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Probiotic-fermented milk is commonly used to maintain intestinal health. However, the effects of heat-treated fermented milk, which does not contain live microorganisms, on intestinal function are not yet fully understood. This study aimed to investigate whether heat-treated Lactobacillus helveticus CP790-fermented milk affects fecal microbiota and gut health as a “postbiotic”. A randomized, double-blind, placebo-controlled trial was conducted in healthy Japanese individuals aged 20–59 years with a tendency toward constipation. Participants consumed 100 mL of either the test beverage (n = 60) or placebo beverage (n = 60) for four weeks. The test beverages were prepared with heat-treated CP790-fermented milk, while the placebo beverages were prepared with nonfermented milk flavored with lactic acid. Fecal samples were analyzed using 16S rRNA gene sequencing. Constipation symptoms were assessed using defecation logs and the Patient Assessment of Constipation Symptoms (PAC-SYM) questionnaire. Mood state was also assessed using the Profile of Mood States 2 (POMS2) questionnaire to explore its potential as a “psychobiotic”. Desulfobacterota were significantly decreased by CP790-fermented milk intake. PICRUSt2 analysis predicted a decrease in the proportion of genes involved in the sulfate reduction pathway following the consumption of CP790-fermented milk. The CP790-fermented milk intervention significantly improved stool consistency and straining during defecation. These improvements were correlated with a decrease in Desulfobacterota. After the intervention, overall mood, expressed as total mood disturbance, and depression–dejection were significantly better in the CP790 group than in the placebo group. These results suggest that the intake of CP790-fermented milk could be effective in modulating gut microbiota and improving constipation symptoms and mood states.
Lactobacillus gasseri CP2305 (CP2305) is a paraprobiotic that exhibits beneficial effects on the intestinal function and microbiota, and increases resistance to psychological stress. The stress response mechanism mainly involves the hypothalamic–pituitary–adrenal axis, which is influenced by the gut–brain axis. Furthermore, the gut–brain axis also communicates bidirectionally with the intestinal microbiota. Additionally, the hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes share a common route that affects both mental and health aspects in women. This double-blind, placebo-controlled, parallel-group clinical trial aimed to analyze the influence of the intake of CP2305 on mild symptoms associated with menopause. Eighty women aged 40–60 years ingested CP2305 or placebo tablets for six consecutive menstrual cycles. Assessment was based on the observation of climacteric symptoms with two validated questionnaires—the Simplified Menopausal Index (SMI) and the Greene Climacteric Scale (GCS). The results showed that CP2305 provided significant relief in the SMI total score, SMI vasomotor score, SMI psychological score, GCS total score, GCS somatic score, and GCS vasomotor score compared to the placebo. The percentage of women with symptom relief for the SMI total score was 75.0%, with 30 of 40 women in the CP2305 group, and 55.0%, with 22 of 40 women in the placebo group (p = 0.0594). These findings provide new insights into the function of paraprobiotic CP2305 in relieving mild climacteric symptoms in women.
Lactobacillus gasseri CP2305 (CP2305) ameliorates stress-induced symptoms in young adults. In this study, we evaluated the effects of CP2305 on the premenstrual symptoms of healthy young women. Fifty-six women ingested CP2305 or placebo tablets over the course of six menstrual cycles. The CP2305 group reported fewer premenstrual symptoms than the placebo group, particularly psychological symptoms, such as depressed mood and anxiety. Whereas water retention-related physical symptom scores, such as those for breast tenderness and swelling, were reduced in the placebo group, they remained unchanged in the CP2305 group. In addition, significant differences were observed in the changes from baseline levels of salivary estradiol and progesterone in the luteal phase between the two groups, resulting in sustained elevated levels of reproductive hormones in the CP2305 group. Therefore, daily intake of CP2305 tablets might improve the premenstrual psychological symptoms of healthy young women in association with changes in reproductive hormone levels.
