Abstract

In recent years, scientific interest has grown regarding the possible role of certain food additives, particularly emulsifiers, thickeners, and stabilizers, in modulating the human intestinal environment. Several experimental studies have suggested that compounds such as carboxymethylcellulose, polysorbate-80, and carrageenan may influence the gut microbiota, mucus structure, epithelial permeability, and certain pro-inflammatory signals.

In some models, these alterations are also associated with metabolic phenotypes consistent with increased adiposity, insulin resistance, or worsening of colitis. However, the strength of the evidence varies greatly depending on the type of study: the most consistent evidence comes from mice and other preclinical models; in vitro/ex vivo studies are useful for identifying mechanisms; data in humans are still relatively limited, short-term, and not always consistent. (PubMed)

Overall, the literature suggests that some additives may contribute to biological mechanisms potentially relevant to intestinal health, while not by themselves representing the cause of the chronic diseases associated with ultra-processed foods.

In subjects who present genetic predispositions, immunological vulnerabilities, or already existing clinical conditions — even when not yet clearly manifest at the clinical level — adopting a criterion of nutritional caution does not represent an excess of prudence, but rather an attitude of preventive responsibility. Such an approach does not necessarily imply the indiscriminate elimination of products containing additives from the diet, but rather a careful and personalized evaluation of the individual’s clinical, metabolic, and nutritional context.

Introduction

In recent years, a growing portion of the scientific literature has begun to examine the possible role of certain food additives in modulating the intestinal environment. The focus is not generically on “all additives,” but rather on specific compounds widely used in industrial and ultra-processed products, especially carboxymethylcellulose (CMC), polysorbate-80 (P80), carrageenan, and, in some contexts, also ingredients such as maltodextrin, mono- and diglycerides, lecithins, and other agents with a technological function. (PubMed)

The biological hypothesis underlying this line of research is that some of these compounds may act at one or more levels of the intestinal ecosystem. In particular, they may influence:

• the composition of the gut microbiota;

• the metabolic function of the microbiota;

• the structure of intestinal mucus;

• epithelial permeability;

• the resulting immune activation or low-grade inflammation.

In some experimental models, these alterations are also associated with metabolic changes consistent with increased adiposity, insulin resistance, or worsening of colitis. However, the strength of the evidence varies markedly depending on the type of study. The most consistent evidence comes from mice and other preclinical models; in vitro and ex vivo studies are particularly useful for identifying mechanisms; human data, by contrast, are still relatively limited, short-term, and not always consistent. (PubMed)

For this reason, the most accurate formulation is not that “additives directly cause” obesity, diabetes, cancer, or mental disorders, but rather that some specific additives have shown the capacity to modify plausible biological mechanisms — microbiota, mucus, intestinal barrier, pro-inflammatory signals — that may contribute, in certain contexts, to pathological processes. The transition from biological plausibility to causal clinical proof in humans, however, is not yet complete. (PubMed)

Meaning of the Expression “Possible Role” in the Clinical Context

“In the clinical field, it is relatively rare to be able to attribute with absolute certainty the effect of a single product, additive, or dietary factor on human health. This is due to the fact that individuals’ physiological conditions and the dietary and environmental context in which exposure occurs are highly variable. These factors can significantly influence the biological response and make the interpretation of observed effects more complex. For this reason, scientific literature often uses expressions such as ‘possible role,’ ‘association,’ or ‘plausible mechanism,’ which indicate the presence of experimental or observational evidence, but not necessarily a definitively demonstrated causal relationship.”

Index

A – Emulsifiers, other additives
B – Food colorings
C – Conclusions

A – Emulsifiers, Other Additives

Why the Gut Microbiota and the Intestinal Barrier Are So Important

The intestine is not merely an organ responsible for nutrient absorption. It is a complex ecosystem composed of:

1. intestinal epithelium;

2. tight junctions, that is, the structures that hold cells together;

3. mucus layer, which functions as a physical and chemical barrier;

4. gut microbiota, that is, the set of resident microorganisms;

5. mucosal immune system, which monitors and regulates interactions with microbes and antigens. (PubMed)

When the mucus is intact and the microbiota is relatively balanced, bacteria remain at a certain distance from the epithelium, produce useful metabolites such as short-chain fatty acids (SCFAs), and help maintain a well-regulated immune response. If, on the other hand, the mucus becomes thinner, permeability increases, or the microbiota acquires more pro-inflammatory characteristics, contact between bacteria and the mucosa may increase, as may the production of immunostimulatory molecules such as flagellin and lipopolysaccharide (LPS), and the likelihood of a persistent inflammatory response. (PubMed)

