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Gut Microbes 2023Dietary fibers/probiotics may relieve constipation via optimizing gut microbiome, yet with limited trial-based evidences. We aimed to evaluate the effects of formulas... (Randomized Controlled Trial)
Randomized Controlled Trial
Dietary fibers/probiotics may relieve constipation via optimizing gut microbiome, yet with limited trial-based evidences. We aimed to evaluate the effects of formulas with dietary fibers or probiotics on functional constipation symptoms, and to identify modulations of gut microbiota of relevance. We conducted a 4-week double-blinded randomized placebo-controlled trial in 250 adults with functional constipation. Intervention: A: polydextrose; B: psyllium husk; C: wheat bran + psyllium husk; D: subsp. HN019 + HN001; Placebo: maltodextrin. Oligosaccharides were also included in group A to D. 16S rRNA sequencing was used to assess the gut microbiota at weeks 0, 2, and 4. A total of 242 participants completed the study. No time-by-group effect was observed for bowel movement frequency (BMF), Bristol stool scale score (BSS), and degree of defecation straining (DDS), while BSS showed mean increases of 0.95-1.05 in group A to D (all < 0.05), but not significantly changed in placebo ( = 0.170), and 4-week change of BSS showed similarly superior effects of the interventions as compared placebo. Group D showed a marginal reduction in plasma 5-hydroxytryptamine. Group A resulted in a higher abundance than placebo at week 2 and 4. Fourteen genera showed intervention-specific increasing or decreasing trends continuously, among which showed increasing trends in groups B and C, associated with BMF increase. Random forest models identified specific baseline microbial genera panels predicting intervention responders. In conclusion, we found that the dietary fibers or probiotics may relieve hard stool, with intervention-specific changes in gut microbiota relevant to constipation relief. Baseline gut microbiota may predispose the intervention responsiveness. number, NCT04667884.
Topics: Adult; Humans; Dietary Fiber; Gastrointestinal Microbiome; Psyllium; RNA, Ribosomal, 16S; Constipation; Probiotics; Bifidobacterium animalis; Gastrointestinal Diseases; Double-Blind Method
PubMed: 37078654
DOI: 10.1080/19490976.2023.2197837 -
Frontiers in Nutrition 2021Optimal gut motility is central to bowel function and gut health. The link between the gut dysmotility related disorders and dysfunctional-intestinal barriers has led to... (Review)
Review
Optimal gut motility is central to bowel function and gut health. The link between the gut dysmotility related disorders and dysfunctional-intestinal barriers has led to a hypothesis that certain probiotics could help in normalizing gut motility and maintain gut health. This review investigates the roles of subsp. HN019 ( HN019™) on gut health, and its mechanisms of action in various pre-clinical and clinical studies. Research supports the hypothesis that HN019™ has a beneficial role in maintaining intestinal barrier function during gastrointestinal infections by competing and excluding potential pathogens via different mechanisms; maintaining normal tight junction function and regulating host immune defense toward pathogens in both and human studies. This has been observed to lead to reduced incidence of diarrhea. Interestingly, HN019™ also supports normal physiological function in immunosenescent elderly and competes and excludes potential pathogens. Furthermore, HN019™ reduced intestinal transit time and increased bowel movement frequency in functional constipation, potentially by modulating gut-brain-microbiota axis, mainly via serotonin signaling pathway, through short chain fatty acids derived from microbial fermentation. HN019™ is thus a probiotic that can contribute to relieving gut dysmotility related disorders.
PubMed: 34970580
DOI: 10.3389/fnut.2021.790561 -
Nutrients Mar 2020The growing worldwide epidemic of obesity and associated metabolic health comorbidities has resulted in an urgent need for safe and efficient nutritional solutions. The... (Review)
Review
The growing worldwide epidemic of obesity and associated metabolic health comorbidities has resulted in an urgent need for safe and efficient nutritional solutions. The research linking obesity with gut microbiota dysbiosis has led to a hypothesis that certain bacterial strains could serve as probiotics helping in weight management and metabolic health. In the search for such strains, the effect of subsp. 420 (B420) on gut microbiota and metabolic health, and the mechanisms of actions, has been investigated in a variety of in vitro, pre-clinical, and clinical studies. In this review, we aim to highlight the research on B420 related to obesity, metabolic health, and the microbiota. Current research supports the hypothesis that gut dysbiosis leads to an imbalance in the inflammatory processes and loss of epithelial integrity. Bacterial components, like endotoxins, that leak out of the gut can invoke low-grade, chronic, and systemic inflammation. This imbalanced state is often referred to as metabolic endotoxemia. Scientific evidence indicates that B420 can slow down many of these detrimental processes via multiple signaling pathways, as supported by mechanistic in vitro and in vivo studies. We discuss the connection of these mechanisms to clinical evidence on the effect of B420 in controlling weight gain in overweight and obese subjects. The research further indicates that B420 may improve the epithelial integrity by rebalancing a dysbiotic state induced by an obesogenic diet, for example by increasing the prevalence of lean phenotype microbes such as . We further discuss, in the context of delivering the health benefits of B420: the safety and technological aspects of the strain including genomic characterization, antibiotic resistance profiling, stability in the product, and survival of the live probiotic in the intestine. In summary, we conclude that the clinical and preclinical studies on metabolic health suggest that B420 may be a potential candidate in combating obesity; however, further clinical studies are needed.
