- [Show abstract] [Hide abstract] ABSTRACT: There is a known association between psoriasis and Crohn's disease (CD). Patients with CD are five times more likely to develop psoriasis, and, conversely, patients with psoriasis are more likely to develop CD. Many gastroenterologists now accept that CD is due to a breakdown of immune tolerance to the microbiota of the intestine in genetically susceptible individuals. The microbiota of the skin has recently been investigated in psoriasis. Firmicutes was the commonest phylum, and Streptococcus the commonest genus identified. Beta-haemolytic streptococci have been implicated in both guttate and chronic plaque psoriasis. Furthermore, the innate immune system has been shown to be activated in psoriasis, and many of the genes associated with the disease are concerned with signalling pathways of the innate immune system, notably IL-23 and NFκB. Psoriasis patients also have an increased incidence of periodontitis a disease thought to be due to an abnormal response to normal oral commensals. Based on the similarities between CD and psoriasis, we propose that psoriasis is due to a breakdown of immune tolerance to the microbiota of the skin. In support of this hypothesis we provide evidence for microbiota in the skin, activation of the innate immune system, and genetic abnormalities involving the innate immune system.
- [Show abstract] [Hide abstract] ABSTRACT: Aim: Necrotizing enterocolitis (NEC) represents one of the gravest complications in premature infants. The suggested role of intestinal microbiota in the development of NEC needs to be elucidated. Methods: This prospective single-centre case-control study applied barcoded pyrosequencing to map the bacterial composition of faecal samples from extremely preterm infants. Ten patients were diagnosed with NEC and matched to healthy controls with regard to sex, gestational age and mode of delivery prior to analysis of the samples. Results: Enterococcus, Bacillales and Enterobacteriaceae dominated the flora. Although not statistically significant, a high relative abundance of Bacillales and Enterobacteriaceae was detected at early time points in patients developing NEC, while healthy controls had a microbiota more dominated by Enterococcus. A low diversity of intestinal microbial flora was found without any differences between NEC patients and controls. In 16 healthy controls, Firmicutes (Enterococcus and Bacillales) dominated the faecal flora during the first weeks after birth and were then succeeded by Enterobacteriaceae. Conclusion: No significant differences in the composition of intestinal microbiota of patients developing NEC were detected; however, some findings need to be scrutinized in subsequent studies.
- [Show abstract] [Hide abstract] ABSTRACT: Microorganisms have been implicated in the pathogenesis of psoriasis. Previous studies of psoriasis and normal skin have used swabs from the surface rather than skin biopsies. In this study, biopsies were taken from 10 patients with psoriasis and 12 control subjects from unmatched sites. Samples were analysed with massive parallel pyrosequencing on the 454 platform targeting the 16S rRNA gene and the variable regions V3-V4. The samples grouped into 19 phyla, 265 taxon and 652 operational units (OTUs) at 97% identity. A cut-off abundance level was set at 1%. The three most common phyla in both normal and psoriasis skin were Firmicutes (39% psoriasis, 43% normal skin), Proteobacteria (38% psoriasis, 27% normal skin) and Actinobacteria (5% psoriasis, 16% normal skin, p = 0.034). In trunk skin, Proteobacteria were present at significantly higher levels in psoriasis compared to controls (52 vs. 32%, p = 0.0113). The commonest genera were Streptococci in both psoriasis (32%) and normal skin (26%). Staphylococci were less common in psoriasis (5%) than in controls (16%), as were Propionibacteria (psoriasis 0.0001669%, controls 0.0254%). Both Staphylococci and Propionibacteria were significantly lower in psoriasis versus control limb skin (p = 0.051, 0.046, respectively). This study has shown some differences in microbiota between psoriasis and normal skin. Whether these are of primary aetiological significance, or secondary to the altered skin of psoriasis remains to be determined.
- [Show abstract] [Hide abstract] ABSTRACT: Patients with severe congenital neutropenia (SCN) often develop periodontitis despite standard medical and dental care. In light of previous findings that mutations in the neutrophil elastase gene, ELANE, are associated with more severe neutropenic phenotypes, we hypothesized an association between the genotype of SCN and development of periodontitis. Fourteen Swedish patients with SCN or cyclic neutropenia harboring different genetic backgrounds were recruited for periodontal examination. Peripheral blood, gingival crevicular fluid (GCF), and subgingival bacterial samples were collected. The levels of cytokines and antibacterial peptides were determined in GCF and plasma by multiplex immunoassay and immunoblotting, respectively. Subgingival bacterial samples were analyzed using 16S rDNA pyrosequencing. ELANE mutations correlated with more severe periodontal status than the HAX1 or unknown mutations in patients with SCN. The subjects with mutant ELANE had higher levels of IL-1β in GCF. Using principal coordinate analysis of the subgingival microbiota, patients with ELANE mutations and reference subjects with periodontitis tended to cluster differently from patients with HAX1 or unknown mutations and non-periodontitis reference subjects. This study demonstrates an association between ELANE mutations in SCN and the development of periodontitis with skewed subgingival microbiota, indicating a potential role of ELANE mutations in the pathogenesis of periodontitis.
- [Show abstract] [Hide abstract] ABSTRACT: Background Bacterial vaginosis (BV) is the most common vaginal infection/disorder. BV is characterised by imbalance in the normal vaginal microbiota with a shift towards higher bacterial diversity and increased pH. The aim of the present study was to describe the differences in vaginal microbiota composition in women suffering from BV compared to healthy women, using massive parallel 454 pyrosequencing. Methods 163 vaginal samples were collected from women diagnosed with characteristic BV (n=73), women with intermediate BV (n=11), and from healthy women on their regular check-ups (n=79). DNA from the samples was isolated and the bacterial compositions as well as the relative abundance of these bacteria were analysed using 454 pyrosequencing, with GS Titanium amplicons kit (Roche Inc.), of the hypervariable region V4 on the 16S rRNA gene. Finally, 17 different species-specific PCRs were used to verify the species of bacteria found in the 454 pyrosequencing. Results Extensive imbalance of the vaginal microbiota of women with BV compared to healthy controls was revealed. The dominating taxons of the 73 BV cases were Gardnerella, Atopobium, Prevotella, Lactobacillus, Megasphera and Sneathia, while most of the 79 healthy controls had a microbiota totally dominated by Lactobacillus with the BV associated taxons hardly detectable. Furthermore, the 11 patients with intermediate BV predominantly had a mix of the BV associated taxon Gardnerella as well as Lactobacillus. A few of the healthy controls seemed to have a microbiota changing towards the intermediate microflora. Gardnerella may be the first bacteria to establish in the transition from healthy vaginal flora towards a BV associated flora. Conclusions A clear difference in the composition of the vaginal microbiota between individuals suffering from BV and healthy controls was identified. The present findings are important steps towards the determination of valid potential bacterial markers for BV, are shedding light upon why some women develop BV, as well as show how the microbiota is involved in the development of BV. Knowledge of the composition of the vaginal microbiota is crucial in the development of a BV diagnostic tool and for elucidating appropriate treatment for use in clinical practice.