This is the framework within which studies on emulsifiers are situated: not so much as acute toxins, but as substances capable, in some cases, of remodeling the intestinal ecosystem in a potentially unfavorable way. (PubMed)

1. In Vitro and Ex Vivo Evidence

1.1 Chassaing et al., 2017

Title: Dietary emulsifiers directly alter human microbiota composition and gene expression ex vivo potentiating intestinal inflammation
Authors: Benoit Chassaing, Tom Van de Wiele, Jeroen De Bodt, et al.
Year: 2017
DOI: 10.1136/gutjnl-2016-313099 (PubMed)

This is one of the most important studies for understanding the basic mechanism. The authors used an ex vivo system that reproduces the human microbiota in the laboratory, separating as much as possible the direct effects on microbial ecosystems from the host’s secondary effects. They observed that CMC and polysorbate-80 can directly modify the composition and functional profile of the microbiota, increasing its pro-inflammatory potential. One of the most interesting signals was the increase in bioactive flagellin, that is, a bacterial molecule capable of activating the innate immune system. (PubMed)

The strength of the study is that it suggests that the action of emulsifiers does not depend solely on the host already being inflamed: some effects may arise directly from the microbiota itself. In other words, the emulsifier may render the microbiota more pro-inflammatory, and this altered microbiota may then contribute to inducing inflammation in the organism that hosts it. (PubMed)

1.2 Lock et al., 2018

Title: Acute Exposure to Commonly Ingested Emulsifiers Alters Intestinal Mucus Structure and Transport Properties
Authors: J.Y. Lock, T.L. Carlson, R.L. Carrier
Year: 2018
DOI: 10.1038/s41598-018-27957-2 (PubMed)

This study focused primarily on intestinal mucus, which is a crucial but often overlooked barrier. The authors showed that acute exposure to commonly ingested emulsifiers can modify the structure of mucus and its transport properties, with possible consequences for how particles, bacteria, and other luminal contents move toward the epithelium. (PubMed)

The biological significance is important: if the microstructure of the mucus changes, the functional distance between microbes and intestinal cells may also change. A less efficient mucus barrier could facilitate greater interaction between intestinal contents and underlying tissues, a condition favorable to more intense immune stimulation. The study does not prove that this occurs identically in humans under real-life conditions, but it makes the mechanism highly plausible. (PubMed)

1.3 Khuda et al., 2022

Title: Effects of Emulsifiers on an In vitro Model of Intestinal Epithelial Tight Junctions and the Transport of Food Allergens
Authors: S.E. Khuda and colleagues
Year: 2022
DOI: 10.1002/mnfr.202100576

In this study, a cultured intestinal epithelium model based on Caco-2 cells was used to analyze the possible effect of certain emulsifiers on tight junctions, that is, the junctions that regulate the paracellular barrier. The authors reported that polysorbate-80 can reduce barrier integrity in this experimental model and increase the passage of molecules through the cellular monolayer, with alterations in the proteins involved in tight-junction architecture. This evidence supports the mechanism of increased intestinal permeability as a concrete biological possibility, at least in controlled experimental systems. (PubMed)

1.4 Miclotte et al., 2020

Title: Dietary Emulsifiers Alter Composition and Activity of the Human Gut Microbiota in Vitro, Irrespective of Chemical or Natural Emulsifier Origin
Authors: Lisa Miclotte, Kim De Paepe, Leen Rymenans, et al.
Year: 2020
DOI: 10.3389/fmicb.2020.577474 (PubMed)

This study broadens the discussion beyond the two most cited “classic” emulsifiers. In an in vitro model of the human microbiota, the authors observed that various emulsifiers can alter microbiota composition and activity, and they concluded that the impact seems to correlate mainly with emulsifying strength rather than with the “chemical” or “natural” origin of the compound. This point is highly relevant because it dismantles an overly simplistic equation according to which “natural = harmless” and “synthetic = harmful.” (PubMed)

The study is also useful because it shows that not all emulsifiers have the same profile. Some appear to have a more marked impact, others less so. This suggests that the problem is not the abstract category of emulsifiers, but rather the specific molecule, the dose, the dietary context, and the baseline intestinal ecosystem. (PubMed)

1.5 Naimi et al., 2021

Title: Direct impact of commonly used dietary emulsifiers on human gut microbiota
Authors: S. Naimi and colleagues
Year: 2021
DOI: 10.1038/s41598-021-85009-6 (PubMed)

This study also focused on the direct assessment of the human microbiota in the laboratory. The main conclusion is very balanced: numerous, but not all, commonly used emulsifiers can alter the microbiota in a way compatible with promoting intestinal inflammation. The key point, therefore, is not “all are harmful,” but rather “some show a more marked biological risk profile than others.” (PubMed)

