LAUSR

Over the past few years there has been a dramatic increase in the number of studies examining the role of the microbiome in autoimmune diseases in general and in psoriasis in particular. Unsurprisingly, changes in the composition of the cutaneous microbiome initially took centre stage, but given the systemic inflammatory nature of psoriasis and its association with inflammatory bowel disease, more recent studies have focused on the role the gastrointestinal dysbiosis in psoriasis pathophysiology. In this issue of the BJD, Todberg et al. maintain the focus on intestinal microbiota in patients with psoriasis and healthy controls matched by age, sex and body mass index, while also providing longitudinal data to examine the stability of the gastrointestinal microbiome over time. Perhaps the most novel aspect of the study is that the microbiome was also investigated in healthy cohabiting partners of patients with psoriasis in order to address shared environmental factors. Shotgun metagenomic sequencing was used to enable more detailed and functional microbiome analysis than is possible with 16S rRNA sequencing. Patients with psoriasis had a distinct gastrointestinal microbiota profile, with significantly lower metagenomic species richness than healthy controls. Intriguingly, while species diversity differed significantly between patients with psoriasis and their partners, this was not the case between patients with psoriasis and healthy controls. In terms of functional data, patients with psoriasis had decreased functional richness than healthy controls and their partners. There was also evidence that psoriasis severity correlated with microbial composition; for example, the Actinobacteria and Euryarchaeota phyla, and Methanobacteriaceae were increased in more severe disease. In contrast, seasonal effects on microbiota composition were not found, in keeping with evidence that the gastrointestinal microbiome is ostensibly stable over time. While reaching for our microbiology textbooks to refresh our knowledge of bacterial taxonomy, it is worth pausing to put the results into context. Several studies have now reported gastrointestinal dysbiosis in patients with psoriasis, but few have followed up these changes longitudinally or provided information on dietary intake. The study by Todberg et al. tackles several of the limitations but did not include metagenomic sequencing analysis of viruses or fungi. On the other hand, it did provide function data, for example the abundance of Methanobacteriaceae and decreased butyrate production potential, which correlated with disease severity. Indeed, shortchain fatty acids, including butyrate, are known for their antiinflammatory properties as well as their immunomodulatory effects on dendritic cells, reducing interleukin-23 production and promoting the transformation of naive lymphocytes to regulatory T cells rather than T helper 17 cells. In an important link to diet, red meat consumption is associated with a gastrointestinal dysbiosis-mediated reduction in butyrate synthesis, at least in mice. Setting aside the perennial cause and effect question that has dogged microbiome research, the evidence to date suggests that psoriasis is associated with gastrointestinal dysbiosis. However, given that we are only beginning to understand the complexity of the skin–gut axis it is too early to draw firm conclusions on the role of the microbiome in psoriasis and its therapeutic targetability; the proof of the pudding may quite literally be in the eating.