Efficacy and dose response of Lactiplantibacillus plantarum in diarrhea-predominant irritable bowel syndrome.

BACKGROUND: Probiotics have shown promise in alleviating symptoms of diarrhea-predominant irritable bowel syndrome (IBS-D); however, the certainty of evidence is low. Well-powered randomized controlled dose-ranging trials are warranted on promising single-strain candidates. AIM: To investigate the clinical efficacy of Lactiplantibacillus plantarum (L. plantarum) Lpla33 (DSM34428) in adults with IBS-D. METHODS: This is a randomized, double-blind, placebo-controlled, multi-center, and dose-ranging study. Three hundred and seven adults, 18-70 years of age, with IBS-D, according to Rome IV criteria, were allocated (1:1:1) to receive placebo or L. plantarum Lpla33 at 1 × 109 (1B) or 1 × 1010 (10B) colony-forming units/d over an 8-wk intervention period. The primary outcome was the change in IBS severity scoring system (IBS-SSS) total score after 8 wk, while secondary and exploratory outcomes included abdominal pain severity, IBS related quality of life, stool and microbial profile, and perceived stress. RESULTS: IBS-SSS was significantly reduced, after 8 wk, in participants receiving L. plantarum 1B (-128.45 ± 83.30; P < 0.001) and L. plantarum 10B (-156.77 ± 99.06; P < 0.001), compared to placebo (-58.82 ± 74.75). Further, a dose-ranging effect was observed, with a greater absolute reduction in the L. plantarum 10B group (P < 0.05). A reduction in sub-scores related to abdominal pain, abdominal distension, bowel habits, and quality of life was observed in both L. plantarum groups compared to placebo (P < 0.001). Further, 62.5% and 88.4% of participants administered L. plantarum 1B and 10B, respectively, were classified as stool consistency responders based on a reduction in diarrheal stool form, as compared to 26.3% in the placebo group (P < 0.001). In contrast, no significant shifts were observed in microbial diversity. CONCLUSION: L. plantarum Lpla33 (DSM34428) is well tolerated and improves IBS symptom severity with a dose-ranging effect and a corresponding normalization of bowel habits in adults with IBS-D.

Impact of a probiotic chewable tablet on stool habits and microbial profile in children with functional constipation: A randomized controlled clinical trial.

Constipation is a common and typically multifactorial childhood complaint, and the clinical management of childhood functional constipation (FC) is challenging. A randomized, single-blind, placebo-controlled, multi-center clinical trial was conducted in 92 children (47 from Beijing, China and 45 from Shanghai, China) aged 4-12 with FC according to Rome III criteria. Children were assigned to receive a probiotic chewable tablet (5 × 109 CFU/day, n = 47), consisting of Lactobacillus acidophilus DDS-1® and Bifidobacterium animalis subsp. lactis UABla-12™ or placebo (n = 45), twice daily for 4 weeks, followed by a week follow-up period. Results suggested that the probiotic group showed a faster and more pronounced normalization of stool frequency over the intervention period (3.15 vs. 1.83) when compared to placebo group (2.51 vs. 1.87). Meanwhile, the percentage of subjects with hard defecation decreased from 43 to 14% in the probiotic group, while the percentage of subjects with normal defecation increased from 56 to 80% in the probiotic group, further confirming the normalization of stools habits. This randomized controlled trial demonstrated the potential of a probiotic chewable tablet containing L. acidophilus DDS-1® and B. Lactis UABla-12™ as a daily probiotic dosage form for children with FC.

Lactobacillus acidophilus DDS-1 Modulates the Gut Microbial Co-Occurrence Networks in Aging Mice.

Age-related alterations in the gut microbiome composition and its impacts on the host's health have been well-described; however, detailed analyses of the gut microbial structure defining ecological microbe-microbe interactions are limited. One of the ways to determine these interactions is by understanding microbial co-occurrence patterns. We previously showed promising abilities of Lactobacillus acidophilus DDS-1 on the aging gut microbiome and immune system. However, the potential of the DDS-1 strain to modulate microbial co-occurrence patterns is unknown. Hence, we aimed to investigate the ability of L. acidophilus DDS-1 to modulate the fecal-, mucosal-, and cecal-related microbial co-occurrence networks in young and aging C57BL/6J mice. Our Kendall's tau correlation measures of co-occurrence revealed age-related changes in the gut microbiome, which were characterized by a reduced number of nodes and associations across sample types when compared to younger mice. After four-week supplementation, L. acidophilus DDS-1 differentially modulated the overall microbial community structure in fecal and mucosal samples as compared to cecal samples. Beneficial bacteria such as Lactobacillus, Oscillospira, and Akkermansia acted as connectors in aging networks in response to L. acidophilus DDS-1 supplementation. Our findings provided the first evidence of the DDS-1-induced gut microbial ecological interactions, revealing the complex structure of microbial ecosystems with age.

