Pirkka Kirjavainen

Bilberries reduce low-grade inflammation in individuals with features of metabolic syndrome

SCOPEnLow-grade inflammation is a hallmark of cardiometabolic risk. Bilberries (Vaccinium myrtillus) are rich in polyphenols with potential anti-inflammatory properties. We studied the impact of bilberries on inflammation and gene expression profile in peripheral blood mononuclear cells in subjects with metabolic syndrome.nnnMETHODS AND RESULTSnIn randomized, controlled dietary intervention, the participants consumed either a diet rich in bilberries (n = 15) or a control diet (n = 12). The bilberry group consumed daily an equivalent dose of 400 g fresh bilberries, while the control group maintained their habitual diet. No differences were found between the groups in body weight, glucose, or lipid metabolism, but bilberry supplementation tended to decrease serum high-sensitivity C-reactive protein, IL-6, IL-12, and LPS concentrations. An inflammation score was significantly different between the groups (p = 0.024). In transcriptomics analyses (three participants with improved oral glucose tolerance test in the bilberry group), Toll-like receptor signaling, cytoplasmic ribosomal proteins, and B-cell receptor signaling pathways were differently regulated. QPCR analyses (n = 13 and 11 in the bilberry and control groups, respectively) showed decreased expression of MMD and CCR2 transcripts associated with monocyte and macrophage function associated genes.nnnCONCLUSIONnRegular bilberry consumption may reduce low-grade inflammation indicating decreased cardiometabolic risk in the long term.

Wild blueberries (Vaccinium myrtillus) alleviate inflammation and hypertension associated with developing obesity in mice fed with a high-fat diet.

Background Low-grade metabolic inflammation and hypertension are primary mechanisms involved in obesity-associated adverse health effects. Berries, especially Nordic wild blueberries (hereafter referred to as bilberries), represent an important source of dietary anthocyanins, a group of polyphenols with potential beneficial effects to combat obesity-associated metabolic disturbances. Methods The effects of 5% or 10% (w/w) of whole bilberries (BB) were studied on the development of obesity and its metabolic disturbances in C57BL mice fed with a high-fat diet (HFD) for three months. Cytokines, inflammatory cells, systolic blood pressure, glucose tolerance, insulin sensitivity, weight gain, body fat, food consumption and energy metabolism were assessed. Results Bilberries ameliorated type 1 pro-inflammatory responsiveness induced by HFD. This was indicated by the altered cytokine profile and the reduced prevalence of interferon gamma -producing T-cells, in particular T helper type 1 cells. Bilberries also prevented the progression of obesity associated long term increase in systolic blood pressure in mice. Conclusions Bilberries reduce the development of systemic inflammation and prevent the progression of chronic hypertension, thus supporting their potential role in alleviating the adverse health effects associated with developing obesity.

Microbial secondary metabolites in homes in association with moisture damage and asthma

We aimed to characterize the presence of microbial secondary metabolites in homes and their association with moisture damage, mold, and asthma development. Living room floor dust was analyzed by LC-MS/MS for 333 secondary metabolites from 93 homes of 1-year-old children. Moisture damage was present in 15 living rooms. At 6xa0years, 8 children had active and 15 lifetime doctor-diagnosed asthma. The median number of different metabolites per house was 17 (range 8-29) and median sum load 65 (4-865) ng/m(2) . Overall 42 different metabolites were detected. The number of metabolites present tended to be higher in homes with mold odor or moisture damage. The higher sum loads and number of metabolites with loads over 10xa0ng/m(2) were associated with lower prevalence of active asthma at 6xa0years (aOR 0.06 (95% CI <0.001-0.96) and 0.05 (<0.001-0.56), respectively). None of the individual metabolites, which presence tended (Pxa0<xa00.2) to be increased by moisture damage or mold, were associated with increased risk of asthma. Microbial secondary metabolites are ubiquitously present in home floor dust. Moisture damage and mold tend to increase their numbers and amount. There was no evidence indicating that the secondary metabolites determined would explain the association between moisture damage, mold, and the development of asthma.

