en Molecular Microbiology Molecular Microbiology مقاله مروری Review Article <span style="font-family:Times New Roman;"><span style="font-size:10.5pt"><span style="line-height:115%"><span style="color:black">The gut microbiome and gut-brain axis are central to systemic homeostasis, with dysbiosis implicated in neurodegenerative (Alzheimer&#39;s and Parkinson&#39;s) disorders and gastrointestinal conditions (inflammatory bowel disease, irritable bowel syndrome, and fibromyalgia). These conditions are marked by a reduction in beneficial taxa (e.g., <i>Faecalibacterium prausnitzii</i> and Bifidobacterium) and an increase in harmful ones (e.g., <i>Escherichia coli</i> and <i>Clostridium scindens</i>). Probiotic, prebiotic, postbiotic, and symbiotic interventions show therapeutic promise, but results can vary. Biotechnological advances, including CRISPR-Cas9 and genetic kill-switch systems, enable precision-engineered probiotics and postbiotics, though concerns about safety, genetic stability, gene transfer, and immune compatibility persist. Encapsulation and nanoencapsulation strategies improve microbial viability and site-specific delivery; i.e., microencapsulating <i>Lactobacillus acidophilus </i>and <i>Bifidobacterium animalis</i> in alginate-pectin matrices enhances survival during freeze-drying, storage, and gastrointestinal transit. Advancing clinical translation requires integrating multi-omics and machine learning with bioengineering approaches. This review examines the microbial-neural interface and surveys emerging biotechnological strategies for improving microbial-based therapeutics. </span></span></span></span> Brain-Gut Axis, Dysbiosis, Gastrointestinal microbiome, Prebiotics, Probiotics 193 211 http://ibj.pasteur.ac.ir/browse.php?a_code=A-10-6488-1&slc_lang=en&sid=1 Maryam Firoozi firoozimaryam@yahoo.com 0000-0002-7551-3172 No 1Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Hamadan University of Medical Sciences, Hamadan, Iran Ali Mahdavinezhad alimahdavin@gmail.com 0000-0002-1314-8229 No 2Department of Molecular Medicine, School of Advanced Medical Sciences and Technologies, Hamadan University of Medical Sciences, Hamadan, Iran Mahdieh Shirzad mahdiehshirzad@gmail.com 0000-0001-5790-9993 No 3Department of Microbial Biotechnology, School of Biology and Center of Excellence in Phylogeny of Living Organism, College of Science, University of Tehran, Tehran, Iran Elahe Motevaseli e_motevaseli@tums.ac.ir 0000-0002-9723-2590 No 4Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran Razieh Dalirfardouei r.dalir@umsha.ac.ir 0000-0001-5162-476X No 1Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Hamadan University of Medical Sciences, Hamadan, Iran Mohammad Hossein Modarressi* modaresi@tums.ac.ir 0000-0003-2763-1964 Yes 5Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Rezvan Najafi* re.najafi@umsha.ac.ir 0000-0003-1326-1288 No 2Department of Molecular Medicine, School of Advanced Medical Sciences and Technologies, Hamadan University of Medical Sciences, Hamadan, Iran