A Western diet rich in sugar and fat leads to an imbalance in the gut's microbial culture and may contribute to inflammatory skin diseases like psoriasis, reports Medicalbrief.
The study, led by University of California researchers and published in the Journal of Investigative Dermatology, suggests that switching to a more balanced diet restores the gut's health and suppresses skin inflammation.
“Earlier studies have shown that Western diet, characterised by its high sugar and fat content, can lead to significant skin inflammation and psoriasis flares,” said Prof Sam T Hwang, chair of dermatology at UC Davis Health and senior author on the study. “Despite having powerful anti-inflammatory drugs for the skin condition, our study indicates that simple changes in diet may also have significant effects on psoriasis.”
Up to 30% of patients with psoriasis also have psoriatic arthritis, with symptoms such as morning stiffness and fatigue, swollen fingers and toes, pain in joints and changes to nails.
Food is one of the major modifiable factors regulating the gut microbiota, the community of microorganisms living in the intestines. Eating a Western diet can cause rapid change to the gut's microbial community and its functions. This disruption in microbial balance, known as dysbiosis, contributes to gut inflammation.
Since bacteria in the gut may play key roles in shaping inflammation, the researchers wanted to test whether intestinal dysbiosis affects skin and joint inflammation. They used a mouse model to study the effect of diet on psoriasis and psoriatic arthritis. They injected mice with Interleukin-23 (IL-23) minicircle DNA to induce a response mimicking psoriasis-like skin and joint diseases.
IL-23 is a protein generated by the immune cells responsible for many inflammatory autoimmune reactions, including psoriasis and inflammatory bowel disease (IBD).
Hwang and his colleagues found that a short-term Western diet appears sufficient to cause microbial imbalance and to enhance susceptibility to IL-23-mediated psoriasis-like skin inflammation. "There is a clear link between skin inflammation and changes in the gut microbiome due to food intake," he said. "The bacterial balance in the gut disrupted shortly after starting a Western diet, and worsened psoriatic skin and joint inflammation."
One critical finding of their work was identifying the intestinal microbiota as a pathogenic link between diet and the displays of psoriatic inflammation. The study also found that antibiotics block the effects of the Western diet, reducing skin and joint inflammation.
The researchers wanted to test if switching to a balanced diet can restore the gut microbiota, despite the presence of IL-23 inflammatory proteins. They fed mice a Western diet for six weeks before giving them an IL-23-inducing agent to trigger psoriasis and psoriatic arthritis features. Then, they randomly divided the mice into two groups: a group that continued the Western diet for another four weeks and a group that switched to a balanced diet for the same duration.
Their study showed that eating a diet high in sugar and fat for 10 weeks predisposed mice to skin and joint inflammation. Mice that were switched to a balanced diet had less scaling of the skin and reduced ear thickness than mice on a Western diet. The improvement in skin inflammation for mice taken off the Western diet indicates a short-term impact of the Western diet on skin inflammation.
This suggests that changes in diet could partially reverse the pro-inflammatory effects and alteration of gut microbiota caused by the Western diet.
"It was quite surprising that a simple diet modification of less sugar and fat may have significant effects on psoriasis," said Zhenrui Shi, visiting assistant researcher in the UC Davis Department of Dermatology and lead author on the study. "These findings reveal that patients with psoriatic skin and joint disease should consider changing to a healthier dietary pattern."
"This work reflects a successful collaboration among researchers, especially with Professor Satya Dandekar and her team at the Department of Medical Microbiology and Immunology and Professor Yu-Jui Yvonne Wan at the Department of Medical Pathology and Laboratory Medicine," Hwang said.