Synergistic proinflammatory interactions of microbial toxins and structural components characteristic to moisture-damaged buildings

Indoor exposure to microbes and their structural and metabolic compounds is notoriously complex. To study proinflammatory interactions between the multiple microbial agents, macrophages derived from human THP-1 monocytic cells were exposed to several concentrations of microbial toxins alone (emodin, enniatin B, physcion, sterigmatocystin, valinomycin) and in combination with microbial structural components (bacterial lipopolysaccharide [LPS] or fungal β-glucan). While the expression of proinflammatory cytokines TNFα and IL-1β to single toxins alone was modest, low-dose co-exposure with structural components increased the responses of emodin, enniatin B, and valinomycin synergistically, both at the mRNA and protein level, as measured by RT-qPCR and ELISA, respectively. Co-exposure of toxins and β-glucan resulted in consistent synergistically increased expression of several inflammation-related genes, while some of the responses with LPS were also inhibitory. Co-exposure of toxins with either β-glucan or LPS induced also mitochondrial damage and autophagocytosis. The results demonstrate that microbial toxins together with bacterial and fungal structural components characteristic to moisture-damaged buildings can have drastic synergistic proinflammatory interactions at low exposure levels.

Mechanism of action of probiotic bacteria on intestinal and systemic immunities and antigen-presenting cells

Immunomodulation has been shown to be one of the major functions of probiotic bacteria. This review is presented to provide detailed information on the immunomodulatory properties of probiotics in various animal models and clinical practices. Probiotics can regulate helper T (Th) responses and release of cytokines in a strain-specific manner. For example, Lactobacillus rhamnosus GG can induce beneficial Th1 immunomodulatory effect in infants with cows milk allergy and relieve intestinal inflammation in atopic children by promoting IL-10 generation. Mechanism of action of probiotics on antigen-presenting cells at gastrointestinal tract is also postulated in this review. Probiotic bacterial cells and their soluble factors may activate dendritic cells, macrophages, and to certain extent monocytes via toll-like-receptor recognition and may further provoke specific Th responses. They are speculated to elicit immunomodulatory effects on intestinal and systemic immunities.

Moisture damage in home associates with systemic inflammation in children

This study investigated the association between confirmed moisture damage in homes and systemic subclinical inflammation in children. Home inspections were performed in homes of 291 children at the age of 6xa0years. Subclinical inflammation at the age of 6xa0years was assessed by measuring the circulating levels of C-reactive protein (CRP) and leukocytes in peripheral blood and fractional exhaled nitric oxide (FeNO). Proinflammatory cytokines interleukin (IL)-1β and IL-6 and tumor necrosis factor (TNF)-α were measured in unstimulated, and in phorbol 12-myristate 13-acetate and ionomycin (PI), lipopolysaccharide (LPS), or peptidoglycan (PPG)-stimulated whole blood. Major moisture damage in the childs main living areas (living room, kitchen, or childs bedroom) and moisture damage with mold in the bathroom were associated with increased levels of CRP and stimulated production of several proinflammatory cytokines. There were no significant associations between moisture damage/visible mold and leukocyte or FeNO values. The results suggest that moisture damage or mold in home may be associated with increased systemic subclinical inflammation and proinflammatory cytokine responsiveness.

Postprandial glucose metabolism and SCFA after consuming wholegrain rye bread and wheat bread enriched with bioprocessed rye bran in individuals with mild gastrointestinal symptoms

BackgroundRye bread benefits glucose metabolism. It is unknown whether the same effect is achieved by rye bran-enriched wheat bread. We tested whether white wheat bread enriched with bioprocessed rye bran (BRBu2009+u2009WW) and sourdough wholegrain rye bread (WGR) have similar effects on glucose metabolism and plasma level of short chain fatty acids (SCFAs).MethodsTwenty-one (12 women) of 23 recruited subjects completed an intervention with a four-week run-in and two four-week test periods in cross-over design. White wheat bread (WW; 3% fibre) was consumed during the run-in, and WGR and BRBu2009+u2009WW (10% fibre) during the test periods. A meal test providing 51/33/11 E % from carbohydrates/fat/protein was conducted at the end of each period. Fasting and postprandial plasma samples were analysed for glucose, insulin, and SCFA.ResultsGlucose and insulin responses and plasma concentrations of SCFAs to the meal test were similar between the WGR and BRBu2009+u2009WW periods. When compared to the WW period, postprandial insulin concentration at 120 min was lower (pu2009=u20090.023) and the first-phase insulin secretion improved (pu2009=u20090.033) only after the WGR period, whereas postprandial concentrations of butyrate (pu2009<u20090.05) and propionate (pu2009=u20090.009) at 30 min increased during both rye bread periods.ConclusionsBeneficial effects of WGR over white wheat bread on glucose and SCFA production were confirmed. The enrichment of the white wheat bread with bioprocessed rye bran (BRBu2009+u2009WW) yielded similar but not as pronounced effects than WGR when compared to WW alone. Postprandially measured glucose metabolism and concentrations of SCFAs provided additional information along with fasting measurements.

