Considered as an essential "metabolic organ", intestinal microbiota plays a key role in human health and the predisposition to diseases. It is an aggregate genome of trillions of microorganisms residing in the human gastrointestinal tract. Since the 20th century, researches have showed that intestinal microbiome possesses a variety of metabolic activities that are able to modulate the fate of more than 30 approved drugs and immune checkpoint inhibitors. These drugs are transformed to bioactive, inactive, or toxic metabolites by microbial direct action or host-microbial co-metabolism. These metabolites are responsible for therapeutic effects exerted by these drugs or side effects induced by these drugs, even for death. In view of the significant effect on the drugs metabolism by the gut microbiota, it is pivotal for personalized medicine to explore additional drugs affected by gut microbiota and their involved strains for further making mechanism clear through suitable animal models. This review mainly focus on specific mechanisms involved, with reference to the current literature about drugs metabolism by related bacteria or its enzymes available.

Introduction: The modulation of immunometabolic pathways is emerging as a promising therapeutic target for immune-mediated diseases. However, the immunometabolic features of psoriatic disease and the potential targets for immunometabolic intervention in the different T-cell subsets involved in its pathogenesis remain unclear.Methods: In this study, we analyzed circulating blood single-cell data from healthy controls (HC), psoriasis (PSO), and psoriatic arthritis (PSA) patients, and revealed their metabolic features of T-cell subsets: CD4+ central memory T cells (TCMs), CD8+ effective memory T cells (TEMs), regulatory T cells (Tregs), mucosal-associated invariant T cells (MAITs ), and γδ T cells. Pearson test was performed to determine the linkages between differential metabolic and inflammatory pathways. Based on these results, we also analyzed the potential impacts of biological antibodies on differential metabolic pathways by comparing the immunometabolism differences between PSA patients without and with biological treatment.Results: Our results suggest that upregulation of ascorbate and aldarate metabolism, as well as fatty acid degradation, may enhance the immune suppression of Tregs. Enhanced metabolism of alpha-linolenic acid, linoleic acid, and arachidonic acid may inhibit the pro-inflammatory functions of CD4+ TCMs and CD8+ TEMs in PSO and PSA, and protect the immune suppression of Tregs in PSA. We propose that supporting ascorbic acid and fatty acid metabolic pathways may be an adjunctive reprogramming strategy with adalimumab and etanercept therapy.Discussion: These findings not only provide insights into immunometabolism characteristics of psoriatic disease, but also offer preliminary options for the auxiliary treatment of psoriasis.

Objectives: Psoriasis is a common chronic recurrent dermatitis. Accumulating observations show gut microbiota dysbiosis in psoriasis. We intend to further investigate the relationship between intestinal microbiota and psoriasis development.Design: We first performed an epidemiological investigation on differences of gastrointestinal discomfort symptoms between patients with psoriasis and general population. Then variation of gut microbiota in patients with psoriasis (un)treated with acitretin plus narrow-band ultraviolet B (NB-UVB) was analyzed by 16S rRNA sequencing. We last compared recovery status and vital cytokines (lesion and intestine) of mouse psoriasiform models, which were transplanted with fecal microbiota from patients with psoriasis or healthy controls.Results: (1) About 85.5% of patients with psoriasis vs. 58.1% of healthy controls presented with at least one gastrointestinal symptom. The prevalence of investigated symptoms (e.g., abdominal distension and constipation) were significantly higher in patients, compared with controls (p < 0.05). Passing flatus and constipation were significantly correlated with psoriasis (p < 0.05 in both cases). (2) The abundance of Ruminococcaceae family, Coprococcus_1 genus, and Blautia genus were decreased with psoriasis improvement (p < 0.05, respectively), which had been demonstrated significantly increased in psoriasis. (3) Mice receiving psoriatic microbes transplantation showed delayed recovery of psoriasiform dermatitis and less reduction of interleukin (IL)-17A than those receiving healthy microbiota or blank control (p < 0.05 and p < 0.01, respectively).Conclusion: Multiple evidence we provided here preliminarily demonstrates the involvement of gut microbiota in the different degree of psoriasis activity. The strategy based on overall microbial communities is expected to be a promising supplementary for long-term management of psoriasis.