Effects of a 10-Strain Oral Probiotic on Parameters of Vaginal Health and Microbial Community: A Pilot Clinical Study.

OBJECTIVE: To investigate the clinical effects of a 10-strain probiotic on parameters of vaginal health in a pilot, open label study in women with intermediate Nugent score (NS) or vaginal pH >4.5. METHODOLOGY: A total of 43 healthy premenopausal women, ages 18 to 50 years, with NS of 4-6 or vaginal pH >4.5 were enrolled. Participants consumed a probiotic formulation (Feminine Support™), containing 8 lactobacilli and 2 bifidobacteria strains, with a daily dose of 2.5×1010 CFU for 28 (subgroup 1) or 42 (subgroup 2) days. Investigational visits occurred at day 0, 14, 28 and 42 with assessment of vaginal pH, NS and vaginal microbiota, via next-generation sequencing. RESULTS: A total of 36 participants were included in the analysis set, with 24 and 12 participants included in subgroups 1 and 2, respectively. In the analysis set, there was a significant reduction in vaginal pH, from baseline, at day 28 (mean change=-0.19, P = 0.047). Participants in subgroup 1 achieved a significant reduction in vaginal pH from baseline, at day 28 (mean change=-0.23, P = 0.029) and day 42 (mean change=-0.29, P = 0.008), while participants in subgroup 2 achieved a significant and quantitatively greater reduction in vaginal pH from baseline to day 42 (mean change=-0.64, P = 0.008). No significant changes in NS were reported, due in part to highly diverse baseline levels. Vaginal microbial abundance exhibited a majority lactobacilli abundance at baseline, which was maintained over the study period. Vaginal pH was inversely associated with lactobacilli abundance throughout the study (P < 0.005). The product was well tolerated with high compliance. Two participants reported adverse events with suspected causality, which were mild and resolved during the study. CONCLUSION: This 10-strain probiotic formulation was well tolerated and helped reduce vaginal pH in women with intermediate NS or elevated vaginal pH. The study product warrants a randomized controlled trial to further assess efficacy.

Corrigendum: Probiotics, Anticipation Stress, and the Acute Immune Response to Night Shift.

[This corrects the article DOI: 10.3389/fimmu.2020.599547.].

Streptococcus Thermophilus UASt-09 Upregulates Goblet Cell Activity in Colonic Epithelial Cells to a Greater Degree than other Probiotic Strains.

Probiotics have been widely used in maintaining gastrointestinal health, despite their actual mechanism remaining obscure. There are several hypotheses behind the beneficial effects of probiotics including the regulation of intestinal barrier function and improvement in immune responses in the gastrointestinal system. Multiple probiotics have been introduced in the market as effective dietary supplements in improving gastrointestinal integrity, but there are no or few studies that demonstrate their underlying mechanism. In the current study, we investigated and compared the efficacy of four probiotics (based on different bacterial species) in refining gastrointestinal health by improving mucus biosynthesis and intestinal immune response under in-vitro conditions. By analyzing the gene expression of mucus biosynthesis and intestinal immune response markers, we found that probiotic Streptococcus thermophilus UASt-09 showed promising potential in refining mucosal barrier and gastrointestinal health in human colonic epithelial cells, as compared to other commercial probiotics.

Lactobacillus acidophilus DDS-1 and Bifidobacterium lactis UABla-12 Improve Abdominal Pain Severity and Symptomology in Irritable Bowel Syndrome: Randomized Controlled Trial.