Short-Term Western Diet Intake Promotes IL-23‒Mediated Skin and Joint Inflammation Accompanied by Changes to the Gut Microbiota in Mice
Zhenrui Shi, Xuesong Wu, Clarissa Santos Rocha, Matthew Rolston, Emma Garcia-Melchor, Mindy Huynh, Mimi Nguyen, Timothy Law, Kelly N. Haas, Daisuke Yamada, Neal L. Millar, Yu-Jui Yvonne Wan, Satya Dandekar, Samuel T. Hwang
Published in Journal of Investigative Dermatology January 2021
We previously showed that exposure to a high-sugar and moderate-fat diet (i.e., Western diet [WD]) in mice induces appreciable skin inflammation and enhances the susceptibility to imiquimod-induced psoriasiform dermatitis, suggesting that dietary components may render the skin susceptible to psoriatic inflammation.
In this study, utilizing an IL-23 minicircle-based model with features of both psoriasiform dermatitis and psoriatic arthritis, we showed that intake of WD for 10 weeks predisposed mice not only to skin but also to joint inflammation. Both WD-induced skin and joint injuries were associated with an expansion of IL-17A‒producing γδ T cells and increased expression of T helper type 17 cytokines. After IL-23 minicircle delivery, WD-fed mice had reduced microbial diversity and pronounced dysbiosis.
Treatment with broad-spectrum antibiotics suppressed IL-23‒mediated skin and joint inflammation in the WD-fed mice. Strikingly, reduced skin and joint inflammation with a partial reversion of the gut microbiota were noted when mice switched from a WD to a standard diet after IL-23 minicircle delivery. These findings reveal that a short-term WD intake‒induced dysbiosis is accompanied by enhanced psoriasis-like skin and joint inflammation. Modifications toward a healthier dietary pattern should be considered in patients with psoriatic skin and/or joint disease.
Psoriasis is a chronic autoimmune skin disease that is associated with multiple comorbidities. One of the most prevalent is psoriatic arthritis, which can develop in up to 30% of patients with psoriasis and lead to a significant decrease in QOL (Ritchlin et al., 2017). Emerging data suggest unhealthy diet patterns as an important and independent risk factor for psoriasis. For example, an increase in dietary saturated fatty acids in healthy, lean mice alone was sufficient to induce an exacerbation of psoriasiform inflammation, and conversely, a reduction in dietary saturated fatty acids diminished the psoriatic phenotype in mice without obesity (Herbert et al., 2018).
Our recently published work further suggested a critical role for dietary composition in the pathogenesis of psoriasis by demonstrating that exposure to a high-sugar, moderate-fat diet (i.e., Western diet [WD]) alone was enough to induce appreciable skin inflammation without inducing obesity (Shi et al., 2020b).
The mechanisms behind dietary regulation of inflammation in psoriasiform dermatitis (PsD) are only beginning to be elucidated in experimental models.
Several studies suggest that gut microbiota may potentially play key roles in shaping inflammation (Stehlikova et al., 2019; Zákostelská et al., 2016). The mammalian intestinal tract is colonized by a large number of microorganisms, including trillions of bacteria referred to collectively as the gut microbiota. Perturbation of the gut microbiome by environmental factors such as diet promotes the overgrowth of harmful pathobionts, disrupts immune homeostasis, and leads to the development of inflammatory diseases (Jena et al., 2020; Sheng et al., 2017b).
Among the numerous factors known to influence gut microbiota composition, dietary composition has repeatedly been shown to be one of the most critical modifiable factors regulating the gut microbiota (Martinez et al., 2017). The WD, in particular, can lead to a rapid and detrimental impact on microbial community and function, contributing to systemic inflammation and other metabolically compromised phenotypes (Jena et al., 2018, 2017; Sheng et al., 2017a). We have previously shown that feeding a diet analogous to the WD in mice induces spontaneous skin inflammation (Shi et al., 2020b) and enhances susceptibility to imiquimod-induced PsD (Yu et al., 2019). I
In this study, we used an IL-23 minicircle (MC) DNA‒based murine model with features of PsD and psoriatic arthritis (Shi et al., 2020a) to study the effect of WD on both psoriasis-like skin and joint diseases and tested the hypothesis that intestinal dysbiosis is implicated in skin and joint inflammation.
WD intake enhances the susceptibility to IL-23‒mediated skin inflammation.
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