Strategies for Reducing Antimicrobial Use in Cattle Through Gut Microbiome Modulation: A Systematic Review of...

The escalating global threat of antimicrobial resistance (AMR) has intensified efforts to identify safe, effective, and sustainable alternatives to in-feed antibiotics in livestock production. The bovine gastrointestinal microbiome plays a central role in host immunity, nutrient utilization, and disease resilience, positioning microbiome-modulating interventions as promising candidates for antimicrobial stewardship. Despite growing experimental interest, a systematic synthesis of the available evidence in cattle is lacking. This systematic review aimed to evaluate the efficacy of microbiome-modulating interventions, including probiotics, prebiotics, postbiotics, phytogenic feed additives, essential oils, organic acids, and native rumen microbial supplements, as strategies to reduce antimicrobial use in cattle, and to characterize their effects on gut microbial diversity, fermentation characteristics, and host health and performance outcomes. A systematic search of Scopus, Web of Science, and EBSCOhost (including Academic Search Ultimate, MEDLINE with full text, and CAB Abstracts with Full text) was conducted in accordance with PRISMA guidelines. Studies were eligible if they used cattle (dairy cattle, beef cattle, calves, or mixed production systems), employed a microbiome-modulating intervention, and reported at least one microbiological or host outcome. Seventeen peer-reviewed studies published between 2010 and 2025 were included after full-text screening. Risk of bias was assessed using an adapted SYRCLE tool, which identified moderate overall study quality; the majority of included studies were randomized controlled trials or controlled experiments, though reporting of allocation concealment and blinding was inconsistent across studies. Across the 17 included studies, five broad categories of interventions were evaluated: probiotics (n = 5 studies), prebiotics (n = 2), postbiotics and organic acids (n = 4), phytogenic additives and essential oils (n = 4), and native rumen microbial supplements (n = 2). Animals spanned neonatal dairy calves, weaned Holstein calves, dairy heifers, lactating dairy cows, and Bos indicus feedlot beef cattle. Probiotics and organic acids most consistently improved growth performance: benzoic acid supplementation increased average daily gain by 8.4% (p < 0.05) and fructo-oligosaccharide prebiotics elevated body weight at weaning by 6.7% (p < 0.01). Native rumen microbial supplements improved energy-corrected milk yield by up to 3.1% without increasing dry matter intake. Polyphenols and bile acids demonstrated the strongest immunological and disease-preventive effects, reducing calf mortality by approximately 40% and disease severity by approximately 35%, respectively. Microbiome analyses revealed intervention-dependent increases in microbial diversity and shifts toward taxa associated with improved fermentation efficiency, including enrichment of propionate-producing Prevotellaceae, butyrate-associated Ruminococcus, and hindgut Bifidobacterium. Rumen fermentation outcomes included reductions in the acetate:propionate ratio and ammonia-N concentrations and improvements in fiber digestibility of 3.6-4.4 percentage units in dairy cows. Phytogenic additives preserved microbial diversity without inducing broad-spectrum suppression, functioning primarily as microbiome stabilizers rather than direct antimicrobial replacements. This systematic review provides evidence that gut microbiome modulation may enhance growth performance, improve fermentation efficiency, and reduce disease susceptibility in cattle, thereby supporting antimicrobial use reduction across dairy, beef, and mixed production systems. Effect magnitudes varied substantially across intervention categories and production contexts, and study quality was moderate, underscoring the need for larger, pre-registered trials with standardized outcome reporting and direct antibiotic comparator arms. Probiotics, prebiotics, and bile acid metabolites showed the greatest potential as components of integrated antimicrobial stewardship strategies in cattle production.