Erika Lindberg

Reduced enterobacterial and increased staphylococcal colonization of the infantile bowel: an effect of hygienic lifestyle?

The modern Western lifestyle may have altered the composition of the commensal microflora. Here, we investigated the first years intestinal colonization pattern in 99 vaginally delivered Swedish infants and 17 delivered by cesarean section. Rectal swabs obtained at 3 d of age were cultured for aerobic bacteria and fecal samples obtained at 1, 2, 4, and 8 wk and at 6 and 12 mo of age were cultivated quantitatively for aerobic and anaerobic bacteria. Vaginally delivered infants more often had Escherichia coli compared with cesarean section–delivered infants, whereas the latter more frequently carried other enterobacteria, such as Klebsiella and Enterobacter. Independent of delivery mode, it took 2 mo until most infants were colonized by enterobacteria, traditionally the first colonizers. In contrast, coagulase-negative staphylococci colonized 99% of the infants from d 3 onwards. The poor adaptation of staphylococci to the gut was shown by declining population sizes after some weeks. Dominating anaerobes were initially bifidobacteria and clostridia, whereas Bacteroides initially colonized only 30% of vaginally delivered infants and increased very slowly in prevalence. Bacteroides colonization was delayed up to 1 y in cesarean section–delivered compared with vaginally delivered infants. Our results show that some “traditional” fecal bacteria are acquired late today especially in cesarean section–delivered infants, probably due to limited environmental circulation. In their absence, skin bacteria like staphylococci have become the first gut colonizers.

Increased levels of circulating soluble CD14 but not CD83 in infants are associated with early intestinal colonization with Staphylococcus aureus

Background Soluble forms of the monocyte marker CD14 and the mature dendritic cell marker CD83 are plasma proteins with immunoregulatory functions. The physiological stimulus for their production is unclear and their possible role in allergy development is unknown.

Superantigenic Staphylococcus aureus Stimulates Production of Interleukin-17 from Memory but Not Naive T Cells

ABSTRACT T-helper 17 (Th17) cells are characterized by their production of interleukin-17 (IL-17) and have a role in the protection against infections and in certain inflammatory diseases. Humans who lack Th17 cells are more susceptible to Staphylococcus aureus infections compared to individuals having Th17 cells. S. aureus is part of the commensal skin microflora and also colonize the infant gut. To investigate whether UV-killed S. aureus would be more capable of inducing IL-17 than other commensal bacteria, we stimulated mononuclear cells from adults, infants, and newborns with various gram-positive and gram-negative commensal bacteria. IL-17 was produced from adult memory Th17 cells after stimulation with superantigen-producing S. aureus but not nonsuperantigenic S. aureus or other common commensal gut bacteria. Cells from newborns were poor IL-17 producers after stimulation with S. aureus, whereas in some cases IL-17 was secreted from cells isolated from infants at the age of 4 and 18 months. These results suggest that superantigenic S. aureus are particularly efficient in stimulating IL-17 production and that the cytokine is produced from memory T cells.

High circulating immunoglobulin A levels in infants are associated with intestinal toxigenic Staphylococcus aureus and a lower frequency of eczema

Background Intestinal bacteria trigger IgA production and delayed maturation of mucosal IgA response is linked to allergy development.

Adhesin and Superantigen Genes and the Capacity of Staphylococcus aureus to Colonize the Infantile Gut

Staphylococcus aureus is a pathogen and a skin commensal that is today also common in the infant gut flora. We examine the role of S. aureus virulence factors for gut colonization. S. aureus isolated from quantitative stool cultures of 49 Swedish infants followed from birth to 12 months of age were assessed for 30 virulence-associated genes, spa type, and agr allele by serial polymerase chain reaction (PCR) assays. Strains carrying genes encoding collagen-binding protein, and the superantigens S. aureus enterotoxin O/M (SEO/SEM) had higher stool counts than strains lacking these genes, whereas genes for S. aureus enterotoxin A (SEA) were associated with low counts. A cluster of strains belonging to agr allele I and the spa clonal cluster 630 (spa-CC 630) that carried genes encoding SEO/SEM, SEC, collagen-binding protein, and elastin-binding protein were all long-time colonizers. Thus, certain S. aureus virulence factors might promote gut colonization.

