{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:26:56Z","timestamp":1792787216990,"version":"4.5.0"},"reference-count":164,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Amyotrophic Lateral Sclerosis (ALS) is a severe, progressive neurodegenerative disorder characterized by the loss of upper and lower motor neurons, affecting 0.5 to 2.6 per 100,000 people, with a median survival of 2 to 5 years. It is increasingly seen as a multisystem disorder, sharing essential clinicopathological features with Frontotemporal Dementia (FTD). This convergence arises from overlapping molecular processes, including severe oxidative stress, glutamate-mediated excitotoxicity, mitochondrial dysfunction, and widespread aggregated TDP-43 proteinopathy in both sporadic and familial cases. Several key genetic factors have been identified, particularly mutations in C9orf72, SOD1, TARDBP, and FUS, which serve as important targets for novel treatments, such as Tofersen, a recently approved SOD1-specific antisense oligonucleotide (ASO) gene therapy. Additionally, there is increasing evidence of the gut\u2013brain connection. Dysbiosis, involving species such as Akkermansia muciniphila, and lower levels of neuroprotective metabolites, such as nicotinamide, may affect the course of the disease. As a result, treatment strategies are shifting toward a personalized approach. This includes using gene therapy, ranging from ASOs and RNA interference (RNAi) to new CRISPR-based genome editing. It also involves exploring microbiome-modulating treatments, such as specific probiotics and Fecal Microbiota Transplantation (FMT). While microbiome and gene therapies remain largely experimental, their potential is promising, as highlighted by the recent approval of Tofersen. These novel approaches could be further enhanced and guided by more robust diagnostic criteria and by investigating early multimodal treatment strategies to slow the progression of this complex disease.<\/jats:p>","DOI":"10.3390\/ijms27041978","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T09:55:31Z","timestamp":1771494931000},"page":"1978","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Amyotrophic Lateral Sclerosis (ALS) Genetics and Microbiota: A Comprehensive Review"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-3442-9523","authenticated-orcid":false,"given":"Mostafa Ahmed","family":"Kurdi","sequence":"first","affiliation":[{"name":"Biology Department, College of Science, Taibah University, Medina 42353, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7774-038X","authenticated-orcid":false,"given":"Hidayah","family":"Alotaibi","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, Riyadh 11671, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0674-5419","authenticated-orcid":false,"given":"Asayel Tawfiq","family":"Alkhuraymi","sequence":"additional","affiliation":[{"name":"Biology Department, Faculty of Science, King Abdul Aziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Layyan Nassar","family":"Aldahery","sequence":"additional","affiliation":[{"name":"Biology Department, Faculty of Science, King Abdul Aziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali Fouad","family":"Alhawaj","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 34212, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8588-0921","authenticated-orcid":false,"given":"Hamzah Jehad","family":"Aldali","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Medicine, College of Biomedical Science, University of Bristol, Bristol BS8 1DT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4693","DOI":"10.1007\/s00415-024-12435-9","article-title":"Update on recent advances in amyotrophic lateral sclerosis","volume":"271","author":"Riva","year":"2024","journal-title":"J. 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