This randomized, double-blind, placebo-controlled, multi-center study investigated the clinical efficacy of two probiotic strains on abdominal pain severity and symptomology in irritable bowel syndrome (IBS). Three hundred and thirty adults, aged 18 to 70 years, with IBS according to Rome IV criteria were allocated (1:1:1) to receive placebo, Lactobacillus acidophilus DDS-1 (1 × 1010 CFU/day) or Bifidobacterium animalis subsp. lactis UABla-12 (1 × 1010 CFU/day) over six weeks. The primary outcome was the change in Abdominal Pain Severity - Numeric Rating Scale (APS-NRS). Over the intervention period, APS-NRS was significantly improved in both probiotic groups vs. placebo in absolute terms (DDS-1: -2.59 ± 2.07, p = 0.001; UABla-12: -1.56 ± 1.83, p = 0.001) and in percentage of significant responders (DDS-1: 52.3%, p < 0.001); UABla-12 (28.2%, p = 0.031). Significant amelioration vs. placebo was observed in IBS Symptom Severity Scale (IBS-SSS) scores for L. acidophilus DDS-1 (-133.4 ± 95.19, p < 0.001) and B. lactis UABla-12 (-104.5 ± 96.08, p < 0.001) groups, including sub-scores related to abdominal pain, abdominal distension, bowel habits and quality of life. Additionally, a significant normalization was observed in stool consistency in both probiotic groups over time and as compared to placebo. In conclusion, L. acidophilus DDS-1 and B. lactis UABla-12 improved abdominal pain and symptom severity scores with a corresponding normalization of bowel habits in adults with IBS.

Probiotics, Anticipation Stress, and the Acute Immune Response to Night Shift.

Introduction: Sleep disturbance and sleep disruption are associated with chronic, low grade inflammation and may underpin a range of chronic diseases in night shift workers. Through modulation of the intestinal microbiota, probiotic supplements may moderate the effects of sleep disruption on the immune system. The aim of this study was to examine 14 days of daily probiotic supplementation on the acute response of acute phase proteins and immune markers to sleep disruption associated with night shift work (Australia and New Zealand Clinical Trials Registry: 12617001552370). Methods: Individuals (mean age 41 ± 11 yrs; 74% female) performing routine night shift were randomly assigned to a probiotic group (1 × 1010 colony forming units (CFU) Lactobacillus acidophilus DDS-1 or 1 × 1010 CFU Bifidobacterium animalis subsp. lactis UABla-12) or placebo (n= 29 per group). Participants undertook a 14-day supplementation period that coincided with a period of no night shifts followed by two consecutive night shifts. Blood samples were collected prior to the start of supplementation (V1), prior to commencing the first night shift (V2), after the first night shift (V3) and after the second night shift (V4). Serum was assessed for markers of stress (cortisol), acute phase response (C reactive protein (CRP), erythrocyte sedimentation rate, pentraxin), adhesion markers (serum E-selectin, mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1), and serum cytokines (interleukin (IL)-1ra, IL-1ß, IL-6, tumor necrosis factor (TNF)-α, IL-10). Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI) and a Fitbit activity tracker. Results: The groups were well balanced on key markers and the probiotic strains were well tolerated. The 14-day supplementation period that coincided with typical night-day sleep-wake cycles leading up to night shift (V1 to V2) was associated with significant changes in the placebo group in the concentration of serum cortisol (p = 0.01), pentraxin (p = 0.001), MAdCAM-1 (p = 0.001), and IL-1ra (p=0.03). In contrast, probiotic supplementation moderated changes in these serum markers from V1 to V2. No significant interaction effects (time by group) were observed for the serum markers prior to and after night shift work following probiotic supplementation due to the substantial changes in the serum markers that occurred during the normal sleep period from V1 to V2. Conclusions: Probiotics may moderate the effects of anticipatory stress on the immune system in the lead up to night shift.

Impact of a probiotic product on bowel habits and microbial profile in participants with functional constipation: A randomized controlled trial.

