Food Additives as Microbiome-Active Dietary Exposures: Mechanisms, Host Susceptibility, and an Operational Case for Microbiome-Inclusive Risk Assessment
- 1Department of Food Technologies, Faculty of Agriculture, “Ion Ionescu de la Brad” Iasi University of Life Sciences, 3 Mihail Sadoveanu Alley, 700489 Iasi, Romania
- 2Research Institute for Agriculture and Environment, “Ion Ionescu de la Brad” Iasi University of Life Sciences, 14 Sadoveanu Alley, 700490 Iasi, Romania
- 3Department of Public Health, Faculty of Veterinary Medicine, “Ion Ionescu de la Brad” Iasi University of Life Sciences, 3 Mihail Sadoveanu Alley, 700490 Iasi, Romania
Abstract
Food additives are defining components of ultra-processed foods, yet microbiome-related effects remain largely outside routine safety assessment. This review evaluates evidence for six additive classes across four pathways—microbial community changes, altered microbial metabolites, mucus-epithelial barrier disruption, and immune modulation—and examines how these findings could inform microbiome-inclusive risk assessment. Mechanistic, translational, and epidemiological evidence was organized using a five-tier hierarchy: in vitro, ex vivo, animal, observational, and controlled human studies. Chronic-disease associations were graded across six domains by two raters using explicit criteria, with sensitivity analysis. Evidence was then translated into a tiered, decision-gated assessment protocol, illustrated with carboxymethylcellulose and back-tested against carrageenan, acesulfame K, and titanium dioxide, which return three different protocol outcomes. Non-nutritive sweeteners and emulsifiers have the strongest direct human and ex vivo evidence, including microbiome-dependent interindividual responses, although null and discordant trials remain. Gastrointestinal and metabolic outcomes received the highest support, cardiovascular associations were intermediate, and autoimmune, neurological, and psychiatric links remained preliminary. Metabolic and cardiovascular epidemiology relied largely on NutriNet-Santé, with modest hazard ratios (generally 1.03–1.15 per exposure increment) and indirect exposure estimation. Recent additive-mixture analyses from the same cohort were also considered. Food additives can act as context-dependent, microbiome-active exposures. Current evidence supports considering microbiome composition, barrier-integrity, and immune endpoints in additive safety evaluation, while causal links with most chronic-disease outcomes remain unproven.
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BibTeX
@article{crivei2026food,
title = {{Food Additives as Microbiome-Active Dietary Exposures: Mechanisms, Host Susceptibility, and an Operational Case for Microbiome-Inclusive Risk Assessment}},
author = {Ioana Cristina Crivei and Roxana Nicoleta Ratu and Ionuț-Dumitru Veleșcu and Andreea Bianca Balint and Florin Daniel Lipșa and Florina Stoica and Luciana Alexandra Crivei},
journal = {Nutrients},
year = {2026},
month = oct,
doi = {10.3390/nu18213461},
url = {https://www.mdpi.com/2072-6643/18/21/3461},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Food Additives as Microbiome-Active Dietary Exposures: Mechanisms, Host Susceptibility, and an Operational Case for Microbiome-Inclusive Risk Assessment
AU - Ioana Cristina Crivei
AU - Roxana Nicoleta Ratu
AU - Ionuț-Dumitru Veleșcu
AU - Andreea Bianca Balint
AU - Florin Daniel Lipșa
AU - Florina Stoica
AU - Luciana Alexandra Crivei
PY - 2026
DA - 2026/10/22
JO - Nutrients
DO - 10.3390/nu18213461
UR - https://www.mdpi.com/2072-6643/18/21/3461
AB - Food additives are defining components of ultra-processed foods, yet microbiome-related effects remain largely outside routine safety assessment. This review evaluates evidence for six additive classes across four pathways—microbial community changes, altered microbial metabolites, mucus-epithelial barrier disruption, and immune modulation—and examines how these findings could inform microbiome-inclusive risk assessment. Mechanistic, translational, and epidemiological evidence was organized using a five-tier hierarchy: in vitro, ex vivo, animal, observational, and controlled human studies. Chronic-disease associations were graded across six domains by two raters using explicit criteria, with sensitivity analysis. Evidence was then translated into a tiered, decision-gated assessment protocol, illustrated with carboxymethylcellulose and back-tested against carrageenan, acesulfame K, and titanium dioxide, which return three different protocol outcomes. Non-nutritive sweeteners and emulsifiers have the strongest direct human and ex vivo evidence, including microbiome-dependent interindividual responses, although null and discordant trials remain. Gastrointestinal and metabolic outcomes received the highest support, cardiovascular associations were intermediate, and autoimmune, neurological, and psychiatric links remained preliminary. Metabolic and cardiovascular epidemiology relied largely on NutriNet-Santé, with modest hazard ratios (generally 1.03–1.15 per exposure increment) and indirect exposure estimation. Recent additive-mixture analyses from the same cohort were also considered. Food additives can act as context-dependent, microbiome-active exposures. Current evidence supports considering microbiome composition, barrier-integrity, and immune endpoints in additive safety evaluation, while causal links with most chronic-disease outcomes remain unproven.
SN - 2072-6643
ER -