We aimed to evaluate the efficacy and safety of a spore-forming probiotic blend containing Clostridium butyricum IDCC 1301, Weizmannia coagulans IDCC 1201, and Bacillus subtilis IDCC 1101 for improving bowel function and well-being in adults with functional constipation (FC). In a randomized, double-blind, placebo-controlled trial, 78 adults with FC (Rome IV criteria) received either probiotic blend (n = 40) or placebo (n = 38) daily for 4 weeks. Primary outcomes were changes in weekly spontaneous bowel movements (WSBM) and stool form. Secondary outcomes included physical functioning scores from the 36-Item Short Form Health Survey. The probiotic blend group showed significant improvements in irritant bowel movements (p = 0.0458), incomplete evacuation (p = 0.0374), and abdominal pain before defecation (p = 0.0090). Stool consistency shifted toward normal types (Bristol types 3-4, p = 0.0176). Physical functioning improved only in the probiotic blend group (p = 0.0300). Probiotic blend effectively alleviated symptoms of FC and improved physical well-being. Trial registration: Clinical Research Information Service (CRIS), KCT0010085.
Probiotics have been extensively investigated as potential food supplements for human health benefits. Metabolites derived from probiotics are the primary factors that characterize each strain's functionality and play a crucial role in shaping their effects on the human host. In this study, we characterized the secreted metabolite profiles of sixteen commercial probiotic strains and identified Streptococcus thermophilus IDCC 2201 as a major folate producer. To investigate its effects on gut microbiota, S. thermophilus was co-cultured with individual species comprising the human gut microbial community. Specific bacteria, such as Bacteroides thetaiotaomicron, Veilonella parvula, and Ruminococcus faecis, grew dependently on both folate and S. thermophilus. These bacteria exhibited greater growth in the presence of folate than in its absence, with 2.8-, 3.6-, and 3.9-fold increases, respectively. Additionally, they showed relatively higher growth when co-cultured with S. thermophilus compared to other bacterial species, with 1.2-, 1.3-, and 1.9-fold increases, respectively. Our results indicate that the interaction between probiotics and the human gut microbiota can influence changes in ecological balance through nutrient cross-feeding, and understanding this interaction can be applied to precision probiotic therapies.
Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths. The gut microbiota is known to be closely associated with CRC development, interacting with each other and influencing host metabolism. Probiotic interventions have been applied to prevent CRC; however, the mechanisms underlying their effects on CRC remain unclear. In this study, we evaluated the effects of the probiotic strain Streptococcus thermophilus IDCC 2201 on its interactions with gut commensal bacteria and CRC cell viability. S. thermophilus inhibited the growth of most bacterial species comprising the human gut microbiota, with the exception of Bacteroides dorei. Further studies identified several factors produced by S. thermophilus, such as xylan-degrading enzymes and B vitamins, which promoted B. dorei growth through nutrient cross-feeding. During co-culture of S. thermophilus with individual gut commensals, bioactive compounds such as folate were significantly produced, further inhibiting CRC cell viability along with the culture supernatant of S. thermophilus. These findings suggest that S. thermophilus IDCC 2201 may serve as a potential prophylactic agent for colon cancer, with its effects mediated through interactions with gut commensal bacteria.
Obesity is a common metabolic disease characterized by abnormal fat accumulation. It contributes to health issues, such as type 2 diabetes, cardiovascular disease, and dyslipidemia, necessitating continuous management through diet and physical activity. Probiotics, particularly Bifidobacterium lactis IDCC 4301 (B. lactis Fit (TM)), have shown promise in positively regulating the gut microbiota. Therefore, this study aimed to evaluate the anti-obesity effect of B. lactis IDCC 4301 (B. lactis Fit (TM)) in obese women. A randomized, double-blind, placebo-controlled, parallel-arm study was performed in 99 volunteers with a body mass index (BMI) of 25-30 kg m(-2). The participants were randomly assigned to probiotics (n = 49, >5.0 x 10(9) CFU day(-1)) or placebo (n = 50) groups. Body fat, lipid profiles, and adipokine levels were assessed at baseline and at 12 weeks. After 12 weeks, changes in total fat (placebo -0.16 +/- 0.83 kg; probiotics -0.45 +/- 0.83 kg; p = 0.0407), trunk fat (placebo -0.03 +/- 0.50 kg; probiotics -0.22 +/- 0.51 kg; p = 0.0200), and serum triglyceride concentration (placebo 13 +/- 60 mg dL(-1); probiotics -15 +/- 62 mg dL(-1); p = 0.0088) were significantly different between the groups. The difference in total fat mass change between groups among postmenopausal women was greater than that of all women. A significant positive correlation was found between the change in total fat mass and log leptin/adiponectin ratio (R = 0.371, p = 0.0112) in the probiotics group. In addition, BMI (26.6 +/- 1.9 kg m(-2) to 26.4 +/- 2.0 kg m(-2), p = 0.0009) and leg fat (42 +/- 5% to 41 +/- 5%, p = 0.0006) significantly decreased in the probiotics group after 12 weeks, but there was no difference in the placebo group. In conclusion, B. lactis IDCC 4301 (B. lactis Fit (TM)) may be associated with body fat loss through changes in metabolic health parameters, such as serum triglyceride and adipokine levels. The clinical trial registry number is KCT0007425 (https://cris.nih.go.kr).