Topics: Bifidobacterium animalis; Biomarkers; Dysbiosis; Energy Metabolism; Gastrointestinal Microbiome; Health Status; Heart Disease Risk Factors; Humans; Immunomodulation; Insulin Resistance; Obesity; Probiotics; Signal Transduction
PubMed: 32218248
DOI: 10.3390/nu12040892 -
Gut Microbes 2022Severe acute pancreatitis (SAP) is a critical illness characterized by a severe systemic inflammatory response resulting in persistent multiple organ failure and sepsis....
Severe acute pancreatitis (SAP) is a critical illness characterized by a severe systemic inflammatory response resulting in persistent multiple organ failure and sepsis. The intestinal microbiome is increasingly appreciated to play a crucial role in modulation of AP disease outcome, but limited information is available about the identity and mechanism of action for specific commensal bacteria involved in AP-associated inflammation. Here we show that , particularly , can protect against AP by regulating pancreatic and systemic inflammation in germ-free (GF) and oral antibiotic-treated (Abx) mouse models. Colonization by and administration of its metabolite lactate protected Abx and GF mice from AP by reducing serum amylase concentration, ameliorating pancreatic lesions and improving survival rate after retrograde injection of sodium taurocholate. relieved macrophage-associated local and systemic inflammation of AP in a TLR4/MyD88- and NLRP3/Caspase1-dependent manner through its metabolite lactate. Supporting our findings from the mouse study, clinical AP patients exhibited a decreased fecal abundance of that was inversely correlated with the severity of systemic inflammatory responses. These results may shed light on the heterogeneity of clinical outcomes and drive the development of more efficacious therapeutic interventions for AP, and potentially for other inflammatory disorders.
Topics: Acute Disease; Amylases; Animals; Anti-Bacterial Agents; Bifidobacterium; Gastrointestinal Microbiome; Inflammation; Lactic Acid; Mice; Myeloid Differentiation Factor 88; NLR Family, Pyrin Domain-Containing 3 Protein; Pancreatitis; Taurocholic Acid; Toll-Like Receptor 4
PubMed: 36195972
DOI: 10.1080/19490976.2022.2127456 -
Gut Dec 2020Patients with renal failure suffer from symptoms caused by uraemic toxins, possibly of gut microbial origin, as deduced from studies in animals. The aim of the study is... (Observational Study)
Observational Study
OBJECTIVE
Patients with renal failure suffer from symptoms caused by uraemic toxins, possibly of gut microbial origin, as deduced from studies in animals. The aim of the study is to characterise relationships between the intestinal microbiome composition, uraemic toxins and renal failure symptoms in human end-stage renal disease (ESRD).
DESIGN
Characterisation of gut microbiome, serum and faecal metabolome and human phenotypes in a cohort of 223 patients with ESRD and 69 healthy controls. Multidimensional data integration to reveal links between these datasets and the use of chronic kidney disease (CKD) rodent models to test the effects of intestinal microbiome on toxin accumulation and disease severity.
RESULTS
A group of microbial species enriched in ESRD correlates tightly to patient clinical variables and encode functions involved in toxin and secondary bile acids synthesis; the relative abundance of the microbial functions correlates with the serum or faecal concentrations of these metabolites. Microbiota from patients transplanted to renal injured germ-free mice or antibiotic-treated rats induce higher production of serum uraemic toxins and aggravated renal fibrosis and oxidative stress more than microbiota from controls. Two of the species, and , increase uraemic toxins production and promote renal disease development in a CKD rat model. A probiotic decreases abundance of these species, reduces levels of toxins and the severity of the disease in rats.
