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The Journals of Gerontology. Series A,... Jan 2021Probiotics have been proposed to ameliorate cognitive impairment and depressive disorder via the gut-brain axis in patients and experimental animal models. However, the... (Randomized Controlled Trial)
Randomized Controlled Trial
Probiotic Supplementation Improves Cognitive Function and Mood with Changes in Gut Microbiota in Community-Dwelling Older Adults: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial.
Probiotics have been proposed to ameliorate cognitive impairment and depressive disorder via the gut-brain axis in patients and experimental animal models. However, the beneficial role of probiotics in brain functions of healthy older adults remains unclear. Therefore, a randomized, double-blind, and placebo-controlled multicenter trial was conducted to determine the effects of probiotics on cognition and mood in community-dwelling older adults. Sixty-three healthy elders (≥65 years) consumed either placebo or probiotics containing Bifidobacterium bifidum BGN4 and Bifidobacterium longum BORI for 12 weeks. The gut microbiota was analyzed using 16S rRNA sequencing and bioinformatics. Brain functions were measured using the Consortium to Establish a Registry for Alzheimer's disease, Satisfaction with life scale, stress questionnaire, Geriatric depression scale, and Positive affect and negative affect schedule. Blood brain-derived neurotrophic factor (BDNF) was determined using enzyme-linked immunosorbent assay. Relative abundance of inflammation-causing gut bacteria was significantly reduced at Week 12 in the probiotics group (p < .05). The probiotics group showed greater improvement in mental flexibility test and stress score than the placebo group (p < .05). Contrary to placebo, probiotics significantly increased serum BDNF level (p < .05). Notably, the gut microbes significantly shifted by probiotics (Eubacterium and Clostridiales) showed significant negative correlation with serum BDNF level only in the probiotics group (RS = -0.37, RS = -0.39, p < .05). In conclusion, probiotics promote mental flexibility and alleviate stress in healthy older adults, along with causing changes in gut microbiota. These results provide evidence supporting health-promoting properties of probiotics as a part of healthy diet in the older adults.
Topics: Affect; Aged; Cognition; Double-Blind Method; Female; Gastrointestinal Microbiome; Humans; Independent Living; Male; Probiotics
PubMed: 32300799
DOI: 10.1093/gerona/glaa090 -
Nutrients Jan 2020Targeting gut microbiota with synbiotics (probiotic supplements containing prebiotic components) is emerging as a promising intervention in the comprehensive nutritional... (Randomized Controlled Trial)
Randomized Controlled Trial
Targeting gut microbiota with synbiotics (probiotic supplements containing prebiotic components) is emerging as a promising intervention in the comprehensive nutritional approach to reducing obesity. Weight loss resulting from low-carbohydrate high-protein diets can be significant but has also been linked to potentially negative health effects due to increased bacterial fermentation of undigested protein within the colon and subsequent changes in gut microbiota composition. Correcting obesity-induced disruption of gut microbiota with synbiotics can be more effective than supplementation with probiotics alone because prebiotic components of synbiotics support the growth and survival of positive bacteria therein. The purpose of this placebo-controlled intervention clinical trial was to evaluate the effects of a synbiotic supplement on the composition, richness and diversity of gut microbiota and associations of microbial species with body composition parameters and biomarkers of obesity in human subjects participating in a weight loss program. The probiotic component of the synbiotic used in the study contained , , , and and the prebiotic component was a galactooligosaccharide mixture. The results showed no statistically significant differences in body composition (body mass, BMI, body fat mass, body fat percentage, body lean mass, and bone mineral content) between the placebo and synbiotic groups at the end of the clinical trial (3-month intervention, 20 human subjects participating in weight loss intervention based on a low-carbohydrate, high-protein, reduced energy diet). Synbiotic supplementation increased the abundance of gut bacteria associated with positive health effects, especially and , and it also appeared to increase the gut microbiota richness. A decreasing trend in the gut microbiota diversity in the placebo and synbiotic groups was observed at the end of trial, which may imply the effect of the high-protein low-carbohydrate diet used in the weight loss program. Regression analysis performed to correlate abundance of species following supplementation with body composition parameters and biomarkers of obesity found an association between a decrease over time in blood glucose and an increase in abundance, particularly in the synbiotic group. However, the decrease over time in body mass, BMI, waist circumstance, and body fat mass was associated with a decrease in abundance. The results obtained support the conclusion that synbiotic supplement used in this clinical trial modulates human gut microbiota by increasing abundance of potentially beneficial microbial species.
