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This study explores how lactulose as a safe molecule can stimulate bodily responses to alleviate salt\u2010sensitive hypertension by regulating the gut microbiotas of HSD\u2010fed mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>After 4 weeks, the blood pressures of mice fed a high\u2010salt plus lactulose diet (HSLD) are significantly lower than those of the HSD\u2010fed mice. The HSD increases the abundances of <jats:italic>Alistipes<\/jats:italic> and <jats:italic>Ruminococcaceae_UCG_009<\/jats:italic> and reduced the abundance of <jats:italic>Lactobacillus<\/jats:italic> in the gut, while lactulose supplementation increases the abundances of <jats:italic>Bifidobacterium<\/jats:italic>, <jats:italic>Alloprevotella<\/jats:italic>, and <jats:italic>Subdoligranulum<\/jats:italic>. Fecal metabolic profiling shows significant increases in metabolites involved in ATP\u2010binding cassette transporter pathways, and tryptophan metabolism is significantly reduced in the HSLD group compared with the HSD group. Lactulose maintains the intestinal microenvironmental health in the HSD\u2010fed mice by improving glycolipid metabolism, decreasing the small intestinal interleukin\u201017a (<jats:italic>IL\u201017a<\/jats:italic>) and interleukin\u201022 (<jats:italic>IL\u201022<\/jats:italic>) mRNA levels and serum IL\u201017a and IL\u201022 levels, relieving constipation, increasing fecal sodium, and reducing intestinal permeability.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Lactulose negates salt\u2010sensitive hypertension. Regulating the gut microbiota is a potential treatment for salt\u2010sensitive hypertension.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mnfr.201800941","type":"journal-article","created":{"date-parts":[[2019,3,2]],"date-time":"2019-03-02T10:39:39Z","timestamp":1551523179000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Targeting the Gut Microbiota to Investigate the Mechanism of Lactulose in Negating the Effects of a High\u2010Salt Diet on Hypertension"],"prefix":"10.1002","volume":"63","author":[{"given":"Zheng","family":"Zhang","sequence":"first","affiliation":[{"name":"College of Food Science South China Agricultural University  Guangzhou 510000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangtao","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology School of Basic Medical Sciences Zhengzhou University  Zhengzhou 450001 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changyu","family":"Tian","sequence":"additional","affiliation":[{"name":"Institute of Disease Control and Prevention  China PLA Beijing 100071 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Food Science South China Agricultural University  Guangzhou 510000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Disease Control and Prevention  China PLA Beijing 100071 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Wei","sequence":"additional","affiliation":[{"name":"Institute of Disease Control and Prevention  China PLA Beijing 100071 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weishi","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Disease Control and Prevention  China PLA Beijing 100071 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naxin","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Fifth Medical Center of PLA General Hospital  Beijing 100071 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aimin","family":"Jiang","sequence":"additional","affiliation":[{"name":"College of Food Science South China Agricultural University  Guangzhou 510000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruo","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology School of Basic Medical Sciences Zhengzhou University  Zhengzhou 450001 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Yuan","sequence":"additional","affiliation":[{"name":"Institute of Disease Control and Prevention  China PLA Beijing 100071 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangna","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institute of Disease Control and Prevention  China PLA Beijing 100071 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,3,13]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1304127"},{"key":"e_1_2_8_3_1","first-page":"16","volume":"21","year":"2013","journal-title":"Cent. 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