CONCLUSION
Aberrant gut microbiota in patients with ESRD sculpts a detrimental metabolome aggravating clinical outcomes, suggesting that the gut microbiota will be a promising target for diminishing uraemic toxicity in those patients.
TRIAL REGISTRATION NUMBER
This study was registered at ClinicalTrials.gov (NCT03010696).
Topics: Animals; Bile Acids and Salts; Case-Control Studies; Disease Models, Animal; Feces; Female; Gastrointestinal Microbiome; Humans; Kidney Failure, Chronic; Male; Metabolome; Mice; Oxidative Stress; Rats; Toxins, Biological; Uremia
PubMed: 32241904
DOI: 10.1136/gutjnl-2019-319766 -
Microbial Biotechnology Mar 2022Obesity and its related metabolic disorders, such as diabetes and cardiovascular disease, are major risk factors for morbidity and mortality in the world population. In...
Obesity and its related metabolic disorders, such as diabetes and cardiovascular disease, are major risk factors for morbidity and mortality in the world population. In this context, supplementation with the probiotic strain Bifidobacterium animalis subsp. lactis BPL1 (CECT8145) has been shown to ameliorate obesity biomarkers. Analyzing the basis of this observation and using the pre-clinical model Caenorhabditis elegans, we have found that lipoteichoic acid (LTA) of BPL1 is responsible for its fat-reducing properties and that this attribute is preserved under hyperglycaemic conditions. This fat-reducing capacity of both BPL1 and LTA-BPL1 is abolished under glucose restriction, as a result of changes in LTA chemical composition. Moreover, we have demonstrated that LTA exerts this function through the IGF-1 pathway, as does BPL1 strain. These results open the possibility of using LTA as a novel postbiotic, whose beneficial properties can be applied therapeutically and/or preventively in metabolic syndrome and diabetes-related disorders.
Topics: Adipogenesis; Animals; Bifidobacterium animalis; Caenorhabditis elegans; Insulin-Like Growth Factor I; Lipopolysaccharides; Obesity; Probiotics; Teichoic Acids
PubMed: 33620143
DOI: 10.1111/1751-7915.13769 -
Gastroenterology May 2020Dysbiosis of the intestinal microbiota has been associated with nonalcoholic fatty liver disease (NAFLD). We investigated whether administration of a synbiotic... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND & AIMS
Dysbiosis of the intestinal microbiota has been associated with nonalcoholic fatty liver disease (NAFLD). We investigated whether administration of a synbiotic combination of probiotic and prebiotic agents affected liver fat content, biomarkers of liver fibrosis, and the composition of the fecal microbiome in patients with NAFLD.
METHODS
We performed a double-blind phase 2 trial of 104 patients with NAFLD in the United Kingdom. Participants (mean age, 50.8 ± 12.6 years; 65% men; 37% with diabetes) were randomly assigned to groups given the synbiotic agents (fructo-oligosaccharides, 4 g twice per day, plus Bifidobacterium animalis subspecies lactis BB-12; n = 55) or placebo (n = 49) for 10-14 months. Liver fat content was measured at the start and end of the study by magnetic resonance spectroscopy, and liver fibrosis was determined from a validated biomarker scoring system and vibration-controlled transient elastography. Fecal samples were collected at the start and end of the study, the fecal microbiome were analyzed by 16S ribosomal DNA sequencing.
RESULTS
Mean baseline and end-of-study magnetic resonance spectroscopy liver fat percentage values were 32.3% ± 24.8% and 28.5% ± 20.1% in the synbiotic group and 31.3% ± 22% and 25.2% ± 17.2% in the placebo group. In the unadjusted intention-to-treat analysis, we found no significant difference in liver fat reduction between groups (β = 2.8; 95% confidence interval, -2.2 to 7.8; P = .30). In a fully adjusted regression model (adjusted for baseline measurement of the outcome plus age, sex, weight difference, and baseline weight), only weight loss was associated with a significant decrease in liver fat (β = 2; 95% confidence interval, 1.5-2.6; P = .03). Fecal samples from patients who received the synbiotic had higher proportions of Bifidobacterium and Faecalibacterium species, and reductions in Oscillibacter and Alistipes species, compared with baseline; these changes were not observed in the placebo group. Changes in the composition of fecal microbiota were not associated with liver fat or markers of fibrosis.
CONCLUSIONS
In a randomized trial of patients with NAFLD, 1 year of administration of a synbiotic combination (probiotic and prebiotic) altered the fecal microbiome but did not reduce liver fat content or markers of liver fibrosis. (ClinicalTrials.gov, Number: NCT01680640).