Topics: Adult; Bifidobacterium; Body Composition; Diet, Reducing; Dietary Supplements; Female; Gastrointestinal Microbiome; Humans; Lactobacillus; Male; Middle Aged; Obesity; Synbiotics; Weight Loss
PubMed: 31952249
DOI: 10.3390/nu12010222 -
Biology Nov 2022The possession of two X chromosomes may come with the risk of various illnesses, females are more likely to be affected by osteoarthritis, heart disease, and anxiety.... (Review)
Review
The possession of two X chromosomes may come with the risk of various illnesses, females are more likely to be affected by osteoarthritis, heart disease, and anxiety. Given the reported correlations between gut microbiome dysbiosis and various illnesses, the female gut microbiome is worthy of exploration. Herein, we discuss the composition of the female gut microbiota and its dysbiosis in pathologies affecting the female population. Using PubMed, we performed a literature search, using key terms, namely: "gut microbiome", "estrogen", "menopause", "polycystic ovarian syndrome", "pregnancy", and "menstruation". In polycystic ovarian syndrome (PCOS), the abundance of and the ratio of was found to be increased while that of ML615J-28 124-7 and S24-7 was reduced. In breast cancer, the abundance of was enhanced, while in cervical cancer, and were enhanced but and members of were decreased. In ovarian cancer, abundance was increased. Interestingly, the administration of , and ameliorated PCOS symptoms while that of a mix of W51, W23, W63, W52, W24, W37, W19, W56, and W58 alleviated vascular malfunction and arterial stiffness in obese postmenopausal women, and finally, while further research is needed, maybe protective against postmenopausal bone mass loss. As several studies report the therapeutic potential of probiotics and since the gut microbiota of certain female pathological states has been relatively characterized, we speculate that the administration of certain bacterial species as probiotics is warranted, as novel independent or adjunct therapies for various female pathologies.
PubMed: 36421397
DOI: 10.3390/biology11111683 -
JAMA Pediatrics Sep 2022The efficacy of multispecies probiotic formulations in the prevention of antibiotic-associated diarrhea (AAD) remains unclear. (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
The efficacy of multispecies probiotic formulations in the prevention of antibiotic-associated diarrhea (AAD) remains unclear.
OBJECTIVE
To assess the effect of a multispecies probiotic on the risk of AAD in children.
DESIGN, SETTING, AND PARTICIPANTS
This randomized, quadruple-blind, placebo-controlled trial was conducted from February 2018 to May 2021 in a multicenter, mixed setting (inpatients and outpatients). Patients were followed up throughout the intervention period. Eligibility criteria included age 3 months to 18 years, recruitment within 24 hours following initiation of broad-spectrum systemic antibiotics, and signed informed consent. In total, 646 eligible patients were approached and 350 patients took part in the trial.
INTERVENTIONS
A multispecies probiotic consisting of Bifidobacterium bifidum W23, Bifidobacterium lactis W51, Lactobacillus acidophilus W37, L acidophilus W55, Lacticaseibacillus paracasei W20, Lactiplantibacillus plantarum W62, Lacticaseibacillus rhamnosus W71, and Ligilactobacillus salivarius W24, for a total dose of 10 billion colony-forming units daily, for the duration of antibiotic treatment and for 7 days after.
MAIN OUTCOMES AND MEASURES
The primary outcome was AAD, defined as 3 or more loose or watery stools per day in a 24-hour period, caused either by Clostridioides difficile or of otherwise unexplained etiology, after testing for common diarrheal pathogens. The secondary outcomes included diarrhea regardless of the etiology, diarrhea duration, and predefined diarrhea complications.
RESULTS
A total of 350 children (192 boys and 158 girls; mean [range] age, 50 [3-212] months) were randomized and 313 were included in the intention-to-treat analysis. Compared with placebo (n = 155), the probiotic (n = 158) had no effect on risk of AAD (relative risk [RR], 0.81; 95% CI, 0.49-1.33). However, children in the probiotic group had a lower risk of diarrhea regardless of the etiology (RR, 0.65; 95% CI, 0.44-0.94). No differences were observed between the groups for most of the secondary outcomes, including adverse events.
CONCLUSIONS AND RELEVANCE
A multispecies probiotic did not reduce the risk of AAD in children when analyzed according to the most stringent definition. However, it reduced the overall risk of diarrhea during and for 7 days after antibiotic treatment. Our study also shows that the AAD definition has a significant effect on clinical trial results and their interpretation.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03334604.
