Unravelling the central role of the gut in preserving lifelong health

“’Trusting our gut’ goes beyond serving as a barometer for sound instinctive decision-making; it acts as a beacon leading us to well-being,” says Dr. Ingrid Renes, Senior Team Leader & Principal Scientist, Gut Biology. Decades of scientific research have underscored the GI tract’s pivotal role in preserving our health. Here, we explore the latest science and technologies that reveal the intricate relationship between nutrition and gut health, offering insights into strategies for optimizing our well-being throughout every stage of life.”

Why is the gut important for our health?

‘The gut’, formally referred to as the gastrointestinal (GI) tract, serves as a multifunctional powerhouse. Beyond its role in digesting food and processing nutrients, it acts as a vital command center for our health, establishing a protective barrier between the inside and outside world, limiting the translocation of potentially harmful substances and microbes from the gut lumen into the bloodstream, and safeguarding us from disease. Furthermore, the gut translates dietary and microbial signals to support immune and metabolic development and function. It also influences our mental well-being by playing an instrumental role in the complex communication of the gut-brain axis.

“But when we discuss ‘gut health’, we’re often referring to the trillions of microorganisms residing in our GI tract, collectively known as the gut microbiota and their functioning in relation to health. Yet, what is often overlooked is that it’s our gut that balances the delicate relationship between the external environment, internal milieu and microbes within,” Dr. Ingrid Renes notes.

At Danone Research & Innovation, we have been at the forefront of gut health and nutritional science for decades. Particularly over the past ten years, we have achieved significant milestones with the aid of sophisticated tools, such as the TIM-1, Tiny TIM and SHIME in vitro models.

Enhancing our understanding of the gut via exploratory research models

TIM-1
The TIM-1, or ‘TNO Intestinal Model’, was co-developed with the Netherlands Organisation for Applied Scientific Research (TNO) over twenty years ago. This innovative tool simulates the conditions of the upper GI tract (i.e., stomach and small intestine), enhancing our understanding of nutritional behavior under specific gastric and intestinal conditions. TIM-1 provides a glimpse into the gut’s control center, shedding light on key aspects of absorption and digestion. It allows us to address questions such as which minerals are soluble for uptake by the small intestine, whether lipids form a cream layer under certain gastric conditions, and how fast proteins and lipids are digested.

“The model can mimic the upper GI tract across various life-stages – including infants, adults and the elderly – and health conditions. Whether in a state of health, experiencing mild digestive disorders or disease, it offers valuable insights into how different conditions may affect speed of digestion and nutrient absorption. Notably, TIM-1 has been key in the development of improved nutritional solutions for critically ill patients,” Dr. Ingrid Renes explains.

For patients who rely on tube feeding, for example, challenges may arise when stomach emptying is delayed due to illness or medication. Consequently, the extended retention of food in the stomach can impact gastro-intestinal tolerance. TIM-1 has helped us identify nutritional solutions that spend less time in the stomach, are better tolerated and thereby support such patients recovery.

Tiny TIM
Tiny TIM takes our scientific capabilities one step further by featuring a stomach model resembling that of a human. Previous studies featuring Tiny TIM have demonstrated how infant formula behaves in the baby’s stomach. This research has led to our latest breakthrough: an innovative formula concept for infants containing large, milk phospholipid-coated lipid droplets and dairy lipids that closely mimic the size, structure and composition of lipids globules found in human ¹An infant formula with large, milk phospholipid-coated lipid droplets containing a mixture of dairy and vegetable lipids supports adequate growth and is well tolerated in healthy, term infants. … Continue reading, ²An Infant Formula with Large, Milk Phospholipid-Coated Lipid Droplets Supports Adequate Growth and Is Well-Tolerated in Healthy, Term Asian Infants. Danone Research & Innovations. Published 2022 … Continue reading

Depending on the specific research issue we are addressing, both the TIM-1 and Tiny TIM tools offer adjustable infant or adult settings, allowing us to carry out the digestion process in real time. This way, samples can then be collected at various stages, enabling assessment of digesta bioactivity on gut-on-chip models or the survival of probiotics.