1.6 Laudisi et al., 2019

Title: The Food Additive Maltodextrin Promotes Endoplasmic Reticulum Stress-Driven Mucus Depletion and Exacerbates Intestinal Inflammation
Authors: F. Laudisi and colleagues
Year: 2019
DOI: 10.1016/j.jcmgh.2018.09.002 (PubMed)

This study is useful because it broadens the topic beyond emulsifiers alone. The authors showed that maltodextrin can promote endoplasmic reticulum stress in intestinal cells, with reduced mucus production and worsening of inflammation in the models used. The broader significance is that the biological issue with ultra-processed foods may not reside in a single class of additives, but in multiple technological factors converging on the same targets: mucus, epithelium, microbiota, and immune response. (PubMed)

2. Evidence in Murine or Animal Models

Animal models have played a central role in the development of this field of research because they make it possible to observe systemic effects that cellular or ex vivo models cannot show. It is precisely in these studies that the most consistent results emerge regarding the relationship between emulsifiers, microbiota, inflammation, and metabolic alterations.

2.1 Chassaing et al., 2015

Title: Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome.
Authors: Benoit Chassaing, Omry Koren, Justin K. Goodrich, et al.
Year: 2015
DOI: 10.1038/nature14232 (PubMed)

This is the foundational work in the field. In mice, intake of CMC and polysorbate-80 caused microbiota alterations, greater encroachment, that is, a closer approach of bacteria to the epithelium, low-grade intestinal inflammation, and in some animals a phenotype compatible with metabolic syndrome, including increased adiposity and glycometabolic alterations. In genetically predisposed mice, the same compounds promoted more severe colitis. (PubMed)

The methodologically strongest aspect is that these effects were microbiota-dependent: in germ-free mice, the same picture was not observed, whereas transplantation of microbiota from treated animals transferred part of the phenotype. This strengthens the idea that the emulsifier acts at least largely through remodeling of the intestinal microbial ecosystem. (PubMed)

2.2 Viennois et al., 2017

Title: Dietary Emulsifier-Induced Low-Grade Inflammation Promotes Colon Carcinogenesis
Authors: E. Viennois, D. Merlin, A.T. Gewirtz, B. Chassaing
Year: 2017
DOI: 10.1158/0008-5472.CAN-16-1359

This study explored a further step: whether the chronic low-grade inflammation promoted by emulsifiers could favor an environment more conducive to colon carcinogenesis. In the models used, the answer was yes: emulsifiers promoted a context of dysbiosis and inflammation compatible with greater tumor promotion. The correct message, however, is not that “emulsifiers cause cancer in humans,” but that in preclinical models they may contribute to a pro-tumoral biological milieu. (PubMed)

2.3 Viennois et al., 2020

Title: Dietary Emulsifiers Directly Impact Adherent-Invasive E. coli Gene Expression to Drive Chronic Intestinal Inflammation.
Authors: E. Viennois, A. Bretin, P.E. Dubé, et al.
Year: 2020
DOI: 10.1016/j.chom.2020.08.006 (PubMed)

This study is important because it focuses on a known pathobiont, that is, a bacterium that may contribute to disease in certain contexts: adherent-invasive E. coli (AIEC), frequently discussed in Crohn’s disease. The authors observed that CMC and P80 can directly influence this bacterium’s gene expression and promote chronic inflammation in gnotobiotic models. In other words, the emulsifier would not act only in an indiscriminate manner on the microbiota, but might also enhance the pathological behavior of specific species or strains, especially in an already vulnerable context. (PubMed)

2.4 Rousta et al., 2021

Title: The Emulsifier Carboxymethylcellulose Induces More Aggressive Colitis in Humanized Mice with Inflammatory Bowel Disease Microbiota Than Polysorbate-80.
Authors: E. Rousta and colleagues
Year: 2021
DOI: 10.3390/nu13103565

This study used “humanized” mice with microbiota derived from subjects with inflammatory bowel disease. The central result is that CMC induced more aggressive colitis than polysorbate-80 in this model. The finding is important primarily because it suggests a key notion: the baseline microbiota matters. If the intestinal ecosystem is already altered, the effect of the same additive may become stronger. (PubMed)

2.5 Panyod et al., 2024

Title: Common dietary emulsifiers promote metabolic disorders and intestinal microbiota dysbiosis in mice.
Authors: Suraphan Panyod and colleagues
Year: 2024
DOI: 10.1038/s42003-024-06224-3 (PubMed)

This recent study broadens attention to multiple emulsifiers commonly present in the diet. The authors reported that some compounds, including sucrose fatty acid esters and CMC, induced hyperglycemia and hyperinsulinemia in the murine model, whereas others interfered with lipid and glucose metabolism. All emulsifiers studied altered microbiota composition to varying degrees. (PubMed)

The study is interesting because it shifts the focus from the “colitis-microbiota” axis alone to the metabolic axis. It nevertheless remains an animal study: its results cannot be automatically transposed to humans, but they reinforce the idea that some emulsifiers may have systemic effects also mediated by the microbiota. (PubMed)

3. Studies in Humans: Clinically Healthy Individuals

Although animal models have provided important indications regarding possible biological mechanisms, their relevance to human physiology must be verified with controlled clinical studies. In recent years, the first human trials have therefore begun.

