanoparticles vs. standard (control) diet for 3 months from weaning 2 | First demonstration that long-term dietary intake of titanium dioxide nanoparticles (which are used as food additives) results in lower body weigh along with colorectal inflammation in mice; and it aggravates DSS-induced chronic colitis and immune response in vivo, reduces the population of CD4+ T cells, regulatory T cells, and macrophages in mesenteric lymph node |
Marlow, G. et al. (2013) [105] | Clinical research | 6-week intervention with a Mediterranean-inspired diet in CD patients (N = 8). Obtention of blood and fecal samples at the beginning and the end of the diet | A Mediterranean-inspired diet appears to benefit the health of CD patients: shows a trend for reducing inflammation and normalizing the microbiota |
To, N. et al. (2016) [110] | Systematic review with metanalysis of the effects of smoking on disease course in CD | Search of MEDLINE, EMBASE and EMBASE classic carried out up to July 2015 (with the resulting 33 eligible studies) | Smokers, compared with non-smokers, have 55–85% higher rates of flares of disease activity, clinical recurrence rates after surgery that are two-fold higher, between 54% and 68% higher rates of need for first surgery, and are twice as likely to need a second operation. Quitting smoking appears to have a beneficial effect on CD course, especially for flare of disease activity or need for a second operation |
Benjamin, J.L. et al. (2012) [111] | Clinical research | Fecal samples from patients with active CD (N = 101; 29 of whom current smokers) and healthy controls (N = 66; 8 of whom current smokers) were analyzed by fluorescent in situ hybridization (using probes targeting 16S rRNA of bacteria previously shown to be altered in active CD) | Smokers with active CD have a clinically relevant dysbiosis of the gastrointestinal microbiota; with strong and significant associations between smoking and higher bacteroides (this novel finding is also present in healthy controls) |
Bergeron, V. et al. (2012) [112] | Clinical research—In vitro study | Study of mononuclear cells extracted from blood samples of CD patients (smokers N = 19, and non-smokers N = 26), UC patients (smokers N = 7, and non-smokers N = 18), and healthy controls (smokers N = 13, and non-smokers N = 18); following either in vivo or in vitro exposure to cigarette smoke | Mononuclear cells from CD patients who smoke are functionally impaired, present a defective sensitivity to anti-inflammatory or antioxidant protection, and particularly synthesize lower levels of cytoprotective Hsp70. Findings suggest that the effects of cigarette smoke are largely dependent on the oxidative stress generated rather than on the nicotine component |
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Alemany-Cosme, E.; Sáez-González, E.; Moret, I.; Mateos, B.; Iborra, M.; Nos, P.; Sandoval, J.; Beltrán, B. Oxidative Stress in the Pathogenesis of Crohn’s Disease and the Interconnection with Immunological Response, Microbiota, External Environmental Factors, and Epigenetics. Antioxidants 2021, 10, 64. https://doi.org/10.3390/antiox10010064
Alemany-Cosme E, Sáez-González E, Moret I, Mateos B, Iborra M, Nos P, Sandoval J, Beltrán B. Oxidative Stress in the Pathogenesis of Crohn’s Disease and the Interconnection with Immunological Response, Microbiota, External Environmental Factors, and Epigenetics. Antioxidants. 2021; 10(1):64. https://doi.org/10.3390/antiox10010064
Chicago/Turabian StyleAlemany-Cosme, Ester, Esteban Sáez-González, Inés Moret, Beatriz Mateos, Marisa Iborra, Pilar Nos, Juan Sandoval, and Belén Beltrán. 2021. "Oxidative Stress in the Pathogenesis of Crohn’s Disease and the Interconnection with Immunological Response, Microbiota, External Environmental Factors, and Epigenetics" Antioxidants 10, no. 1: 64. https://doi.org/10.3390/antiox10010064
APA StyleAlemany-Cosme, E., Sáez-González, E., Moret, I., Mateos, B., Iborra, M., Nos, P., Sandoval, J., & Beltrán, B. (2021). Oxidative Stress in the Pathogenesis of Crohn’s Disease and the Interconnection with Immunological Response, Microbiota, External Environmental Factors, and Epigenetics. Antioxidants, 10(1), 64. https://doi.org/10.3390/antiox10010064