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.

Silybin, a flavonolignan extracted from the seeds of the plant species Silybum marianum (L.) Gaertn., has a variety of pharmacological activities, including antimicrobial activity against several microorganisms of clinical interest. This review analyzes the existing studies on silybin’s antimicrobial activity and possible mechanisms of action. Silybin has been shown to inhibit the growth of Gram-positive and Gram-negative bacteria, as well as some fungi, viruses, and protozoa. In general, possible mechanisms of antimicrobial action include the inhibition of efflux pumps, prevention of biofilm formation, reduction of the expression of virulence factors, induction of apoptosis-like effects, and plasma membrane damage, as well as the inhibition of nucleic acid and protein synthesis. Silybin has been shown to have synergistic effects when combined with conventional antibiotics against both drug-sensitive and drug-resistant microorganisms. However, the low bioavailability observed for this flavonolignan has been a challenge to its clinical use. In this context, nanotechnology has been used to increase silybin’s bioavailability while enhancing its antimicrobial activity. Furthermore, certain structural modifications have been able to enhance its antimicrobial activity in comparison to that of the natural molecule. Overall, this review provides insights into the scientific understanding of the mechanism of action of silybin and its desired properties for the effective treatment of infections.

Background/Objectives: Antifungal resistance to azoles, coupled with the increasing prevalence of Candida albicans infections, represents a significant public health challenge and has driven the search for new natural compounds that can act as alternatives or adjuvants to the current antifungals. Ellagic acid (EA) has demonstrated antifungal activity; however, its effects are not fully understood. In this study, we investigated the in vitro anti-Candida activity of EA and its ability to potentiate the effects of fluconazole (FLZ) on C. albicans. Methods: The Minimum Inhibitory Concentration (MIC) of EA was determined by broth microdilution and its interaction with FLZ was assessed using a checkerboard assay. Additionally, we examined the effects of EA on yeast-to-hypha transition, inhibition of biofilm formation, time–kill kinetics, hemolytic activity, and cytotoxicity in HeLa ATCC^® CCL-2™ cells. Results: EA exhibited MIC values ranging from 250 to 2000 µg/mL and showed synergistic and additive interactions with FLZ, resulting in a marked reduction in the MIC values of FLZ (up to 32-fold) and EA (up to 16-fold). In the time–kill assay, the most effective combinations were 4× EA MIC, 2× EA MIC, and FIC EA + FLZ, which showed fungicidal activity. Furthermore, EA did not show hemolytic activity and demonstrated low and dose-dependent cytotoxicity in HeLa cells, with no cytotoxic effects observed in combination with FLZ. EA and the synergistic combination of EA and FLZ interfered with both the yeast-to-hypha transition process in C. albicans cells and biofilm formation. In addition to its antifungal efficacy, EA demonstrated a favorable safety profile at the concentrations used. Conclusions: This study presents promising results regarding the potential use of EA in combination with FLZ for the treatment of C. albicans infections.

The genus Arrabidaea, consisting of ~170 species, belongs to the family Bignoniaceae, distributed around the Neotropics and temperate zone. The center of diversity of the family is in Brazil, where 56 genera and about 340 species exist. Most species of the genus Arrabidaea are traditionally utilized as diuretics and antiseptics, as well as for treating intestinal colic, diarrhea, kidney stones, rheumatoid arthritis, wounds, and enterocolitis. The genus is chemically diverse with different substance classes; most of them are triterpenes, phenolic acids, and flavonoids, and they exhibit valuable pharmacological properties, such as antitumor, antioxidant, leishmanicidal, trypanocidal, anti-inflammatory, and healing properties. This review presents information on the chemical constituents isolated from seven Arrabidaea species, and the pharmacological activities of the extracts, fractions and pure substances isolated since 1994, obtained from electronic databases. The various constituents present in the different species of this genus demonstrate a wide pharmacological potential for the development of new therapeutic agents, however its potential has been underestimated.

Ellagic acid (EA), a naturally occurring phenolic compound, has garnered significant interest as a potential antifungal agent owing to increasing fungal resistance and a scarce therapeutic pipeline. This review consolidates the evidence of the broad-spectrum activity of EA against critical priority pathogens, including Candida auris and Cryptococcus neoformans. We highlight its multi-target mechanisms of action, such as the impairment of cell wall integrity and plasma membrane disruption resulting from the inhibition of ergosterol biosynthesis, and inhibition of key enzymes, such as laccase. In addition to its direct growth-inhibitory effects, EA exhibits antivirulence properties, reducing biofilm formation and hyphal morphogenesis. Notably, it demonstrates synergistic potential with conventional antifungals, such as fluconazole, enhancing efficacy and potentially hindering the emergence of resistance. Although its poor solubility and bioavailability pose therapeutic challenges, advanced formulations such as liposomal systems show promise for improving its delivery. We conclude that EA is a promising candidate for developing new antifungal strategies, particularly as a synergistic agent or in nanoformulations, warranting further investigation to translate its potential into clinical practice.

Antimicrobial resistance (AMR) is an urgent global challenge as microbial pathogens are increasingly developing resistance to traditional antibiotics