In contemporary society, the increasing number of pet-owning households has significantly heightened interest in companion animal health, expanding the probiotics market aimed at enhancing pet well-being. Consequently, research into the gut microbiota of companion animals has gained momentum, however, ethical and societal challenges associated with experiments on intelligent and pain-sensitive animals necessitate alternative research methodologies to reduce reliance on live animal testing. To address this need, the Fermenter for Intestinal Microbiota Model (FIMM) is being investigated as an in vitro tool designed to replicate gastrointestinal conditions of living animals, offering a means to study gut microbiota while minimizing animal experimentation. The FIMM system explored interactions between intestinal microbiota and probiotics within a simulated gut environment. Two strains of commercial probiotic bacteria, Enterococcus faecium IDCC 2102 and Bifidobacterium lactis IDCC 4301, along with a newly isolated strain from domestic dogs, Lactobacillus acidophilus SLAM AK001, were introduced into the FIMM system with gut microbiota from a beagle model. Findings highlight the system's capacity to mirror and modulate the gut environment, evidenced by an increase in beneficial bacteria like Lactobacillus and Faecalibacterium and a decrease in the pathogen Clostridium. The study also verified the system's ability to facilitate accurate interactions between probiotics and commensal bacteria, demonstrated by the production of short-chain fatty acids and bacterial metabolites, including amino acids and gamma-aminobutyric acid precursors. Thus, the results advocate for FIMM as an in vitro system that authentically simulates the intestinal environment, presenting a viable alternative for examining gut microbiota and metabolites in companion animals.
Obesity and overweight among companion animals are significant concerns, paralleling the issues observed in human populations. Recent research has highlighted the potential benefits of various probiotics in addressing weight-related changes, obesity, and associated pathologies. In this study, we delved into the beneficial probiotic mechanisms in high-fat-induced obese canines, revealing that Enterococcus faecium IDCC 2102 (IDCC 2102) and Bifidobacterium lactis IDCC 4301 (IDCC 4301) have the capacity to mitigate the increase in body weight and lipid accumulation in obese canines subjected to a high-fat diet and hyperlipidemic Caenorhabditis elegans (C. elegans) strain VS29. Both IDCC 2102 and IDCC 4301 demonstrated the ability to reduce systemic inflammation and hormonal disruptions induced by obesity. Notably, these probiotics induced modifications in the microbiota by promoting lactic acid bacteria, including Lactobacillaceae, Ruminococcaceae, and S24-7, with concomitant activation of pyruvate metabolism. IDCC 4301, through the generation of bacterial short-chain fatty acids and carboxylic acids, facilitated glycolysis and contributed to ATP synthesis. Meanwhile, IDCC 2102 produced bacterial metabolites such as acetic acid and butyric acid, exhibiting a particular ability to stimulate dopamine synthesis in a canine model. This stimulation led to the restoration of eating behavior and improvements in glucose and insulin tolerance. In summary, we propose novel probiotics for the treatment of obese animals based on the modifications induced by IDCC 2102 and IDCC 4301. These probiotics enhanced systemic energy utilization in response to high caloric intake, thereby preventing lipid accumulation and restoring stability to the fecal microbiota. Consequently, this intervention resulted in a reduction in systemic inflammation caused by the high-fat diet.IMPORTANCEProbiotic supplementation affected commensal bacterial proliferation, and administering probiotics increased glycolysis and activated pyruvate metabolism in the body, which is related to propanate metabolism as a result of pyruvate metabolism activation boosting bacterial fatty acid production via dopamine and carboxylic acid specialized pathways, hence contributing to increased ATP synthesis and energy metabolism activity.
Lactic acid bacteria (LAB) are probiotic microorganisms widely used for their health benefits in the food industry. However, recent concerns regarding their safety have highlighted the need for comprehensive safety assessments. In this study, we aimed to evaluate the safety of L. bulgaricus IDCC 3601, isolated from homemade plain yogurt, via genomic, phenotypic, and toxicity-based analyses. L. bulgaricus IDCC 3601 possessed a single circular chromosome of 1,865,001 bp, with a GC content of 49.72%, and 1910 predicted coding sequences. No virulence or antibiotic resistance genes were detected. Although L. bulgaricus IDCC 3601 exhibited antibiotic resistance to gentamicin and kanamycin, this resistance is an intrinsic feature of this species. L. bulgaricus IDCC 3601 did not produce biogenic amines and did not exhibit hemolytic activity. Phenotypic analysis of enzyme activity and carbohydrate fermentation profiles revealed the metabolic features of L. bulgaricus IDCC 3601. Moreover, no deaths or abnormalities were observed in single-dose oral toxicity tests, suggesting that L. bulgaricus IDCC 3601 has no adverse effect on human health. Finally, L. bulgaricus IDCC 3601 inhibited the growth of potential carbapenem-resistant Enterobacteriaceae. Therefore, our results suggest that L. bulgaricus IDCC 3601 is a safe probiotic strain for human consumption.