Despite the fact that gut microbiota is closely associated with obesity, few studies have focused on the influences of paraprobiotics as food ingredients on both obesity prevention and the gut microbial community. In this study, we evaluated the effects of fragmented Lactobacillus amylovorus CP1563 (CP1563) as a paraprobiotic for obesity prevention and investigated its effects on the gut microbial community in pre-obese subjects. One hundred sixty-nine healthy subjects with a body mass index from 25.0 to 29.9 kg/m2 ingested beverages with or without the fragmented CP1563 containing 10-hydroxyoctadecanoic acid (10-HOA) for 12 weeks. The changes in abdominal, total, visceral, and subcutaneous fatty areas were significantly lower in the CP1563-10-HOA group than in the placebo group at 12 weeks. Furthermore, 16S rRNA gene sequencing of fecal DNA revealed that the changes in the abundances of the genera Roseburia and Lachnospiraceae;g were significantly greater in the CP1563-10-HOA group than in the placebo group, and the changes in the abundances of the genus Collinsella was significantly smaller in the CP1563-10HOA group than in the placebo group. Our results showed that continuous ingestion of the fragmented CP1563 containing 10-HOA reduced abdominal body fat and affected the gut microbial community in pre-obese healthy subjects. Our findings may contribute to the understanding of the relationship between the anti-obesity effect of paraprobiotics and gut microbiota.
The effect of non-viable lactic acid bacteria on gastrointestinal physiology and dysfunction remains still unclear. Previous clinical trials have reported that Lactobacillus gasseri CP2305 (CP2305) exerts stress-relieving and anti-flatulent effects regardless of cell viability. In this study, we investigated the effect of viable and non-viable CP2305 cells on electrical field stimulation (EFS)-evoked increases in short-circuit current (Isc) using the Ussing chamber technique. In mucosal-submucosal preparations of rats, both viable and non-viable CP2305 cells significantly and acutely inhibited the EFS-evoked increases in Isc in the middle and distal colon and rectum but not in proximal colon. The inhibition of EFS-evoked Isc differed from strain to strain. Peripheral injection of corticotropin releasing factor (CRF) is known to mimic diarrhea symptoms in rats. Therefore, we examined the chronic effects of CP2305 cells on CRF-induced diarrhea in the rat model. Treatment with viable and non-viable CP2305 cells significantly improved CRF-induced diarrhea in the rat model. However, the treatment did not affect the fecal pellet output. These findings suggest that CP2305 has an important role in gastrointestinal physiology and dysfunction.
Short-term administration of Lactobacillus gasseri CP2305 improves stress-associated symptoms and clinical symptoms in healthy young adults and in patients with irritable bowel syndrome, respectively. We evaluated the efficacy and health benefits of the long-term use of a tablet containing heat-inactivated, washed Lactobacillus gasseri CP2305 (CP2305) in healthy young adults. Sixty Japanese medical students (41 men and 19 women) preparing for the national examination for medical practitioners ingested CP2305-containing or placebo tablets once daily for 24 weeks. Intake of the CP2305 tablet significantly reduced anxiety and sleep disturbance relative to placebo, as quantitated by the Spielberger State-Trait Anxiety Inventory and the Pittsburgh Sleep Quality Index. Single-channel sleep electroencephalograms show that CP2305 significantly shortened sleep latency and wake time after sleep onset and increased the delta power ratio in the first sleep cycle. CP2305 also significantly lowered salivary chromogranin A levels compared with placebo. Furthermore, 16S rRNA gene sequencing of participant feces demonstrated that CP2305 administration attenuated the stress-induced decline of Bifidobacterium spp. and the stress-induced elevation of Streptococcus spp. We conclude that the long-term use of CP2305-containing tablets may improve the mental state, sleep quality, and gut microbiota of healthy adults under stressful conditions.
The heat-inactivated, enteric-colonizing Lactobacillus gasseri CP2305 (CP2305) ameliorates psychological stress-related symptoms. In this study, we examined effects of CP2305 on top athletes experiencing physical and mental stresses. Forty-nine male university Ekiden (long distance relay race) runners daily took the CP2305-containing beverage for 12 weeks during training for and competing in All-Japan university championships. The CP2305 intake significantly facilitated recovery from fatigue and relieved anxiety and depressive mood, compared with placebo intake. The CP2305 intake significantly prevented the training-induced reduction of hemoglobin and facilitated exercise-induced increase in serum growth hormone levels. The CP2305 intake significantly increased the alpha- and beta-diversities of fecal microbiota, and the compositions of Bifidobacterium and Faecalibacterium. Gene expression profiling of peripheral blood leukocytes indicated that CP2305 prevented the stress-induced changes in the expression of genes related to mitochondrial functions. Our results suggest that daily intake of paraprobiotic CP2305 may be beneficial to athletes facing stressful situations.
