Preclinical Trials for Gut Support
A look at four different studies are highlighted in this section.
1. Possemiers, S., et al. 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. J Agric Food Chem 2013, 61 (39), 9380-9392. [Online reference: http://www.ncbi.nlm.nih.gov/pubmed/24006902]
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.
2. Marzorati, M., et al. The HMI module: a new tool to study the Host-Microbiota Interaction in the human gastrointestinal tract in vitro. BMC Microbiol 2014, 14 (1), 133. [Online reference: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4039060/]
Background: Recent scientific developments have shed more light on the importance of the host-microbe interaction, particularly in the gut. However, the mechanistic study of the host-microbe interplay is complicated by the intrinsic limitations in reaching the different areas of the gastrointestinal tract (GIT) in vivo. In this paper, we present the technical validation of a new device - the Host-Microbiota Interaction (HMI) module - and the evidence that it can be used in combination with a gut dynamic simulator to evaluate the effect of a specific treatment at the level of the luminal microbial community and of the host surface colonization and signaling.
Results: The HMI module recreates conditions that are physiologically relevant for the GIT: i) a mucosal area to which bacteria can adhere under relevant shear stress (3 dynes cm−2); ii) the bilateral transport of low molecular weight metabolites (4 to 150 kDa) with permeation coefficients ranging from 2.4 × 10−6 to 7.1 × 10−9 cm sec−1; and iii) microaerophilic conditions at the bottom of the growing biofilm (PmO2 = 2.5 × 10−4 cm sec−1). In a long-term study, the host’s cells in the HMI module were still viable after a 48-hour exposure to a complex microbial community. The dominant mucus-associated microbiota differed from the luminal one and its composition was influenced by the treatment with a dried product derived from yeast fermentation. The latter - with known anti-inflammatory properties - induced a decrease of pro-inflammatory IL-8 production between 24 and 48 h.
Conclusions: The study of the in vivo functionality of adhering bacterial communities in the human GIT and of the localized effect on the host is frequently hindered by the complexity of reaching particular areas of the GIT. The HMI module offers the possibility of co-culturing a gut representative microbial community with enterocyte-like cells up to 48 h and may therefore contribute to the mechanistic understanding of host-microbiome interactions.
Heat stress results in a multitude of biological and physiological responses which can become lethal if not properly managed. It has been shown that heat stress causes significant adverse effects in both human and animals. Different approaches have been proposed to mitigate the adverse effects caused by heat stress, among which are special diet and probiotics. We characterized the effect of the yeast fermentate EpiCor (EH) on the prevention of heat stress-related complications in rats. We found that increasing the body temperature of animals from 37.1±0.2 to 40.6±0.2°C by exposure to heat (45°C for 25min) resulted in significant morphological changes in the intestine. Villi height and total mucosal thickness decreased in heat-stressed rats pre-treated with PBS in comparison with control animals not exposed to the heat. Oral treatment of rats with EH before heat stress prevented the traumatic effects of heat on the intestine. Changes in intestinal morphology of heat-stressed rats, pre-treated with PBS resulted in significant elevation of lipopolysaccharides (LPS) level in the serum of these animals. Pre-treatment with EH was effective in the prevention of LPS release into the bloodstream of heat-stressed rats. Our study revealed that elevation of body temperature also resulted in a significant increase of the concentration of vesicles released by erythrocytes in rats, pre-treated with PBS. This is an indication of a pathological impact of heat on the erythrocyte structure. Treatment of rats with EH completely protected their erythrocytes from this heat-induced pathology. Finally, exposure to heat stress conditions resulted in a significant increase of white blood cells in rats. In the group of animals pre-treated with EH before heat stress, the white blood cell count remained the same as in non-heated controls. These results showed the protective effect of the EH product in the prevention of complications, caused by heat stress.
Aims: To evaluate efficacy of Saccharomyces cerevisiae fermentate prebiotic (EH) in protection of intestinal barrier integrity in rats during heat stress, to analyze the impact of heat stress and preventive treatment with EH on the structure of the gut microbiota.
Methods and results: Two groups of rats were treated orally with EH or phosphate-buffered saline for 14 days. On day 15, half of the rats in each group were exposed to heat stress conditions, while control animals were kept at room temperature. Histological and Western blot analyses of the intestine, culture-based microbiological analysis and high-throughput 16S rRNA sequencing for the gut microbiota were performed for each rat. Exposure of animals to heat stress conditions resulted in inhibition of tight junction (TJ) proteins expression, decrease of Paneth and goblet cells, decrease of beneficial and increase of pathogenic bacteria. Oral treatment of rats with EH before stress significantly prevents these adverse effects by elevation of the gut beneficial bacteria, particularly butyrate-producing bacteria.
Conclusions: Essential effect of EH in protection of intestinal barrier integrity during heat stress is connected with beneficial modulation of the gut microbiota.
Significance and impact of the study: Our results will contribute to the development of new approaches to prevention of heat stress-related complications.
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