Western Diet and Psoriatic-Like Skin and Joint Diseases: A Potential Role for the Gut Microbiota

Shi et al. (2021) in “Short-term Western diet intake promotes IL-23-mediated skin and joint inflammation accompanied by changes to the gut microbiota mice” show that (WD) exacerbates an IL-23 minicircle‒mediated model of psoriasis psoriatic arthritis, with expansion IL-17A‒expressing γδ T cells shifts microbial community. WD-associated is mitigated manipulation or antibiotic administration. These results suggest dietary may be useful treatment IL-23‒mediated disease, possibly through modulation microbiota. Clinical Implications•Actinic keratoses (AKs) are similar cutaneous squamous cell carcinoma (cSCC) at genomic level harboring mutations 44 driver genes, including TP53, NOTCH1, NOTCH2, FAT1, KMT2C.•Mutational signature #32 was identified all samples from patients exposed azathioprine, strongly supporting its role as a keratinocytic carcinogen.•TGFβ signaling regulate progression AK cSCC. •Actinic Hippocrates noted, “Let medicine thy food let medicine.” With timeless focus on more recent discoveries implicating mediating health disease (Singh al., 2017Singh R.K. Chang H.W. Yan D. Lee K.M. Ucmak Wong K. al.Influence microbiome implications for human health.J Transl Med. 2017; 15: 73Crossref PubMed Scopus (972) Google Scholar), many autoimmune diseases, such arthritis (PsA), inquire whether alleviate inflammatory Anecdotally, subset find interventions (e.g., reduction sugar processed intake) seemingly aspects their disease. A systematic review literature (Ford 2018Ford A.R. Siegel M. Bagel J. Cordoro Garg A. Gottlieb al.Dietary recommendations adults Medical Board National Psoriasis Foundation: review.JAMA Dermatol. 2018; 154: 934-950Crossref (67) Scholar) suggests weight hypocaloric individuals who overweight obese beneficial adjunctive intervention pharmacologic therapy. Despite these findings, mechanisms which modulate severity remain unclear. In new study, 2021Shi Z. Wu X. Rocha C.S. Rolston Garcia Melcor E. Huynh al.Short-term mice.J Invest 2021; 141: 1780-1792Abstract Full Text PDF (5) Scholar, using murine PsA, leads composition, raising possibility influence host immunity Scholar treated C57BL/6 mice either conventional (CD) WD 6 weeks, followed injection minicircle DNA; received each four weeks. They found cytokine‒mediated were exacerbated relative those CD (Figure 1a-e). Skin immune populations, neutrophils cells, IL-17A cytokine production elevated CD. diet-induced exacerbations reproduced second autoimmune-prone mouse model. Together, findings demonstrate altering immunity, has been reported authors different dermatitis (Shi 2020Shi Yu S. Jena P.K. Nguyen exposure western induces psoriasiform promoting accumulation IL-17A-producing cells.J 2020; 140: 1815-1823Abstract (21) this study extended arthritis. To investigate alters community, undertook 16S ribosomal RNA gene amplicon sequencing fecal alterations community composition well differential abundance several taxa CD, consistent multiple studies both humans models (Bisanz 2019Bisanz J.E. Upadhyay V. Turnbaugh J.A. Ly P.J. Meta-analysis reveals reproducible response high-fat diet.Cell Host Microbe. 2019; 26: 265-272.e4Abstract (91) Scholar). addition diet, overexpression shifted so fed than suggesting synergistic effect activation modulating composition. then WD-fed IL-23‒expressing broad-spectrum antibiotics improvement Interestingly, also true Switching diets led improvements 1f). Fecal transplant (FMT) experiments donors into pretreated revealed WD-exposed induced T-cell infiltration dermis without concomitant worsening severity. WD-induced contribute altered immune-activating properties Overall, support hypothesis high-fat, high-sugar can exacerbate Dietary components act begin bridge gap our understanding diet‒host‒microbiota interactions diseases. As intriguing studies, raises additional questions. Are effects versus disease? seemed responsive Does even absence WD? Mice derived benefit WD. Alternatively, secondary direct host? Studies germ-free animals have demonstrated although developed target microbes, they programs (Yang 2017Yang J.H. Bhargava P. McCloskey Mao N. Palsson B.O. Collins J.J. Antibiotic-induced metabolic environment inhibit drug efficacy alter function.Cell 22: 757-765.e3Abstract (111) Thus, equivalents undertaken would contribution Relatedly, transfer phenotype but not FMT affects promote featured incomplete engraftment disease-exacerbating communities transplanted strains could outcompete resident strains. Many open questions before translated clinical practice. Although diseases (Manzel 2014Manzel Muller D.N. Hafler D.A. Erdman S.E. Linker R.A. Kleinewietfeld Role “Western diet” diseases.Curr Allergy Asthma Rep. 2014; 14: 404Crossref (247) advising avoid likely prudent, we lack ability guide regarding what should eat. There much learned about specific lead inflammation, factors mediate system, effectors responsible (Alexander Turnbaugh, 2020Alexander Deconstructing diet-microbiome-immune interactions.Immunity. 53: 264-276Abstract (27) Such mechanistic necessary help us counsel effective strategies treat summary, add mounting evidence prominent PsA (Herbert 2018Herbert Franz Popkova Y. Anderegg U. Schiller Schwede al.High-fat early independent obesity: saturated fatty acids key players.J 138: 1999-2009Abstract (60) Scholar; Nakamizo 2017Nakamizo Honda T. Adachi Nagatake Kunisawa Kitoh al.High fat increasing number IL-17-producing cells.Sci 7: 14076Crossref (43) raise Expansion pathways implicate microbiota, identification relevant microbes causal genes remains elucidated. The recapitulation investigated, caveat tremendous genetic, dietary, variation make patterns challenging. bring step closer targeting diet-dependent modulated autoimmunity. Renuka R. Nayak: http://orcid.org/0000-0002-1123-4668 author states no conflict interest.