A yeast fermentate improves gastrointestinal discomfort and constipation by modulation of the gut microbiome: results from a randomized double-blind placebo-controlled pilot trial.

BACKGROUND: Constipation and symptoms of gastrointestinal discomfort such as bloating are common among otherwise healthy individuals, but with significant impact on quality of life. Despite the recognized contribution of the gut microbiome to this pathology, little is known about which group(s) of microorganism(s) are playing a role. A previous study performed in vitro suggests that EpiCor® fermentate has prebiotic-like properties, being able to favorably modulate the composition of the gut microbiome. Therefore, the aim of this study was to investigate the effects of EpiCor fermentate in a population with symptoms of gastrointestinal discomfort and reduced bowel movements and to evaluate its effect at the level of the gut microbiome. METHODS: This pilot study was performed according to a randomized, double-blind, placebo-controlled parallel design. Eighty subjects with symptoms of gastrointestinal discomfort and constipation were allocated to one of two trial arms (placebo or EpiCor fermentate). Randomization was done in a stratified manner according to symptom severity, resulting in two subgroups of patients: severe and moderate. Daily records of gastrointestinal symptoms were assessed on a 5-point scale, and also stool frequency and consistency were documented during a 2-week run-in and a 6-week intervention phases. Averages over two-week intervals were calculated. Constipation-associated quality of life and general perceived stress were assessed at baseline and after 3 and 6 weeks of intervention. Fecal samples were also collected at these same time points. RESULTS: EpiCor fermentate led to a significant improvement of symptoms such as bloating/distension (p = 0.033 and p = 0.024 after 2 and 4 weeks of intervention, respectively), feeling of fullness (p = 0.004 and p = 0.023 after 2 and 4 weeks of intervention, respectively) and general daily scores (p = 0.046 after 2 weeks of intervention) in the moderate subgroup. A significant improvement in stool consistency was observed for the total population (p = 0.023 after 2 weeks of intervention) as well as for the severe subgroup (p = 0.046 after 2 weeks of intervention), and a nearly significant increase in stool frequency was detected for the total cohort (p = 0.083 and p = 0.090 after 2 and 4 weeks of intervention, respectively). These effects were accompanied by an improvement in constipation-associated quality of life and general perceived stress, particularly in the moderate subgroup. Members of the families Bacteroidaceae and Prevotellaceae, two groups of bacteria that have been previously reported to be deficient in constipated patients, were found to increase with EpiCor fermentate in the severe subgroup. In the moderate subgroup, a significant increase in Akkermansia muciniphila was observed. CONCLUSIONS: Despite the relatively low dose administered (500 mg/day), particularly when comparing to the high recommended doses for prebiotic fibers, EpiCor fermentate was able to modulate the composition of the gut microbiome, resulting in improvement of constipation-associated symptoms. Conversely, the reported increase in bowel movements may have altered the gut microbial community by increasing those groups of bacteria that are better adapted to a faster gastrointestinal transit time. TRIAL REGISTRATION: NCT03051399 at ClinicalTrials.gov. Retrospectively registered. Registration date: 13 February 2017.

A dried yeast fermentate selectively modulates both the luminal and mucosal gut microbiota and protects against inflammation, as studied in an integrated in vitro approach.

EpiCor, derived from Saccharomyces cerevisiae, has been shown to have immunomodulating properties in human clinical trials and in vitro. However, the underlying mechanisms behind its immune protection via the gut remain largely unknown. Therefore, the aim of this study was to use an integrated in vitro approach to evaluate the metabolism of EpiCor by the intestinal microflora, its modulating effect on the gut microbiota, and its anti-inflammatory activity on human-derived cell lines. Using the SHIME model, in combination with a mucus adhesion assay, has shown that low doses of EpiCor have a prebiotic-like modulatory effect on the luminal- and mucosa-associated microbiota. These include gradual changes in general community structure, reduction of potential pathogens, quantitative increase in lactobacilli, and qualitative modulation of bifidobacteria. Moreover, by combination of the SHIME with Caco-2 cells and Caco-2/THP1 cocultures, a significant decrease in pro-inflammatory cytokines was observed at the end of the treatment period.