Topics: Anti-Bacterial Agents; Child; Data Collection; Diarrhea; Double-Blind Method; Female; Humans; Inpatients; Male; Middle Aged; Probiotics
PubMed: 35727573
DOI: 10.1001/jamapediatrics.2022.1973 -
Acta Pharmaceutica Sinica. B Mar 2020ProBiotic-4 is a probiotic preparation composed of , , , and . This study aims to investigate the effects of ProBiotic-4 on the microbiota-gut-brain axis and cognitive...
ProBiotic-4 is a probiotic preparation composed of , , , and . This study aims to investigate the effects of ProBiotic-4 on the microbiota-gut-brain axis and cognitive deficits, and to explore the underlying molecular mechanism using senescence-accelerated mouse prone 8 (SAMP8) mice. ProBiotic-4 was orally administered to 9-month-old SAMP8 mice for 12 weeks. We observed that ProBiotic-4 significantly improved the memory deficits, cerebral neuronal and synaptic injuries, glial activation, and microbiota composition in the feces and brains of aged SAMP8 mice. ProBiotic-4 substantially attenuated aging-related disruption of the intestinal barrier and blood-brain barrier, decreased interleukin-6 and tumor necrosis factor- at both mRNA and protein levels, reduced plasma and cerebral lipopolysaccharide (LPS) concentration, toll-like receptor 4 (TLR4) expression, and nuclear factor-B (NF-B) nuclear translocation in the brain. In addition, not only did ProBiotic-4 significantly decreased the levels of -H2AX, 8-hydroxydesoxyguanosine, and retinoic-acid-inducible gene-I (RIG-I), it also abrogated RIG-I multimerization in the brain. These findings suggest that targeting gut microbiota with probiotics may have a therapeutic potential for the deficits of the microbiota-gut-brain axis and cognitive function in aging, and that its mechanism is associated with inhibition of both TLR4-and RIG-I-mediated NF-B signaling pathway and inflammatory responses.
PubMed: 32140393
DOI: 10.1016/j.apsb.2019.07.001 -
Nature Oct 2018The development of the microbiome from infancy to childhood is dependent on a range of factors, with microbial-immune crosstalk during this time thought to be involved...
The development of the microbiome from infancy to childhood is dependent on a range of factors, with microbial-immune crosstalk during this time thought to be involved in the pathobiology of later life diseases such as persistent islet autoimmunity and type 1 diabetes. However, to our knowledge, no studies have performed extensive characterization of the microbiome in early life in a large, multi-centre population. Here we analyse longitudinal stool samples from 903 children between 3 and 46 months of age by 16S rRNA gene sequencing (n = 12,005) and metagenomic sequencing (n = 10,867), as part of the The Environmental Determinants of Diabetes in the Young (TEDDY) study. We show that the developing gut microbiome undergoes three distinct phases of microbiome progression: a developmental phase (months 3-14), a transitional phase (months 15-30), and a stable phase (months 31-46). Receipt of breast milk, either exclusive or partial, was the most significant factor associated with the microbiome structure. Breastfeeding was associated with higher levels of Bifidobacterium species (B. breve and B. bifidum), and the cessation of breast milk resulted in faster maturation of the gut microbiome, as marked by the phylum Firmicutes. Birth mode was also significantly associated with the microbiome during the developmental phase, driven by higher levels of Bacteroides species (particularly B. fragilis) in infants delivered vaginally. Bacteroides was also associated with increased gut diversity and faster maturation, regardless of the birth mode. Environmental factors including geographical location and household exposures (such as siblings and furry pets) also represented important covariates. A nested case-control analysis revealed subtle associations between microbial taxonomy and the development of islet autoimmunity or type 1 diabetes. These data determine the structural and functional assembly of the microbiome in early life and provide a foundation for targeted mechanistic investigation into the consequences of microbial-immune crosstalk for long-term health.
Topics: Adolescent; Animals; Bifidobacterium; Breast Feeding; Case-Control Studies; Child; Child, Preschool; Cluster Analysis; Datasets as Topic; Diabetes Mellitus, Type 1; Female; Firmicutes; Gastrointestinal Microbiome; Humans; Infant; Male; Milk, Human; Pets; RNA, Ribosomal, 16S; Siblings; Surveys and Questionnaires; Time Factors
PubMed: 30356187
DOI: 10.1038/s41586-018-0617-x -
JPMA. the Journal of the Pakistan... Oct 2022To compare the efficacy of only dietary recommendations, zinc, probiotics and combination therapies in children admitted with acute gastroenteritis. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To compare the efficacy of only dietary recommendations, zinc, probiotics and combination therapies in children admitted with acute gastroenteritis.