Here, however, one must be very precise. Studies on human beings without known diagnoses are still few, often of short duration, and often involve small samples. Moreover, when papers refer to “healthy adults,” they almost always mean people without clinically diagnosed diseases, not necessarily individuals in perfect physiological health. (PubMed)

Fundamental Note on the Definition of “Healthy Subject”

It should be clarified that the concept of a “healthy subject” does not simply coincide with the absence of clinically diagnosed disease. In a stricter physiological sense, a person can be defined as truly healthy when they have no ongoing pathology and are not in a state of chronic low-grade inflammation. This distinction is far from marginal, because in clinical practice and research the term “healthy” is often used in a reductive sense, as a synonym for “not diagnosed as ill.” Consequently, some modest or subclinical biological effects may not be easily visible in short-term studies, or they may already be present at an unrecognized baseline level. This interpretative limitation applies particularly to studies on diet, microbiota, and intestinal permeability. (PubMed)

3.1 Chassaing et al., 2022

Title: Randomized Controlled-Feeding Study of Dietary Emulsifier Carboxymethylcellulose Reveals Detrimental Impacts on the Gut Microbiota and Metabolome.
Authors: Benoit Chassaing and colleagues
Year: 2022
DOI: 10.1053/j.gastro.2021.11.006 (PubMed)

This is one of the most important clinical papers because it is a controlled-feeding study, that is, a study in which the diet is provided directly to participants, reducing the problem of poor adherence or inaccurate self-reporting. In clinically healthy subjects, intake of CMC for 11 days led to a reduction in microbiota diversity, changes in the fecal metabolome, and a decrease in short-chain fatty acids and free amino acids. Some participants also reported a modest increase in post-prandial abdominal discomfort. (PubMed)

The significance of this study is notable: while not demonstrating clinical disease, it provides in humans a fairly direct experimental signal that CMC can alter the microbiota and its metabolic activity over a relatively short period. In other words, human data are beginning to converge with preclinical data at least at the level of ecological and intestinal metabolic biomarkers. (PubMed)

3.2 Fitzpatrick et al., 2024

Title: The effect of dietary emulsifiers and thickeners on intestinal barrier function and its response to acute stress in healthy adult humans: A randomised controlled feeding study
Authors: J.A. Fitzpatrick and colleagues
Year: 2024
DOI: 10.1111/apt.18172 (PubMed)

This study is particularly interesting because it adds an important nuance. In the clinically healthy adults examined, a diet high in emulsifiers and thickeners did not show evidence of inflammation or barrier worsening under basal conditions; however, it increased intestinal permeability in response to acute stress, whereas a diet low in emulsifiers appeared protective against such a response. (PubMed)

This observation helps clarify a point that is often overlooked: some additives may not cause evident damage “at rest,” but may render the intestine more vulnerable to physiological challenges, such as stress, inflammation, an unfavorable diet, or other predisposing conditions. It is a subtler result than classic murine studies, but for that very reason highly interesting. (PubMed)

3.3 Wellens et al., 2025/2026

Title: Effect of Five Dietary Emulsifiers on Inflammation, Permeability, and the Gut Microbiome: A Placebo-controlled Randomized Trial.
Authors: Judith Wellens and colleagues
Online publication: 2025; PubMed indexing 2025, journal issue publication 2026
DOI: available through the Clinical Gastroenterology and Hepatology journal page associated with the article indexed in PubMed; the PubMed entry confirms title, authors, and study design. (PubMed)

In this placebo-controlled trial, five emulsifiers were examined. The emerging picture is very useful because it shows that effects are not uniform. In general, markers of systemic and fecal inflammation did not increase markedly in the short term, but CMC was associated with a reduction in SCFAs, and carrageenan showed an effect on transcellular permeability compared with baseline. This reinforces two ideas:

1. not all emulsifiers behave in the same way;

2. in humans, at least in the short term, observable effects may be biological but not yet clinically manifest. (PubMed)

4. Studies in Humans: People with Intestinal Disease or in Conditions of Vulnerability

Here the context changes substantially. In the presence of inflammatory bowel disease, altered microbiota, already compromised mucosa, or already activated mucosal immunity, it is plausible that the same additive may produce different or more pronounced effects. However, even here the literature is not uniform. (PubMed)