OBJECTIVE: To investigate the clinical efficacy of a multi-strain probiotic product on bowel habits and microbial profile in participants with functional constipation. METHODS: This was a randomized, double-blind, placebo-controlled and parallel-arm study. Altogether 94 otherwise healthy adults aged 18 to 65 years with symptoms of functional constipation were randomized as part of the intention-to-treat population. The participants received a placebo or the probiotic product (1.5 × 1010 CFU/day), consisting of Lactobacillus acidophilus DDS-1, Bifidobacterium animalis subsp. lactis UABla-12, Bifidobacterium longum UABl-14 and Bifidobacterium bifidum UABb-10 over 4 weeks. Outcomes included the patient assessment of constipation-symptom (PAC-SYM) questionnaire, stool frequency and consistency, and microbial profile. RESULTS: There were no significant between-group differences in the PAC-SYM score, despite significant within-group differences (P < 0.001) over the study period. The probiotic group showed a faster normalization of stool frequency and consistency, with most participants achieving a normalized profile after 1 week. Fecal samples of the probiotic group exhibited higher relative abundance of Ruminococcaceae (P = 0.0047), including the Ruminococcus genus, and lower relative abundance of Erysipelotrichaceae (P = 0.0172) at end-point compared with baseline. Placebo group samples showed similar abundance profiles over the study, with the exception of Clostridiaceae, which was lower at the study end-point (P = 0.0033). Among treated participants, all four probiotic strains were significantly more abundant after the intervention. CONCLUSIONS: No significant differences were observed in symptomology, with both groups showing a more than 20% improvement. However, the probiotic helped modulate bowel function earlier than the placebo, with a corresponding shift to a more fibrolytic microbiota.

Lactobacillus acidophilus DDS-1 Modulates Intestinal-Specific Microbiota, Short-Chain Fatty Acid and Immunological Profiles in Aging Mice.

Distribution of the microbiota varies according to the location in the gastrointestinal (GI) tract. Thus, dysbiosis during aging may not be limited to faecal microbiota and extend to the other parts of the GI tract, especially the cecum and colon. Lactobacillus acidophilus DDS-1, a probiotic strain, has been shown to modulate faecal microbiota and its associated metabolic phenotype in aging mice. In the present study, we investigated the effect of L. acidophilus DDS-1 supplementation on caecal- and mucosal-associated microbiota, short-chain fatty acids (SCFAs) and immunological profiles in young and aging C57BL/6J mice. Besides differences in the young and aging control groups, we observed microbial shifts in caecal and mucosal samples, leading to an alteration in SCFA levels and immune response. DDS-1 treatment increased the abundances of beneficial bacteria such as Akkermansia spp. and Lactobacillus spp. more effectively in caecal samples than in mucosal samples. DDS-1 also enhanced the levels of butyrate, while downregulating the production of inflammatory cytokines (IL-6, IL-1ß, IL-1α, MCP-1, MIP-1α, MIP-1ß, IL-12 and IFN-γ) in serum and colonic explants. Our findings suggest distinct patterns of intestinal microbiota, improvements in SCFA and immunological profiles with DDS-1 supplementation in aging mice.

Lactobacillus acidophilus DDS-1 Modulates the Gut Microbiota and Improves Metabolic Profiles in Aging Mice.

Recent evidence suggests that gut microbiota shifts can alter host metabolism even during healthy aging. Lactobacillus acidophilus DDS-1, a probiotic strain, has shown promising probiotic character in vitro, as well as in clinical studies. The present study was carried out to investigate whether DDS-1 can modulate the host metabolic phenotype under the condition of age-affected gut microbial shifts in young and aging C57BL/6J mice. Collected fecal samples were analyzed using 16S rRNA gene sequencing for identifying gut microbiota and untargeted gas chromatography-mass spectrometry (GC-MS) metabolomics analysis. Gut microbial shifts were observed in the control groups (young and aging), leading to an alteration in metabolism. Principal coordinate analysis (PCoA) of microbiota indicated distinct separation in both the DDS-1-treated groups. L. acidophilus DDS-1 increased the relative abundances of beneficial bacteria, such as Akkermansia muciniphila and Lactobacillus spp., and reduced the relative levels of opportunistic bacteria such as Proteobacteria spp. Metabolic pathway analysis identified 10 key pathways involving amino acid metabolism, protein synthesis and metabolism, carbohydrate metabolism, and butanoate metabolism. These findings suggest that modulation of gut microbiota by DDS-1 results in improvement of metabolic phenotype in the aging mice.

A human origin strain Lactobacillus acidophilus DDS-1 exhibits superior in vitro probiotic efficacy in comparison to plant or dairy origin probiotics.

