Chronic kidney disease and the gut microbiome.

The gut microbiome is composed of a diverse population of bacteria that have beneficial and adverse effects on human health. The microbiome has recently gained attention and is increasingly noted to play a significant role in health and a number of disease states. Increasing urea concentration during chronic kidney disease (CKD) leads to alterations in the intestinal flora that can increase production of gut-derived toxins and alter the intestinal epithelial barrier. These changes can lead to an acceleration of the process of kidney injury. A number of strategies have been proposed to interrupt this pathway of injury in CKD. The purpose of this review is to summarize the role of the gut microbiome in CKD, tools used to study this microbial population, and attempts to alter its composition for therapeutic purposes.

Quercus cerris extracts limit Staphylococcus aureus biofilm formation.

ETHNOPHARMACOLOGICAL RELEVANCE: Quercus cerris L., Fagaceae has been used in traditional Mediterranean medicine for numerous purposes, including anti-infective therapies for diarrhea and wound care. AIM OF THE STUDY: To evaluate the anti-staphylococcal activity of fractions of ethanolic extracts of Quercus cerris leaf and stem/fruit samples in models for biofilm and growth inhibition. MATERIALS AND METHODS: Ethanolic extracts of Quercus cerris leaves and stems/fruits were prepared, resuspended in water and fractioned by successively partitioning with hexane, ethyl acetate and butanol. The ability of the fractions to inhibit Staphylococcus aureus biofilm formation was tested using static crystal violet staining methods and confocal laser scanning microscopy. Growth studies were conducted to determine if the diminished capacity to form a biofilm was related to growth inhibition. RESULTS: The butanol extracts of both the leaf and stem/fruit samples were the most active, and at a dose of 200 µg/ml, the capacity to form a biofilm was limited to a level equivalent to that of the sarA mutant controls. Further examination of the impact of these fractions on Staphylococcus aureus growth revealed that biofilm inhibition by the leaf butanol fraction was due to its bacteriostatic activity. The stem/fruit butanol fraction, however, showed a limited impact on growth, thus demonstrating that biofilm inhibition in this case is not related to the bacteriostatic activity of the extract. CONCLUSION: Our evaluation of a medicinal plant used in Mediterranean ethnotherapies for infectious disease has demonstrated significant activity in the inhibition of staphylococcal biofilm formation with a mechanism unrelated to staphylococcal growth inhibition. These results contribute towards validation of this botanical remedy and form the groundwork for future studies in the search for novel biofilm inhibiting drugs.

Ellagic acid derivatives from Rubus ulmifolius inhibit Staphylococcus aureus biofilm formation and improve response to antibiotics.

BACKGROUND: Biofilms contribute to the pathogenesis of many forms of Staphylococcus aureus infection. Treatment of these infections is complicated by intrinsic resistance to conventional antibiotics, thus creating an urgent need for strategies that can be used for the prevention and treatment of biofilm-associated infections. METHODOLOGY/PRINCIPAL FINDINGS: This study demonstrates that a botanical natural product composition (220D-F2) rich in ellagic acid and its derivatives can limit S. aureus biofilm formation to a degree that can be correlated with increased antibiotic susceptibility. The source of this composition is Rubus ulmifolius Schott. (Rosaceae), a plant used in complementary and alternative medicine in southern Italy for the treatment of skin and soft tissue infections. All S. aureus clonal lineages tested exhibited a reduced capacity to form a biofilm at 220D-F2 concentrations ranging from 50-200 µg/mL, which were well below the concentrations required to limit bacterial growth (530-1040 µg/mL). This limitation was therapeutically relevant in that inclusion of 220D-F2 resulted in enhanced susceptibility to the functionally-distinct antibiotics daptomycin, clindamycin and oxacillin. Testing with kidney and liver cell lines also demonstrated a lack of host cell cytotoxicity at concentrations of 220D-F2 required to achieve these effects. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that extract 220D-F2 from the root of Rubus ulmifolius can be used to inhibit S. aureus biofilm formation to a degree that can be correlated with increased antibiotic susceptibility without toxic effects on normal mammalian cells. Hence, 220D-F2 is a strong candidate for development as a botanical drug for use in the prevention and treatment of S. aureus biofilm-associated infections.