METHODS
The comparative, prospective, double-blind, placebo-controlled study was conducted from October 2020 to April 2021 at the Paediatric Emergency Service after approval from the ethics review committee of Diyarbakir Gazi Yasargil Training and Research Hospital, Turkey, and comprised infants with a diagnosis of acute gastroenteritis who were divided into four groups. Only appropriate dietary recommendations were given to the control group 1, while group 2 was given a single probiotic containing bifidobacterium breve, bifidobacterium bifidum, bifidobacterium infantis and bifidobacterium longum strains. Group 3 was given zinc and group 4 was given probiotics and zinc. Demographic data of the patients, admission complaints, physical examination findings, dehydration degrees, and laboratory findings were recorded and analysed.
RESULTS
Of the 132 subjects, 79 (59.8%) were males. The overall mean age was 27.5±3.6 months. There were 22 (16.7%) patients in group 1, 34 (25.8%) in group 2, 28 (21.2%) in group 3, and 48 (36.4%) in group 4. The mean duration time to diarrhoea termination was 84.5±10.7 hours (range: 79-89 hours) in group 1, 73.05±6.8 hours (range: 70.5-75.4 hours) in group 2, 80.1±10.3 hours (range: 76-84 hours) in group 3, and 43.5±9.6 hours (range: 46-48 hours) in group 4. Group 4 outcome was statistically significant (p<0.001).
CONCLUSIONS
The efficiency of combined treatment with probiotics and zinc was found to be significantly better in the treatment of childhood acute gastroenteritis.
Topics: Infant; Male; Humans; Child; Child, Preschool; Female; Prospective Studies; Gastroenteritis; Diarrhea; Probiotics; Double-Blind Method; Zinc; Treatment Outcome
PubMed: 36660970
DOI: 10.47391/JPMA.4438 -
Nature Microbiology Nov 2021Breastfeeding profoundly shapes the infant gut microbiota, which is critical for early life immune development, and the gut microbiota can impact host physiology in... (Observational Study)
Observational Study
Breastfeeding profoundly shapes the infant gut microbiota, which is critical for early life immune development, and the gut microbiota can impact host physiology in various ways, such as through the production of metabolites. However, few breastmilk-dependent microbial metabolites mediating host-microbiota interactions are currently known. Here, we demonstrate that breastmilk-promoted Bifidobacterium species convert aromatic amino acids (tryptophan, phenylalanine and tyrosine) into their respective aromatic lactic acids (indolelactic acid, phenyllactic acid and 4-hydroxyphenyllactic acid) via a previously unrecognized aromatic lactate dehydrogenase (ALDH). The ability of Bifidobacterium species to convert aromatic amino acids to their lactic acid derivatives was confirmed using monocolonized mice. Longitudinal profiling of the faecal microbiota composition and metabolome of Danish infants (n = 25), from birth until 6 months of age, showed that faecal concentrations of aromatic lactic acids are correlated positively with the abundance of human milk oligosaccharide-degrading Bifidobacterium species containing the ALDH, including Bifidobacterium longum, B. breve and B. bifidum. We further demonstrate that faecal concentrations of Bifidobacterium-derived indolelactic acid are associated with the capacity of these samples to activate in vitro the aryl hydrocarbon receptor (AhR), a receptor important for controlling intestinal homoeostasis and immune responses. Finally, we show that indolelactic acid modulates ex vivo immune responses of human CD4 T cells and monocytes in a dose-dependent manner by acting as an agonist of both the AhR and hydroxycarboxylic acid receptor 3 (HCA). Our findings reveal that breastmilk-promoted Bifidobacterium species produce aromatic lactic acids in the gut of infants and suggest that these microbial metabolites may impact immune function in early life.
Topics: Adult; Animals; Bacteria; Bifidobacterium; Breast Feeding; Cohort Studies; Feces; Female; Gastrointestinal Microbiome; Humans; Infant; Lactic Acid; Male; Mice; Receptors, Aryl Hydrocarbon; Young Adult
PubMed: 34675385
DOI: 10.1038/s41564-021-00970-4 -
A randomized double-blind placebo-controlled trial of probiotics in post-surgical colorectal cancer.BMC Gastroenterology Jul 2019Our study aimed to determine the effect of probiotic consumption containing six viable microorganisms of 30 × 10 cfu Lactobacillus and Bifidobacteria strains for... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Our study aimed to determine the effect of probiotic consumption containing six viable microorganisms of 30 × 10 cfu Lactobacillus and Bifidobacteria strains for six months on clinical outcomes and inflammatory cytokines (TNF-α, IFN-γ, IL-6, IL-10, IL-12, IL-17A, IL-17C and IL-22) in patients with colorectal cancer.