Irritable bowel syndrome is a chronic disorder affecting the gastrointestinal tract, negatively impacting patients’ quality of life. Here, we aimed to evaluate the effects of Lacticaseibacillus rhamnosus IDCC 3201 (RH 3201) on irritable bowel syndrome with constipation (IBS-C). In this randomised, double-blind, placebo-controlled trial, a total of 30 subjects with IBS-C were randomly assigned (1:1) to receive 8 weeks of probiotics administration or placebo. Concerning bowel activities, both irritant bowel movements and discomfort caused by constipation showed significant improvement with RH 3201 at 8 weeks. Symptoms including severity of abdominal bloating, frequency of abdominal bloating, and satisfaction of bowel habits based on the irritable bowel syndrome-severity scoring system also ameliorated in the probiotic group. Analysis of the fecal microbiome revealed that the abundance of Bacteroides cellulosilyticus and Akkermansia muciniphila was higher during the period of RH 3201 administration compared to the placebo. Untargeted metabolome analysis further suggested a correlation between specific metabolites, such as N-acetylornithine, xanthine, and 3-phenylpropionic acid, and the improvement of clinical symptoms. These results indicate that RH 3201 was effective in ameliorating IBS-C, potentially by enriching beneficial microbes and associated metabolites in the gut environment.
Ceramides are essential lipids in stratum corneum for skin permeability barrier function in that they retain the skin moisture and protect from the invasion of foreign pathogens. Previously, we demonstrated that ferment lysates of Lacticaseibacillus rhamnosus IDCC 3201 enhanced ceramide production in human epidermal keratinocytes. Furthermore, for comprehensive knowledge of this effect, in vitro experiments and multi‐omics analysis were conducted to explore the underlying mechanisms.
A randomized, double-blind, placebo-controlled trial was designed to assess the efficacy of the parabiotic Bifidobacterium breve IDCC 4401, named BBR 4401, for lowering cholesterol levels. The 66 subjects (per protocol set, n = 60) with low-density lipoprotein-cholesterol (LDL-C) levels between 100 mg/dL and 150 mg/dL were enrolled after a 4-week run-in period (e.g., no probiotics, low cholesterol diet and no food affecting lipid profiles). The two groups were prescribed 1 × 1010 (low-dose) and 1 × 1011 CFU (high-dose), whereas the placebo group was prescribed 97% (w/w) of maltodextrin for 4 weeks. The compliance rates exceeded 97% in the subjects who completed the study. Comparison of the mean changes from baseline between the placebo group and test groups after the 12 weeks of BBR 4401 consumption showed a statistically significant reduction in LDL-C (up to −10.8%, p-value = 0.008) and apolipoproteinB (up to −8.1%, p-value = 0.008). Meanwhile, there were no clinically significant changes in vital signs, clinical pathology tests or electrocardiograms and no significant adverse events were reported during the study period. Concerning bowel habits, the consumption of BBR 4401 alleviated defecation strain, distension and watery feces in the high-dose group. Thus, BBR 4401 may be a safe and functional food for adults with moderate hypercholesterolemia.
The use of dietary protein products has increased with interests in health promotion, and demand for sports supplements. Among various protein sources, milk protein is one of the most widely employed, given its economic and nutritional advantages. However, recent studies have revealed that milk protein undergoes fecal excretion without complete hydrolysis in the intestines. To increase protein digestibility, heating and drying were implemented; however, these methods reduce protein quality by causing denaturation, aggregation, and chemical modification of amino acids. In the present study, we observed that Lacticaseibacillus rhamnosus IDCC 3201 actively secretes proteases that hydrolyze milk proteins. Furthermore, we showed that co-administration of milk proteins and L. rhamnosus IDCC 3201 increased the digestibility and plasma concentrations of amino acids in a high-protein diet mouse model. Thus, food supplementation of L. rhamnosus IDCC 3201 can be an alternative strategy to increase the digestibility of proteins.
