Crucial Role of Microbiota in Experimental Psoriasis Revealed by a Gnotobiotic Mouse Model.
Stehlikova Z, Kostovcikova K, Kverka M, Rossmann P, Dvorak J, Novosadova I, Kostovcik M, Coufal S, Srutkova D, Prochazkova P, Hudcovic T, Kozakova H, Stepankova R, Rob F, Juzlova K, Hercogova J, Tlaskalova-Hogenova H, Jiraskova Zakostelska Z
Front Microbiol. 2019. doi: 10.3389/fmicb.2019.00236
COMMENT: Psoriasis is a chronic inflammatory disease in which Th17 cells play a crucial role. It is well stablished that skin microbiota is involved in psoriasis induction and pathogenesis. Oral administration of a broad-spectrum antibiotic mixture is used in the treatment of psoriasis. Authors in this work analyzed which antibiotic is the responsible of the beneficial effect, which microbes are affected by the treatment and if the effect is microbiota-dependent or independent.
In the present study, we aim to investigate whether the individual constituents of antibiotic mixture used in our previous work have the potential to mitigate IISI on their own and to examine the resulting changes in microbiota composition and in the immune response both on the skin and in the intestine. Furthermore, we monocolonized mice with a well-known probiotic species Lactobacillus plantarum WCFS1 (LP) or with segmented filamentous bacteria (SFB) and compared them with conventional and GF mice to explore how a microbial diversity impact the severity of IISI.
Metronidazole showed the similar beneficial effect on IISI as the whole mixture of antibiotics (metronidazole, vancomycin, colistin, streptomycn) used to decrease the severity of IISI. The anti-inflammatory effect of metronidazole is mediated by its antimicrobial activity.
MIX reduced the diversity of microbiota composition, and the vacant niche in the intestine was filled by Firmicutes, especially Lactobacillales, even though Clostridiales and Bacillales declined. Additionally, treatment with MIX led to reduction of Coriobacteriales in the intestine. Similarly to the MIX-treated group, mice in the MET-treated group showed lower abundance of the family Ruminococcaceae, Clostridiales, and genus Oscillospira and Dorea in the intestine compared to the control group. MET, but not MIX, treatment significantly increased the presence of Parabacteroides distasonis in the intestine. Moreover, MET significantly increased the abundance of the genera Bifidobacterium and Enterococcus compared to MIX or control groups, both in the intestine and on the skin (...). Mice in the MIX group had a significantly higher abundance of genus Lactobacillus in the intestine and on the skin compared to controls.
Conventional mice were less resistant to IISI than germ-free mice and mice monocolonized with Lactobacillus plantarum or segmented filamentous bacteria (SFB).
In mice monocolonized with SFB, imiquimod induced a higher degree of systemic Th17 activation compared to germ-free mice.
In summary, we suggest that MET and MIX are sufficient to decrease the severity of IISI in a microbiota-dependent manner. While these beneficial changes are accompanied with downregulation of Th17 activity and an increase in abundance of intestinal lactobacilli in group treated with antibiotic MIX, monocolonization with neither lactobacillus nor Th17-promoting SFB is sufficient to change the IISI severity. (...). These data suggest a therapeutic potential via influencing the microbiota composition in psoriatic patients.
IISI: Imiquimod-induced skin inflammation
MIX: Broad spectrum of antibiotics