AIMS: To confirm the stress-relieving effects of heat-inactivated, enteric-colonizing Lactobacillus gasseri CP2305 (paraprobiotic CP2305) in medical students taking a cadaver dissection course. METHODS AND RESULTS: Healthy students (21 males and 11 females) took paraprobiotic CP2305 daily for 5 weeks during a cadaver dissection course. The General Health Questionnaire and the Pittsburgh Sleep Quality Index were employed to assess stress-related somatic symptoms and sleep quality respectively. The aggravation of stress-associated somatic symptoms was observed in female students (P = 0·029). Sleep quality was improved in the paraprobiotic CP2305 group (P = 0·038), particularly in men (P = 0·004). Among men, paraprobiotic CP2305 shortened sleep latency (P = 0·035) and increased sleep duration (P = 0·048). Diarrhoea-like symptoms were also effectively controlled with CP2305 (P = 0·005) in men. Thus, we observed sex-related differences in the effects of paraprobiotic CP2305. In addition, CP2305 affected the growth of faecal Bacteroides vulgatus and Dorea longicatena, which are involved in intestinal inflammation. CONCLUSIONS: CP2305 is a potential paraprobiotic that regulates stress responses, and its beneficial effects may depend on specific cell component(s). SIGNIFICANCE AND IMPACT OF THE STUDY: This study characterizes the effects of a stress-relieving para-psychobiotic in humans.
Randomized trial demonstrates improved stress-related symptoms in medical students, suggesting a new therapeutic approach.
Increasing recognition of the interaction between the brain and gut microbiota has spurred interest in the efficacy of probiotics on stress-related behaviours. This study aimed to elucidate the effects of Lactobacillus gasseri CP2305 (CP2305) on mental and physical states in healthy male students enrolled in a cadaver dissection course in a double-blinded, placebo-controlled, crossover-designed trial. Daily administration of CP2305 for 4 weeks significantly improved anxiety, depressive mood and global sleep quality compared with placebo. CP2305 also suppressed salivary cortisol release. In the faecal microbiota, CP2305 suppressed the growth of Enterobacteriaceae. Differential changes in gene expression in peripheral blood leukocytes during the administration period were observed between the placebo and CP2305 groups. Eukaryotic initiation factor 2-related genes were down-regulated only in the placebo group. Thus, the ingestion of CP2305 may have beneficial effects on stress-associated behaviours.
Although probiotics have been proposed to benefit IBS patients, objective clinical evidence and elucidation of the functional mechanism remain insufficient. Our study demonstrated that CP2305 administration beneficially influences IBS patients in both subjective and objective evaluations, and gene expression profiling provided insights into the functional mechanism.
BACKGROUND: Previously, we showed that fragmented Lactobacillus amylovorus CP1563 (CP1563) functions as a dual agonist of peroxisome proliferator-activated receptor α and γ in vitro and in vivo. OBJECTIVE: Here, we examined the safety and effect of CP1563 ingestion on body fat in obese class I participants in a double-blinded, placebo-controlled, randomized clinical trial (RCT). DESIGN: In the RCT, 200 participants with a body mass index (BMI) of 25-30 kg/m(2) consumed test beverages with or without 200 mg of CP1563 daily for 12 weeks. In total, 197 subjects completed the study without any adverse effects. RESULTS: Body fat percentage, whole body fat, and visceral fat were significantly decreased in the test group compared with the placebo group (p<0.001, p<0.001, and p<0.001, respectively). Triglycerides, total cholesterol, LDL-cholesterol, and diastolic blood pressure showed significant reductions in the test group compared with the placebo group (p<0.001, p<0.001, p<0.001, and p<0.001, respectively). Additionally, significant differences in the changes in blood glucose, insulin, homeostasis model assessment-insulin resistance (HOMA-IR), and uric acid were observed between the two groups (p<0.001, p=0.004, p<0.001, and p<0.001, respectively). Improvements in anthropometric measurements and markers were observed in obese class I subjects in the test group. CONCLUSIONS: Daily consumption of beverages containing fragmented CP1563 for 12 weeks by obese class I subjects improved anthropometric measurements and markers related to lipid and glucose metabolism without any adverse effects. These results suggest that the consumption of foods containing fragmented CP1563 reduces body fat and prevents metabolic syndrome.