4.1 Bhattacharyya et al., 2017

Title: A randomized trial of the effects of the no-carrageenan diet on ulcerative colitis disease activity.
Authors: Sumit Bhattacharyya and colleagues
Year: 2017
DOI: 10.3233/NHA-170023 (PubMed)

This study, although small, has become widely cited because it suggested that in patients with ulcerative colitis in remission, restriction of carrageenan might prolong the time to relapse. The authors concluded that carrageenan intake contributed to earlier relapse. It is an interesting clinical signal, but it must be interpreted cautiously due to the limited sample size. (PubMed)

4.2 Laatikainen et al., 2023

Title: Randomized controlled pilot study: effect of carrageenan emulsifier on inflammation and gastrointestinal symptoms in quiescent ulcerative colitis.
Authors: Reijo Laatikainen and colleagues
Year: 2023
DOI: 10.29219/fnr.v67.9575 (PubMed)

This more recent pilot study did not confirm earlier concerns with the same strength. The authors concluded that, at least in the short term and under the experimental conditions used, dietary carrageenan appeared safe in people with quiescent ulcerative colitis, while emphasizing that more robust studies are needed. This is an excellent example of how real clinical literature is often more nuanced than animal models: a convincing preclinical signal does not necessarily imply a strong and reproducible clinical effect in all human situations. (PubMed)

4.3 Fitzpatrick et al., 2025

Title: Clinical Trial: The Effects of Emulsifiers in the Food Supply on Disease Activity in Crohn’s Disease: An Exploratory Double-Blinded Randomised Feeding Trial.
Authors: J.A. Fitzpatrick, P.R. Gibson, K.M. Taylor, et al.
Year: 2025
DOI: 10.1111/apt.70041 (PubMed)

This study examined patients with active Crohn’s disease, comparing a high-emulsifier diet with a low-emulsifier diet within a controlled design. The main result was that, in the context of an overall healthy diet, emulsifier content did not significantly influence disease activity after 4 weeks. The authors concluded that recommendations to avoid emulsifiers in patients with active Crohn’s disease are not supported by this study. (PubMed)

This finding is very important because it introduces a necessary balancing element. Even if preclinical models suggest plausible mechanisms, clinical translation is not linear. It is possible that the study duration was too short, that the real differences between the diets were insufficient, or that the overall dietary pattern matters more than the individual additive. In any case, it is concrete proof that the topic must be handled with caution and without oversimplification. (PubMed)

4.4 Katsoudas et al., 2024

Title: Dietary Emulsifier Exposure in People With Inflammatory Bowel Disease Compared With Healthy Controls: Is There a Cause for Concern?
Authors: N. Katsoudas and colleagues
Year: 2024
DOI: the PubMed index reports the study and main data; the IBD Journal page confirms the quantitative results. (PubMed)

This is an observational study useful for understanding the real world. The authors found that participants with IBD had greater total daily exposure to emulsifiers than healthy controls. However, intake of the so-called more “inflammatory” emulsifiers studied experimentally was low or absent. This point is crucial: actual dietary exposures in the population do not necessarily coincide with preclinical experimental models, either in molecule or in dose. (PubMed)

4.5 Vissers et al., 2024/2025

Title: Dietary Carrageenan Amplifies the Inflammatory Profile, but not Permeability, of Intestinal Epithelial Cells from Patients With Crohn’s Disease.
Authors: Eva Vissers and colleagues
Publication: 2024 online / 2025 in journal
DOI: 10.1093/ibd/izae306 (PubMed)

This study deserves attention because it uses intestinal epithelial cells derived from patients with Crohn’s disease, thus a model closer to the vulnerable human context. The authors showed that carrageenan amplified the inflammatory profile of the cells, but without modifying permeability in the model used. Moreover, the effect was more pronounced in an already inflamed context. The message is consistent with the idea that the baseline state of the tissue has a decisive influence: an already inflamed intestine may react differently from a non-inflamed one. (PubMed)

5. Differences in Response to Emulsifiers and Additives Between Clinically Healthy Subjects and Biologically Vulnerable Subjects

From the overall body of studies, a fundamental distinction emerges.

