Postnatal effects of obstetrical epidural anesthesia on allergic sensitization.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to M Kalliomäki.
Explore the source record for details and available documents.
The notion of food allergy in irritable bowel syndrome (IBS) is not new. However, recent evidence suggests significant reduction in IBS symptom severity in patients on elimination diets, provided that dietary elimination is based on foods against which the individual had raised IgG antibodies. These findings should encourage studies dissecting the mechanisms responsible for IgG production against dietary antigens and their putative role in IBS
Explore the source record for details and available documents.
Improved hygienic conditions in Western societies have reduced early microbial exposure, which has been proposed as a reason for the continuously rising prevalence of atopy and subsequent atopic diseases: atopic eczema, allergic rhinitis and asthma (The Hygiene Hypothesis of Allergy). This hypothesis is supported by immunological data showing that the immune response to microbial antigens, both pathogenic and non-pathogenic ones, is accompanied by preferential expression of cytokines that counterbalance the T-helper 2-polarized cytokine production of neonates, the continuity of which might lead to enhanced IgE production, atopy, and atopic disease. Experimental, epidemiological and clinical studies, conducted over the last decade, indicate that non-pathogenic microbes in the gut might be a major factor essential for the maturation of the human immune system to a nonatopic mode. A recent randomised, placebo-controlled trial demonstrated that perinatal administration of probiotics, cultures of potentially beneficial bacteria of the healthy gut microflora, halved the later development of atopic eczema during the first two years of life. Some putative mechanisms of action of gut commensals in host-microbe interactions have been described. Two structural components of bacteria, the lipopolysaccharide portion of Gram-negative bacteria and specified CpG motif in bacterial DNA, activate immunomodulatory genes via Toll-like receptors present e.g. on intestinal epithelial cells thus controlling physiological cytokine milieu in the gut. Probiotics have also been shown to reverse increased intestinal permeability and to reduce antigen load in the gut by degrading and modifying macromolecules. The actual preventive role of natural and genetically constructed supplementary microbes in the development of immunological diseases, like allergy, remains to be elucidated.
Explore the source record for details and available documents.
BACKGROUND: Reversal of the progressive increase in frequency of atopic disease would be an important breakthrough for health care and wellbeing in western societies. In the hygiene hypothesis this increase is attributed to reduced microbial exposure in early life. Probiotics are cultures of potentially beneficial bacteria of the healthy gut microflora. We assessed the effect on atopic disease of Lactobacillus GG (which is safe at an early age and effective in treatment of allergic inflammation and food allergy). METHODS: In a double-blind, randomised placebo-controlled trial we gave Lactobacillus GG prenatally to mothers who had at least one first-degree relative (or partner) with atopic eczema, allergic rhinitis, or asthma, and postnatally for 6 months to their infants. Chronic recurring atopic eczema, which is the main sign of atopic disease in the first years of life, was the primary endpoint. FINDINGS: Atopic eczema was diagnosed in 46 of 132 (35%) children aged 2 years. Asthma was diagnosed in six of these children and allergic rhinitis in one. The frequency of atopic eczema in the probiotic group was half that of the placebo group (15/64 [23%] vs 31/68 [46%]; relative risk 0.51 [95% CI 0.32-0.84]). The number needed to treat was 4.5 (95% CI 2.6-15.6). INTERPRETATIONS: Lactobacillus GG was effective in prevention of early atopic disease in children at high risk. Thus, gut microflora might be a hitherto unexplored source of natural immunomodulators and probiotics, for prevention of atopic disease.
Breastfeeding holds a key position with regard to the increasing burden of allergic diseases in the industrialized countries. Not only does it provide the infant with nutrients for growth and development, it also confers immunological protection during a critical period in life, when the infant's own defense mechanisms are immature. A delicate balance of stimulatory, even inflammatory, maturational signals, together with a myriad of anti-inflammatory compounds, is transferred from mother to infant via breastfeeding. Breastfeeding mothers, however, do not constitute a uniform group. The composition of breast milk shows marked individual variation and so, consequently, does the success of breastfeeding in reducing the risk of disease. Recent clinical studies indicate that the potential of breastfeeding to counteract allergic disease may be promoted by dietary means. While uncoordinated elimination diets result in a risk of general nutritional inadequacy or deficiency of essential single nutrients, a balanced diet following current dietary recommendations, specifically containing fresh fruits and vegetables (antioxidants) and fat of predominantly vegetable origin, may be associated with a lower incidence of atopy in the infant. As early nutrition appears to program the subsequent health of the child, the importance of the maternal dietary composition during breastfeeding should be emphasized. In future, an improved understanding of the mechanisms of this programming may offer specific therapeutic modalities for the prevention of allergic disease.
