{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T06:28:59Z","timestamp":1791872939862,"version":"4.3.4"},"reference-count":114,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T00:00:00Z","timestamp":1744675200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diseases"],"abstract":"<jats:p>Background and Aim: The human gut microbiome plays a crucial role in maintaining health. Artificial sweeteners, also known as non-nutritive sweeteners (NNS), have garnered attention for their potential to disrupt the balance of the gut microbiome. This review explores the complex relationship between NNS and the gut microbiome, highlighting their potential benefits and risks. By synthesizing current evidence, we aim to provide a balanced perspective on the role of AS in dietary practices and health outcomes, emphasizing the need for targeted research to guide their safe and effective use. Methods: A comprehensive literature review was conducted through searches in PubMed and Google Scholar, focusing on the effects of artificial sweeteners on gut microbiota. The search utilized key terms including \u201cGut Microbiome\u201d, \u201cgut microbiota\u201d, \u201cEubiosis\u201d, \u201cDysbiosis\u201d, \u201cArtificial Sweeteners\u201d, and \u201cNonnutritive Sweeteners\u201d. Results: NNS may alter the gut microbiome, but findings remain inconsistent. Animal studies often report a decrease in beneficial bacteria like Bifidobacterium and Lactobacillus, and an increase in harmful strains such as Clostridium difficile and E. coli, potentially leading to inflammation and gut imbalance. Disruptions in short-chain fatty acid (SCFA) production and gut hormone signaling have also been observed. However, human studies generally show milder or no significant changes, highlighting the limitations in translating animal model findings directly to humans. Differences in study design, dosage, exposure time, and sweetener type likely contribute to these varied outcomes. Conclusions: While NNS offer certain benefits, including reduced caloric intake and improved blood sugar regulation, their impact on gut microbiome health raises important concerns. The observed reduction in beneficial bacteria and the rise in pathogenic strains underscore the need for caution in NNS consumption. Furthermore, the disruption of SCFA production and metabolic pathways illustrates the intricate relationship between diet and gut health.<\/jats:p>","DOI":"10.3390\/diseases13040115","type":"journal-article","created":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T06:50:27Z","timestamp":1744699827000},"page":"115","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Artificial Sweeteners: A Double-Edged Sword for Gut Microbiome"],"prefix":"10.3390","volume":"13","author":[{"given":"Helal F.","family":"Hetta","sequence":"first","affiliation":[{"name":"Division of Microbiology, Immunology and Biotechnology, Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5453-6332","authenticated-orcid":false,"given":"Nizar","family":"Sirag","sequence":"additional","affiliation":[{"name":"Division of Pharmacognosy, Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7964-1294","authenticated-orcid":false,"given":"Hassabelrasoul","family":"Elfadil","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Immunology and Biotechnology, Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7946-4477","authenticated-orcid":false,"given":"Ayman","family":"Salama","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara F.","family":"Aljadrawi","sequence":"additional","affiliation":[{"name":"PharmD Program, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amani J.","family":"Alfaifi","sequence":"additional","affiliation":[{"name":"PharmD Program, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asma N.","family":"Alwabisi","sequence":"additional","affiliation":[{"name":"PharmD Program, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bothinah M.","family":"AbuAlhasan","sequence":"additional","affiliation":[{"name":"PharmD Program, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Layan S.","family":"Alanazi","sequence":"additional","affiliation":[{"name":"PharmD Program, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yara A.","family":"Aljohani","sequence":"additional","affiliation":[{"name":"PharmD Program, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7374-9334","authenticated-orcid":false,"given":"Yasmin N.","family":"Ramadan","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Pharmacy, Assiut University, Assiut 71515, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noura H.","family":"Abd Ellah","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Badr University in Assiut, Naser City 2014101, Assiut, Egypt"},{"name":"Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut 71515, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5580-1559","authenticated-orcid":false,"given":"Abdelazeem M.","family":"Algammal","sequence":"additional","affiliation":[{"name":"Department of Bacteriology, Immunology and Mycology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia 41522, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.physbeh.2016.03.030","article-title":"Trends in the consumption of low-calorie sweeteners","volume":"164","author":"Sylvetsky","year":"2016","journal-title":"Physiol. 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