{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T14:31:58Z","timestamp":1784903518512,"version":"3.55.0"},"reference-count":51,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T00:00:00Z","timestamp":1624406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"China Postdoctoral Science Foundation","award":["2019M651867"],"award-info":[{"award-number":["2019M651867"]}]},{"DOI":"10.13039\/100007540","name":"Jiangsu Agricultural Science and Technology Innovation Fund","doi-asserted-by":"publisher","award":["CX (18)2002"],"award-info":[{"award-number":["CX (18)2002"]}],"id":[{"id":"10.13039\/100007540","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>The effects of saccharin, as a type of sweetener additive, on the metabolism and development of mammals are still controversial. Our previous research revealed that saccharin sodium (SS) promoted the feed intake and growth of guinea pigs. In this experiment, we used the guinea pig model to study the physiological effect of SS in the microbiota-gut-hypothalamus axis. Adding 1.5 mM SS to drinking water increased the serum level of glucose, followed by the improvement in the morphology and barrier function of the ileal villus, such as SS supplementation which increased the villus height and villus height\/crypt depth ratio. Saccharin sodium (SS) treatment activated the sweet receptor signaling in the ileum and altered GHRP hormone secretion. In the hypothalamus of SS and control (CN) group, RNA-seq identified 1370 differently expressed genes (796 upregulated, 574 downregulated), enriching into the taste signaling transduction, and neuroactive ligand\u2013receptor interaction. LEfSe analysis suggested that Lactobacillaceae-Lactobacillus was the microbe with significantly increased abundance of ileum microorganisms in the SS-treated group, while Brevinema-Andersonii and Erysipelotrichaceae-Ilebacterium were the microbes with significantly increased abundance of the control. Furthermore, SS treatment significantly enhanced the functions of chemoheterotrophy and fermentation of ileal microflora compared to the CN group. Accordingly, SS treatment increased levels of lactic acid and short-chain fatty acids (acetic acid, propionic acid and N-valeric acid) in the ileal digesta. In summary, drinking water with 1.5 mM SS activated sweet receptor signaling in the gut and altered GHRP hormone secretion, followed by the taste signaling transduction in the hypothalamus.<\/jats:p>","DOI":"10.3390\/ani11071875","type":"journal-article","created":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T11:28:41Z","timestamp":1624447721000},"page":"1875","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Drinking Water with Saccharin Sodium Alters the Microbiota-Gut-Hypothalamus Axis in Guinea Pig"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7642-7981","authenticated-orcid":false,"given":"Junrong","family":"Li","sequence":"first","affiliation":[{"name":"College of Animal Science, Zhejiang University, Hangzhou 310058, China"},{"name":"College of Agriculture, Jinhua Polytechnic, Jinhua 321000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanli","family":"Zhu","sequence":"additional","affiliation":[{"name":"College of Agriculture, Jinhua Polytechnic, Jinhua 321000, China"},{"name":"College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zengpeng","family":"Lv","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjian","family":"Dai","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quanwei","family":"Wei","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7117-2403","authenticated-orcid":false,"given":"Enayatullah","family":"Hamdard","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5039-6478","authenticated-orcid":false,"given":"Sheeraz","family":"Mustafa","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6271-6184","authenticated-orcid":false,"given":"Fangxiong","family":"Shi","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Fu","sequence":"additional","affiliation":[{"name":"College of Animal Science, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1146\/annurev-food-022811-101236","article-title":"Non-Caloric Sweeteners, Sweetness Modulators, and Sweetener Enhancers","volume":"Volume 3","author":"Doyle","year":"2012","journal-title":"Annual Review of Food Science and Technology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1146\/annurev-food-022814-015635","article-title":"Non-nutritive sweeteners and obesity","volume":"Volume 6","author":"Doyle","year":"2015","journal-title":"Annual Review of Food Science and Technology"},{"key":"ref_3","first-page":"G241","article-title":"Expression of monosaccharide transporters in intestine of diabetic humans","volume":"282","author":"Dyer","year":"2002","journal-title":"Am. 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