Department of Pediatrics, Far Eastern Memorial Hospital, New Taipei City, Taiwan.
Asia Eastern University of Science and Technology, New Taipei City, Taiwan.
J Gastroenterol. 2022 Nov;57(11):913-925. doi: 10.1007/s00535-022-01909-0. Epub 2022 Aug 17.
Although we know the key role of gut dysbiosis in nonalcoholic fatty liver disease (NAFLD), it remains unclear what microbe(s) are responsible. This study aims to identify the microbes that cause NAFLD.
C57BL/6JNarl male mice fed a high-fat diet (HFD) were orally administered Lactobacillus reuteri (L. reuteri) or Lactobacillus rhamnosus GG plus Bifidobacterium animalis subsp. lactis BB12 (LGG plus BB12). Their fecal microbiomes identified by 16S rRNA sequencing were correlated with the severity of fatty liver. We then used a human cohort to confirm the role of the microbe(s). The HFD-fed mice were administrated with the identified bacterium, Desulfovibrio. The histopathological changes in the liver and ileum were analyzed.
Lactobacillus and Bifidobacterium improved hepatic steatosis and fibrosis in HFD-fed mice, which was related to the decreased abundance of Desulfovibrio in feces. Further human study confirmed the amount of D. piger in the fecal microbiota of obese children with NAFLD was increased. We then administered D. piger and found aggravated hepatic steatosis and fibrosis in HFD-fed mice. Hepatic expression of CD36 was significantly increased in HFD-fed mice gavaged with D. piger. In HepG2 cells, overexpression of CD36 increased lipid droplets, whereas knockdown of CD36 decreased lipid droplets. HFD-fed mice gavaged with D. piger had a decrease in the villus length, crypt depth, and zonula occludens-1 density in the ileum tissue.
Our findings provide novel insights into the role of Desulfovibrio dysregulation in NAFLD. Modulation of Desulfovibrio may be a potential target for the treatment of NAFLD.
虽然我们知道肠道菌群失调在非酒精性脂肪性肝病（NAFLD）中起着关键作用，但仍不清楚是哪种微生物在起作用。本研究旨在确定导致 NAFLD 的微生物。
用高脂肪饮食（HFD）喂养 C57BL/6JNarl 雄性小鼠，通过口服给予鼠李糖乳杆菌（L. reuteri）或鼠李糖乳杆菌 GG 加双歧杆菌动物亚种。通过 16S rRNA 测序鉴定其粪便微生物组与脂肪肝的严重程度相关。然后，我们使用人类队列来确认微生物的作用。用鉴定出的细菌脱硫弧菌（Desulfovibrio）给 HFD 喂养的小鼠进行处理。分析肝脏和回肠的组织病理学变化。
乳杆菌和双歧杆菌改善了 HFD 喂养小鼠的肝脂肪变性和纤维化，这与粪便中脱硫弧菌丰度的降低有关。进一步的人类研究证实，肥胖儿童 NAFLD 粪便微生物群中 D. piger 的数量增加。然后，我们给予 D. piger，发现 HFD 喂养的小鼠肝脂肪变性和纤维化加重。HFD 喂养的小鼠给予 D. piger 后，肝组织中 CD36 的表达明显增加。在 HepG2 细胞中，CD36 的过表达增加了脂滴，而 CD36 的敲低减少了脂滴。给予 D. piger 的 HFD 喂养小鼠回肠组织绒毛长度、隐窝深度和闭合蛋白-1 密度降低。
我们的研究结果为脱硫弧菌失调在 NAFLD 中的作用提供了新的见解。调节脱硫弧菌可能是治疗 NAFLD 的一个潜在靶点。