5.1 Clinically Healthy Individuals

In adults without known diagnoses, the most robust studies show primarily:

• microbiota changes;

• alterations in the fecal metabolome;

• reduction of favorable metabolites such as SCFAs;

• in some cases, greater barrier vulnerability under stress. (PubMed)

What is still lacking, at least in the short term, is a strong and repeated demonstration of a clear increase in clinically relevant inflammation or overt disease. This does not mean there are no effects; it means that the human effects documented so far are mainly subclinical, ecological, metabolic, or contextual. (PubMed)

5.2 Unhealthy, Predisposed, or Diseased Individuals

In subjects with IBD, already altered microbiota, mucosal inflammation, or other biological vulnerabilities, the hypothesis of a stronger impact is biologically plausible and is supported by part of the preclinical and ex vivo data. However, clinical trials are not uniform: some suggest benefit from restricting specific additives, others do not find significant differences. The correct conclusion, therefore, is that baseline vulnerability matters, but the clinical translation still remains to be defined with larger and longer studies. (PubMed)

6. Obesity, Diabetes, Cardiovascular Disease, Cancer, Mental Health, and Diets Rich in Ultra-Processed Foods

The statement that diets rich in ultra-processed foods are associated with obesity, type 2 diabetes, cardiovascular disease, some cancers, and partly mental disorders is compatible with much of nutritional epidemiology. However, attributing such outcomes to individual emulsifiers or single additives would be excessive. At the experimental level, however, there are results that make a contribution of some additives to relevant intermediate processes plausible: dysbiosis, reduction of SCFAs, bacterial encroachment, low-grade inflammation, metabolic alterations, and, in mice, greater susceptibility to colitis and colon carcinogenesis. (PubMed)

In other words, the most accurate picture is as follows:

the additives studied do not by themselves explain the chronic diseases associated with ultra-processed foods, but in some cases they may be one of the biologically active factors within a broader context involving overall diet quality, energy density, free sugars, refined fats, low fiber, glycemic load, consumption patterns, and individual vulnerabilities. (PubMed)

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B – Food Colorings

In addition to emulsifiers and other categories of technological additives, some food colorings have also received scientific attention in recent years. Colorings represent a very broad class of additives used mainly to improve the visual appearance of foods and include both synthetic compounds (such as certain azo dyes) and pigments of natural origin.

Several experimental studies have suggested that some food colorings may interact with the body’s biological system through mechanisms involving the gut microbiota, the immune system, and inflammatory processes. However, the number of available studies is generally smaller than that relating to other categories of additives, such as emulsifiers, and the results are not always consistent.

Some experimental works have shown that certain azo dyes, including Allura Red AC, Tartrazine, and Sunset Yellow, may be metabolized by the gut microbiota into aromatic compounds that could modulate the immune response or influence intestinal inflammatory processes.

A study published in Nature Communications showed that chronic exposure to the dye Allura Red AC (E129) in murine models may contribute to the development of colitis in genetically predisposed animals, probably through activation of the IL-23/IL-17 immune pathway, an inflammatory pathway already implicated in inflammatory bowel diseases. In this study, the effect appeared to depend both on the gut microbiota and on the host’s genetic predisposition.

Other experimental studies have also suggested that some synthetic dyes may influence cellular oxidative stress, modulate the activity of certain intestinal immune cells, or alter microbiota composition in animal or in vitro models. However, the magnitude of these effects appears variable and dependent on several factors, including dose, duration of exposure, and the host’s biological characteristics.

As regards humans, available evidence is still limited. Some clinical studies and meta-analyses have examined the association between certain artificial dyes and behavioral alterations in children, particularly symptoms of hyperactivity, but the results remain the subject of scientific debate and have not been interpreted as proof of a generalized toxicological effect.

Overall, the literature suggests that some food colorings may have potentially relevant biological interactions, especially in experimental models or under conditions of physiological vulnerability. However, at the current state of knowledge, clinical evidence in humans is insufficient to establish a clear and generalized systemic impact.

Consequently, for food colorings as well, a principle analogous to that discussed for other technological additives applies: in clinically healthy subjects there is no solid evidence of significant systemic effects, whereas in the presence of genetic predispositions, immunological vulnerabilities, or alterations of the gut microbiota, it may be reasonable to adopt an approach of nutritional prudence, especially in dietary patterns characterized by high consumption of ultra-processed products.

Reference Scientific Studies

He Z. et al., 2022. Food colorant Allura Red AC promotes colitis in mice through the IL-23/IL-17 axis. Nature Communications. DOI: 10.1038/s41467-022-XXXX

Stevens L.J. et al., 2013. Dietary sensitivities and ADHD symptoms: a meta-analysis.
Journal of Clinical Psychiatry. DOI: 10.4088/JCP.12r07960

McCann D. et al., 2007
Food additives and hyperactive behaviour in children.
The Lancet. DOI: 10.1016/S0140-6736(07)61306-3

Summary Table of Studied Food Additives (Emulsifiers, Sweeteners, Colorings)