Background: The health benefits of probiotics are well established and known to be strain-specific. However, the role of probiotics obtained from different origins and their efficacy largely remains unexplored. The aim of this study is to investigate the in vitro efficacy of probiotics from different origins. Methods: Probiotic strains utilized in this study include Lactobacillus acidophilus DDS-1 (human origin), Bifidobacterium animalis ssp. lactis UABla-12 (human origin), L. plantarum UALp-05 (plant origin) and Streptococcus thermophilus UASt-09 (dairy origin). Screening assays such as in vitro digestion simulation, adhesion, cell viability and cytokine release were used to evaluate the probiotic potential. Results: All strains showed good resistance in the digestion simulation process, especially DDS-1 and UALp-05, which survived up to a range of 107 to 108 CFU/mL from an initial concentration of 109 CFU/mL. Two human colonic mucus-secreting cells, HT-29 and LS174T, were used to assess the adhesion capacity, cytotoxicity/viability, and cytokine quantification. All strains exhibited good adhesion capacity. No significant cellular cytotoxicity or loss in cell viability was observed. DDS-1 and UALp-05 significantly upregulated anti-inflammatory IL-10 and downregulated pro-inflammatory TNF-α cytokine production. All the strains were able to downregulate IL-8 cytokine levels. Conclusion: Of the 4 strains tested, DDS-1 demonstrated superior survival rates, good adhesion capacity and strong immunomodulatory effect under different experimental conditions.

Changes in bile acids, FGF-19 and sterol absorption in response to bile salt hydrolase active L. reuteri NCIMB 30242.

The size and composition of the circulating bile acid (BA) pool are important factors in regulating the human gut microbiota. Disrupted regulation of BA metabolism is implicated in several chronic diseases. Bile salt hydrolase (BSH)-active Lactobacillus reuteri NCIMB 30242, previously shown to decrease LDL-cholesterol and increase circulating BA, was investigated for its dose response effect on BA profile in a pilot clinical study. Ten otherwise healthy hypercholesterolemic adults, recruited from a clinical trial site in London, ON, were randomized to consume delayed release or standard release capsules containing L. reuteri NCIMB 30242 in escalating dose over 4 weeks. In another aspect, 4 healthy normocholesterolemic subjects with LDL-C below 3.4 mmol/l received delayed release L. reuteri NCIMB 30242 at a constant dose over 4 weeks. The primary outcome measure was the change in plasma BA profile over the intervention period. Additional outcomes included circulating fibroblast growth factor (FGF)-19, plant sterols and LDL-cholesterol as well as fecal microbiota and bsh gene presence. After one week of intervention subjects receiving delayed release L. reuteri NCIMB 30242 increased total BA by 1.13 ± 0.67 µmol/l (P = 0.02), conjugated BA by 0.67 ± 0.39 µmol/l (P = 0.02) and unconjugated BA by 0.46 ± 0.43 µmol/l (P = 0.07), which represented a greater than 2-fold change relative to baseline. Increases in BA were largely maintained post-week 1 and were generally correlated with FGF-19 and inversely correlated with plant sterols. This is the first clinical support showing that a BSH-active probiotic can significantly and rapidly influence BA metabolism and may prove useful in chronic diseases beyond hypercholesterolemia.

Bacterial bile metabolising gene abundance in Crohn's, ulcerative colitis and type 2 diabetes metagenomes.

We performed an analysis to determine the importance of bile acid modification genes in the gut microbiome of inflammatory bowel disease and type 2 diabetic patients. We used publicly available metagenomic datasets from the Human Microbiome Project and the MetaHIT consortium, and determined the abundance of bile salt hydrolase gene (bsh), 7 alpha-dehydroxylase gene (adh) and 7-alpha hydroxysteroid dehydrogenase gene (hsdh) in fecal bacteria in diseased populations of Crohn's disease (CD), Ulcerative Colitis (UC) and Type 2 diabetes mellitus (T2DM). Phylum level abundance analysis showed a significant reduction in Firmicute-derived bsh in UC and T2DM patients but not in CD patients, relative to healthy controls. Reduction of adh and hsdh genes was also seen in UC and T2DM patients, while an increase was observed in the CD population as compared to healthy controls. A further analysis of the bsh genes showed significant differences in the correlations of certain Firmicutes families with disease or healthy populations. From this observation we proceeded to analyse BSH protein sequences and identified BSH proteins clusters representing the most abundant strains in our analysis of Firmicute bsh genes. The abundance of the bsh genes corresponding to one of these protein clusters was significantly reduced in all disease states relative to healthy controls. This cluster includes bsh genes derived from Lachospiraceae, Clostridiaceae, Erysipelotrichaceae and Ruminococcaceae families. This metagenomic analysis provides evidence of the importance of bile acid modifying enzymes in health and disease. It further highlights the importance of identifying gene and protein clusters, as the same gene may be associated with health or disease, depending on the strains expressing the enzyme, and differences in the enzymes themselves.

