Recent research argues that organ-on-chip (OoC) models address a major gap in current nutrition research — the limited capacity to capture the complex interactions among diet, gut microbiota, and human organs. These models enable scientists to study nutrient absorption, barrier integrity, and host-microbiota interactions, providing human-relevant insights. Nutrition Insight speaks to the lead experts to learn about the future of nutrition research in a One Health world.
This framework by the WHO is based on understanding the interconnectedness and interdependence of human, animal, and environmental health, living in shared ecosystems.
Nutrition plays a major role in boosting health, food security, and sustainability, says Dr. Manuela Cassotta, member of the Research Group on Foods, Nutritional Biochemistry & Health at the Universidad Europea del Atlántico, Spain.
OoCs are slated to bring significant contributions to the One Health goals, believe professor Maurizio Battino, Ph.D., department of Clinical Sciences, and Dr. Francesca Giampieri, assistant professor in Nutrition at Università Politecnica delle Marche, Italy.
Their review examines the potential of OoCs within the One Health framework, focusing on their ability to replicate human and animal organ functions, applications in food safety and ecotoxicology, and their use in studying food components’ health effects.
For instance, such models have been used in food safety to see how food-chain pollutants cause subtle gene expression changes and stress responses, note the researchers. They believe that the tech can change the way new foods, like cultured meat or edible insects, undergo safety testing.
What animal studies often miss
The researchers state that OoC models replicate human-specifics that only conventional models can approximate.
“For example, advanced intestine-on-chip systems reproduce peristaltic motion, fluid flow, gut microbiota interactions, and oxygen gradients under controlled conditions, enabling the detailed study of nutrient absorption, barrier integrity, and host-microbiota crosstalk in a human-relevant setting,” says Battino. “This is critical because rodent gut physiology and microbiota composition differ substantially from humans, making translation of findings uncertain.”
“In nutrition research, a major challenge is the species-specific metabolism of dietary compounds: rodents often generate metabolites that differ from those in humans, as seen, for example, with polyphenols and flavonoids, where key metabolites are either absent in humans or occur at very different levels.”
Cassotta adds that gut-liver-on-chip methods tell us about bioavailability and physiological effects reflecting human metabolic pathways. She further explains how OoCs have been used in food safety.
“Liver- and placenta-on-chip platforms have revealed subtle gene expression changes and stress responses after exposure to food-chain pollutants such as PFAS and bisphenol A at concentrations relevant to humans — effects that are often difficult to detect with traditional models.”
“Similarly, gut-on-chip studies have shown how foodborne pathogens like Shigella or enterohemorrhagic E. coli exploit the human intestinal microenvironment, a mechanism that cannot be reproduced in standard animal models because of species-specific resistance,” Cassotta explains.
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Precision on steroids
Giampieri says OoCs could help uncover the biggest blind spot in current nutrition research as animal studies or static cell cultures are insufficient.
“They do not adequately reproduce key features such as peristalsis, oxygen gradients, or the intricate crosstalk between microbes, epithelial barriers, and the immune system. As a result, many mechanisms by which foods or contaminants influence human health remain poorly understood.”
“OoC systems help to fill this gap by recreating human-relevant conditions and by linking multiple organs together. For example, gut-liver and gut-brain chips can reveal how dietary compounds or microbiota-derived metabolites are processed and how they impact systemic health — processes that traditional models routinely miss.”
Battino adds that placenta- or blood-brain-barrier-on-chip platforms can also reveal how nutrients, bioactives, or environmental toxicants can cross boundaries. This can reveal insight into fetal development or neurotoxicity that is “inaccessible” with current approaches.
“When combined with other NAMs, such as in silico modeling and omics sciences, OoC systems could provide a powerful toolkit to reconstruct and interrogate these dynamic networks with a precision not possible in animals.”
“In this way, they have the potential to uncover mechanisms that remain hidden with traditional methods, offering a more predictive understanding of how nutrition impacts human health.”
Call for chips’ uptake
Cassotta says OoCs are no longer confined to specialized labs and are now commercially available, making them realistic tools for various labs.
“Companies provide technical support and training to help researchers adopt them without needing in-house microengineering expertise. This means that nutrition and food safety groups can already integrate OoCs into their studies.”
“Broader uptake will still depend on reducing costs, improving standardization, and ensuring reproducibility across labs,” she adds. “As these challenges are addressed, OoC technologies are poised to move from niche applications to more widespread use, making them realistic tools for many research settings rather than only high-tech centers.”
Regulatory uptake
The researchers claim that if authorities started to have more faith in OoC systems, the effect on the world’s food supply would be profound. They highlight that most regulatory frameworks today still heavily rely on animal studies, despite their well-known limitations in predicting human outcomes.
“By integrating OoCs, authorities would have access to human-relevant data on digestion, absorption, metabolism, and barrier integrity, enabling earlier and more precise identification of potential hazards,” says Giampieri.
“This could lead to faster, more reliable approval processes and reduce the need for extensive animal testing, in line with international commitments to the 3Rs principle. Such a shift would also allow regulators to address emerging risks with greater confidence.”
The 3Rs principle, which is based on the humane use of animals in experiments, stands for replace, reduce, and refine.
“For example, human liver-on-chip systems have been shown to predict drug-induced liver injury with far greater accuracy than conventional animal models, highlighting how human-relevant platforms can detect toxic effects that animal testing often misses,” explains Battino.
“Moreover, OoCs have already been applied to study the effects of microplastics, PFAS, pesticides, and foodborne pathogens under physiologically realistic conditions. Using these tools systematically could strengthen the evaluation of novel foods, additives, and contaminants, ensuring that safety standards reflect human biology rather than extrapolations from other species.”
The researchers believe that over time, OoC-based evidence can transform global food law by making safety tests ethical, predictive, consistent, and transparent. They say that it would take safeguarding public health in an era of rapid innovation in food systems to the next level.
Future of food safety
Cassotta elaborates on how OoCs can change how scientists judge whether new foods are safe, citing allergic response prediction, food digestion, metabolization, and safety testing for cultured meat, organs, and compounds.
OoCs can reveal how foods are digested, absorbed, and metabolized, and whether there are toxicological or inflammatory effects that animal models might miss
“One important application is predicting allergic responses to novel proteins, something animal models cannot do reliably because immune reactions are highly species-specific.”
“Intestine- and immune-on-chip devices can replicate the human epithelial barrier together with immune cells, making it possible to observe whether new dietary proteins cross the barrier, activate immune signaling, or disrupt gut homeostasis,” she concludes.