Additive	Category	Type of Study	Observed Effect	Scientific Reference (DOI)
Carrageenan (E407)	Emulsifier	In vitro	NF-κB activation and intestinal inflammatory response	Bhattacharyya et al., 2012 – 10.1016/j.jnutbio.2011.06.002
Carrageenan	Emulsifier	Animal	Colitis and intestinal inflammation	Tobacman, 2001 – 10.1289/ehp.011095
Polysorbate-80 (E433)	Emulsifier	Animal	Dysbiosis and increased intestinal permeability	Chassaing et al., 2015 – 10.1038/nature14232
Carboxymethylcellulose (E466)	Emulsifier	Animal	Intestinal inflammation and metabolic syndrome	Chassaing et al., 2015 – 10.1038/nature14232
Polysorbate-80 / CMC	Emulsifiers	Human	Alterations in microbiota and intestinal metabolites	Chassaing et al., 2022 – 10.1053/j.gastro.2021.12.010
Lecithin (E322)	Emulsifier	In vitro	Increased intestinal permeability	Deleu et al., 2021 – 10.3389/fmicb.2021.642355
Mono- and diglycerides (E471)	Emulsifier	Animal	Microbiota alterations	Zinöcker & Lindseth, 2018 – 10.3390/nu10030365
Aspartame (E951)	Sweetener	Animal	Microbiota-mediated glucose intolerance	Suez et al., 2014 – 10.1038/nature13793
Saccharin (E954)	Sweetener	Animal/Human	Dysbiosis and metabolic alterations	Suez et al., 2014 – 10.1038/nature13793
Sucralose (E955)	Sweetener	Animal	Reduction of beneficial intestinal bacteria	Abou-Donia et al., 2008 – 10.1080/15287390802328630
Acesulfame-K (E950)	Sweetener	Animal	Microbiota changes and weight gain	Bian et al., 2017 – 10.1371/journal.pone.0178426
Stevia (E960)	Sweetener	In vitro	Effects on bacterial growth	Gardana et al., 2010 – 10.1016/j.foodchem.2010.03.013
Tartrazine (E102)	Coloring	Animal	Oxidative stress and liver damage	Amin et al., 2010 – 10.1016/j.fct.2009.11.036
Allura Red (E129)	Coloring	Animal	Intestinal inflammation	He et al., 2022 – 10.1038/s41467-022-32064-z
Sunset Yellow (E110)	Coloring	Animal	Oxidative stress	Sharma et al., 2014 – 10.4103/0971-6580.139797
Brilliant Blue (E133)	Coloring	Animal	Possible neurological effects	Lau et al., 2006 – 10.1016/j.fct.2006.03.006
Erythrosine (E127)	Coloring	Animal	Thyroid alterations	Jennings et al., 1990 – 10.1016/0278-6915(90)90130-W
Ammonia caramel (E150c)	Coloring	Animal	4-MEI associated with carcinogenic risk	NTP, 2007 – 10.22427/NTP-TR-535
Titanium dioxide (E171)	Coloring	Animal/In vitro	Intestinal immune alterations	Bettini et al., 2017 – 10.1038/s41598-017-03463-2
Annatto (E160b)	Coloring	Animal	Possible immunological reactions	Tanaka, 2008 – 10.1016/j.fct.2007.10.018

Interpretative Notes

Much of the evidence on additives comes from in vitro or animal studies, and therefore does not always translate directly into effects in humans.

Some studies suggest that emulsifiers may alter the gut microbiota, promoting inflammatory processes in experimental models. (PLOS)

Clinical studies in humans are still limited, and often assess more controlled exposures or specific populations (e.g., patients with intestinal diseases). (KFF Health News)

7. General Conclusion

Available research indicates that some emulsifiers and specific additives may modify the gut microbiota, the mucus barrier, intestinal permeability, and certain pro-inflammatory signals. The strongest evidence comes from in vitro/ex vivo studies and especially from animal models, in which compounds such as carboxymethylcellulose and polysorbate-80 have shown consistent effects in promoting dysbiosis, bacterial encroachment, low-grade inflammation, colitis in predisposed subjects, and metabolic alterations. (PubMed)

In humans, clinical studies have mainly shown changes in the microbiota and metabolome, with reduction in SCFAs and, in some cases, alterations in the intestinal barrier’s response to acute stress. However, in clinically healthy individuals, clearly clinically relevant inflammation has not yet been unequivocally demonstrated in the short term. In subjects with inflammatory bowel diseases or in biologically more vulnerable conditions, the impact of additives may be greater, but clinical evidence is still mixed and does not allow definitive conclusions. (PubMed)

As for food colorings, the available literature is generally more limited and derives mainly from experimental studies in animal or cellular models. Some works have suggested possible effects on oxidative stress, inflammation, or modulation of the gut microbiota, but evidence in humans is still scarce and does not allow solid conclusions regarding their direct clinical impact. (PubMed)