According to Dr. Ingrid Renes: “These cutting-edge models help us delve into the intricate ecosystem of the gut and its microbial connections, enriching our understanding of overall health, including cognitive well-being. While we are in the early stages of comprehending gut-brain interventions and their potential in preventing neurodevelopmental disorders, our primary focus remains on unravelling the central role of the gut. Through modulation of the gut microbiota, we aim to improve health across the human lifespan, catering to diverse populations and varying health conditions”.

Optimizing health by balancing the gut microbiota

SHIME
At the forefront of this exploration is the Simulator of Human Intestinal Microbial Ecosystem, or SHIME model. Housed within Danone Research & Innovation’s facility in Singapore, SHIME simulates interactions between the microbiota and various biotic solutions in the large intestine. Like TIM-1, it provides valuable insights concerning the behavior of human microbiota extractions across different stages of life and health conditions.

“The SHIME model is particularly adept at demonstrating how an imbalance in the gut microbiota – that often occurs in real life – can be addressed through the administration of prebiotics, probiotics, postbiotics or synbiotics, which help restore the gut’s microbial equilibrium”, says Dr. Ingrid Renes.

“We can also collect fermentation samples that emulate the human colon’s fermentation process and incorporate them into gut-on-chip models or gut organoids. This approach allows for an in-depth analysis of how the gut barrier and other intestinal cell functions are affected. By inputting different conditions, nutritional solutions and basal microbiota compositions into the models, we are provided with a comprehensive picture of the multifaceted factors influencing gut function and digestive processes in diverse groups with distinct health needs”.

All these innovative tools help us streamline our scientific research, for example, by circumventing the complexities of collecting blood samples from infants. They serve as a foundation to refine hypotheses before advancing into clinical trials.

This comprehensive array of in vitro models provides Danone Research & Innovation with unmatched expertise. They act as a crucible for scientific discovery, empowering us to address the intricacies of gut health with precision and adaptability. These models underscore our dedication to crafting targeted health interventions and pushing the boundaries of nutritional science.

From models to humans

While cutting-edge technologies have propelled scientific discovery, they can only take us so far. Combining these tools with other in vitro methods enriches our comprehension of the gut epithelial cells’ protective functions and the intricate communication among various cell types — fibroblasts, immune cells, microbes — as well as the interplay between neurons and gut epithelial cells. It is this holistic approach that contributes to our unique understanding of how to support the gut for lifelong health.

Our experts at Danone Research & Innovation also glean insights that inform the development of nutritional and biotic strategies by leveraging clinical, observational, and intervention studies, alongside the sophisticated data analytics and gut models. These strategies are tailored to bolster the dietary needs of specific groups, including those with Parkinson’s, cancer, the elderly and individuals with swallowing difficulties.

Dr. Ingrid Renes highlights: “There is much to learn from studying healthy subjects as well. Through extensive, collaborative research projects and clinical studies, we examine vast populations to grasp the health necessities of millions. Projects like The Human Diet and Microbiome Initiative (THDMI), The American Gut Project, and Le French Gut grant us the opportunity to analyze samples from varied demographics, painting a global portrait of robust ³Global branches and local states of the human gut microbiome define associations with environmental and intrinsic factors. Danone Research & Innovations. Published 2023 … Continue reading. These initiatives underscore our leadership in deciphering how eating patterns impact human microbiome composition”.

Aging in the best of health

Looking ahead, a profound understanding of the gut — especially the gut barrier and the microbiome — is imperative. Continually enhancing biotics to modulate the gut microbiome, thereby rectifying imbalances and dysbiosis, is a crucial strategy for optimizing health. Investigating the effects of aging on gut and immunenescence, inflammaging and overall health unveils exciting new research opportunities. Addressing common complaints among adults and infants, such as digestive discomfort and cramping, will empower individuals to thrive throughout life.

Dr. Ingrid Renes envisions a future where nutrition is tailored to each person’s unique health requirements: “I anticipate that we’ll be able to offer highly personalized nutritional solutions. Understanding the interplay between the microbiome, gut, immune cells, and neurons throughout the lifespan, and examining the aging process and its complex interactions, will be pivotal in devising superior nutritional strategies for everyone. By establishing partnerships with leading experts, academic institutions, and medical centers globally, and utilizing our advanced gut models and expertise, we aim to demystify the intricate microbiome-gut-wellness connection and expedite our advancements”.

Learn more about the work Danone Research & Innovation conducts on Gut Health.