Probiotic mixture VSL#3 reduce high fat diet induced vascular inflammation and atherosclerosis in ApoE −/− mice

Atherosclerosis results from chronic inflammation potentially caused by translocation of bacterial components from the oro-gastrointestinal tract to circulation. Specific probiotics have anti-inflammatory effects and may reduce bacterial translocation. We thereby tested whether a probiotic mixture with documented anti-inflammatory potential could reduce atherosclerosis. ApoE−/− mice were fed high fat diet alone or with VSL#3 or a positive control treatment, telmisartan or both for 12xa0weeks. All treatments reduced atherosclerotic plaques significantly compared to high fat diet alone. VSL#3 significantly reduced proinflammatory adhesion molecules and risk factors of plaque rupture, reduced vascular inflammation and atherosclerosis to a comparable extent to telmisartan; and VSL#3 treated mice had the most distinctly different intestinal microbiota composition from the control groups. Combining the VSL#3 and telmisartan brought no further benefits. Our findings showed the therapeutic potential of VSL#3 in reducing atherosclerosis and vascular inflammation.

Crawling-induced floor dust resuspension affects the microbiota of the infant breathing zone

BackgroundFloor dust is commonly used for microbial determinations in epidemiological studies to estimate early-life indoor microbial exposures. Resuspension of floor dust and its impact on infant microbial exposure is, however, little explored. The aim of our study was to investigate how floor dust resuspension induced by an infant’s crawling motion and an adult walking affects infant inhalation exposure to microbes.ResultsWe conducted controlled chamber experiments with a simplified mechanical crawling infant robot and an adult volunteer walking over carpeted flooring. We applied bacterial 16S rRNA gene sequencing and quantitative PCR to monitor the infant breathing zone microbial content and compared that to the adult breathing zone and the carpet dust as the source. During crawling, fungal and bacterial levels were, on average, 8- to 21-fold higher in the infant breathing zone compared to measurements from the adult breathing zone. During walking experiments, the increase in microbial levels in the infant breathing zone was far less pronounced. The correlation in rank orders of microbial levels in the carpet dust and the corresponding infant breathing zone sample varied between different microbial groups but was mostly moderate. The relative abundance of bacterial taxa was characteristically distinct in carpet dust and infant and adult breathing zones during the infant crawling experiments. Bacterial diversity in carpet dust and the infant breathing zone did not correlate significantly.ConclusionsThe microbiota in the infant breathing zone differ in absolute quantitative and compositional terms from that of the adult breathing zone and of floor dust. Crawling induces resuspension of floor dust from carpeted flooring, creating a concentrated and localized cloud of microbial content around the infant. Thus, the microbial exposure of infants following dust resuspension is difficult to predict based on common house dust or bulk air measurements. Improved approaches for the assessment of infant microbial exposure, such as sampling at the infant breathing zone level, are needed.

Indoor microbiota in severely moisture damaged homes and the impact of interventions

BackgroundThe limited understanding of microbial characteristics in moisture-damaged buildings impedes efforts to clarify which adverse health effects in the occupants are associated with the damage and to develop effective building intervention strategies. The objectives of this current study were (i) to characterize fungal and bacterial microbiota in house dust of severely moisture-damaged residences, (ii) to identify microbial taxa associated with moisture damage renovations, and (iii) to test whether the associations between the identified taxa and moisture damage are replicable in another cohort of homes. We applied bacterial 16S rRNA gene and fungal ITS amplicon sequencing complemented with quantitative PCR and chemical-analytical approaches to samples of house dust, and also performed traditional cultivation of bacteria and fungi from building material samples.ResultsActive microbial growth on building materials had significant though small influence on the house dust bacterial and fungal communities. Moisture damage interventions—including actual renovation of damaged homes and cases where families moved to another home—had only a subtle effect on bacterial community structure, seen as shifts in abundance weighted bacterial profiles after intervention. While bacterial and fungal species richness were reduced in homes that were renovated, they were not reduced for families that moved houses. Using different discriminant analysis tools, we were able identify taxa that were significantly reduced in relative abundance during renovation of moisture damage. For bacteria, the majority of candidates belonged to different families within the Actinomycetales order. Results for fungi were overall less consistent. A replication study in approximately 400 homes highlighted some of the identified taxa, confirming associations with observations of moisture damage and mold.ConclusionsThe present study is one of the first studies to analyze changes in microbiota due to moisture damage interventions using high-throughput sequencing. Our results suggest that effects of moisture damage and moisture damage interventions may appear as changes in the abundance of individual, less common, and especially bacterial taxa, rather than in overall community structure.