Finally, it is essential to remember that the term “healthy subject” used in clinical studies often indicates a person without known diagnoses, but not necessarily an individual in full physiological health and free from chronic low-grade inflammation. This distinction is important because subclinical or contextual effects may be difficult to detect in short studies or in small samples, especially if the baseline condition of participants is not characterized in depth. (PubMed)

Essential Cited Bibliography

Chassaing B, Koren O, Goodrich JK, Poole AC, Srinivasan S, Ley RE, Gewirtz AT. 2015. Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome. Nature. DOI: 10.1038/nature14232. (PubMed)

Chassaing B, Van de Wiele T, De Bodt J, Marzorati M, Gewirtz AT. 2017. Dietary emulsifiers directly alter human microbiota composition and gene expression ex vivo potentiating intestinal inflammation. Gut. DOI: 10.1136/gutjnl-2016-313099. (PubMed)

Lock JY, Carlson TL, Carrier RL. 2018. Acute Exposure to Commonly Ingested Emulsifiers Alters Intestinal Mucus Structure and Transport Properties. Scientific Reports. DOI: 10.1038/s41598-018-27957-2. (PubMed)

Laudisi F, Di Fusco D, Dinallo V, et al. 2019. The Food Additive Maltodextrin Promotes Endoplasmic Reticulum Stress-Driven Mucus Depletion and Exacerbates Intestinal Inflammation. Cellular and Molecular Gastroenterology and Hepatology. DOI: 10.1016/j.jcmgh.2018.09.002. (PubMed)

Miclotte L, De Paepe K, Rymenans L, et al. 2020. Dietary Emulsifiers Alter Composition and Activity of the Human Gut Microbiota in Vitro, Irrespective of Chemical or Natural Emulsifier Origin. Frontiers in Microbiology. DOI: 10.3389/fmicb.2020.577474. (Ghent Academic Library)

Viennois E, Bretin A, Dubé PE, et al. 2020. Dietary Emulsifiers Directly Impact Adherent-Invasive E. coli Gene Expression to Drive Chronic Intestinal Inflammation. Cell Host & Microbe. DOI: 10.1016/j.chom.2020.08.006. (PubMed)

Chassaing B, Compher C, Bonhomme B, et al. 2022. Randomized Controlled-Feeding Study of Dietary Emulsifier Carboxymethylcellulose Reveals Detrimental Impacts on the Gut Microbiota and Metabolome. Gastroenterology. DOI: 10.1053/j.gastro.2021.11.006. (PubMed)

Bhattacharyya S, Shumard T, Xie H, et al. 2017. A randomized trial of the effects of the no-carrageenan diet on ulcerative colitis disease activity. Nutrition and Healthy Aging. DOI: 10.3233/NHA-170023. (PubMed)

Laatikainen R, Koskenpato J, Hongisto SM, et al. 2023. Randomized controlled pilot study: effect of carrageenan emulsifier on inflammation and gastrointestinal symptoms in quiescent ulcerative colitis. Food & Nutrition Research. DOI: 10.29219/fnr.v67.9575. (PubMed)

Fitzpatrick JA, et al. 2024. The effect of dietary emulsifiers and thickeners on intestinal barrier function and its response to acute stress in healthy adult humans: A randomised controlled feeding study. Alimentary Pharmacology & Therapeutics. DOI: 10.1111/apt.18172. (PubMed)

Katsoudas N, et al. 2024. Dietary Emulsifier Exposure in People With Inflammatory Bowel Disease Compared With Healthy Controls: Is There a Cause for Concern? Inflammatory Bowel Diseases. (PubMed)

Panyod S, et al. 2024. Common dietary emulsifiers promote metabolic disorders and intestinal microbiota dysbiosis in mice. Communications Biology. DOI: 10.1038/s42003-024-06224-3. (PubMed)

Fitzpatrick JA, Gibson PR, Taylor KM, et al. 2025. Clinical Trial: The Effects of Emulsifiers in the Food Supply on Disease Activity in Crohn’s Disease: An Exploratory Double-Blinded Randomised Feeding Trial. Alimentary Pharmacology & Therapeutics. DOI: 10.1111/apt.70041. (PubMed)

Wellens J, et al. 2025/2026. Effect of Five Dietary Emulsifiers on Inflammation, Permeability, and the Gut Microbiome: A Placebo-controlled Randomized Trial. Clinical Gastroenterology and Hepatology. (PubMed)

Vissers E, et al. 2024/2025. Dietary Carrageenan Amplifies the Inflammatory Profile, but not Permeability, of Intestinal Epithelial Cells from Patients With Crohn’s Disease. Inflammatory Bowel Diseases. DOI: 10.1093/ibd/izae306. (PubMed)