BACKGROUND: The increased consumption of n-6 polyunsaturated fatty acids (PUFA) has been shown to coincide with the increased prevalence of atopic diseases. We aimed to investigate whether maternal diet and atopic status influence the PUFA composition of breast milk and the serum lipid fatty acids of infants. METHODS: Maternal diet was assessed by a food questionnaire. The PUFA composition of breast milk obtained at 3 months from 20 allergic and 20 healthy mothers and of their infants' (10 atopic and 10 nonatopic/group of mothers) serum lipids was analyzed. RESULTS: Although no differences in maternal PUFA intake were observed, the breast milk of allergic mothers contained less gamma-linolenic acid (18:3 n-6) than that of healthy mothers. Similarly, atopic infants had less gamma-linolenic acid in phospholipids than healthy infants, although n-6 PUFA were elevated in other serum lipid fractions in atopic infants. The serum lipid fatty acids in atopic infants did not correlate with those in maternal breast milk. CONCLUSION: Our results suggest that dietary n-6 PUFA are not as readily transferred into breast milk or incorporated into serum phospholipids, but may be utilized for other purposes, such as eicosanoid precursors, in allergic/atopic individuals. Subsequently, high dietary proportions of n-6 PUFA, or reduced proportions of regulatory PUFA, such as gamma-linolenic acid and n-3 PUFA, may be a risk factor for the development of atopic disease.
BACKGROUND: Improved hygiene has altered early microbial exposure by reducing childhood infections, which has been suggested as a cause for the continuously rising prevalence of atopic diseases. On the basis of both intensity and timing of stimulus, it has been hypothesized that exposure to commensal microflora may represent another key protective modulator of immunity against atopy and subsequent atopic diseases. OBJECTIVE: We sought to investigate whether differences in early gut microflora precede the later development of atopic sensitization. METHODS: Intestinal microflora from 76 infants at high risk of atopic diseases were analyzed at 3 weeks and 3 months of age by using conventional bacterial cultivation and 2 culture-independent methods, gas-liquid chromatography of bacterial cellular fatty acids and quantitative fluorescence in situ hybridization of bacterial cells. Infants evincing at least one positive skin prick reaction at 12 months were grouped as atopic subjects, and those without positive reactions were grouped as nonatopic subjects. RESULTS: Atopic sensitization was observed in 22 (29%) of 76 children. At 3 weeks, the bacterial cellular fatty acid profile in fecal samples differed significantly between infants in whom atopy was and was not developing (P =.005). By using fluorescence in situ hydridization, atopic subjects had more clostridia (geometric mean [95% confidence interval]: 9.3 x 10(7) [3.8-22.9 x 10(7)] vs 3.3 x 10(7) [1.8-6.1 x 10(7)], P =.04) and tended to have fewer bifidobacteria (1.8 x 10(9) [0.4-7.6 x 10(9)] vs 6.1 x 10(9) [2.5-14.6 x 10(9)], P =.11) in their stools than nonatopic subjects, resulting in a reduced ratio of bifidobacteria to clostridia (P =.03). The differences were not detected by bacterial cultivation. CONCLUSION: Differences in the neonatal gut microflora precede the development of atopy, suggesting a crucial role of the balance of indigenous intestinal bacteria for the maturation of human immunity to a nonatopic mode.
In a prospective follow up of 116 high risk infants, a 24 hour behavioural chart on seven consecutive days was analysed at seven and 12 weeks of age. Of children who manifested atopic disease at 2 years, 44/116 (38%), had shown significantly more fussing during the seventh, and colic type cry during the twelfth week than those who remained healthy (72/116, 62%).
Diabetes mellitus (DM) is a complex metabolic disease associated with increased accumulation of extracellular matrix by endothelial cells and contributing to vascular complications of long-standing diabetes. On the other hand, DM is also associated with decreased accumulation of extracellular matrix in granulation tissue, which is suggested to be a consequence of impaired angiogenesis. The role of hyperglycemia in these situations is not fully understood. We examined the effects of high glucose concentrations on the gene expression and secretion of various collagens in cultured EAhy 926 endothelial cells. EAhy 926 endothelial cells expressed alpha 1(I) collagen mRNA at a low level and small amount of the corresponding peptide was secreted from the cells; mRNA was not affected but peptide secretion was increased by elevated glucose concentration. mRNAs for type III and VI collagens were not detected in the endothelial cells Furthermore, high glucose concentration in long term had no morphological effects on cultured endothelial cells but increased the expression of type IV collagen, which could rather be beneficial for angiogenesis in a healing wound. Our results suggest that high glucose concentration per se may contribute to increased accumulation of extracellular matrix in blood vessels but probably is not responsible for decreased angiogenesis and granulation tissue formation in diabetic patients.