Barcoded pyrosequencing analysis of the microbial community in a simulator of the human gastrointestinal tract showed a colon region-specific microbiota modulation for two plant-derived polysaccharide blends.

The combination of a Simulator of the Human Intestinal Microbial Ecosystem with ad hoc molecular techniques (i.e. pyrosequencing, denaturing gradient gel electrophoresis and quantitative PCR) allowed an evaluation of the extent to which two plant polysaccharide supplements could modify a complex gut microbial community. The presence of Aloe vera gel powder and algae extract in product B as compared to the standard blend (product A) improved its fermentation along the entire simulated colon. The potential extended effect of product B in the simulated distal colon, as compared to product A, was confirmed by: (i) the separate clustering of the samples before and after the treatment in the phylogenetic-based dendrogram and OTU-based PCoA plot only for product B; (ii) a higher richness estimator (+33 vs. -36 % of product A); and (iii) a higher dynamic parameter (21 vs. 13 %). These data show that the combination of well designed in vitro simulators with barcoded pyrosequencing is a powerful tool for characterizing changes occurring in the gut microbiota following a treatment. However, for the quantification of low-abundance species-of interest because of their relationship to potential positive health effects (i.e. bifidobacteria or lactobacilli)-conventional molecular ecological approaches, such as PCR-DGGE and qPCR, still remain a very useful complementary tool.

Paenibacillus cineris sp. nov. and Paenibacillus cookii sp. nov., from Antarctic volcanic soils and a gelatin-processing plant.

Seven strains of aerobic, endospore-forming bacteria were found in soil taken from an active fumarole on Lucifer Hill, Candlemas Island, South Sandwich archipelago, Antarctica, and four strains were from soil of an inactive fumarole at the foot of the hill. Amplified rDNA restriction analysis, 16S rDNA sequence comparisons, SDS-PAGE and routine phenotypic tests support the proposal of two novel species of Paenibacillus, Paenibacillus cineris sp. nov. and Paenibacillus cookii sp. nov., the type strains of which are LMG 18439T (=CIP 108109T) and LMG 18419T (=CIP 108110T), respectively. A further strain, isolated from a gelatin-production process, showed more than 99% 16S rDNA sequence similarity to the proposed P. cookii type strain and, although the gelatin isolate was atypical when compared with the fumarole isolates by repeated element primed-PCR, SDS-PAGE and phenotypic analyses, it was shown by DNA-DNA reassociation studies to belong to the same species. Strains of P. cookii produce spreading growth with motile microcolonies. Both species produce swollen sporangia that are typical for the genus, they both show 97.6% 16S rDNA sequence similarity to Paenibacillus azoreducens, they have 51.5-51.6 mol% G+C in their DNA and their major fatty acid is anteiso-C(15 : 0); however, fatty acids C(16 : 0) and anteiso-C(17 : 0) represent, respectively, 18 and 10 % of the total in P. cineris, but 11 and 20% in P. cookii.

Bacillus shackletonii sp. nov., from volcanic soil on Candlemas Island, South Sandwich archipelago.

A sample of mossy soil taken from the eastern lava flow of northern Candlemas Island, South Sandwich archipelago, yielded six isolates of aerobic, endospore-forming bacteria. Miniaturized routine phenotypic tests and other observations, amplified rDNA restriction analysis and SDS-PAGE analysis suggested that the strains represent a novel taxon. 16S rDNA sequence comparisons support the proposal of a novel species, Bacillus shackletonii sp. nov., the type strain of which is LMG 18435(T) (=CIP 107762(T)).

Bacillus luciferensis sp. nov., from volcanic soil on Candlemas Island, South Sandwich archipelago.

Aerobic, endospore-forming bacteria were found in soil taken from an active fumarole on Lucifer Hill, Candlemas Island, South Sandwich archipelago. Amplified rDNA restriction analysis, SDS-PAGE, repetitive element primed-PCR (rep-PCR) and routine phenotypic tests suggested that six of the isolates represent a novel taxon, and 16S rDNA sequence comparisons support the proposal of a novel species, Bacillus luciferensis sp. nov., the type strain of which is strain LMG 18422(T) (= CIP 107105(T)).