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1.
Bifidobacteria-mediated immune system imprinting early in life.
Henrick, BM, Rodriguez, L, Lakshmikanth, T, Pou, C, Henckel, E, Arzoomand, A, Olin, A, Wang, J, Mikes, J, Tan, Z, et al
Cell. 2021;(15):3884-3898.e11
Abstract
Immune-microbe interactions early in life influence the risk of allergies, asthma, and other inflammatory diseases. Breastfeeding guides healthier immune-microbe relationships by providing nutrients to specialized microbes that in turn benefit the host's immune system. Such bacteria have co-evolved with humans but are now increasingly rare in modern societies. Here we show that a lack of bifidobacteria, and in particular depletion of genes required for human milk oligosaccharide (HMO) utilization from the metagenome, is associated with systemic inflammation and immune dysregulation early in life. In breastfed infants given Bifidobacterium infantis EVC001, which expresses all HMO-utilization genes, intestinal T helper 2 (Th2) and Th17 cytokines were silenced and interferon β (IFNβ) was induced. Fecal water from EVC001-supplemented infants contains abundant indolelactate and B. infantis-derived indole-3-lactic acid (ILA) upregulated immunoregulatory galectin-1 in Th2 and Th17 cells during polarization, providing a functional link between beneficial microbes and immunoregulation during the first months of life.
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Effectiveness and safety of Bifidobacterium and berberine in human hyperglycemia and their regulatory effect on the gut microbiota: a multi-center, double-blind, randomized, parallel-controlled study.
Ming, J, Yu, X, Xu, X, Wang, L, Ding, C, Wang, Z, Xie, X, Li, S, Yang, W, Luo, S, et al
Genome medicine. 2021;(1):125
Abstract
BACKGROUND Berberine and Bifidobacterium have been reported to improve glucose tolerance in people with hyperglycemia or other metabolic disorders. This study aimed to assess the hypoglycemic effect and the regulation of the gut microbiota caused by berberine and Bifidobacterium and the possible additive benefits of their combination. METHODS This was an 18-week, multi-center, randomized, double-blind, parallel-controlled study of patients newly diagnosed with hyperglycemia. After a 2-week run-in period, 300 participants were randomly assigned to the following four groups for 16 weeks of treatment: berberine (Be), Bifidobacterium (Bi), berberine and Bifidobacterium (BB), and placebo group. The primary efficacy endpoint was the absolute value of fasting plasma glucose (FPG) compared with baseline after 16 weeks of treatment. RESULTS Between October 2015 and April 2018, a total of 297 participants were included in the primary analysis. Significant reductions of FPG were observed in the Be and BB groups compared with the placebo group, with a least square (LS) mean difference of - 0.50, 95% CI [- 0.85, - 0.15] mmol/L, and - 0.55, 95% CI [- 0.91, - 0.20] mmol/L, respectively. The Be and BB groups also showed significant reductions in 2-h postprandial plasma glucose. A pronounced decrease in HbA1c occurred in the BB group compared to the placebo group. Moreover, compared with the Bi and placebo groups, the Be and BB groups had more changes in the gut microbiota from the baseline. CONCLUSIONS Berberine could regulate the structure and function of the human gut microbiota, and Bifidobacterium has the potential to enhance the hypoglycemic effect of berberine. These findings provide new insights into the hypoglycemic potential of berberine and Bifidobacterium. TRIAL REGISTRATION ClinicalTrials.gov , NCT03330184. Retrospectively registered on 18 October 2017.
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Galacto-oligosaccharides supplementation in prefrail older and healthy adults increased faecal bifidobacteria, but did not impact immune function and oxidative stress.
