Intestinal Dysbiosis Featuring Abundance of Ruminococcus gnavus Associates With Allergic Diseases in Infants.

BACKGROUND & AIMS: Dysbiosis of the intestinal microbiota has been associated with development of allergies in infants. However, it is not clear what microbes might contribute to this process. We investigated what microbe(s) might be involved in analyses of infant twins and mice. METHODS: We studied fecal specimens prospectively in a twin cohort (n = 30) and age-matched singletons (n = 14) born at National Taiwan University Children's Hospital, Taipei, Taiwan, from April 2011 to March 2013. Clinical parameters (gestational age, birth body weight, mode of delivery and feeding, immunizations, and medical events) were recorded. Fecal samples were collected beginning immediately after birth and for 1 year; the children were followed until 3 years of age and allergic symptoms (repetitive and continuous for at least 6 months) were noted. A skin prick test was used to ascertain atopy. Bacterial communities in fecal samples were profiled by 16S ribosomal RNA-based polymerase chain reaction-temporal temperature gradient gel electrophoresis and next-generation sequencing. BALB/c mice without and with ovalbumin sensitization/challenge were infected with candidate bacteria by oral gauge intragastric intubation. Fecal, serum, lung, and colon tissue samples were collected from mice and analyzed for mechanisms of allergy development. RESULTS: During the investigation period, 20 children (45.5%) developed allergic diseases, including respiratory (allergic rhinitis and asthma) and skin (atopic dermatitis and eczema) allergies. Lachnospiraceae were detected at significantly higher frequency in allergic infants than nonallergic infants (P < .004); the high fecal count of Lachnospiraceae in allergic subjects appeared at 2 months of age and persisted until 12 months of age. The enrichment of Lachnospiraceae in allergic infants was attributed to the overgrowth of Ruminococcus gnavus, which tended to have a low frequency in nonallergic subjects (P = .0004). Increased R gnavus was observed before the onset of allergic manifestations, and was associated with respiratory allergies (P < .002) or respiratory allergies coexistent with atopic eczema (P < .001). In mice, endogenous R gnavus grew rapidly after sensitization and challenge with ovalbumin. Mice gavaged with purified R gnavus developed airway hyper-responsiveness and had histologic evidence of airway inflammation (asthma). Expansion of R gnavus in mice stimulated secretion of cytokines (interleukin [IL] 25, IL33, and thymic stromal lymphopoietin) by colon tissues, which activated type 2 innate lymphoid cells and dendritic cells to promote differentiation of T-helper 2 cells and production of their cytokines (IL4, IL5, and IL13). This led to infiltration of the colon and lung parenchyma by eosinophils and mast cells. CONCLUSIONS: In a study of a twin cohort (some infants with, some without allergies), we associated development of allergies, particularly respiratory allergies, with increased fecal abundance of R gnavus. Mice fed R gnavus developed airway inflammation, characterized by expansion of T-helper 2 cells in the colon and lung, and infiltration of colon and lung parenchyma by eosinophils and mast cells.

Inhibition of protein kinase C promotes differentiation of neuroblastoma × glioma NG108-15 hybrid cells.

Differentiation of neuroblastoma × glioma NG108-15 hybrid cells can be induced by different means, but the mechanisms involved are unclear. Our aim was to characterize the role of protein kinase C (PKC) in this process. The PKCs present in NG108-15 cells, i.e. PKCα, PKCδ, PKCε and PKCζ, were inhibited using a cocktail of Go6983 and Ro318220 or were downregulated by treatment with phorbol 12-myristate 13-acetate (PMA). In high-glucose Dulbecco's modified Eagle medium, neuritogenesis was induced by 24 h treatment with a cocktail of Go6983 and Ro318220 or by 48 h treatment with PMA, the latter process thus requiring a longer treatment. However, when cells treated with PMA for only 24 h were placed in extracellular standard salts solution, e.g. Locke's buffer, for 3 h, morphological and functional differentiation occurred, with rounding of the cell body, actin polymerization subjacent to the plasma membrane and an increase in voltage-sensitive Ca(2+) channel activity in the absence of cell death. This rapid differentiation was not due to autophagy, growth arrest or increased cyclic AMP response element binding protein phosphorylation, but coincided with combined activation of p38 mitogen-activated protein kinase (MAPK) and inhibition of extracellular signal-regulated kinase (ERK) and Akt, as confirmed by the effects of selective inhibitors. Furthermore, PKC activation blocked thapsigargin-induced neuritogenesis, whereas PKC downregulation did not. These results show that PKC downregulation promotes differentiation and this effect is accelerated by exposure to Locke's buffer. Although this experimental paradigm cannot be related to the in vivo situation and disease, it implies that combined inhibition of Akt and p44/p42 ERK and activation of p38 MAPK promotes differentiation.

Correlates of perceived autonomy among elders in a senior citizen home: a cross-sectional survey.

BACKGROUND: Researchers have pointed out several factors that correlated with or influenced autonomy in older people. However, these studies covered only a range of socio-demographic or physical factors, while factors from psychosociological and spiritual domains remain ignored. Also, there is lack of quantitative research and publications in this area. OBJECTIVES: To explore factors related to autonomy among elders in a senior citizen home. DESIGN: A cross-sectional design utilizing a correlational approach was adopted. PARTICIPANTS: A stratified random sample of 121 subjects older than 64 years was recruited at a senior citizen home. METHODS: Questionnaires and interviews were used to collect data. The structured questionnaire consisted of five parts, each gauging socio-demographic information, life attitudes, frequency and satisfaction of social support, and autonomy. Descriptive and stepwise multiple linear regression analysis were used to analyze the data. FINDINGS: Subjects had a high autonomy score (mean = 3.63), with the greatest score in independence (mean = 4.39), followed by individuality (mean = 3.74) and freedom (mean = 3.22). Multiple regression analysis showed that satisfaction of social support (beta = .57), functional ability (beta = .25), life attitudes (beta = .20), and level of education (beta = .14) significantly affected autonomy in these elderly subjects and explained 64.2% of the total variance of autonomy in this population. CONCLUSIONS: Findings from this study indicate that perceived autonomy is influenced by social support, functional ability, life attitude, and literacy among institutionalized elders.