Kidney360 · 2025
Lactulose, a Disaccharide Prebiotic, Improves the Gut-Kidney Axis via Enhancement of Akkermansia Muciniphila Production.
СтатьяНазвание и аннотация: Перевод в очереди
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Sueyoshi Miyu, Watanabe Hiroshi, Goto Moritaka, Sato Takao, Hashimoto Mai, Oki Mayu, Ofori-Attah Ebenezer, Nakano Takehiro, Maeda Hitoshi, Tanaka Motoko, Matsushita Kazutaka, Jinnouchi Hideaki, Maruyama Toru, Kadowaki Daisuke
Аннотация
KEY POINTS: Lactulose, a synthetic disaccharide, promotes Akkermansia muciniphila proliferation. The oral administration of both live and pasteurized forms of Akkermansia muciniphila significantly improved renal function in CKD-induced mice. Lactulose as a prebiotic therapeutic agent exerts the therapeutic effects on the gut-kidney axis via enhancing Akkermansia muciniphila production.
BACKGROUND: Recently, we reported that lactulose, a synthetic disaccharide used to treat chronic constipation, improved the gut-renal axis in mice with adenine-induced CKD. However, the underlying mechanism remains unclear. Akkermansia muciniphila (AKK), a next-generation probiotic, mitigates multiorgan dysfunction, including kidney impairment, by modulating intestinal health. This study aimed to investigate whether lactulose induces AKK proliferation and contributes to its renoprotective effects.
METHODS: CKD was induced in 7-week-old male C57BL/6N mice by administering 0.2% adenine for 4 weeks. After adenine discontinuation, the CKD mice received oral administration of lactulose (7.5% or 10%) or AKK (2×10 CFU/mouse) for 3 weeks. Intestinal permeability was assessed by measuring plasma levels of fluorescent probe for fluorescein isothiocyanate-dextran (4 kDa) and lipopolysaccharides. The composition of the gut microbiota was analyzed using 16S rRNA sequencing.
RESULTS: Lactulose administration significantly ameliorated renal impairment in CKD mice and improved intestinal barrier integrity by increasing intestinal mucosal thickness. In addition, lactulose modulated CKD-induced gut dysbiosis, thereby altering microbiota diversity and composition with a notable increase in AKK abundance. This was further supported by in vitro findings that demonstrated a significant increase in AKK proliferation upon lactulose treatment. Similar to lactulose, oral administration of AKK (both live and pasteurized forms) for 3 weeks attenuated renal damage in CKD mice. Moreover, both forms of AKK significantly improved intestinal barrier function by enhancing mucosal integrity.
CONCLUSIONS: Our findings suggest that lactulose functions as an in vivo AKK inducer, exerting renoprotective effects by improving intestinal barrier function in CKD. These results highlight the potential of lactulose as a prebiotic therapeutic agent for CKD management.
BACKGROUND: Recently, we reported that lactulose, a synthetic disaccharide used to treat chronic constipation, improved the gut-renal axis in mice with adenine-induced CKD. However, the underlying mechanism remains unclear. Akkermansia muciniphila (AKK), a next-generation probiotic, mitigates multiorgan dysfunction, including kidney impairment, by modulating intestinal health. This study aimed to investigate whether lactulose induces AKK proliferation and contributes to its renoprotective effects.
METHODS: CKD was induced in 7-week-old male C57BL/6N mice by administering 0.2% adenine for 4 weeks. After adenine discontinuation, the CKD mice received oral administration of lactulose (7.5% or 10%) or AKK (2×10 CFU/mouse) for 3 weeks. Intestinal permeability was assessed by measuring plasma levels of fluorescent probe for fluorescein isothiocyanate-dextran (4 kDa) and lipopolysaccharides. The composition of the gut microbiota was analyzed using 16S rRNA sequencing.
RESULTS: Lactulose administration significantly ameliorated renal impairment in CKD mice and improved intestinal barrier integrity by increasing intestinal mucosal thickness. In addition, lactulose modulated CKD-induced gut dysbiosis, thereby altering microbiota diversity and composition with a notable increase in AKK abundance. This was further supported by in vitro findings that demonstrated a significant increase in AKK proliferation upon lactulose treatment. Similar to lactulose, oral administration of AKK (both live and pasteurized forms) for 3 weeks attenuated renal damage in CKD mice. Moreover, both forms of AKK significantly improved intestinal barrier function by enhancing mucosal integrity.
CONCLUSIONS: Our findings suggest that lactulose functions as an in vivo AKK inducer, exerting renoprotective effects by improving intestinal barrier function in CKD. These results highlight the potential of lactulose as a prebiotic therapeutic agent for CKD management.