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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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2.
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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3.
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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4.
The effect of dietary fiber (oat bran) supplement on blood pressure in patients with essential hypertension: A randomized controlled trial.
Xue, Y, Cui, L, Qi, J, Ojo, O, Du, X, Liu, Y, Wang, X
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2021;(8):2458-2470
Abstract
BACKGROUND AND AIMS Insufficient dietary fiber (DF) intake is associated with increased blood pressure (BP) and the mode of action is unclear. The intake of DF supplements by participants in previous interventional studies was still far below the amount recommended by the World Health Organization. Therefore, this study aims to explore the effect of supplementing relatively sufficient DF on BP and gut microbiota in patients with essential hypertension (HTN). METHODS AND RESULTS Fifty participants who met the inclusion criteria were randomly divided into the DF group (n = 25) and control group (n = 25). All the participants received education on regular dietary guidance for HTN. In addition to dietary guidance, one bag of oat bran (30 g/d) supplement (containing DF 8.9 g) was delivered to the DF group. The office BP (oBP), 24 h ambulatory blood pressure, and gut microbiota were measured at baseline and third month. After intervention, the office systolic blood pressure (oSBP; P < 0.001) and office diastolic blood pressure (oDBP; P < 0.028) in the DF group were lower than those in the control group. Similarly, the changes in 24hmaxSBP (P = 0.002), 24hmaxDBP (P = 0.001), 24haveSBP (P < 0.007), and 24haveDBP (P = 0.008) were greater in the DF group than in the control group. The use of antihypertensive drugs in the DF group was significantly reduced (P = 0.021). The β diversity, including Jaccard (P = 0.008) and Bray-Curtis distance (P = 0.004), showed significant differences (P < 0.05) between two groups by the third month. The changes of Bifidobacterium (P = 0.019) and Spirillum (P = 0.006) in the DF group were significant. CONCLUSIONS Increased DF (oat bran) supplement improved BP, reduced the amount of antihypertensive drugs, and modulated the gut microbiota. TRIAL REGISTRATION NUMBER ChiCTR1900024055.
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5.
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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6.
β-Galactooligosaccharide in Conjunction With Low FODMAP Diet Improves Irritable Bowel Syndrome Symptoms but Reduces Fecal Bifidobacteria.
Wilson, B, Rossi, M, Kanno, T, Parkes, GC, Anderson, S, Mason, AJ, Irving, PM, Lomer, MC, Whelan, K
The American journal of gastroenterology. 2020;(6):906-915
Abstract
INTRODUCTION The low FODMAP diet (LFD) reduces symptoms and bifidobacteria in irritable bowel syndrome (IBS). β-galactooligosaccharides (B-GOS) may reduce the symptoms and increase bifidobacteria in IBS. We investigated whether B-GOS supplementation alongside the LFD improves IBS symptoms while preventing the decline in bifidobacteria. METHODS We performed a randomized, placebo-controlled, 3-arm trial of 69 Rome III adult patients with IBS from secondary care in the United Kingdom. Patients were randomized to a sham diet with placebo supplement (control) or LFD supplemented with either placebo (LFD) or 1.4 g/d B-GOS (LFD/B-GOS) for 4 weeks. Gastrointestinal symptoms, fecal microbiota (fluorescent in situ hybridization and 16S rRNA sequencing), fecal short-chain fatty acids (gas-liquid chromatography) and pH (probe), and urine metabolites (H NMR) were analyzed. RESULTS At 4 weeks, adequate symptom relief was higher in the LFD/B-GOS group (16/24, 67%) than in the control group (7/23, 30%) (odds ratio 4.6, 95% confidence interval: 1.3-15.6; P = 0.015); Bifidobacterium concentrations (log10 cells/g dry weight) were not different between LFD and LFD/B-GOS but were lower in the LFD/B-GOS (9.49 [0.73]) than in the control (9.77 [0.41], P = 0.018). A proportion of Actinobacteria was lower in LFD (1.9%, P = 0.003) and LFD/B-GOS (1.8%, P < 0.001) groups than in the control group (4.2%). Fecal butyrate was lower in the LFD (387.3, P = 0.028) and LFD/B-GOS (346.0, P = 0.007) groups than in the control group (609.2). DISCUSSION The LFD combined with B-GOS prebiotic produced a greater symptom response than the sham diet plus placebo, but addition of 1.4 g/d B-GOS did not prevent the reduction of bifidobacteria. The LFD reduces fecal Actinobacteria and butyrate thus strict long-term use should not be advised.
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7.
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.