Plant growth-promoting microorganisms (PGPMs) and microbial biocontrol agents have emerged as key tools for improving crop productivity while maintaining environmental sustainability. However, central questions remain regarding which factors determine their consistent field performance and how these factors interact under real agronomic conditions. Previous research has demonstrated that PGPMs enhance nutrient acquisition, regulate phytohormone balance, improve stress tolerance, and suppress plant pathogens through diverse biochemical and ecological mechanisms. Advances in omics technologies, genome mining, and synthetic microbial communities have further expanded understanding of their functional potential. Nevertheless, many studies rely on laboratory-scale experiments or short-term trials, with limited multi-season and cross-regional validation. This gap contributes to inconsistent field outcomes and restricts large-scale agricultural adoption. Long-term multi-season validation and reproducibility assessment remain essential priorities for improving reliability of microbial agricultural products. This review synthesizes recent advances in PGPM-based biofertilizers and microbial biocontrol technologies, critically examining their mechanisms of action, scalability constraints, formulation challenges, and regulatory limitations. It identifies major translational barriers, including context dependency, mechanistic uncertainties, reproducibility gaps, and insufficient systems-level integration.

Natural products, including medicinal plants, are an important source of medicines. However, the natural origin does not exclude undesirable effects with prolonged use, which requires a systematic assessment of their safety. Background/Objectives: The aim of this work is to evaluate the safety of an antituberculous medicinal agent based on the probiotic association of lactic acid bacteria Lacticaseibacillus rhamnosus 7n, Lacticaseibacillus paracasei B-3/43, Lacticaseibacillus casei 14d/13 and 1% licorice extract (Glycyrrhiza glabra) with repeated administration. Methods: The experimental study was conducted on laboratory mice in accordance with a 60-day oral administration protocol at doses of 25 mg/kg, 250 mg/kg, and 2500 mg/kg body weight. The control group of animals received saline solution. The analysis included hematological, biochemical parameters, and a study of urine composition, as well as macro- and histological examinations of organs. The work was performed in accordance with the basic principles of GLP. Results: The agent did not cause general toxic effects, behavioral disorders and changes in feed intake were not noted. Morphofunctional changes were not detected. Macroscopic examination revealed no pathological changes in the internal organs. Histological analysis confirmed the absence of signs of degeneration and necrosis in the tissues of organs. Hematological parameters were within the limits of physiological norms. Blood biochemical parameters showed no significant differences compared to the control group. The parameters of the general urinalysis were without significant changes between the groups and gender. Conclusions: The medicinal agent showed a favorable safety profile without signs of toxicity.

Soil microbiomes are essential for nutrient cycling, plant health, stress resilience, and sustainable agriculture. Recent advances in high-throughput sequencing, multi-omics technologies, systems biology, and artificial intelligence (AI) have transformed our understanding of plant–microbiome interactions and enabled the development of innovative microbiome engineering strategies. This review provides a comprehensive overview of the mechanisms governing plant-associated soil microbiome assembly, microbial community functions, plant–microbe communication, and microbiome-mediated stress resistance in agricultural ecosystems. Current approaches to plant-associated soil microbiome manipulation and engineering, including microbial inoculants, synthetic microbial communities (SynComs), microbiome transplantation, rhizosphere steering, and synthetic biology-based interventions, are critically examined. The review further discusses the growing role of metagenomics, metabolomics, metatranscriptomics, machine learning (ML), and precision agriculture technologies in improving microbiome characterization, prediction, and management. Particular attention is given to the application of microbiome-based solutions for sustainable crop production, nutrient management, biological control, climate-smart agriculture, and ecosystem restoration. Despite significant progress, challenges related to field-scale variability, colonization stability, biosafety, regulatory frameworks, and data integration continue to limit large-scale implementation. Future advances in precision microbiome engineering are expected to combine ecological principles, multi-omics technologies, AI, and synthetic biology to develop predictive and resilient microbiome-based solutions for sustainable and climate-resilient agriculture.