Wilms, E, An, R, Smolinska, A, Stevens, Y, Weseler, AR, Elizalde, M, Drittij, MJ, Ioannou, A, van Schooten, FJ, Smidt, H, et al
Clinical nutrition (Edinburgh, Scotland). 2021;(5):3019-3031
Abstract
BACKGROUND & AIMS Ageing is associated with an increased risk of frailty, intestinal microbiota perturbations, immunosenescence and oxidative stress. Prebiotics such as galacto-oligosaccharides (GOS) may ameliorate these ageing-related alterations. We aimed to compare the faecal microbiota composition, metabolite production, immune and oxidative stress markers in prefrail elderly and younger adults, and investigate the effects of GOS supplementation in both groups. METHODS In a randomised controlled cross-over study, 20 prefrail elderly and 24 healthy adults received 21.6 g/day Biotis™ GOS (containing 15.0 g/day GOS) or placebo. Faecal 16S rRNA gene-based microbiota and short-chain fatty acids were analysed at 0, 1 and 4 weeks of intervention.Volatile organic compounds were analysed in breath, and stimulated cytokine production, CRP, malondialdehyde, trolox equivalent antioxidant capacity (TEAC) and uric acid (UA) in blood at 0 and 4 weeks. RESULTS Principle coordinate analysis showed differences in microbial composition between elderly and adults (P≤0.05), with elderly having lower bifidobacteria (P≤0.033) at baseline. In both groups, GOS affected microbiota composition (P≤0.05), accompanied by increases in bifidobacteria (P<0.001) and decreased microbial diversity (P≤0.023). Faecal and breath metabolites, immune and oxidative stress markers neither differed between groups (P ≥ 0.125) nor were affected by GOS (P ≥ 0.236). TEAC values corrected for UA were higher in elderly versus adults (P<0.001), but not different between interventions (P ≥ 0.455). CONCLUSIONS Elderly showed lower faecal bifidobacterial (relative) abundance than adults, which increased after GOS intake in both groups. Faecal and breath metabolites, parameters of immune function and oxidative stress were not different at baseline, and not impacted by GOS supplementation. CLINICALTRIALS. GOV WITH STUDY ID NUMBER NCT03077529.
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Regulation of Alcohol and Acetaldehyde Metabolism by a Mixture of Lactobacillus and Bifidobacterium Species in Human.
Jung, SJ, Hwang, JH, Park, EO, Lee, SO, Chung, YJ, Chung, MJ, Lim, S, Lim, TJ, Ha, Y, Park, BH, et al
Nutrients. 2021;(6)
Abstract
Excessive alcohol consumption is one of the most significant causes of morbidity and mortality worldwide. Alcohol is oxidized to toxic and carcinogenic acetaldehyde by alcohol dehydrogenase (ADH) and further oxidized to a non-toxic acetate by aldehyde dehydrogenase (ALDH). There are two major ALDH isoforms, cytosolic and mitochondrial, encoded by ALDH1 and ALDH2 genes, respectively. The ALDH2 polymorphism is associated with flushing response to alcohol use. Emerging evidence shows that Lactobacillus and Bifidobacterium species encode alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) mediate alcohol and acetaldehyde metabolism, respectively. A randomized, double-blind, placebo-controlled crossover clinical trial was designed to study the effects of Lactobacillus and Bifidobacterium probiotic mixture in humans and assessed their effects on alcohol and acetaldehyde metabolism. Here, twenty-seven wild types (ALDH2*1/*1) and the same number of heterozygotes (ALDH2*2/*1) were recruited for the study. The enrolled participants were randomly divided into either the probiotic (Duolac ProAP4) or the placebo group. Each group received a probiotic or placebo capsule for 15 days with subsequent crossover. Primary outcomes were measurement of alcohol and acetaldehyde in the blood after the alcohol intake. Blood levels of alcohol and acetaldehyde were significantly downregulated by probiotic supplementation in subjects with ALDH2*2/*1 genotype, but not in those with ALDH2*1/*1 genotype. However, there were no marked improvements in hangover score parameters between test and placebo groups. No clinically significant changes were observed in safety parameters. These results suggest that Duolac ProAP4 has a potential to downregulate the alcohol and acetaldehyde concentrations, and their effects depend on the presence or absence of polymorphism on the ALDH2 gene.
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A randomized double-blind placebo-controlled trial of probiotics in post-surgical colorectal cancer.
Zaharuddin, L, Mokhtar, NM, Muhammad Nawawi, KN, Raja Ali, RA
BMC gastroenterology. 2019;(1):131
Abstract
BACKGROUND Our study aimed to determine the effect of probiotic consumption containing six viable microorganisms of 30 × 1010 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.
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Probiotic supplementation restores normal microbiota composition and function in antibiotic-treated and in caesarean-born infants.
