Background/Objectives: Prebiotics, which are non-digestible compounds that selectively modulate gut microbiota, are recognized for their potential to promote host health. Although their bifidogenic effect is well documented, a systematic synthesis of how this microbial modulation translates into clinical gastrointestinal (GI) and metabolic outcomes across diverse populations is needed. This review aims to integrate mechanistic insights with clinical evidence to elucidate the pathway from prebiotic structures to tangible health benefits. Methods: This comprehensive narrative review details the structural properties of major prebiotics (e.g., inulin, FOS, and GOS) that govern their fermentation and the production of short-chain fatty acids (SCFAs). To evaluate clinical efficacy, an analysis of 22 randomized controlled trials from the past decade was conducted, focusing on human studies that utilized ISAPP-recognized prebiotics as the sole intervention. Results: The analysis confirms that prebiotic supplementation consistently increased the abundance of beneficial bacteria (e.g., Bifidobacterium and Lactobacillus) and SCFA production. These changes are associated with significant clinical improvements, including enhanced stool frequency and consistency, strengthened intestinal barrier function, and modulated immune responses. Benefits have been documented in healthy individuals, children, the elderly, and those with conditions such as constipation, metabolic syndrome, and antibiotic-associated dysbiosis. However, significant inter-individual variability in response was evident, and the study designs showed notable heterogeneity in prebiotic type, dosage, and duration. Conclusions: Prebiotics are effective modulators of gut health, driving clinical benefits through selective microbial fermentation and SCFA production. The documented heterogeneity and variability highlight the need for future research to focus on personalized nutritional strategies. Key priorities include standardizing intervention protocols, elucidating dose–response relationships, integrating multi-omics data to link taxonomy to function, and exploring novel applications such as synbiotic formulations and gut–brain axis modulation.
Monteiro et al. (Fri,) studied this question.