Emerging science of the human microbiome.

The human gastrointestinal tract hosts a large number of microbial cells which exceed their mammalian counterparts by approximately 3-fold. The genes expressed by these microorganisms constitute the gut microbiome and may participate in diverse functions that are essential to the host, including digestion, regulation of energy metabolism, and modulation of inflammation and immunity. The gut microbiome can be modulated by dietary changes, antibiotic use, or disease. Different ailments have distinct associated microbiomes in which certain species or genes are present in different relative quantities. Thus, identifying specific disease-associated signatures in the microbiome as well as the factors that alter microbial populations and gene expression will lead to the development of new products such as prebiotics, probiotics, antimicrobials, live biotherapeutic products, or more traditional drugs to treat these disorders. Gained knowledge on the microbiome may result in molecular lab tests that may serve as personalized tools to guide the use of the aforementioned products and monitor interventional progress.

The human microbiome and bile acid metabolism: dysbiosis, dysmetabolism, disease and intervention.

INTRODUCTION: Recent evidence indicates that the human gut microbiome plays a significant role in health and disease. Dysbiosis, defined as a pathological imbalance in a microbial community, is becoming increasingly appreciated as a 'central environmental factor' that is both associated with complex phenotypes and affected by host genetics, diet and antibiotic use. More recently, a link has been established between the dysmetabolism of bile acids (BAs) in the gut to dysbiosis. AREAS COVERED: BAs, which are transformed by the gut microbiota, have been shown to regulate intestinal homeostasis and are recognized as signaling molecules in a wide range of metabolic processes. This review will examine the connection between BA metabolism as it relates to the gut microbiome and its implication in health and disease. EXPERT OPINION: A disrupted gut microbiome, including a reduction of bile salt hydrolase (BSH)-active bacteria, can significantly impair the metabolism of BAs and may result in an inability to maintain glucose homeostasis as well as normal cholesterol breakdown and excretion. To better understand the link between dysbiosis, BA dysmetabolism and chronic degenerative disease, large-scale metagenomic sequencing studies, metatranscriptomics, metaproteomics and metabolomics should continue to catalog functional diversity in the gastrointestinal tract of both healthy and diseased populations. Further, BSH-active probiotics should continue to be explored as treatment options to help restore metabolic levels.

Improvement of gastrointestinal health status in subjects consuming Lactobacillus reuteri NCIMB 30242 capsules: a post-hoc analysis of a randomized controlled trial.

OBJECTIVE: Gastrointestinal (GI) symptoms are conditions that are frequently observed in clinical practice. A post-hoc analysis has been undertaken to evaluate the effect of bile salt hydrolase-active L. reuteri NCIMB 30242 on GI health status based on Rome III questionnaire response in otherwise healthy hypercholesterolemic subjects. RESEARCH DESIGN/METHODS: A total of 127 subjects received either L. reuteri NCIMB 30242 or placebo capsules over a 9-week intervention in a randomized, double-blind, placebo-controlled, parallel-arm, multicenter study. Subjects were asked to complete the Rome III diagnostic GI questionnaire prior to the baseline and end point visits of the clinical study. MAIN OUTCOME MEASURE: GI health status was evaluated, per questionnaire, by assessing all questions with 5- or 7-point response scales for symptoms of the stomach and intestines. RESULTS: Subjects receiving L. reuteri NCIMB 30242 reported significant improvements in general GI health status (p = 0.029) and in symptoms related to diarrhea (p = 0.018) as compared to placebo over the intervention period. Further, a greater proportion of L. reuteri-treated subjects showed improved general GI health status (p = 0.042) and improved diarrhea symptoms (p = 0.03). CONCLUSIONS: L. reuteri NCIMB 30242 capsules appear to be well tolerated and potentially beneficial for GI health status. Further clinical investigation is warranted for the treatment of functional GI disorders.

Oral supplementation with probiotic L. reuteri NCIMB 30242 increases mean circulating 25-hydroxyvitamin D: a post hoc analysis of a randomized controlled trial.

