{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T23:36:22Z","timestamp":1792452982735,"version":"4.5.0"},"reference-count":581,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T00:00:00Z","timestamp":1774310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Probiotics, defined as living microorganisms, are widely recognized for their ability to positively influence the gut microbiota, an effect increasingly linked to a wide array of health benefits. They are claimed to treat or prevent conditions ranging from infant colic to cardiovascular disease, respiratory infections, and certain cancers. Since the beginning of the 21st century, consumer demand for probiotic-enriched foods has risen significantly, propelled by these health assertions. The consumption of such products has been associated with the alleviation of disorders, including irritable bowel syndrome, lactose intolerance, gastroenteritis, obesity, chronic diarrhea, allergies, atopic dermatitis, and infectious diseases. Recent advancements in microbiome and microbiota research are fundamentally transforming probiotic science. Cutting-edge studies on novel strains, their mechanisms, and potential applications are expected to revolutionize our understanding of their roles in human nutrition and medicine. Nevertheless, despite extensive research efforts, critical gaps remain regarding strain-specific mechanisms, optimal dosages, long-term safety, and interactions among probiotics, host genetics, and dietary factors. Addressing these gaps necessitates a comprehensive synthesis of current knowledge and emerging trends. This review aims to critically integrate historical foundations, dosage strategies, mechanisms of action, therapeutic applications, and potential risks associated with probiotics. Unlike previous reviews, this review emphasizes next-generation probiotics, live biotherapeutics, and genetically engineered microbes, and their synergistic interactions with dietary bioactives such as polyphenols and fibers. By providing a forward-looking perspective, this work contributes to the rational design of functional foods, targeted therapies, and microbiome-based interventions, thereby informing future advancements in human nutrition and medicine. It critically examines current and emerging trends in probiotic research, while acknowledging potential adverse effects and risks.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1713426","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T05:24:38Z","timestamp":1774329878000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Probiotics and human health: biological activities, nutritional aspects, immunomodulatory properties, applications, and future perspectives - a comprehensive review"],"prefix":"10.3389","volume":"16","author":[{"given":"Mohamed T.","family":"El-Saadony","sequence":"first","affiliation":[{"name":"Department of Agricultural Microbiology, Faculty of Agriculture, Zagazig University","place":["Zagazig, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed M.","family":"Saad","sequence":"additional","affiliation":[{"name":"Biochemistry Department, 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