{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T20:12:58Z","timestamp":1790280778414,"version":"4.1.0"},"reference-count":49,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,3]],"date-time":"2026-01-03T00:00:00Z","timestamp":1767398400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>Background: Sodium glucose co-transporter-2 (SGLT-2) inhibitors are antihyperglycemic drugs used in type 2 diabetes mellitus management, and they have associated cardiovascular and renal advantages beyond their glucose-lowering effects, with maintained proof linking gut microbiota modulation to their multiple therapeutic benefits. Aim: This review aims to deliver an overview of the current knowledge regarding the relationship between SGLT-2 inhibitors and the gut microbiota and how this interplay impacts the gut\u2013organ axes such as the lung, heart, brain, liver, and hematological system. Methodology: A literature review was performed in Web of Science, PubMed, and Google Scholar to discover studies that assessed the effects of SGLT-2 inhibitors on gut microbiota composition, microbial metabolites, and associated systemic consequences. Results: SGLT-2 inhibitors modulate gut microbiota and its driven metabolites, strengthening the barrier integrity and alleviating endotoxemia, inflammation, and oxidative stress, resulting in beneficial outcomes across the different gut\u2013organ axes. Conclusion: Gut microbiota modulation is an emerging approach in mediating the multifaceted beneficial impacts of SGLT-2 inhibitors, revealing that their effectiveness goes beyond glycemic control. Future research should concentrate on the microbial taxa and metabolites that mediate these impacts and testing combination approaches that target SGLT-2 pathways and gut microbiota to enhance preservation of different organs.<\/jats:p>","DOI":"10.3390\/medsci14010022","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T10:03:48Z","timestamp":1767607428000},"page":"22","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["From Glucose Transport to Microbial Modulation: The Impact of Sodium Glucose Co-Transporter-2 Inhibitors on the Gut Microbiota"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2887-9937","authenticated-orcid":false,"given":"Mina Y.","family":"George","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nada K.","family":"Gamal","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerolos","family":"Safwat","sequence":"additional","affiliation":[{"name":"PharmD Clinical Program, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Mamdouh","sequence":"additional","affiliation":[{"name":"PharmD Clinical Program, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"AbdElFatah","sequence":"additional","affiliation":[{"name":"PharmD Clinical Program, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdelrahman","family":"Atallah","sequence":"additional","affiliation":[{"name":"PharmD Clinical Program, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9104-5436","authenticated-orcid":false,"given":"Claudio","family":"Cerchione","sequence":"additional","affiliation":[{"name":"Hematology Unit, Istituto Romagnolo per lo Studio dei Tumori \u201cDino Amadori\u201d\u2014IRST IRCCS, Via Piero Maroncelli 40, 47014 Meldola, FC, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1038\/s41586-021-04211-w","article-title":"Structure and mechanism of the SGLT family of glucose transporters","volume":"601","author":"Han","year":"2022","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1007\/s40200-024-01435-1","article-title":"The impact of sodium-glucose cotransporter inhibitors on gut microbiota: A scoping review","volume":"23","author":"Afsar","year":"2024","journal-title":"J. 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