Stress-induced abdominal dysfunction is an attractive target for probiotics. To investigate the effects of the probiotic Lactobacillus casei strain Shirota on abdominal dysfunction, a double-blind, placebo-controlled trial was conducted with healthy medical students undertaking an authorized nationwide examination for academic advancement. For 8 weeks, until the day before the examination, 23 and 24 subjects consumed an L. casei strain Shirota-fermented milk and a placebo milk daily, respectively. In addition to assessments of abdominal symptoms, psychophysical state, and salivary stress markers, gene expression changes in peripheral blood leukocytes and composition of the gut microbiota were analyzed using DNA microarray analysis and 16S rRNA gene amplicon sequence analysis, respectively, before and after the intervention. Stress-induced increases in a visual analog scale measuring feelings of stress, the total score of abdominal dysfunction, and the number of genes with changes in expression of more than 2-fold in leukocytes were significantly suppressed in the L. casei strain Shirota group compared with those in the placebo group. A significant increase in salivary cortisol levels before the examination was observed only in the placebo group. The administration of L. casei strain Shirota, but not placebo, significantly reduced gastrointestinal symptoms. Moreover, 16S rRNA gene amplicon sequencing demonstrated that the L. casei strain Shirota group had significantly higher numbers of species, a marker of the alpha-diversity index, in their gut microbiota and a significantly lower percentage of Bacteroidaceae than the placebo group. Our findings indicate that the daily consumption of probiotics, such as L. casei strain Shirota, preserves the diversity of the gut microbiota and may relieve stress-associated responses of abdominal dysfunction in healthy subjects exposed to stressful situations. IMPORTANCEA novel clinical trial was conducted with healthy medical students under examination stress conditions. It was demonstrated that the daily consumption of lactic acid bacteria provided health benefits to prevent the onset of stress-associated abdominal symptoms and a good change of gut microbiota in healthy medical students. The gut microbiota, a large, diverse, and dynamic ecosystem that generates cross talk between the gut and host, can communicate with the host by modulating the gut-brain axis, which is a bidirectional neurohumoral communication system between the gut and brain. That is, signals from the brain modify the motor, sensory, and secretory modalities of the gastrointestinal tract; in turn, signals from the gut can affect emotional behavior and stress and pain modulation systems through neural, endocrine, and immune pathways (1-3). Thus, the gut-brain axis has now been expanded to the microbiota-gut-brain axis (3).It is particularly interesting to consider the possibility that probiotics (4), which are live microorganisms, can affect emotion in health and disease by modulating the microbiota-g...

This pilot study investigated the effects of the probiotic Lactobacillus casei strain Shirota (LcS) on psychological, physiological, and physical stress responses in medical students undertaking an authorised nationwide examination for promotion. In a double-blind, placebo-controlled trial, 24 and 23 healthy medical students consumed a fermented milk containing LcS and a placebo milk, respectively, once a day for 8 weeks until the day before the examination. Psychophysical state, salivary cortisol, faecal serotonin, and plasma L-tryptophan were analysed on 5 different sampling days (8 weeks before, 2 weeks before, 1 day before, immediately after, and 2 weeks after the examination). Physical symptoms were also recorded in a diary by subjects during the intervention period for 8 weeks. In association with a significant elevation of anxiety at 1 day before the examination, salivary cortisol and plasma L-tryptophan levels were significantly increased in only the placebo group (P<0.05). Two weeks after the examination, the LcS group had significantly higher faecal serotonin levels (P<0.05) than the placebo group. Moreover, the rate of subjects experiencing common abdominal and cold symptoms and total number of days experiencing these physical symptoms per subject were significantly lower in the LcS group than in the placebo group during the pre-examination period at 5-6 weeks (each P<0.05) and 7-8 weeks (each P<0.01) during the intervention period. Our results suggest that the daily consumption of fermented milk containing LcS may exert beneficial effects preventing the onset of physical symptoms in healthy subjects exposed to stressful situations.

Soybean-derived phosphatidylserine (Soy-PS) is a phosphatidylserine made from soybean lecithin by enzymatic reaction with L-serine. A double-blind, randomized controlled study was conducted to investigate the effects of Soy-PS on the cognitive functions of the elderly Japanese subjects with memory complaints. Seventy-eight elderly people with mild cognitive impairment (50–69 years old) were randomly allocated to take Soy-PS (100 mg, 300 mg/day) or placebo for 6 months. As a result, there was no difference in blood markers and vital signs during Soy-PS treatment and any side effect caused by Soy-PS treatment was not observed. Neuropsychological test scores were similarly increased in all groups including placebo group. However, in the subjects with relatively low score at baseline, the memory scores in PS treated groups were significantly increased against the baseline, while those of placebo group remained unchanged. And the memory improvements in Soy-PS-treated groups were mostly attributed to the increase in delayed verbal recall, a memory ability attenuated in the earliest stage of dementia. In conclusion, Soy-PS used in this study is considered as safety food ingredient and 6 months of Soy-PS supplementation could improve the memory functions of the elderly with memory complaints.

Aims/Introduction: Previously, it was observed that long-term ingestion of a probiotic strain Lactobacillus casei Shirota (LcS) ameliorates insulin resistance and glucose intolerance in rats fed a high-fat diet. In the present study, we examined its possible role in the autonomic nervous system during LcS-induced modulations in glucose and lipid metabolism or cardiovascular functions. Materials and Methods: The present study examined the effects of intragastric (IG) LcS injection on autonomic nerve tones in anesthetized rats by electrophysiological method. Results: We found that an IG injection of LcS suppressed neural activity of sympathetic nerves supplying the white adipose tissue of urethane-anesthetized rats in a dose-dependent manner, whereas sympathetic nerve outflow to brown adipose tissue was not affected by the IG LcS injection. Furthermore, the IG LcS injection reduced efferent sympathetic nerve outflow to the adrenal gland and liver, but did not alter gastric vagal nerve activity, renal sympathetic nerve activity, as well as mean arterial pressure. To test the involvement of afferent vagal nerves and the abdominal organs, we examined the adrenal sympathetic response to an LcS injection in rats with ablated afferent vagal nerves, and found that the adrenal sympathetic nerve response to LcS was inhibited in vagotomized rats. In addition, we found that oral ingestion of LcS attenuated the hyperglycemic response to glucose loading and blood glycerol levels in conscious rats. Conclusions: Our data suggest that LcS might affect tissue-specific autonomic nerves through the afferent vagal nerve pathway to modulate glucose and lipid metabolism.

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