Topics: Adult; Bifidobacterium animalis; Biomarkers; Biopsy; Double-Blind Method; Dysbiosis; Elasticity Imaging Techniques; Feces; Female; Gastrointestinal Microbiome; Humans; Lipids; Liver; Liver Cirrhosis; Magnetic Resonance Spectroscopy; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Oligosaccharides; Proof of Concept Study; Synbiotics; United Kingdom
PubMed: 31987796
DOI: 10.1053/j.gastro.2020.01.031 -
Frontiers in Endocrinology 2022Type 1 diabetes mellitus (T1DM) is characterized by autoimmune destruction of pancreatic β cells. Previous study has discovered that probiotic strains residing in the... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Type 1 diabetes mellitus (T1DM) is characterized by autoimmune destruction of pancreatic β cells. Previous study has discovered that probiotic strains residing in the gut play essential roles in host immune regulation. However, few clinical results demonstrated probiotic would actually benefit in attenuating glycated hemoglobin (HbA1c) along with inflammatory cytokine levels of the T1DM patients and analyzed their gut microbiota profile at the same time. In this clinical trial, we evaluated the therapeutic efficacy of probiotics on HbA1c along with inflammatory cytokine levels of T1DM patients to determine an alternative administration mode for T1DM medication. The probiotics changed T1DM gut microbiota profile will be measured by next-generation sequencing (NGS).
RESEARCH DESIGN AND METHODS
A randomized, double-blind, placebo-controlled trial was performed at China Medical University Hospital. T1DM patients between 6 and 18 years of age were enrolled. 27 patients were administered regular insulin therapy plus capsules containing probiotic strains subsp. AP-32, MH-68, and subsp. CP-9 daily for 6 months, and 29 patients were administered insulin therapy without extra probiotic supplement as placebo group. The variations of fasting blood glucose and HbA1c in these patients were analyzed. In addition, serum levels of inflammatory cytokines and anti-inflammatory cytokine were assessed using enzyme-linked immunosorbent assay. Patients' stool microbiota were all subjects to NGS analysis.
RESULTS
NGS data showed elevated populations of and in the gut of patients with T1DM who were taking probiotics. Patients with T1DM who were administered probiotics showed significantly reduced fasting blood glucose levels compared with the before-intervention levels. The HbA1c levels of the patients also improved after administration of probiotics. The concentrations of IL-8, IL-17, MIP-1β, RANTES, and TNF-α were significantly reduced and were associated with an increased TGF-β1 expression after probiotic intervention. The persistence effect of glycemic control and immunomodulation were observed even 3 months after discontinuation of the probiotics.
CONCLUSIONS
Here, we found that conventional insulin therapy plus probiotics supplementation attenuated T1DM symptoms than receiving insulin treatment only. Probiotics supplementation with insulin treatment changed gut microbiota and revealed better outcome in stabilizing glycemic levels and reducing HbA1c levels in patients with T1DM through beneficial regulation of immune cytokines.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov, identifier NCT03880760.
Topics: Bifidobacterium animalis; Blood Glucose; Cytokines; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Humans; Insulin; Ligilactobacillus salivarius; Probiotics
PubMed: 35299968
DOI: 10.3389/fendo.2022.754401 -
Nutrients Jul 2020The purpose of the randomized double-blind placebo-controlled trial was to assess the effectiveness of synbiotic preparation containing probiotic FloraActive™... (Randomized Controlled Trial)
Randomized Controlled Trial
The Effectiveness of Synbiotic Preparation Containing and Probiotic Strains and Short Chain Fructooligosaccharides in Patients with Diarrhea Predominant Irritable Bowel Syndrome-A Randomized Double-Blind, Placebo-Controlled Study.