Korpela, K, Salonen, A, Vepsäläinen, O, Suomalainen, M, Kolmeder, C, Varjosalo, M, Miettinen, S, Kukkonen, K, Savilahti, E, Kuitunen, M, et al
Microbiome. 2018;(1):182
Abstract
BACKGROUND Infants born by caesarean section or receiving antibiotics are at increased risk of developing metabolic, inflammatory and immunological diseases, potentially due to disruption of normal gut microbiota at a critical developmental time window. We investigated whether probiotic supplementation could ameliorate the effects of antibiotic use or caesarean birth on infant microbiota in a double blind, placebo-controlled randomized clinical trial. Mothers were given a multispecies probiotic, consisting of Bifidobacterium breve Bb99 (Bp99 2 × 108 cfu) Propionibacterium freundenreichii subsp. shermanii JS (2 × 109cfu), Lactobacillus rhamnosus Lc705 (5 × 109 cfu) and Lactobacillus rhamnosus GG (5 × 109 cfu) (N = 168 breastfed and 31 formula-fed), or placebo supplement (N = 201 breastfed and 22 formula-fed) during pregnancy, and the infants were given the same supplement. Faecal samples of the infants were collected at 3 months and analyzed using taxonomic, metagenomic and metaproteomic approaches. RESULTS The probiotic supplement had a strong overall impact on the microbiota composition, but the effect depended on the infant's diet. Only breastfed infants showed the expected increase in bifidobacteria and reduction in Proteobacteria and Clostridia. In the placebo group, both birth mode and antibiotic use were significantly associated with altered microbiota composition and function, particularly reduced Bifidobacterium abundance. In the probiotic group, the effects of antibiotics and birth mode were either completely eliminated or reduced. CONCLUSIONS The results indicate that it is possible to correct undesired changes in microbiota composition and function caused by antibiotic treatments or caesarean birth by supplementing infants with a probiotic mixture together with at least partial breastfeeding. TRIAL REGISTRATION clinicaltrials.gov NCT00298337 . Registered March 2, 2006.
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[A machine learning model based on initial gut microbiome data for predicting changes of Bifidobacterium after prebiotics consumption].
Luo, YM, Liu, FT, Chen, MX, Tang, WL, Yang, YL, Tan, XL, Zhou, HW
Nan fang yi ke da xue xue bao = Journal of Southern Medical University. 2018;(3):251-260
Abstract
OBJECTIVE To investigate the effects of prebiotics supplementation for 9 days on gut microbiota structure and function and establish a machine learning model based on the initial gut microbiota data for predicting the variation of Bifidobacterium after prebiotic intake. METHODS With a randomized double-blind self-controlled design, 35 healthy volunteers were asked to consume fructo-oligosaccharides (FOS) or galacto-oligosaccharides (GOS) for 9 days (16 g per day). 16S rRNA gene high-throughput sequencing was performed to investigate the changes of gut microbiota after prebiotics intake. PICRUSt was used to infer the differences between the functional modules of the bacterial communities. Random forest model based on the initial gut microbiota data was used to identify the changes in Bifidobacterium after 5 days of prebiotic intake and then to build a continuous index to predict the changes of Bifidobacterium. The data of fecal samples collected after 9 days of GOS intervention were used to validate the model. RESULTS Fecal samples analysis with QIIME revealed that FOS intervention for 5 days reduced the intestinal flora alpha diversity, which rebounded on day 9; in GOS group, gut microbiota alpha diversity decreased progressively during the intervention. Neither FOS nor GOS supplement caused significant changes in β diversity of gut microbiota. The area under the curve (AUC) of the prediction model was 89.6%. The continuous index could successfully predict the changes in Bifidobacterium (R=0.45, P=0.01), and the prediction accuracy was verified by the validation model (R=0.62, P=0.01). CONCLUSION Short-term prebiotics intervention can significantly decrease α-diversity of the intestinal flora. The machine learning model based on initial gut microbiota data can accurately predict the changes in Bifidobacterium, which sheds light on personalized nutrition intervention and precise modulation of the intestinal flora.
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Inulin-Type Fructan Supplementation of 3- to 6-Year-Old Children Is Associated with Higher Fecal Bifidobacterium Concentrations and Fewer Febrile Episodes Requiring Medical Attention.
