Antibiotic resistance emerged shortly after the discovery of the first antibiotic and has remained a critical public health issue ever since. Managing antibiotic resistance in clinical settings continues to be challenging, particularly with the rise of superbugs, or bacteria resistant to multiple antibiotics, known as multidrug-resistant (MDR) bacteria. This rapid development of resistance has compelled researchers to continuously seek new antimicrobial agents to curb resistance, despite a shrinking pipeline of new drugs. Recently, the focus of antimicrobial discovery has shifted to plants, fungi, lichens, endophytes, and various marine sources, such as seaweeds, corals, and other microorganisms, due to their promising properties. For this review, an extensive search was conducted across multiple scientific databases, including PubMed, Elsevier, ResearchGate, Scopus, and Google Scholar, encompassing publications from 1929 to 2024. This review provides a concise overview of the mechanisms employed by bacteria to develop antibiotic resistance, followed by an in-depth exploration of plant secondary metabolites as a potential solution to MDR pathogens. In recent years, the interest in plant-based medicines has surged, driven by their advantageous properties. However, additional research is essential to fully understand the mechanisms of action and verify the safety of antimicrobial phytochemicals. Future prospects for enhancing the use of plant secondary metabolites in combating antibiotic-resistant pathogens will also be discussed.

The human gut microbiota—an intricate and dynamic ecosystem—plays a pivotal role in metabolic regulation, immune modulation, and the maintenance of intestinal barrier integrity. Although antibiotic therapy is indispensable for managing bacterial infections, it profoundly disrupts gut microbial communities. Such dysbiosis is typified by diminished diversity and shifts in community structure, especially among beneficial bacterial genera (e.g., Bifidobacterium and Eubacterium), and fosters antibiotic-resistant strains and the horizontal transfer of resistance genes. These alterations compromise colonization resistance, increase intestinal permeability, and amplify susceptibility to opportunistic pathogens like Clostridioides difficile. Beyond gastrointestinal disorders, emerging evidence associates dysbiosis with systemic conditions, including chronic inflammation, metabolic syndrome, and neurodegenerative diseases, underscoring the relevance of the microbiota–gut–brain axis. The recovery of pre-existing gut communities post-antibiotic therapy is highly variable, influenced by drug spectrum, dosage, and treatment duration. Innovative interventions—such as fecal microbiota transplantation (FMT), probiotics, synbiotics, and precision microbiome therapeutics—have shown promise in counteracting dysbiosis and mitigating its adverse effects. These therapies align closely with antibiotic stewardship programs aimed at minimizing unnecessary antibiotic use to preserve microbial diversity and curtail the spread of multidrug-resistant organisms. This review emphasizes the pressing need for microbiota-centered strategies to optimize antibiotic administration, promote long-term health resilience, and alleviate the disease burden associated with antibiotic-induced dysbiosis.

Prostatitis is an inflammatory condition that is related to multiple infectious agents, including bacteria and fungi. Traditional herbal extracts proved efficacious in controlling clinical symptoms associated with prostatitis. In this context, the aim of the present study was to explore the efficacy of extracts from Solidago virga-aurea, Ononis spinosa, Peumus boldus, Epilobium angustifolium, and Phyllanthus niruri against bacterial (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus cereus) and fungi strains (Candida albicans; C. tropicalis) involved in prostatitis. Additionally, anti-mycotic effects were tested against multiple species of dermatophytes (Trichophyton rubrum, T. tonsurans, T. erinacei, Arthroderma crocatum, A. quadrifidum, A. gypseum, A. currey, and A. insingulare). Antioxidant effects were also evaluated in isolated rat prostates challenged with lipopolysaccharide (LPS), and phytochemical analyses were conducted to identify and quantify selected phenolic compounds, in the extracts. Finally, a bioinformatics analysis was conducted to predict putative human and microbial enzymes targeted by extracts’ phytocompounds and underlying the observed bio-pharmacological effects. The phytochemical analysis highlighted that rutin levels could be crucial for explaining the highest antibacterial activity of P. boldus extract, especially against E. coli and B. cereus. On the other hand, in the E. angustifolium extract, catechin concentration could partially explain the highest efficacy of this extract in reducing lipid peroxidation, in isolated rat prostates stimulated with LPS. Concluding, the results of the present study showed moderate antimicrobial and anti-inflammatory effects induced by water extracts of S. virga-aurea, P. boldus, E. angustifolium, P. niruri, and O. spinosa that could be related, at least partially, to the phenolic composition of the phytocomplex.

Living organisms establish complex networks of mutualistic and antagonistic interactions in nature, which impact strongly on their own survival and on the stability of the whole population. Fungi, in particular, can shape natural as well as man-managed ecosystems due to their ubiquitous occurrence and the range of interactions they establish with plants, animals and other microbes. This review describes some examples of mutualistic and antagonistic fungal interactions that are of particular interest for their ecological role, or because they can be exploited by man to improve plant health and/or productivity in sustainable agriculture and forestry.