The purpose of the randomized double-blind placebo-controlled trial was to assess the effectiveness of synbiotic preparation containing probiotic FloraActive™ 19070-2, DSMZ 32418, DSMZ 32269, DSMZ 32946, DSMZ 32403 and fructooligosaccharides in adult patients with diarrhea-dominant IBS (IBS-D). The study included eighty patients with moderate and severe IBS-D who were randomized to receive synbiotics or placebo for eight weeks. Finally, a total of sixty-eight patients finished the study. The primary endpoints included the assessment of the symptoms' severity with IBS symptom severity scale (IBS-SSS), an improvement of IBS global symptoms with Global Improvement Scale (IBS-GIS) and adequate relief of symptoms after four and eight weeks of therapy. Secondary endpoints, which were collected by telephone interviewers three times a week included the assessment of individual IBS symptoms and adverse events. Synbiotic treatment in comparison to placebo significantly improved IBS-GIS ( = 0.043), and IBS-SSS score inducing a decrease in the total IBS-SSS ( = 0.042) and in domain-specific scores related to flatulence ( = 0.028) and bowel habit ( = 0.028) after four and eight weeks. Patients treated with synbiotics reported in weekly observations a significant amelioration in a feeling of incomplete bowel movements, flatulence, pain, stool pressure and diarrheal stools compared to those receiving placebo. There were no differences in adverse events between both groups. Concluding, the multi-strain synbiotic preparation was associated with a significant improvement in symptoms in IBS-D patients and was well-tolerated. These results suggest that the use of synbiotics offers a benefit for IBS-D patients. [Clinicaltrials.gov NCT04206410 registered 20 December 2019].
Topics: Adolescent; Adult; Bifidobacterium animalis; Bifidobacterium bifidum; Bifidobacterium longum; Defecation; Diarrhea; Double-Blind Method; Feces; Female; Flatulence; Humans; Irritable Bowel Syndrome; Lactobacillus acidophilus; Lacticaseibacillus rhamnosus; Male; Middle Aged; Oligosaccharides; Severity of Illness Index; Synbiotics; Treatment Outcome; Young Adult
PubMed: 32635661
DOI: 10.3390/nu12071999 -
Microbiology Spectrum Oct 2021Asthma is a multifactorial disorder, and microbial dysbiosis enhances lung inflammation and asthma-related symptoms. Probiotics have shown anti-inflammatory effects and... (Randomized Controlled Trial)
Randomized Controlled Trial
Asthma is a multifactorial disorder, and microbial dysbiosis enhances lung inflammation and asthma-related symptoms. Probiotics have shown anti-inflammatory effects and could regulate the gut-lung axis. Thus, a 3-month randomized, double-blind, and placebo-controlled human trial was performed to investigate the adjunctive efficacy of probiotics in managing asthma. Fifty-five asthmatic patients were randomly assigned to a probiotic group ( = 29; received Bifidobacterium lactis Probio-M8 powder and Symbicort Turbuhaler) and a placebo group ( = 26; received placebo and Symbicort Turbuhaler), and all 55 subjects provided details of their clinical history and demographic data. However, only 31 patients donated a complete set of fecal and blood samples at all three time points for further analysis. Compared with those of the placebo group, co-administering Probio-M8 with Symbicort Turbuhaler significantly decreased the fractional exhaled nitric oxide level at day 30 (= 0.049) and improved the asthma control test score at the end of the intervention (= 0.023). More importantly, the level of alveolar nitric oxide concentration decreased significantly among the probiotic receivers at day 30 (= 0.038), and the symptom relief effect was even more obvious at day 90 (= 0.001). Probiotic co-administration increased the resilience of the gut microbiome, which was reflected by only minor fluctuations in the gut microbiome diversity (> 0.05, probiotic receivers; < 0.05, placebo receivers). Additionally, the probiotic receivers showed significantly changes in some species-level genome bins (SGBs), namely, increases in potentially beneficial species Bifidobacterium animalis, Bifidobacterium longum, and sp. CAG and decreases in Parabacteroides distasonis and (< 0.05). Compared with that of the placebo group, the gut metabolic potential of probiotic receivers exhibited increased levels of predicted microbial bioactive metabolites (linoleoyl ethanolamide, adrenergic acid, erythronic acid) and serum metabolites (5-dodecenoic acid, tryptophan, sphingomyelin) during/after intervention. Collectively, our results suggested that co-administering Probio-M8 synergized with conventional therapy to alleviate diseases associated with the gut-lung axis, like asthma, possibly via activating multiple anti-inflammatory pathways. The human gut microbiota has a potential effect on the pathogenesis of asthma and is closely related to the disease phenotype. Our trial has demonstrated that co-administering Probio-M8 synergized with conventional therapy to alleviate asthma symptoms. The findings of the present study provide new insights into the pathogenesis and treatment of asthma, mechanisms of novel therapeutic strategies, and application of probiotics-based therapy.
Topics: Adolescent; Adult; Aged; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Bifidobacterium animalis; Budesonide, Formoterol Fumarate Drug Combination; Double-Blind Method; Dysbiosis; Female; Gastrointestinal Microbiome; Humans; Lung; Male; Middle Aged; Nitric Oxide; Placebos; Probiotics; Young Adult
PubMed: 34612663
DOI: 10.1128/Spectrum.00859-21