Lohner, S, Jakobik, V, Mihályi, K, Soldi, S, Vasileiadis, S, Theis, S, Sailer, M, Sieland, C, Berényi, K, Boehm, G, et al
The Journal of nutrition. 2018;(8):1300-1308
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Abstract
BACKGROUND Inulin-type fructans used in formula have been shown to promote microbiota composition and stool consistency closer to those of breastfed infants and to have beneficial effects on fever occurrence, diarrhea, and incidence of infections requiring antibiotic treatment in infants. OBJECTIVES The primary study aim was to explore whether prophylactic supplementation with prebiotic fructans is able to influence the frequency of infectious diseases in kindergarten children during a winter period. A secondary objective was to ascertain the effect on the intestinal microbiota. METHODS 142 boys and 128 girls aged 3-6 y were randomly allocated to consume 6 g/d fructans or maltodextrin for 24 wk. At baseline, stool samples were collected for microbiota analysis and anthropometric measurements were made. During the intervention period diagnoses were recorded by physicians, whereas disease symptoms, kindergarten absenteeism, dietary habits, and stool consistency were recorded by parents. Baseline measurements were repeated at wk 24. RESULTS In total 219 children finished the study. Both the relative abundance of Bifidobacterium (P < 0.001) and that of Lactobacillus (P = 0.014) were 19.9% and 7.8% higher, respectively, post data normalization, in stool samples of children receiving fructans as compared with those of controls at wk 24. This was accompanied by significantly softer stools within the normal range in the prebiotic group from wk 12 onwards. The incidence of febrile episodes requiring medical attention [0.65 ± 1.09 compared with 0.9 ± 1.11 infections/(24 wk × child), P = 0.04] and that of sinusitis (0.01 ± 0.1 compared with 0.06 ± 0.25, P = 0.03) were significantly lower in the prebiotic group. The number of infectious episodes and their duration reported by parents did not differ significantly between the 2 intervention groups. CONCLUSIONS Prebiotic supplementation modified the composition of the intestinal microbiota and resulted in softer stools in kindergarten-aged children. The reduction in febrile episodes requiring medical attention supports the concept of further studies on prebiotics in young children. This trial was registered at clinicaltrials.gov as NCT03241355.
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Fructooligosaccharide (FOS) and Galactooligosaccharide (GOS) Increase Bifidobacterium but Reduce Butyrate Producing Bacteria with Adverse Glycemic Metabolism in healthy young population.
Liu, F, Li, P, Chen, M, Luo, Y, Prabhakar, M, Zheng, H, He, Y, Qi, Q, Long, H, Zhang, Y, et al
Scientific reports. 2017;(1):11789
Abstract
The gut microbiota has been implicated in glucose intolerance and its progression towards type-2 diabetes mellitus (T2DM). Relevant randomized clinical trial with prebiotic intervention was inadequate. We sought to evaluate the impact of fructooligosaccharides (FOS) and galactooligosaccharides (GOS) on glycemia during oral glucose tolerance test (OGTT) and intestinal microbiota. A randomized double-blind cross-over study was performed with 35 adults treated with FOS and GOS for 14 days (16 g/day). Faeces sampling, OGTT and anthropometric parameters were performed. Short-term intake of high-dose prebiotics had adverse effect on glucose metabolism, as in FOS intervention demonstrated by OGTT (P < 0.001), and in GOS intervention demonstrated by fasting glucose (P < 0.05). A significant increase in the relative abundance of Bifidobacterium was observed both in FOS and GOS group, while the butyrate-producing bacteria like Phascolarctobacterium in FOS group and Ruminococcus in GOS group were decreased. A random forest model using the initial microbiota was developed to predict OGTT levels after prebiotic intervention with relative success (R = 0.726). Our study alerted even though FOS and GOS increased Bifidobacterium, they might have adverse effect on glucose metabolism by reducing butyrate-producing microbes. Individualized prebiotics intervention based on gut microbiome needs to be evaluated in future.
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Long-term use of probiotics Lactobacillus and Bifidobacterium has a prophylactic effect on the occurrence and severity of pouchitis: a randomized prospective study.
Tomasz, B, Zoran, S, Jarosław, W, Ryszard, M, Marcin, G, Robert, B, Piotr, K, Lukasz, K, Jacek, P, Piotr, G, et al
BioMed research international. 2014;:208064
Abstract
AIM: The aim of the study was to assess the impact of the long-term use of the composite probiotics in patients after restorative proctocolectomy. METHOD Forty-three patients (20 females and 23 males, aged 21 to 68 years) after restorative proctocolectomy were included in the study. After randomization patients were divided into placebo group and treatment group with oral intake of probiotic containing Lactobacillus acidophilus, Lactobacillus delbrueckii subsp. bulgaricus, and Bifidobacterium bifidus. Patients were investigated during initial visit and during final visit after 9 months. All patients were subjected to standard clinical and endoscopic examination with microscopic study of the specimens. Concentrations of calprotectin and pyruvate kinase isoenzyme M2-PK were determined in all cases. RESULTS The average severity of pouchitis and the number of patients with pouchitis significantly decrease after 9 months of the probiotic taking. The concentrations of calprotectin and pyruvate kinase isoenzyme M2-PK significantly decreased after the therapy. CONCLUSIONS Nine months of the probiotic treatment (Lactobacillus acidophilus, Lactobacillus delbrueckii subsp. bulgaricus, and Bifidobacterium bifidus) reduced the number of patients with pouchitis, decreased the PDAI score, and also decreased the fecal pyruvate kinase and calprotectin. The long-term probiotics use is safe and well accepted and can be an effective method of the pouchitis prevention.