br Cutaneous Microbiome in Inflammatory Skin Diseases The sk

Cutaneous Microbiome in Inflammatory Skin Diseases The skin acts as an important interface between the organism and the external environment, but also represents an ecosystem providing distinct niches for microbial communities. Next-generation-sequencing approaches used to characterize the cutaneous microbiome in healthy skin compared to lesional skin from psoriasis patients revealed significant differences in the composition of the microbiota. The vast majority of bacteria present in healthy human skin belong to the four phyla Actinobacteria, Firmicutes, Proteobacteria and Bacteroidetes. However, a marked decrease in the total diversity of microbial communities, an over-representation of Proteobacteria and an under-representation of Actinobacteria has been observed in lesional skin from psoriasis patients compared to corresponding non-lesional skin from the same individual. Karin Loser (Muenster, Germany) and colleagues characterized the cutaneous microbiota in lesional and corresponding non-lesional skin from psoriasis patients before and at different time points after the start of treatment with different biologics, including TNF-α blockade, IL-12/23 blockade, fumaric rifampicin esters or phosphodiesterase inhibitors. The researchers found that clinical improvement as measured by Psoriasis Area Severity Index (PASI) correlated with alterations in the composition of the microbiome. Thus, successful treatment could help to “normalize” the microbiota in lesional skin of psoriasis patients.
Circulating Bile Acids as Biomarkers of Metabolic Health The gut microbiota modulates bile acids (BA) enterohepatic circulation, and the profile of these potent cell signaling molecules in the blood. However, human data confirming dietary modulation of circulating BA profiles and subsequent regulation of physiological homeostasis remains elusive. The EU (ERA-HDHL) funded project CABALA_DIET&HEALTH, led by Fondazione Edmund Mach, Italy with partners in the UK (University of Reading), Italy (University of Insubria), Ireland (University College Cork) and Israel (Ben Gurion University of the Negev), aims to establish circulating BA profiles as biomarkers of health. Using samples from existing studies the researchers will correlate circulating BA profiles with adherence to the Mediterranean diet and measures of metabolic health (BMI, insulin/glucose and lipid homeostasis). In a short-term randomized controlled trial (RCT), they will measure the ability of probiotics, prebiotics and polyphenols to modulate post-prandial BA profiles. In a long-term (18-month), large-scale (n=300) existing dietary and lifestyle RCT, they will also measure how polyphenol-rich foods and exercise, through BA signaling, promote metabolic health in susceptible individuals. Finally, the researchers will link BA profiles with microbiome signatures using high-resolution metagenomics and establish the molecular basis of BA regulation of immune and metabolic homeostasis by measuring the relative BA-metabotype receptor activation potential.
Genetically Modified Probiotics as Biotherapeutics There is a strong interest in unraveling the molecular mechanisms involved in industrial robustness, cognate stress resistance and health-promoting phenotypes of food bacteria. This strategy, which involves the construction of genetically modified probiotics, can be divided into three distinct approaches: (i) delivery: engineering technological robustness; (ii) survival: improved competitiveness in the gut and other mucosa, and (iii) efficacy: improved therapeutic properties. During the past two decades, major health benefits of genetically modified probiotics have been demonstrated using animal models. The field has recently moved into the era of human clinical trials which showed biological containment, safety, and tolerability with preliminary data demonstrating positive efficacy in human subjects against oral mucositis. The potential of genetically modified probiotics as therapeutic tools for their safe and efficient use in human health was outlined. Catherine Daniel and colleagues (Lille, France) showed that a recombinant lactic acid bacterium producing a Yersinia protein has a dual potential in mice models: inhibition of experimental intestinal inflammation and protection against a pathogenic Yersinia challenge. Moreover, they developed multicolor bioluminescent bacteria for simultaneous visualization of different lactic acid bacterial strains by in vivo imaging in live mice.