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Characterized as a homogalacturonan with minor rhamnogalacturonan I, PEP-2 consists of galacturonic acid, galactose, rhamnose, and arabinose. In high-fat diet-induced mice, PEP-2 significantly improved metabolic phenotypes, reducing obesity, insulin resistance, and hepatic steatosis. Mechanistically, PEP-2 modulated the gut\u2013liver axis by enriching Akkermansia and enhancing short-chain fatty acid (SCFA) production. These changes were associated with increased colonic mRNA expression of SCFA receptor-related genes, including GPR41, GPR43, and GPR109A, and favorable regulation of hepatic lipid metabolism-related genes, including AMPK, PPAR\u03b1, and CPT1. In vitro, PEP-2 promoted Akkermansia muciniphila growth, while its fermentation products effectively reduced lipid accumulation in cell models. These findings support a microbiota-SCFA-associated mechanism underlying the beneficial effects of PEP-2 and highlight its potential as a prebiotic candidate for functional food development against metabolic disorders.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c04467","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T14:02:21Z","timestamp":1785852141000},"page":"24361-24376","source":"Crossref","is-referenced-by-count":0,"title":["<i>Phyllanthus emblica<\/i>\n                    Polysaccharide Improves Metabolic\nAssociated Fatty Liver Disease\nby Regulating Gut\u2013Liver Axis through\n                    <i>Akkermansia<\/i>\n                    and Short-Chain Fatty Acid Receptors"],"prefix":"10.1021","volume":"74","author":[{"given":"Bin","family":"Zhang","sequence":"first","affiliation":[{"name":"Ganjiang Chinese Medicine Innovation Center , ,","place":["Nanchang, China, 330000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyu","family":"Yao","sequence":"additional","affiliation":[{"name":"Jiangxi Normal University , ,","place":["Nanchang, China, 330022"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Yu","sequence":"additional","affiliation":[{"name":"Ganjiang Chinese Medicine Innovation Center , ,","place":["Nanchang, China, 330000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huilin","family":"Yang","sequence":"additional","affiliation":[{"name":"Jiangxi Normal University , ,","place":["Nanchang, China, 330022"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7172-7502","authenticated-orcid":true,"given":"Xuan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Ganjiang Chinese Medicine Innovation Center , ,","place":["Nanchang, China, 330000"]},{"name":"Dalian Institute of Chemical Physics, Chinese Academy of Sciences , , Zhongshan Road 457 , ,","place":["Dalian, China, 116023"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianlong","family":"Ye","sequence":"additional","affiliation":[{"name":"Ganjiang Chinese Medicine Innovation Center , ,","place":["Nanchang, China, 330000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4394-4274","authenticated-orcid":true,"given":"Xinmiao","family":"Liang","sequence":"additional","affiliation":[{"name":"Ganjiang Chinese Medicine Innovation Center , ,","place":["Nanchang, China, 330000"]},{"name":"Dalian Institute of Chemical Physics, Chinese Academy of Sciences , , Zhongshan Road 457 , ,","place":["Dalian, China, 116023"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,30]]},"reference":[{"key":"2026081208081108600_cit1","doi-asserted-by":"publisher","first-page":"20420188221145549","DOI":"10.1177\/20420188221145549","article-title":"MAFLD: a multisystem disease","volume":"14","author":"Pipitone","year":"2023","journal-title":"Ther. 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Hepatol."},{"issue":"12","key":"2026081208081108600_cit4","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1001\/jama.2020.2298","article-title":"Nonalcoholic\nsteatohepatitis: a review","volume":"323","author":"Sheka","year":"2020","journal-title":"JAMA"},{"issue":"17","key":"2026081208081108600_cit5","doi-asserted-by":"publisher","first-page":"3722","DOI":"10.3390\/nu15173722","article-title":"Polysaccharides:\nthe potential prebiotics for metabolic associated fatty liver disease\n(MAFLD)","volume":"15","author":"Guo","year":"2023","journal-title":"Nutrients"},{"issue":"1","key":"2026081208081108600_cit6","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1002\/hep.26494","article-title":"Microbiota-liver axis in hepatic\ndisease","volume":"59","author":"Chassaing","year":"2014","journal-title":"Hepatology"},{"issue":"13\u201314","key":"2026081208081108600_cit7","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1016\/j.clinbiochem.2015.06.023","article-title":"Gut-liver\naxis, nutrition, and non-alcoholic\nfatty liver disease","volume":"48","author":"Kirpich","year":"2015","journal-title":"Clin. 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