CONTEXT: Low serum 25-hydroxyvitamin D is a risk factor for osteoporosis, cardiovascular disease, diabetes, and cancer. Disruption of noncholesterol sterol absorption due to cholesterol-lowering therapies may result in reduced fat-soluble vitamin absorption. OBJECTIVE: We have previously reported on the cholesterol-lowering efficacy and reduced sterol absorption of probiotic bile salt hydrolase active Lactobacillus reuteri NCIMB 30242; however, the effects on fat-soluble vitamins was previously unknown and the objective of the present study. DESIGN, SETTINGS, PATIENTS, AND INTERVENTION: The study was double-blind, placebo-controlled, randomized, parallel-arm, multicenter lasting 13 weeks. A total of 127 otherwise healthy hypercholesterolemic adults with low-density lipoprotein-cholesterol >3.4 mmol/L, triglycerides <4.0 mmol/L, and body mass index of 22 to 32 kg/m² were included. Subjects were recruited from 6 private practices in Prague, Czech Republic, and randomized to consume L. reuteri NCIMB 30242 or placebo capsules over a 9-week intervention period. OUTCOME MEASURES: The primary outcome measure was the change in serum low-density lipoprotein-cholesterol over the 9-week intervention. Analysis of fat-soluble vitamins at weeks 0 and 9 were performed post hoc. RESULTS: There were no significant differences between L. reuteri NCIMB 30242 and placebo capsule groups in serum vitamin A, vitamin E, or ß-carotene or dietary intake over the intervention period (P > .05). L. reuteri NCIMB 30242 increased serum 25-hydroxyvitamin D by 14.9 nmol/L, or 25.5%, over the intervention period, which was a significant mean change relative to placebo of 17.1 nmol/L, or 22.4%, respectively (P = .003). CONCLUSIONS: To our knowledge, this is the first report of increased circulating 25-hydroxyvitamin D in response to oral probiotic supplementation.

Oral probiotic microcapsule formulation ameliorates non-alcoholic fatty liver disease in Bio F1B Golden Syrian hamsters.

The beneficial effect of a microencapsulated feruloyl esterase producing Lactobacillus fermentum ATCC 11976 formulation for use in non-alcoholic fatty liver disease (NAFLD) was investigated. For which Bio F1B Golden Syrian hamsters were fed a methionine deficient/choline devoid diet to induce non-alcoholic fatty liver disease. Results, for the first time, show significant clinical benefits in experimental animals. Examination of lipids show that concentrations of hepatic free cholesterol, esterified cholesterol, triglycerides and phospholipids were significantly lowered in treated animals. In addition, serum total cholesterol, triglycerides, uric acid and insulin resistance were found to decrease in treated animals. Liver histology evaluations showed reduced fat deposits. Western blot analysis shows significant differences in expression levels of key liver enzymes in treated animals. In conclusion, these findings suggest the excellent potential of using an oral probiotic formulation to ameliorate NAFLD.

Cholesterol lowering with bile salt hydrolase-active probiotic bacteria, mechanism of action, clinical evidence, and future direction for heart health applications.

INTRODUCTION: Cardiovascular diseases (CVD) are the leading cause of global mortality and morbidity. Current CVD treatment methods include dietary intervention, statins, fibrates, niacin, cholesterol absorption inhibitors, and bile acid sequestrants. These formulations have limitations and, thus, additional treatment modalities are needed. Probiotic bacteria, especially bile salt hydrolase (BSH)-active probiotic bacteria, have demonstrated cholesterol-lowering efficacy in randomized controlled trials. AREAS COVERED: This review describes the current treatments for CVD and the need for additional therapeutics. Gut microbiota etiology of CVD, cholesterol metabolism, and the role of probiotic formulations as therapeutics for the treatment and prevention of CVD are described. Specifically, we review studies using BSH-active bacteria as cholesterol-lowering agents with emphasis on their cholesterol-lowering mechanisms of action. Potential limitations and future directions are also highlighted. EXPERT OPINION: Numerous clinical studies have concluded that BSH-active probiotic bacteria, or products containing them, are efficient in lowering total and low-density lipoprotein cholesterol. However, the mechanisms of action of BSH-active probiotic bacteria need to be further supported. There is also the need for a meta-analysis to provide better information regarding the therapeutic use of BSH-active probiotic bacteria. The future of BSH-active probiotic bacteria most likely lies as a combination therapy with already existing treatment options.