Melanogenesis is responsible for skin pigmentation and the enzymatic browning of foods. Tyrosinases play a major role in melanin synthesis, and many attempts have been made to identify new natural tyrosinase inhibitors, but few have sought to do in microbes. Postbiotics are bioactive compounds produced by the metabolism of probiotics and have been reported to be safe and effective. In this study, we evaluated the tyrosinase inhibitory effects of culture supernatants of probiotics and discovered novel bacterial metabolites that can be used as a potent tyrosinase inhibitor based on metabolomics. Cultures of Bifidobacterium bifidum IDCC 4201 and Lactiplantibacillus plantarum IDCC 3501 showed effective anti-tyrosinase, reduced melanin synthesis, and altered protein expression associated with the melanogenesis pathway. Comparative metabolomics analyses conducted by GC-MS identified metabolites commonly produced by B. bifidum and L. plantarum. Of eight selected metabolites, phenyllactic acid exhibited significant tyrosinase-inhibitory activity. Our findings suggest that applications of probiotic culture supernatants containing high amounts of phenyllactic acid have potential use as anti-melanogenesis agents in food and medicines.
A combined usage of animal and plant proteins-mixture could aid to solve environmental and social problems arising from the use of animal protein alone, while also improving the taste and texture of plant protein. Protein mixtures could be a better protein source due to the high availability of amino acids in the body compared with single proteins. Consuming proteins with probiotics can provide more beneficial health effects by helping to hydrolyze protein and absorb amino acids in the body. In this study, coadministration of an animal and plant protein mixture with a high concentration of probiotics was investigated to increase protein digestibility and amino acids absorbability in a mice model. Lactiplantibacillus plantarum IDCC 3501, which has the maximum ability to hydrolyze a protein mixture, composed of soybean protein and milk protein, was selected, and the changes in mice (C57BL/6J, male, six weeks) were investigated after the coadministration of protein mixture and 5 × 108 or 5 × 109 CFU/mL of L. plantarum for eight weeks. Normal diet, high-protein diet (HPD), and HPD supplementing L. plantarum were separately administered to mice. Food and water consumption of the mice did not differ depending on diet type. Measurements of the serum concentrations of amino acids showed that the absorption of aspartate, glutamate, isoleucine, leucine, valine, and lysine increased when high concentrations of protein and probiotics were administered. Thus, high L. plantarum concentrations could be a protein diet supplementation to improve health by promoting the absorption of amino acids.
It is important to predict the neurological prognoses of in-hospital cardiac arrest (IHCA) patients immediately after recovery of spontaneous circulation (ROSC) to make further critical management. The aim of this study was to confirm the usefulness of the Cardiac Arrest Survival Post-Resuscitation In-hospital (CASPRI) and Good Outcome Following Attempted Resuscitation (GO-FAR) scores for predicting the IHCA immediately after the ROSC. This is a retrospective analysis of patient data from a tertiary general hospital located in South Korea. A total of 488 adult patients who had IHCA and achieved sustained ROSC from September 2016 to August 2021 were analyzed to compare effectiveness of the CASPRI and GO-FAR scores related to neurologic prognosis. The primary outcome was Cerebral Performance Category (CPC) score at discharge, defined as a CPC score of 1 or 2. The secondary outcomes were survival-to-discharge and normal neurological status or minimal neurological damage at discharge. Of the 488 included patients, 85 (20.8%) were discharged with good prognoses (CPC score of 1 or 2). The area under the receiver operating characteristic curve of CASPRI score for the prediction of a good neurological outcome was 0.75 (95% CI 0.69-0.81), whereas that of GO-FAR score was 0.67 (95% CI 0.60-0.73). The results of this study show that these scoring systems can be used for timely and satisfactory prediction of the neurological prognoses of IHCA patients after ROSC.
ScopeChronic hypernutrition promotes lipid accumulation in the body and excessive lipid accumulation leads to obesity. An increase in the number and size of adipocytes, a characteristic of obesity is closely associated with adipose dysfunction. Recent in vitro and in vivo studies have shown that probiotics may prevent this dysfunction by regulating lipid metabolism. However, the mechanisms of action of probiotics in obesity are not fully understood and their usage for treating obesity remains limited. Methods and resultsBifidobacterium lactis IDCC 4301 is selected for its anti-obesity potential after evaluating inhibitory activity of pancreatic lipase and cholesterol reducing activity. Next, this study investigates the roles of B. lactis IDCC 4301 on lipid metabolism in 3T3-L1 preadipocytes and high-fat diet (HFD)-fed mice. B. lactis IDCC 4301 inhibits cell differentiation and lipid accumulation by suppressing the expression of adipogenic enzymes in 3T3-L1 cells. Moreover, the administration of B. lactis IDCC 4301 decreases body and adipose tissue weight, improves serum lipid levels, and downregulates adipogenic mRNA expression in HFD-fed mice. Additionally, metabolomic analysis suggests that 2-ketobutyrate should be a possible target compound against obesity. ConclusionsB. lactis IDCC 4301 may be used as an alternative treatment for obesity.