Effect of lifestyle factors on Staphylococcus aureus gut colonization in Swedish and Italian infants

In recent years, Staphylococcus aureus has become a common bowel colonizer in Swedish infants. We aimed to identify host factors that determine such colonization. Stool samples from 100 Italian and 100 Swedish infants were obtained on seven occasions during the first year of life and cultured quantitatively for S. aureus. In a subgroup of infants in each cohort, individual strains were identified by random amplified polymorphic DNA analysis. Colonization at each time-point was related to delivery mode, siblings in family and antibiotic treatment. In total, 66% of the Italian and 78% of the Swedish infants had S. aureus in their stools on at least one time-point (p 0.08) and 4% of Italian and 27% of Swedish infants were positive on at least six of the seven time-points investigated (p 0.0001). Most infants analysed regarding strain carriage harboured a single strain in their microbiota for several months. The S. aureus stool populations in colonized infants decreased from 10(7) to 10(4) colony-forming units/g between 1 week and 1 year of age in both cohorts. In multivariate analysis, the strongest predictor for S. aureus colonization was being born in Sweden (OR 3.4 at 1 week of age, p 0.002). Having (an) elder sibling(s) increased colonization at peak phase (OR 1.8 at 6 months, p 0.047). Antibiotic treatment was more prevalent among Italian infants and correlated negatively with S. aureus colonization at 6 months of age (OR 0.3, p 0.01). To conclude, S. aureus is a more common gut colonizer in Swedish than Italian infants, a fact that could not be attributed to feeding or delivery mode.

Lower levels of the host protective IL-10 in DCM—a feature of autoimmune pathogenesis?

Objectives: To investigate whether cytokine patterns differ with respect to heart failure (HF) etiology, and to study how cytokine concentrations relate to hemodynamic alterations. Methods: Plasma levels of interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor alpha (TNF-α) and high sensitive-CRP (hs-CRP) were analysed with enzyme-linked-immunosorbent serologic assay and turbidimetry in 45 healthy subjects and 89 patients with HF, of whom 65 were diagnosed with dilated cardiomyopathy (DCM) and 24 had ischemic heart disease (IHD). Results: IL-6, IL-10 and hs-CRP were significantly higher in patients with HF as compared to healthy controls. The IL-10 was significantly lower in patients with DCM as compared to IHD, also when adjusting for clinical variables. Diastolic filling pressure correlated with IL-6, IL-10 and hs-CRP while heart rate (HR) correlated with IL-6 and TNF-α. Conclusions: Proinflammatory cytokines are elevated in patients with HF and display a positive correlation with filling pressures and HR. Most significant, the regulatory and protective cytokine IL-10 was much lower in patients with DCM as compared to IHD, indicating a differentiation in cytokine patterns with respect to HF etiology.

Superantigens and adhesins of infant gut commensal Staphylococcus aureus strains and association with subsequent development of atopic eczema

According to the hygiene hypothesis, insufficient immune activation by microbes increases the risk of allergy development. Staphylococcus aureus, which is part of the skin and gut microbiota of infants in Western countries, produces a variety of T‐cell‐activating enterotoxins, called superantigens.

Exploring bacterial phenotypic diversity using factorial design and FTIR multivariate fingerprinting

Transmission Fourier transform infrared (FTIR) spectra were obtained from cultures of Staphylococcus aureus that were grown under sets of various environmental conditions enclosing ranges of potential conditions in wound sites. The primary aim of this study was to determine whether bacterial phenotypic diversity could be characterized by FTIR spectroscopy analyses of cultures of S. aureus grown under variable sets of environmental conditions. Designing experiments with full factorial design has shown to be a powerful way to explore an expectedly large array of phenotypic diversity of S. aureus. Various combinations of environmental conditions caused the bacteria to adapt their phenotype, which was assessed via FTIR spectral fingerprinting. Transmission FTIR spectroscopy was found to be superior to other vibrational spectroscopy techniques for this purpose because of its high sensitivity, reproducibility, and rapidity of analysis. The sample preparation presented was fundamental for reproducible results. Different spectral preprocessing methods were compared in combination with scaling methods to obtain distinguishable phenotypes in principal component analysis (PCA) models. Spectral preprocessing with combined filters, including standard normal variate transformation, Savitzky–Golay smoothing, and use of the first derivative in a PCA model with unit variance scaling, gave the most optimal clustering for the data in this study. Spectra obtained from each treatment group were found to have a unique FTIR profile with good reproducibility, and thus PCA resulted in full separation between all groups on three principal components. In conclusion, transmission FTIR spectroscopy in conjunction with design of experiment, and multivariate analysis are powerful tools to investigate phenotypic diversity of S. aureus. Copyright

Impaired activation of IFN-γ+CD4+ T cells in peripheral blood of patients with dilated cardiomyopathy

Viral persistence and autoantibodies are pathogenic components in patients with idiopathic dilated cardiomyopathy (DCM). The aim was to evaluate T-cell function in DCM using different flow cytometry based detection techniques. Following stimulation, the frequency of IFN-gamma-producing CD4+ T cells was significantly lower in patients compared with controls. In contrast, the frequency of IL-4 producing CD4+ T cells was no different. In supernatants of cultured PBMC, IFN-gamma and IL-10 were significantly lower in patients. In addition, lymphocyte proliferation was significantly lower in patients compared with controls, whereas major lymphocyte subsets were not different. IFN-gamma and IL-10 are key cytokines in the ability to mount protective immune responses and to maintain self-tolerance. A reduced activation of T-helper 1 (IFN-gamma producing) cells and a decreased capacity to produce IL-10, found in the present study, could explain parts of the autoimmune features seen in patients with DCM.