Sweeteners and the Gut: A Systematic Review of Synthetic Versus Natural Impacts on Gut Microbial Diversity

Abstract

Synthetic and natural sweeteners are widely consumed, yet their effects on gut microbiota diversity and host metabolism remain contested. This systematic review synthesized evidence from ten studies, including human trials, animal models, and in vitro experiments, to evaluate microbial and metabolic outcomes associated with sweetener exposure in healthy adults. Synthetic sweeteners such as sucralose and neotame were consistently associated with reduced alpha diversity, enrichment of pro-inflammatory taxa, and impaired glucose tolerance. In contrast, natural sweeteners including steviol glycosides, erythritol, rebaudiosde A, and xylitol preserved microbial richness and promoted short-chain fatty acid (SCFA) production. The findings support the hypothesis that synthetic sweeteners negatively affect microbial diversity, whereas natural sweeteners preserve or enhance microbial resilience.

Interpretation of results was complicated by heterogeneity in dosage, duration, and delivery methods, underscoring the need for standardized protocols. Professional organizations such as the Academy of Nutrition and Dietetics and the U.S. Food Drug Administration affirm the safety of approved nonnutritive sweeteners within established intake levels, while federal agencies emphasize the importance of long-term research into microbiota outcomes. Collectively, the evidence supports cautious use of synthetic sweeteners and highlights natural alternatives as potential microbiota-supportive options. Practitioners should apply individualized recommendations, balancing organizational guidance with patient-specific needs.