BACKGROUND: Lactobacillus gasseri CP2305 (CP2305) is a strain of Lactobacillus isolated from a stool sample from a healthy adult that showed beneficial effects on health as a paraprobiotic. In a previous study, we demonstrated that CP2305-fermented heat-treated milk modified gut functions more than artificially acidified sour milk. Thus, the regulatory activity of the former beverage was attributed to the inactivated CP2305 cells. OBJECTIVE: The aim of this study was to elucidate the contribution of non-viable paraprobiotic CP2305 cells to regulating human gut functions. We thus conducted a randomized, placebo-controlled, double-blinded parallel group trial. DESIGN: The trial included 118 healthy participants with relatively low or high stool frequencies. The test beverage was prepared by adding 1×10(10) washed, heat-treated, and dried CP2305 cells directly to the placebo beverage. The participants ingested a bottle of the assigned beverage daily for 3 weeks and answered daily questionnaires about defecation and quality of life. Fecal samples were collected and the fecal characteristics, microbial metabolite contents of the feces and composition of fecal microbiota were evaluated. RESULTS: The number of evacuations and the scores for fecal odors were significantly improved in the group that consumed the CP2305-containing beverage compared with those of the group that consumed the placebo (p=0.035 and p=0.040, respectively). Regarding the fecal contents of microbial metabolites, the level of fecal p-cresol was significantly decreased in the CP2305 group relative to that of the placebo group (p=0.013). The Bifidobacterium content of the intestinal microbiota was significantly increased in the CP2305 group relative to that of the placebo group (p<0.008), whereas the content of Clostridium cluster IV was significantly decreased (p<0.003). The parasympathetic nerve activity of the autonomic nervous system became dominant and the total power of autonomic activity was elevated in the CP2305 group (p=0.0401 and p=0.011, respectively). CONCLUSIONS: The continuous ingestion of heat-treated CP2305 cells clearly affected intestinal functionality. This is the first report of sterilized Lactobacillus cells having a significant impact on the environment and functions of the intestinal tract. The observed effects might be due, at least in part, to the brain-gut interaction.
Recent studies suggest that peroxisome proliferator-activated receptor (PPAR) activation ameliorates metabolic disorders, including dyslipidemia. To identify an effective PPAR agonist, we screened the in vitro PPARα/γ activation ability of organic solvent extracts from food-oriented bacterial strains belonging to 5 genera and 32 species, including lactic acid bacteria, and of these, Lactobacillus amylovorus CP1563 demonstrated the highest PPARα/γ agonist activity. We also found that physical fragmentation of the strain could substitute organic solvent extraction for the expression of CP1563 activity in vitro. For functional food manufacturing, we selected the fragmented CP1563 and conducted subsequent animal experiments. In an obese mouse model, we found that treatment with fragmented CP1563 for 12 weeks decreased the levels of low-density lipoprotein (LDL)-cholesterol and triglyceride in plasma, significantly decreased the atherosclerosis index, and increased the plasma high-density lipoprotein (HDL)-cholesterol level. Thus, we conclude that fragmented CP1563 may be a candidate for the prevention and treatment of dyslipidemia.
Commercialized products containing live lactic acid bacteria (LAB) are available for the purpose of modifying gastrointestinal function. In contrast, the impact of sterilized LAB, especially rod-shaped LAB, on intestinal regulation is not fully understood. Here, we examined the beneficial effects of sterilized Lactobacillus gasseri CP2305 (CP2305) as a “paraprobiotic” on gastrointestinal function in a double-blind, placebo-controlled trial. Subjects (n = 39) were healthy individuals who had a tendency toward constipation (n = 20) or frequent bowel movements (n = 19). They included both genders (15 males and 24 females) and were 20–70 years of age (mean 44.4 ± 12.4 years). Subjects with constipation or frequent bowel movements were randomly divided into two groups, and they ingested either an artificially acidified milk-based placebo beverage or a heat-inactivated CP2305 fermented milk (FM)-based beverage for 3 weeks. Subjects kept a stool diary to record the frequency of bowel movements, the feeling after defecation and the fecal conditions. Fresh fecal samples were collected to evaluate the fecal characteristics and to analyze the fecal metabolites and the composition of intestinal microbiota. The stool characteristics, including the subjective and objective Bristol stool scale scores, output, and color tone, were improved in the heat-inactivated CP2305 FM-based beverage group (CP2305 group), especially in subjects who had a tendency toward constipation. Analyses of the fecal samples showed that the concentrations of short-chain fatty acids (SCFAs) were significantly increased in the CP2305 group. The population of Clostridium cluster IV was significantly increased in the CP2305 group. The heat-inactivated CP2305 FM had a beneficial effect on the regulation of intestinal function. Improvement was observed chiefly in subjects that had a tendency toward constipation. These results suggest that heat-inactivated CP2305 functions as a “paraprobiotic”.
