Department of Anatomy, Physiology, and Cell Biology, University of California Davis School of Veterinary Medicine, Davis, CA 95616, USA.
Department of Food Science and Technology, University of California Davis, CA 95616, Davis, USA.
Nutrients. 2020 Apr 5;12(4):1003. doi: 10.3390/nu12041003.
Obesity is characterized by fat accumulation, chronic inflammation and impaired satiety signaling, which may be due in part to gut microbial dysbiosis. Manipulations of the gut microbiota and its metabolites are attractive targets for obesity treatment. The predominant oligosaccharide found in human milk, acts as a prebiotic with beneficial effects on the host. However, little is known about the beneficial effects of 2'-FL in obesity. The aim of this study was to determine the beneficial effects of 2'-FL supplementation on the microbiota-gut-brain axis and the diet-induced obese phenotype in high fat (HF)-fed mice. Male C57/BL6 mice (n = 6/group; six weeks old) were counter-balanced into six weight-matched groups and fed either a low-fat (LF; 10% kcal as fat), HF (45% kcal as fat) or HF diet with 2'-FL (HF_2'-FL) at 1, 2, 5 and 10% (w/v) in drinking water for six weeks. General phenotypes (body weight, energy intake, fat and lean mass), cecal microbiome and metabolites, gut-brain signaling, intestinal permeability and inflammatory and lipid profiles were assessed. Only 10% 2'-FL, but not 1, 2 or 5%, decreased HF diet-induced increases in energy intake, fat mass and body weight gain. A supplementation of 10% 2'-FL changed the composition of cecal microbiota and metabolites compared to LF- and HF-fed mice with an increase in abundance and lactate and pyruvate, respectively, whose metabolic effects corresponded to our study findings. In particular, 10% 2'-FL significantly reversed the HF diet-induced impairment of cholecystokinin-induced inhibition of food intake. Gene expressions of interleukin (IL)-1β, IL-6, and macrophage chemoattractant protein-1 in the cecum were significantly downregulated by 10% 2'-FL compared to the HF group. Furthermore, 10% 2'-FL suppressed HF diet-induced upregulation of hepatic peroxisome proliferator-activated receptor gamma, a transcription factor for adipogenesis, at the gene level. In conclusion, 10% 2'-FL led to compositional changes in gut microbiota and metabolites associated with improvements in metabolic profiles and gut-brain signaling in HF-fed mice. These findings support the use of 2'-FL for modulating the hyperphagic response to HF diets and improving the microbiota-gut-brain axis.
肥胖的特征是脂肪积累、慢性炎症和饱腹感信号受损，这可能部分归因于肠道微生物失调。操纵肠道微生物群及其代谢物是治疗肥胖的有吸引力的目标。人乳中发现的主要低聚糖作为一种益生元，对宿主有有益的影响。然而，关于 2'-FL 在肥胖中的有益作用知之甚少。本研究旨在确定 2'-FL 补充对高脂肪（HF）喂养小鼠的肠道微生物群-肠道-大脑轴和饮食诱导肥胖表型的有益作用。雄性 C57/BL6 小鼠（n = 6/组；六周龄）按体重平衡分为六组，分别用低脂肪（LF；10%热量来自脂肪）、高脂肪（HF；45%热量来自脂肪）或高脂肪饮食加 2'-FL（HF_2'-FL）喂养，2'-FL 浓度分别为 1%、2%、5%和 10%（w/v），在饮用水中喂养六周。评估一般表型（体重、能量摄入、脂肪和瘦体重）、盲肠微生物群和代谢物、肠道-大脑信号、肠道通透性、炎症和脂质谱。只有 10%的 2'-FL，而不是 1%、2%或 5%，可以降低 HF 饮食诱导的能量摄入、脂肪量和体重增加。10%的 2'-FL 补充改变了盲肠微生物群和代谢物的组成，与 LF 和 HF 喂养的小鼠相比，2'-FL 组的丰度增加，乳酸和丙酮酸分别增加，其代谢作用与我们的研究结果一致。特别是，10%的 2'-FL 显著逆转了 HF 饮食诱导的胆囊收缩素抑制食物摄入的损伤。与 HF 组相比，10%的 2'-FL 可显著下调盲肠中白细胞介素（IL）-1β、IL-6 和巨噬细胞趋化因子-1 的基因表达。此外，10%的 2'-FL 抑制了 HF 饮食诱导的肝过氧化物酶体增殖物激活受体γ（一种脂肪生成的转录因子）的基因水平上调。总之，10%的 2'-FL 导致肠道微生物群和代谢物的组成发生变化，与 HF 喂养小鼠的代谢谱和肠道-大脑信号的改善相关。这些发现支持使用 2'-FL 来调节对 HF 饮食的过度摄食反应，并改善肠道微生物群-肠道-大脑轴。
