Artificial Sweeteners and Host Response Variability: Insights from the Gut Microbiota for Precise Application

Jie Cai; Qingping Wu; Alaa El-Din Ahmed Bekhit; Juan Wang; Yu-Long Li; Rong Huang; Fen Zhang; Hang Xiao; Zhenjun Zhu; Yu Ding

doi:10.1016/j.eng.2026.05.004

Engineering ›› :202605004 DOI: 10.1016/j.eng.2026.05.004

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Artificial Sweeteners and Host Response Variability: Insights from the Gut Microbiota for Precise Application

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^aState Key Laboratory of Bioactive Molecules and Drug ability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Department of Food Science and Engineering, College of Life Science and Technology , Jinan University, Guangzhou 510632, China

^b Institute of Microbiology, Guangdong Academy of Sciences, State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Safety and Health, National Health Commission Science and Technology Innovation Platform for Nutrition and Safety of Microbial Food, Key Laboratory of Big Data Technologies for Food Microbiological Safety, State Administration for Market Regulation ; Guangzhou 510070, China

^c Food and Drug Laboratory, Guangdong Detection Center of Microbiology , Guangzhou 510070, China

^d Department of Food Science, University of Otago , Dunedin 9054, New Zealand

^e College of Food Science, South China Agricultural University , Guangzhou 510642, China

^f Department of Emergency Medicine, University of Nebraska Medical Center , Omaha NE 68198, USA

^g Department of Food Science, University of Massachusetts , Amherst MA 01003, USA

^*E-mail addresses: dingyu@jnu.edu.cn (Y. Ding),

zzj1904@jnu.edu.cn (Z. Zhu).

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Abstract

Artificial sweeteners (ASs) are widely used as sugar substitutes, valued for their low-calorie content and minimal impact on blood glucose levels, which aligns with current dietary demands. However, recent studies have raised concerns about their potential effects on gut microbiota homeostasis and subsequent health outcomes, making a comprehensive evaluation of their impacts increasingly relevant. This article systematically reviews recent findings from cohort studies, clinical trials, and animal experiments, providing a synthesis of current knowledge on ASs. We discuss the controversies surrounding the health effects of ASs and explore the potential mechanisms through the lens of gut microbiota, with particular attention to special populations that have distinct physiological needs. Key findings suggest that gut microbiota may mediate the effects of ASs on host health through four potential mechanisms: disruption of bile acid homeostasis, regulation of tryptophan metabolism, alteration of short-chain fatty acid levels, and modulation of lipopolysaccharide leakage. Notably, the effects of ASs may be more complex in special populations due to their unique physiological states (e.g., developmental stages, metabolic fragility, or immune dysregulation), which necessitate targeted investigation. Such evidence underscores the need for a balanced assessment of ASs, taking into account both their practical benefits and the nuances of their biological effects across diverse populations. A more thorough understanding of these mechanisms may help inform evidence-based dietary strategies for optimizing the use of ASs while minimizing potential adverse effects, particularly in context-specific scenarios.

Keywords

Artificial sweetener / Gut microbiota / Bile acid / Tryptophan metabolite / Short-chain fatty acid

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Jie Cai, Qingping Wu, Alaa El-Din Ahmed Bekhit, Juan Wang, Yu-Long Li, Rong Huang, Fen Zhang, Hang Xiao, Zhenjun Zhu, Yu Ding. Artificial Sweeteners and Host Response Variability: Insights from the Gut Microbiota for Precise Application. Engineering 202605004 DOI:10.1016/j.eng.2026.05.004

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