This paper proposes a joint control method for tendon-driven mechanisms (TDMs) with branching tendons, in which multiple tendons are connected at a point, and which are often found in musculoskeletal systems. TDMs usually require the same number of tendons as actuators, which are one of the heaviest components in a robotic system. The utilization of branching tendons is useful for reducing the number of actuators needed when making lightweight robotic mechanisms, such as prosthetic hands. However, the under-actuation of branching tendons makes it difficult to accurately control the joint motion of TDMs. Therefore, TDMs with branching tendons have been used only for simple adaptive grasping mechanisms. In this paper, we derive the tendon kinematics of TDMs with branching tendons and design a joint PD controller for the mechanisms. We demonstrate the stability of the control system using Lyapunov's direct method. We show that the bias force setting, which does not appear in conventional TDMs, is important in the realization of accurate control in TDMs with branching tendons. Simulations were performed to evaluate the proposed method.
BACKGROUND: Few studies have investigated the complementary effects of long-term oral administration of Lactobacillus acidophilus on traditional medical therapy in the treatment of patients with atopic dermatitis (AD). METHODS: The Atopic Dermatitis Area and Severity Index was used to evaluate AD severity. Symptom severity was assessed using the symptom score. The effect of medical therapy was evaluated by adding the medication score, calculated as the sum of each product of the amount of steroid ointment used for therapy and its designated strength graded on a 4-point scale, to the symptom score. The complementary effect of long-term oral administration of L. acidophilus strain L-92 (L-92) as a probiotic or biogenic strain in patients with AD was evaluated using the symptom-medication score, which was calculated as the sum of the symptom score and medication score. Both a preliminary casuistic study and a double-blinded, placebo-controlled study were performed to evaluate the effects of L-92 on the symptoms of AD in children. RESULTS: Orally administered L-92 significantly ameliorated the symptoms of AD in Japanese children. L-92 also affected the serum concentrations of thymus and activation-regulated chemokine in a time-dependent manner. CONCLUSIONS: The results of the preliminary trial and the double-blinded, placebo-controlled study revealed a complementary effect of oral L-92 on the standard medical therapy (topical application of a steroid ointment) in patients with AD that was mediated, at least in part, by alterations in the Th1/Th2 balance.
Studies in animals have suggested that lactic acid bacteria alleviate allergic diseases, however, little information is available on their clinical effect on allergy in humans. Thus, we examined the efficacy of orally administered Lactobacillus acidophilus strain L-92 (L-92) on perennial allergic rhinitis. In a randomized, double-blind, placebo-controlled clinical trial, 49 patients with perennial allergic rhinitis were randomized to receive either 100 mL of heat-treated fermented milk containing L-92 (n = 25) or acidified milk without lactic acid bacteria (placebo; n = 24) for 8 wk. The severity of symptoms was evaluated based on the changes in the scores of clinical symptoms. Oral administration of milk fermented with L-92 resulted in a statistically significant improvement of nasal symptom-medication scores. Ocular symptom-medication scores of patients in the L-92 intervention group tended to improve compared with those in the placebo group. In addition, clear decreases of the scores of swelling and color of the nasal mucosa were observed in the L-92 intervention group at 6 and 8 wk after the start of ingestion of fermented milk. There were no significant differences in serum antihouse dust mite immunoglobulin E levels nor in T helper type 1/T helper type 2 ratio between the 2 groups. These results suggest that oral administration of L-92 can alleviate the symptoms of perennial allergic rhinitis, however, statistically significant changes were not shown in blood parameters.
A placebo-controlled, single-blind study was conducted to evaluate the effects of Lactobacillus acidophilus strain L-92 (L-92) on the symptoms of Japanese cedar-pollen allergy. This study was carried out during the 2002 and 2003 seasons of Japanese cedar pollination. Twenty-three in-house volunteers were asked to drink 100 ml of heat-treated milk fermented with L-92 containing 5 x 10(10) of the bacteria, twice a day, for 6 consecutive weeks. A similar study was carried out during the 2003 season for 10 weeks, but the daily dose of bacteria was 2 x 10(10). A significant improvement of the ocular symptom-medication score (SMS) was observed in 2002 and of the score of distress of life in 2003. These data show that a daily oral intake of not less than 2 x 10(10) heat-treated L-92 cells improved the symptoms of Japanese cedar pollinosis, thereby contributing to reduce the dose of concomitant medications. However, no blood parameter was significantly affected in these trials.