Probiotics and human health: Biological activities, nutritional aspects, immunomodulatory properties, applications, and future perspectives - A comprehensive review

Mohamed T. El-Saadony^1*Ahmed M. Saad²Mahmoud Sitohy²Samar Sami Alkafaas³Mthokozisi Dladla⁴Soumya Ghosh⁵Dr. Dina Mostafa Mohammed⁶Essam Ibrahim⁷Mohamed A. Fahmy⁸Amr Elkelish⁹Synan F. AbuQamar^10*Khaled A. El- Tarabily^10*

• ¹Department of Agricultural Microbiology, Faculty of Agriculture, Zagazig University, Zagazig, Egypt
• ²Biochemistry Department, Faculty of Agriculture, Zagazig University, Zagazig, 44511, Egypt, zagazig, Egypt
• ³Molecular Cell Biology Unit, Division of Biochemistry, Department of Chemistry, Faculty of Science, Tanta University, Tanta, 31527, Egypt, zagazig, Egypt
• ⁴Human Molecular Biology Unit (School of Biomedical Sciences), Faculty of Health Sciences, University of the Free State, Bloemfontein, 9300, South Africa, Bloemfontein, South Africa
• ⁵Natural and Medical Sciences Research Center, University of Nizwa, Nizwa, 616, Oman, Nizwa, Oman
• ⁶Nutrition and Food Sciences Department, National Research Centre, Dokki, Giza, 12622, Egypt, Giza, Egypt
• ⁷Biology Department, Faculty of Science, King Khalid University, Abha, 61413, Saudi Arabia, Abha, Saudi Arabia
• ⁸Department of Agricultural Microbiology, Faculty of Agriculture, Zagazig University, Zagazig, 44511, Egypt, zagazig, Egypt
• ⁹Biology Department, College of Science, Imam Mohammad ibn Saud Islamic University (IMSIU), P.O. Box 1690950, Riyadh 11623, Saudi Arabia, Riyadh, Saudi Arabia
• ¹⁰Department of Biology, College of Science, United Arab Emirates University, Al Ain, 15551, United Arab Emirates, Al Ain, United Arab Emirates

ABSTRACT Probiotics, characterized as live microorganisms, are extensively acknowledged for their capacity 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 concerning strain-specific mechanisms, optimal dosages, long-term safety, and the interactions between 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, it emphasizes next-generation probiotics, live biotherapeutics, genetically engineered microbes, and their synergistic interactions with dietary bio-actives 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.