Editorial: Functional Nutritional Strategies as Alternatives to Antimicrobials

Matteo Dell'Anno^1*Monika Hejna²Francesca Riva³Luciana ROSSI⁴

• ¹Department of Veterinary Sciences, University of Messina, Messina, Italy
• ²Uniwersytet Warszawski Wydzial Biologii, Warsaw, Poland
• ³University of Glasgow, Glasgow, United Kingdom
• ⁴Universita degli Studi di Milano, Milan, Italy

The challenge of antimicrobial resistance (AMR) emerged as one of the major concerns within the One Health perspective and it is currently being addressed at multiple levels by international organizations, policymakers, and the scientific community. Important efforts are focused on both human and animal health, promoting the judicious use of antimicrobials and encouraging the development of sustainable alternatives to safeguard public health, animal welfare, and environmental sustainability. In particular, over the past few decades, scientific research has increasingly focused on exploring innovative nutritional interventions as functional strategies to enhance disease prevention, overall animal health, reduce the antibiotic need, and mitigate the spread of AMR. This research topic includes nineteen contributions focused on the potential of functional nutritional strategies as promising alternatives to antibiotic treatments in both livestock and companion animals. Among them, several papers in this collection explored the role of probiotics, prebiotics, postbiotics, natural and plant-derived compounds in modulating the microbiome, immune responses, and metabolic pathways. These studies highlight how dietary supplementation can strengthen host defenses, mitigate oxidative stress, and reduce the incidence of disease conditions.Taken together, the contributions of this research topic focusing on swine highlight a multi-mechanistic mode of action of functional compounds, encompassing anti-inflammatory and antioxidant effects, enhancement of barrier function, and modulation of the microbiome, metabolome axis. Several nutritional strategies have been investigated to mitigate weaning stress, shape the gut microbiota and metabolite profile, and ultimately improve animal performance and health. For instance, mmicroencapsulated essential oils were shown to support both health and performance in weaned piglets (1), while essential oil from Alpinia oxyphylla modulated immunity, antioxidant capacity, and gut microbiota profile in fattening pigs (2). Probiotic supplementation increased beneficial short-chain fatty acids in the feces and improved average daily gain in weaned piglets (3). Another trial in piglets demonstrated that oral supplementation with an egg yolk immunoglobulin-based product improved growth performance and mucosal immunity, particularly supporting low-birth-weight neonates by enhancing β-defensin expression, modulating inflammatory responses, and stabilizing intestinal barrier function in the pre-weaning period (4). Maternal nutrition has also emerged as a critical determinant of offspring resilience. Fang et al. (5) showed that perinatal fish-oil supplementation in sows protected piglets from LPS-induced damage, while Daneshi et al. (2024) reported that maternal one-carbon metabolite supplementation modulated the expression of antimicrobial peptides in both fetal and maternal tissues, suggesting an epigenetic route through which perinatal nutrition may shape innate immunity.Plant-derived polyphenols have also confirmed their beneficial properties. Supplementation with Ampelopsis grossedentata extract improved intestinal morphology, enhanced antioxidant status, and modulated the gut microbiota in growing-finishing pigs (7). Two complementary studies focused on seaweed supplementation. The first, included an in vivo trial in post-weaning piglets, demonstrated that a blend of Ascophyllum nodosum and Phymatolithon calcareum protected against F4+ E. coli infection by improving gut morphology and antioxidant status (8), while a second companion in vitro characterization and zootechnical trial confirmed that bioactive compounds retained their functionality after simulated digestion, indicating synergistic antioxidant and antimicrobial properties (9). A dedicated review highlighted the importance of lactoferrin as a multifunctional protein as an antimicrobial alternative. Beyond its well-documented immunomodulatory and antimicrobial properties, the authors focused on its proteolytic activity, which can impair bacterial virulence factors and decrease pathogen colonization. While the exact mechanisms are not always clear, the proteolytic feature of lactoferrin could represent a valuable avenue for limiting pathogenicity and tackling multidrug-resistant bacteria (10).Analogously, in broilers, a synbiotics-enzyme complex (mannose oligosaccharides, Clostridium butyricum, Bacillus subtilis, glucose oxidase, α-galactosidase) improved growth, carcass traits, immune organ indices, and intestinal histomorphology compared with an antibiotic treated control group (11). Similarly, a dietary inclusion of Bacillus subtilis-derived postbiotic enhanced performance and mortality rates in broiler chicks (12). Furthermore, the evaluation of an antimicrobial peptide derived from the Isalo scorpion demonstrated beneficial effect on growth performance, immune function, and gut microbiota in yellow-feathered broilers (13), underscoring the value of natural bioactive compounds as alternatives to antibiotics.Ruminants' studies in this collection emphasized both direct and maternal nutritional pathways. A trial with Saccharomyces cerevisiae strain KA500 supplemented in feedlot buffaloes diet revealed a trend toward increased daily weight gain (14). In cattle study, maternal nutrition and neonatal antimicrobial peptide responses (6) highlighted how early-life immune competence may be "nutritionally primed". Another study investigated a promising medium-chain fatty acids combination used as silage additives, which reduced undesirable fermentations and pathogenic risks in corn silage (15), helping to mitigate contamination pressure before it reaches the animal. In weaned yaks, traditional Chinese medicinebased compounds were shown to enhance physical fitness, antioxidant capacity and immune status under high-altitude conditions (16), underlining how local functional solutions can further align with precision nutrition strategies along with the general sustainability.Beyond terrestrial systems, supplementation with low-dose dietary arabinoxylan (<5%) was well tolerated in rainbow trout, whereas high-dose supplementation (10%) impaired intestinal barrier function, altered gut microbiota, reduced antioxidant capacity and protein metabolism, thereby clarifying its antinutritional effects and supporting adjustments in plant-based aquaculture feed formulation (17). Given the rapid growth of aquaculture and its specific antimicrobial demand challenges, the optimization of functional ingredients feed formulas offers scalable solutions that align well with large-scale feed production.Furthermore, two studies have emphasized the potential of probiotic and prebiotic strategies in companion animals. Lactic acid bacterial strains isolated from canine feces were characterized as promising probiotic candidates (18), while a trial revealed that a prebiotic fiber blend enhanced fecal quality and raised the concentrations of short-chain fatty acids in the feces of puppies (19).Across species, several key themes emerge: (i) improvements in growth or feed efficiency are often associated with changes in gut morphology, immune function and antioxidant status; (ii) shifts in microbiota and metabolite profiles may be crucial in unraveling the mechanisms of action of functional compounds; and (iii) algae, plant polyphenols, essential oils, and pro-, pre-, and postbiotics offer complementary strategies that can also be used in combination.In conclusion, the published papers included in this research topic demonstrated that functional nutritional strategies can significantly enhance animal health and performance while reducing the need for antibiotics treatments. The variety of approaches and species emphasizes the broad applicability of these strategies.As demonstrated by these studies, reducing antibiotic use relies fundamentally on promoting animal health. Alternatives to antibiotics encompass all strategies aimed at minimizing antibiotic administration. Ensuring good health in animals reduces the need for antibiotics, thereby lowering the selective pressure for antimicrobial resistance and limiting the dissemination of resistance genes among animal, human, and environmental bacterial populations, encompassing both pathogenic and commensal strains.