The effects of probiotic bacteria on glycaemic control in overweight men and women: a randomised controlled trial

Background/Objectives: Evidence from animal and in vitro models suggest a role of probiotic bacteria in improving glycaemic control and delaying the onset of type 2 diabetes. However, the evidence from controlled trials in humans is limited. The objective was to determine if the probiotic bacteria L. acidophilus La5 and B. animalis subsp lactis Bb12, supplemented in a whole food (yoghurt) or isolated (capsules) form, can improve biomarkers of glycaemic control. Subjects/methods: Following a 3-week washout period, 156 overweight men and women over 55 years (mean age: 67±8 years; mean body mass index (31±4 kg/m2) were randomized to a 6-week double-blinded parallel study. The four intervention groups were: (A) probiotic yoghurt plus probiotic capsules; (B) probiotic yoghurt plus placebo capsules; (C) control milk plus probiotic capsules; and (D) control milk plus placebo capsules. Outcome measurements, including fasting glucose, insulin, glycated haemoglobin and Homoeostasis Model Assessment of Insulin Resistance (HOMA-IR), were performed at baseline and week 6. Results: Relative to the milk-control group, probiotic yoghurt resulted in a significantly higher HOMA-IR (0.32±0.15, P=0.038), but did not have a significant effect on the other three measures of glycaemic control (P>0.05). Relative to placebo capsules, probiotic capsules resulted in a significantly higher fasting glucose (0.15±0.07 mmol/l, P=0.037), with no significant effect on the other three measures of glycaemic control (P>0.05). Further analyses did not identify other variables as contributing to these adverse findings. Conclusions: Data from this study does not support the hypothesis that L. acidophilus La5 and B. animalis subsp lactis Bb12, either in isolated form or as part of a whole food, benefit short-term glycaemic control. Indeed, there is weak data for an adverse effect of these strains on glucose homoeostasis

The vaginal microflora in relation to gingivitis

<p>Abstract</p> <p>Background</p> <p>Gingivitis has been linked to adverse pregnancy outcome (APO). Bacterial vaginosis (BV) has been associated with APO. We assessed if bacterial counts in BV is associated with gingivitis suggesting a systemic infectious susceptibilty.</p> <p>Methods</p> <p>Vaginal samples were collected from 180 women (mean age 29.4 years, SD ± 6.8, range: 18 to 46), and at least six months after delivery, and assessed by semi-quantitative DNA-DNA checkerboard hybridization assay (74 bacterial species). BV was defined by Gram stain (Nugent criteria). Gingivitis was defined as bleeding on probing at ≥ 20% of tooth sites.</p> <p>Results</p> <p>A Nugent score of 0–3 (normal vaginal microflora) was found in 83 women (46.1%), and a score of > 7 (BV) in 49 women (27.2%). Gingivitis was diagnosed in 114 women (63.3%). Women with a diagnosis of BV were more likely to have gingivitis (p = 0.01). Independent of gingival conditions, vaginal bacterial counts were higher (p < 0.001) for 38/74 species in BV+ in comparison to BV- women. Counts of four lactobacilli species were higher in BV- women (p < 0.001). Independent of BV diagnosis, women with gingivitis had higher counts of <it>Prevotella bivia </it>(p < 0.001), and <it>Prevotella disiens </it>(p < 0.001). <it>P. bivia, P. disiens, M. curtisii </it>and <it>M. mulieris </it>(all at the p < 0.01 level) were found at higher levels in the BV+/G+ group than in the BV+/G- group. The sum of bacterial load (74 species) was higher in the BV+/G+ group than in the BV+/G- group (p < 0.05). The highest odds ratio for the presence of bacteria in vaginal samples (> 1.0 × 10⁴cells) and a diagnosis of gingivitis was 3.9 for <it>P. bivia </it>(95% CI 1.5–5.7, p < 0.001) and 3.6 for <it>P. disiens </it>(95%CI: 1.8–7.5, p < 0.001), and a diagnosis of BV for <it>P. bivia </it>(odds ratio: 5.3, 95%CI: 2.6 to 10.4, p < 0.001) and <it>P. disiens </it>(odds ratio: 4.4, 95% CI: 2.2 to 8.8, p < 0.001).</p> <p>Conclusion</p> <p>Higher vaginal bacterial counts can be found in women with BV and gingivitis in comparison to women with BV but not gingivitis. <it>P. bivia </it>and <it>P. disiens </it>may be of specific significance in a relationship between vaginal and gingival infections.</p

Mechanism-Based Screen Establishes Signalling Framework for DNA Damage-Associated G1 Checkpoint Response

DNA damage activates checkpoint controls which block progression of cells through the division cycle. Several different checkpoints exist that control transit at different positions in the cell cycle. A role for checkpoint activation in providing resistance of cells to genotoxic anticancer therapy, including chemotherapy and ionizing radiation, is widely recognized. Although the core molecular functions that execute different damage activated checkpoints are known, the signals that control checkpoint activation are far from understood. We used a kinome-spanning RNA interference screen to delineate signalling required for radiation-mediated retinoblastoma protein activation, the recognized executor of G1 checkpoint control. Our results corroborate the involvement of the p53 tumour suppressor (TP53) and its downstream targets p21CIP1/WAF1 but infer lack of involvement of canonical double strand break (DSB) recognition known for its role in activating TP53 in damaged cells. Instead our results predict signalling involving the known TP53 phosphorylating kinase PRPK/TP53RK and the JNK/p38MAPK activating kinase STK4/MST1, both hitherto unrecognised for their contribution to DNA damage G1 checkpoint signalling. Our results further predict a network topology whereby induction of p21CIP1/WAF1 is required but not sufficient to elicit checkpoint activation. Our experiments document a role of the kinases identified in radiation protection proposing their pharmacological inhibition as a potential strategy to increase radiation sensitivity in proliferating cancer cells

How Linear Tension Converts to Curvature: Geometric Control of Bone Tissue Growth

This study investigated how substrate geometry influences in-vitro tissue formation at length scales much larger than a single cell. Two-millimetre thick hydroxyapatite plates containing circular pores and semi-circular channels of 0.5 mm radius, mimicking osteons and hemi-osteons respectively, were incubated with MC3T3-E1 cells for 4 weeks. The amount and shape of the tissue formed in the pores, as measured using phase contrast microscopy, depended on the substrate geometry. It was further demonstrated, using a simple geometric model, that the observed curvature-controlled growth can be derived from the assembly of tensile elements on a curved substrate. These tensile elements are cells anchored on distant points of the curved surface, thus creating an actin “chord” by generating tension between the adhesion sites. Such a chord model was used to link the shape of the substrate to cell organisation and tissue patterning. In a pore with a circular cross-section, tissue growth increases the average curvature of the surface, whereas a semi-circular channel tends to be flattened out. Thereby, a single mechanism could describe new tissue growth in both cortical and trabecular bone after resorption due to remodelling. These similarities between in-vitro and in-vivo patterns suggest geometry as an important signal for bone remodelling