Background: Probiotics use has been associated with modulation of inflammation and considered as a possible intervention for CNS diseases such as mild cognitive impairment (MCI) and dementia. Objective: We aimed to test the effect of the probiotic strain, Bifidobacterium breve A1 (MCC1274), to restore cognition in a physically healthy, suspected MCI population. Methods: In this randomized, double-blind, placebo-controlled trial, 80 healthy older adults suffering from MCI were divided into two even groups to receive once daily either probiotic ( B. breve A1, 2×10 10 CFU) or placebo for 16 weeks using a computer-generated algorithm. Cognitive functions were assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Japanese version of the MCI Screen (JMCIS) tests before and after the study as primary and secondary endpoints, respectively. Results: 79 participants completed the study, and no adverse events were observed. RBANS total score was significantly improved in probiotic group compared with placebo (mean between-group difference 11.3 [95% CI 6.7 to 15.8]; p < 0.0001) after 16 weeks of consumption, in particular with significant improvement in domain scores of immediate memory, visuospatial/constructional, and delayed memory ( p < 0.0001), in both intention-to-treat (ITT) analysis and per-protocol (PP) analysis. JMCIS score was also improved versus placebo in ITT analysis ( p = 0.052) and PP analysis ( p = 0.036). Conclusion: Study results indicate B. breve A1 is a safe and effective approach for improving memory functions of suspected MCI subjects.

Background: Probiotic supplementation reestablishes microbiome diversity and improves brain function in Alzheimer’s disease (AD); their molecular mechanisms, however, have not yet been fully illustrated. Objective: We investigated the effects of orally supplemented Bifidobacterium breve MCC1274 on cognitive function and AD-like pathologies in AppNL-G-F mice. Methods: Three-month-old AppNL-G-F mice were orally supplemented with B. breve MCC1274 for four months. The short-term memory function was evaluated using a novel object recognition test. Amyloid plaques, amyloid-β (Aβ) levels, Aβ fibril, amyloid-β protein precursor and its processing enzymes, its metabolic products, glial activity, and cell proliferation in the subgranular zone of the dentate gyrus were evaluated by immunohistochemistry, Aβ ELISA, western blotting, and immunofluorescence staining. The mRNA expression levels of pro- and anti-inflammatory cytokines were determined by qRT-PCR analysis. Results: We found that the oral B. breve MCC1 274 supplementation prevented memory impairment in AppNL-G-F mice and decreased hippocampal Aβ levels through the enhancement of the a-disintegrin and metalloproteinase 10 (ADAM10) level. Moreover, administration of the probiotic activated the ERK/HIF-1α signaling pathway responsible for increasing the ADAM10 level and also attenuated microglial activation, which in turn led to reduction in the mRNA expression levels of pro-inflammatory cytokines in the brain. In addition, B. breve MCC1274 supplementation increased the level of synaptic proteins in the hippocampus. Conclusion: Our findings support the possibility that oral B. breve MCC1274 supplementation might be used as a potential preventive therapy for AD progression.

BackgroundIn the WHO 2010 classification, the neuroendocrine tumors (NETs) are subdivided by their mitotic index or Ki67 index into either G1 or G2 NETs. Tumors with a Ki67 index of <2% are classified as G1 and those with 3—20% are classified as G2. However, the assessment of tumors with Ki67 index of greater than 2% and less than or equal to 3% is still unclear. To resolve the problem, we validated the Ki67 index criteria of gastrointestinal NETs of the WHO 2010 classification.MethodsThe medical records of 45 patients who were pathologically diagnosed as having NET G1/G2 of the gastrointestinal tract were analyzed retrospectively. According to the WHO 2010 classification, Ki67 index were calculated. Computer-assisted cytometrical analysis of Ki67 immunoreactivity was performed using the WinRooF image processing software. Receiver operating characteristic (ROC) curves were generated to determine the best discriminating Ki67 index. To clarify the assessment of tumors with Ki67 index between 2—3%, the calculated cutoff of Ki67 index was evaluated using Fisher’s exact test.ResultsROC curve analysis confirmed that 2.8% was the best Ki67 index cutoff value for predicting metastasis or recurrence. The sensitivity of the new Ki67 index cutoff was 42.9%, and the specificity was 86.8%.ConclusionsDivision of NETs into G1/G2 based on Ki67 index of 3% was appropriate to predict metastases or recurrences. The WHO grading system may be the most useful classification to predict metastases or recurrences.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1553036118943799