To innovate in a better and more sustainable way, Gnosis by Lesaffre has developed, with a partner, a new dynamic model that mimics the human model in preclinical stages called the gut-on-chip model.
‘Exploring life to improve living’ is what we do at Gnosis by Lesaffre in order to provide innovative ingredients through biotransformation, which is dedicated to improving human health. To innovate better, faster and in a more sustainable way, we are moving toward more efficient models.
- Better: through models closer to human beings.
- Faster: through reducing the waiting time to obtain results.
- Sustainable: through adapting our science to ingredients made from biotransformation and making sure our agricultural areas remain viable for producing all our important micro-organisms.
Here at Gnosis by Lesaffre, we develop new models for evaluating the health effects of our products without using animal testing. Our approach to innovation is fully in line with the 3Rs principle, which strives to improve animal welfare in research:
- Replace: we develop news pre-clinical models in place of animal models
- Reduce: our new models need fewer operations
- Refine: we develop models closer to the human physiology
New Models will Reduce Translational Failure
Our new research aims to harness more human-relevant models that can reduce translational failure inherent to current preclinical models (animal models, 2D Cell Line Culture or Organoid Suspension Culture).
To do this, we have teamed up with an innovative start-up called Emulate. Emulate, is an innovator in creating new dynamic preclinical models based on a chip: the ‘Organs-on-Chips’ technology, which is will serve as the next generation in vitro models to emulate biology and predict the human response.
The technology consists of recreating cellular microenvironments with 3D human-derived cells. To do this, intestinal endothelial cells coming from pre-qualified biopsies are incorporated into a ‘chip’ and then are exposed to mechanical forces, which emulate in vivo physiology. Under these dynamic conditions, cells differentiate into distinctive populations and structures. From an intestinal biopsy, the model allows for the creation of the intestinal barrier and to form microvilli. This is quite different from the conventional cell culture method, which is limited to largely undifferentiated cell populations and lacks any type of physical stimuli. Through controlling for different experimental parameters and multiple measurements, the model allows our experts to evaluate the biochemical, genetic, and cellular responses of ingredients such as probiotics.
Validating the New Model with LifeinU™ BSCU1
To validate this new dynamic model in the field of immune response, we have used our well-studied probiotic LifeinU™ BSCU1 (Bacillus subtilis strain CNCM I-2745) that is already known to have a strong effect on immunity, which has been backed up by strong science, including a clinical study1. This randomized double-blind, placebo-controlled study has shown that the probiotic significantly reduces the frequency of upper respiratory tract infections and increases the secretory immunoglobulin A (sIgA) in the intestine and in the saliva. To test the model on the immune response, our researchers have used the gut-on-chip, which shows normal epithelial villus morphology and architecture and combines it with immune cells. Researchers then exposed this intestinal environment to a probiotic2.
Intestinal Immune Response to Probiotics
The co-culture of the organoid in the chips with the probiotic LifeinU™ BSCU1 revealed firstly that the morphology of the intestine model and the endothelium has stayed normal. Secondly, LifeinU™BSCU1 co-culture shows a high level of intestinal tight junction protein expression and maintains a tight barrier. This suggests that the probiotic may contribute to reducing the gut permeability. Increased gut permeability has been associated with impaired immune responses and numerous metabolic disorders. Thirdly, the effect of the probiotic on the integrity of the gut mucosal is suggested by its impact on the regulation of ionic channels and cell receptors. Finally, the model shows that LifeinU™ BSCU1 significantly increases the sIgA in the intestinal lumen, which is consistent with previous human clinical trial.
This research confirms that this gut-on-chip model may by suitable for future estimates and deeper understanding of the clinically observed impacts of the probiotics LifeinU™ BSCU1 on the gut immune system. Moreover, this model provides a revolutionary window into human biology and disease and opens many new doors to highlight the mechanisms by which developed ingredients/probiotics can provide health benefits.
1 Lefevre M et al. Probiotic strain LifeinU™ BSCU1 stimulates immune system of elderly during common infectious disease period: a randomized, double-blind placebo-controlled study. Immunity & Ageing (2015) 12:24; -DOI 10.1186/s12979-015-0051-y.
2 Reference : Gnosis by Lesaffre study
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