METHODS
Fifty-two patients with colorectal cancer were randomized at four weeks after surgery to receive either a placebo (n = 25) or 30 billion colony-forming unit (CFU) of a mixture of six viable strains including 107 mg of Lactobacillus acidophilus BCMC® 12,130, Lactobacillus lactis BCMC® 12,451, Lactobacillus casei subsp BCMC® 12,313, Bifidobacterium longum BCMC® 02120, Bifidobacterium bifidum BCMC® 02290 and Bifidobacterium infantis BCMC® 02129 (n = 27). Patients were instructed to take the product orally twice daily for six months. Infection status, diarrhea or hospital admission were recorded throughout the study. Blood was taken pre- and post-intervention to measure TNF-α, IFN-γ, IL-6, IL-10, IL-12, IL-17A, IL-17C and IL-22 using ELISA multiplex kit.
RESULTS
The majority of cases (~ 70%) were in Duke's C colorectal cancer for both groups. No surgical infection occurred and no antibiotics were required. Chemotherapy induced diarrhea was observed in both groups. Significant reduction in the level of pro-inflammatory cytokine, TNF-α, IL-6, IL-10, IL-12, IL-17A, IL-17C and IL-22 were observed in CRC patients who received probiotics as compared to pre-treatment level (P < 0.05). However, there was no significant difference in the IFN-γ in both groups.
CONCLUSIONS
We have shown that probiotics containing six viable microorganisms of Lactobacillus and Bifidobacteria strains are safe to be consumed at four weeks after surgery in colorectal cancer patients and have reduced pro-inflammatory cytokines (except for IFN-gamma). Probiotic may modify intestinal microenvironment resulting in a decline in pro-inflammatory cytokines.
TRIAL REGISTRATION
NCT03782428; retrospectively registered on 20th December 2018.
Topics: Antineoplastic Agents; Bifidobacterium; Colectomy; Colorectal Neoplasms; Cytokines; Diarrhea; Dietary Supplements; Double-Blind Method; Drug Monitoring; Female; Gastrointestinal Microbiome; Humans; Lactobacillus; Male; Middle Aged; Postoperative Period; Probiotics; Treatment Outcome
PubMed: 31340751
DOI: 10.1186/s12876-019-1047-4 -
Nature Oct 2018Type 1 diabetes (T1D) is an autoimmune disease that targets pancreatic islet beta cells and incorporates genetic and environmental factors, including complex genetic...
Type 1 diabetes (T1D) is an autoimmune disease that targets pancreatic islet beta cells and incorporates genetic and environmental factors, including complex genetic elements, patient exposures and the gut microbiome. Viral infections and broader gut dysbioses have been identified as potential causes or contributing factors; however, human studies have not yet identified microbial compositional or functional triggers that are predictive of islet autoimmunity or T1D. Here we analyse 10,913 metagenomes in stool samples from 783 mostly white, non-Hispanic children. The samples were collected monthly from three months of age until the clinical end point (islet autoimmunity or T1D) in the The Environmental Determinants of Diabetes in the Young (TEDDY) study, to characterize the natural history of the early gut microbiome in connection to islet autoimmunity, T1D diagnosis, and other common early life events such as antibiotic treatments and probiotics. The microbiomes of control children contained more genes that were related to fermentation and the biosynthesis of short-chain fatty acids, but these were not consistently associated with particular taxa across geographically diverse clinical centres, suggesting that microbial factors associated with T1D are taxonomically diffuse but functionally more coherent. When we investigated the broader establishment and development of the infant microbiome, both taxonomic and functional profiles were dynamic and highly individualized, and dominated in the first year of life by one of three largely exclusive Bifidobacterium species (B. bifidum, B. breve or B. longum) or by the phylum Proteobacteria. In particular, the strain-specific carriage of genes for the utilization of human milk oligosaccharide within a subset of B. longum was present specifically in breast-fed infants. These analyses of TEDDY gut metagenomes provide, to our knowledge, the largest and most detailed longitudinal functional profile of the developing gut microbiome in relation to islet autoimmunity, T1D and other early childhood events. Together with existing evidence from human cohorts and a T1D mouse model, these data support the protective effects of short-chain fatty acids in early-onset human T1D.
Topics: Age of Onset; Animals; Bifidobacterium; Breast Feeding; Child, Preschool; Diabetes Mellitus, Type 1; Disease Models, Animal; Fatty Acids, Volatile; Feces; Female; Gastrointestinal Microbiome; Health Surveys; Humans; Infant; Islets of Langerhans; Longitudinal Studies; Male; Mice; Milk, Human; Proteobacteria; White People
PubMed: 30356183
DOI: 10.1038/s41586-018-0620-2