{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T13:16:41Z","timestamp":1764595001838,"version":"3.46.0"},"reference-count":121,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Background: Rotavirus gastroenteritis (RVGE) remains a leading cause of severe infant diarrhea worldwide, with growing evidence supporting the role of the gut microbiome in modulating the disease. However, the interplay between early-life demographic factors, the gut microbiome, and their combined impact on RVGE clinical severity remains inadequately characterized, particularly in specific geographic populations. Aim: We aimed to investigate how demographic determinants shape gut microbiome composition and function in RVGE and how these features relate to clinical severity. Methods: In our comprehensive case\u2013control study of 165 infants (120 RVGE cases and 45 healthy controls, aged 0\u201312 months), we utilized 16S rRNA sequencing combined with advanced statistical modeling and machine learning to investigate how demographic factors influence microbiome composition and clinical outcomes. Results: RVGE cases exhibited significantly reduced bacterial diversity (Kruskal\u2013Wallis, Static = 14.85, p &lt; 0.001) and distinct patterns, with community structure most strongly associated with dehydration severity (PERMANOVA; R2 = 0.15, p &lt; 0.001). Substantial taxonomic alterations were identified characterized by depletion of beneficial commensals including Akkermansia (LDA score = 3.8, p &lt; 0.001), Faecalibacterium (Random Forest AUC = 0.82, p &lt; 0.001), and Bifidobacterium (r = \u22120.42 with breastfeeding, p &lt; 0.001), alongside enrichment of inflammation-associated taxa such as Escherichia-Shigella (WBC; r = 0.49, p &lt; 0.001, and CRP; r = 0.56, p &lt; 0.001), Streptococcus (LDA score = 4.2, p &lt; 0.001), and Staphylococcus. Proteobacteria was the top potential biomarker of severe outcomes (Random Forest AUC = 0.85), with abundance positively correlated with systemic inflammation (CRP: r = 0.51, p = 0.003). Functional predictions revealed increased lipopolysaccharide biosynthesis (ko00540) and reduced butanoate metabolism (ko00650, p &lt; 0.001) in severe disease. Importantly, demographic factors significantly modulated clinical outcomes: cesarean-delivered, formula-fed infants presented the most dysbiotic profiles and experienced 3.2-fold longer hospitalization (95% CI: 1.8\u20135.6, p &lt; 0.001) than vaginally delivered, breastfed infants did. Conclusions: Collectively, these findings demonstrate that early-life demographic factors potentially shape the gut microbiome composition and function, may influence RVGE severity and recovery trajectories, thus providing candidate biomarkers for risk stratification and identifying targets for microbiota-based interventions.<\/jats:p>","DOI":"10.3390\/v17121542","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T10:04:57Z","timestamp":1764151497000},"page":"1542","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Early-Life Demographic Factors Shape Gut Microbiome Patterns Associated with Rotavirus Gastroenteritis Severity"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2555-8193","authenticated-orcid":false,"given":"Eman R.","family":"Abdelbary","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Pharmacy, Al-Azhar University, Assiut 71526, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4577-0418","authenticated-orcid":false,"given":"Mohammed","family":"Ramadan","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Pharmacy, Al-Azhar University, Assiut 71526, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ibrahim A.","family":"Amin","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Pharmacy, Al-Azhar University, Assiut 71526, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatma S.","family":"Abd-Elsamea","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashraf Mohamed","family":"Elsaghier","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Gastroenterology and Hepatology Unit, Assiut University Children Hospital, Faculty of Medicine, Assiut University, Assiut 71515, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eman Ahmed","family":"Abd-Alrahman","sequence":"additional","affiliation":[{"name":"Medical Microbiology and Immunology, Faculty of Medicine for Girls, Al-Azhar University, Assiut 71526, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2651-9017","authenticated-orcid":false,"given":"Hani A.","family":"Ozbak","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taibah University, Madinah 42353, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0394-4512","authenticated-orcid":false,"given":"Hassan A.","family":"Hemeg","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taibah University, Madinah 42353, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5654-6139","authenticated-orcid":false,"given":"Yahya A.","family":"Almutawif","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taibah University, Madinah 42353, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3261-304X","authenticated-orcid":false,"given":"Shadi A.","family":"Zakai","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology and Immunology, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali A.","family":"Abdelrahman","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed","family":"Salah","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Pharmacy, Port-Said University, Port-Said 42526, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1016\/S1473-3099(17)30276-1","article-title":"Estimates of global, regional, and national morbidity, mortality, and aetiologies of diarrhoeal diseases: A systematic analysis for the Global Burden of Disease Study 2015","volume":"17","author":"Troeger","year":"2017","journal-title":"Lancet Infect. 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