Although evidence for mitochondrial dysfunction in the pathogenesis of bipolar disorder (BD) has been reported, the precise biological basis remains unknown, hampering the search for novel biomarkers. In this study, we performed metabolomics of cerebrospinal fluid (CSF) from male BD patients (n=54) and age-matched male healthy controls (n=40). Subsequently, post-mortem brain analyses, genetic analyses, metabolomics of CSF samples from rats treated with lithium or valproic acid were also performed. After multivariate logistic regression, isocitric acid (isocitrate) levels were significantly higher in the CSF from BD patients than healthy controls. Furthermore, gene expression of two subtypes (IDH3A and IDH3B) of isocitrate dehydrogenase (IDH) in the dorsolateral prefrontal cortex from BD patients was significantly lower than that of controls, although the expression of other genes including, aconitase (ACO1, ACO2), IDH1, IDH2 and IDH3G, were not altered. Moreover, protein expression of IDH3A in the cerebellum from BD patients was higher than that of controls. Genetic analyses showed that IDH genes (IDH1, IDH2, IDH3A, IDH3B) and ACO genes (ACO1, ACO2) were not associated with BD. Chronic (4 weeks) treatment with lithium or valproic acid in rats did not alter CSF levels of isocitrate, and mRNA levels of Idh3a, Idh3b, Aco1 and Aco2 genes in the rat brain. These findings suggest that abnormality in the metabolism of isocitrate by IDH3A in the mitochondria plays a key role in the pathogenesis of BD, supporting the mitochondrial dysfunction hypothesis of BD. Therefore, IDH3 in the citric acid cycle could potentially be a novel therapeutic target for BD.

Oral intake of Lactobacillus pentosus strain b240 (b240) has been shown to enhance the secretion of salivary secretory IgA in elderly adults. However, its clinical benefits remain to be determined. We tested the hypothesis that b240 exerts a protective effect against the common cold in elderly adults. The design of the present study was a randomised, double-blind, placebo-controlled trial (RCT) with parallel threegroup comparison. For this purpose, 300 eligible elderly adults were randomly allocated to one of three groups, namely a placebo, lowdose or high-dose b240 group. Participants in the low-dose and high-dose b240 groups were given tablets containing 2 £ 10 9 or 2 £ 10 10 cells, respectively, of heat-killed b240, while those in the placebo group were given tablets without b240. Each group consumed their respective tablets once daily for 20 weeks. The common cold was assessed on the basis of a diary. Change in quality of life was evaluated using the SF-36 w . Of the total participants, 280 completed the 20-week RCT. The accumulated incidence rate of the common cold was 47·3, 34·8 and 29·0 % for the placebo, low-dose b240 and high-dose b240 groups, respectively (P for trend¼ 0·012). Lower incidence rates were consistently observed throughout the experimental period in the b240 groups (log-rank test, P¼0·034). General health perception, as determined by the SF-36 w , dose-dependently increased in the b240 groups (P for trend¼ 0·016). In conclusion, oral intake of b240 significantly reduced the incidence rate of the common cold in elderly adults, indicating that b240 might be useful in improving resistance against infection through mucosal immunity.

BackgroundBipolar disorder (BD) is a severe and debilitating psychiatric disorder. However, the precise biological basis remains unknown, hampering the search for novel biomarkers. We performed a metabolomics analysis to discover novel peripheral biomarkers for BD.MethodsWe quantified serum levels of 116 metabolites in mood-stabilized male BD patients (n = 54) and age-matched male healthy controls (n = 39).ResultsAfter multivariate logistic regression, serum levels of pyruvate, N-acetylglutamic acid, α-ketoglutarate, and arginine were significantly higher in BD patients than in healthy controls. Conversely, serum levels of β-alanine, and serine were significantly lower in BD patients than in healthy controls. Chronic (4-weeks) administration of lithium or valproic acid to adult male rats did not alter serum levels of pyruvate, N-acetylglutamic acid, β-alanine, serine, or arginine, but lithium administration significantly increased serum levels of α-ketoglutarate.ConclusionsThe metabolomics analysis demonstrated altered serum levels of pyruvate, N-acetylglutamic acid, β-alanine, serine, and arginine in BD patients.General significanceThe present findings suggest that abnormalities in the citric acid cycle, urea cycle, and amino acid metabolism play a role in the pathogenesis of BD.

BackgroundImmunoglobulin A (IgA) secretion in saliva decreases with age and may be the cause of increased vulnerability of the elderly to respiratory infections. The effect of oral intake of lactic acid bacteria on salivary secretory IgA (SIgA) in the elderly has not been reported. The objective of this study was to demonstrate the acceleration of salivary SIgA secretion by oral intake of Lactobacillus pentosus strain b240 (b240) in the elderly.ResultsA total of 80 healthy elderly individuals were randomly allocated to either an intervention (i.e., b240) or a control (i.e., placebo) group. The elderly individuals in the b240 group were given a sterile water beverage (125 mL) containing heat-killed b240 (4 × 109 cells), while those in the placebo group were given only a sterile water beverage (125 mL); both groups received their respective beverages once daily for 12 weeks. Saliva was collected before initiation of the study and every 2 weeks thereafter. Saliva flow rate and SIgA concentration were determined, and the SIgA secretion rate was calculated. The mean salivary SIgA secretion rate in the b240 group steadily increased until week 4 (exhibiting a 20% elevation relative to that at week 0), and then remained stable until week 12. Changes in SIgA secretion rate over the intervention period were significantly greater in the b240 group than in the placebo group. The treatment groups exhibited no significant differences in adverse events.ConclusionsOral intake of L. pentosus strain b240 for 12 weeks significantly accelerated salivary SIgA secretion, thereby indicating its potential utility in the improvement of mucosal immunity and resistance against infection in the elderly.

White rice is a dominant grain-based food in Japan, but excess intake of polished rice may cause obesity. Barley is a grain-based food, similar to white rice, but it has the potential to control appetite and reduce energy intake. We investigated the effect of cooked white rice with high β-glucan barley on appetite and energy intake. The study was conducted as a randomized crossover design with twenty-one healthy Japanese women [mean ± standard deviation body mass index (BMI) 23.3 ± 0.7 kg/m2]. Subjects consumed a breakfast of cooked white rice with high β-glucan barley (BAR) or white rice (WR), followed by an ad libitum lunch and dinner. Energy intake was measured at the lunch and the dinner using plate waste. Subjects’ perception scores on hunger, fullness, satiety, and prospective food consumption were assessed using a visual analogue scale (VAS) before and after the breakfast, lunch and dinner. BAR significantly reduced the VAS scores of hunger and prospective food consumption, and increased fullness before lunch compared to WR (P = 0.032, 0.019 and 0.038, respectively). Energy intake at lunch and the cumulative energy intake (lunch + dinner) subsequent to BAR consumption were significantly lower than WR (P = 0.035 and 0.021, respectively). BAR was able to modulate appetite and reduce energy intake. The combination of white rice with high β-glucan barley could play a beneficial role in preventing and treating obesity and other obesity-related metabolic diseases.