Diabetes mellitus (DM) is a complex metabolic disease associated with increased accumulation of extracellular matrix by endothelial cells and contributing to vascular complications of long-standing diabetes. On the other hand, DM is also associated with decreased accumulation of extracellular matrix in granulation tissue, which is suggested to be a consequence of impaired angiogenesis. The role of hyperglycemia in these situations is not fully understood. We examined the effects of high glucose concentrations on the gene expression and secretion of various collagens in cultured EAhy 926 endothelial cells. EAhy 926 endothelial cells expressed alpha1(I) collagen mRNA at a low level and small amount of the corresponding peptide was secreted from the cells; mRNA was not affected but peptide secretion was increased by elevated glucose concentration. mRNAs for type III and VI collagens were not detected in the endothelial cells. Furthermore, high glucose concentration in long term had no morphological effects on cultured endothelial cells but increased the expression of type IV collagen, which could rather be beneficial for angiogenesis in a healing wound. Our results suggest that high glucose concentration per se may contribute to increased accumulation of extracellular matrix in blood vessels but probably is not responsible for decreased angiogenesis and granulation tissue formation in diabetic patients.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
OBJECTIVE: To investigate the impact of maternal diet during breastfeeding on atopic sensitization of infants at risk. DESIGN: Prospective cohort study. SETTING: Turku University Central Hospital, Finland. SUBJECTS AND METHODS: Altogether 114 infants with a family history of atopic disease were followed during their first year of life. The mothers completed a 4 day food record during breastfeeding just before the infants were 3 months old. Atopic sensitization of the infants was determined by a positive skin prick test result at 12 months. RESULTS: Positive skin prick test reactivity to at least one antigen was detected in 27/114 (24%) infants at 12 months. The energy intake of the mothers was low, mean 8.0 MJ/day (95% CI 7.7-8. 3), and the proportion of energy derived from fat was high, mean 36. 6 E% (95% CI 35.6-37.6). Atopic mothers had a higher intake of total fat and saturated fat and a lower intake of carbohydrate as a percentage of total energy intake than non-atopic mothers; P=0.017, P=0.050, P=0.004 respectively. Maternal intake of saturated fat during breastfeeding was associated with atopic sensitization of the infant, OR=1.16 (95% CI 1.001-1.36); P=0.048 irrespective of the maternal atopic status. CONCLUSIONS: Our results show that an unbalanced maternal diet during breastfeeding may be a risk factor underlying the later development of atopic sensitization of the infant regardless of maternal atopic disease. The observation thus extends findings implying that early nutrition programmes the subsequent health of the child to the risk of developing atopic disease. SPONSORSHIP: Academy of Finland and National Technology Agency.
Explore the source record for details and available documents.
BACKGROUND: According to data from animal and in vitro studies, transforming growth factor-beta (TGF-beta) has a crucial effect on 2 essential parts of the mucosal immune system: IgA production and oral tolerance induction. OBJECTIVE: We sought to ascertain whether TGF-beta in breast milk is associated with specific IgA production and atopic disease in human subjects. METHODS: Forty-seven infants with several atopic family members were followed during their first year of life. The concentrations of TGF-beta1 and TGF-beta2 in maternal colostrum, mature milk, and the infants' sera were determined. The enzyme-linked immunospot assay was used to assess the infants' specific IgA production in response to beta-lactoglobulin, casein, gliadin, and ovalbumin. RESULTS: At 12 months, atopic dermatitis was confirmed in 29 of 47 infants; in 11, atopic disease had begun during exclusive breast-feeding (preweaning onset), whereas in 18 the disease manifested itself after weaning (postweaning onset). The concentrations of both TGF-beta1 and TGF-beta2 were higher in maternal colostrum, but not in mature milk and infants' serum, in infants with postweaning-onset atopic disease compared with those with preweaning-onset disease (P =.0008 and P =. 015, respectively). The concentration of TGF-beta2 was, and that of TGF-beta1 tended to be, higher in the colostrum of mothers whose infants had specific IgA-secreting cells at 3 months in response to at least one of the dietary antigens tested compared with those who did not have such cells (P =.048 and P =.076, respectively). CONCLUSION: TGF-beta in colostrum may prevent the development of atopic disease during exclusive breast-feeding and promote specific IgA production in human subjects.
Explore the source record for details and available documents.