Characterizing microbiota-directed fiber snack food prototypes in gnotobiotic mice and humans. Characterizing microbiota-directed fiber snack food prototypes in gnotobiotic mice and humans

Malnutrition, encompassing the dual burden of undernutrition and obesity, is a global health challenge. Developing microbiota-directed foods (MDF) that reconfigure the gut community in ways that improve nutritional status is a formidable challenge given microbiota complexity, dynamism and interpersonal variations, and limited knowledge of how products of microbial biotransformation of food components influence host physiology. In the present study, gnotobiotic mice, colonized with intact microbiota from nine obese adults, were fed a diet high in saturated fats and low in fruits and vegetables (HiSF-LoFV). Fiber-discriminatory responses of bacterial taxa, carbohydrate active enzyme genes (CAZymes) and metabolic pathways were identified using feature reduction methods. Snack food prototypes containing one, two or four fibers were administered for 2-week periods in a study of overweight and obese adults consuming a controlled HiSF-LoFV diet. Applying feature reduction methods to datasets of serially sampled microbiomes, concurrent measurements of 1300 plasma proteins, and mass spectrometry of fecal glycans identified fiber-specific changes in the representation of CAZymes that correlated with alterations in the plasma proteome indicative of improved metabolic and immune status. These results provide an example of the translatability of results from gnotobiotic mice to humans and an approach for deciphering structure-function relationships connecting food, the microbiome and aspects of host physiology.

营养不良涵盖营养不足与肥胖的双重负担，是一项全球性公共卫生挑战。开发以微生物群为导向的食品（microbiota-directed foods, MDF），通过重塑肠道菌群结构以改善宿主营养状况，却面临诸多严峻挑战：微生物群本身具有复杂性、动态性与个体间差异，且目前对食物成分经微生物生物转化后的产物如何影响宿主生理机制的认知仍较为有限。本研究中，研究人员将9名肥胖成人的完整肠道微生物群移植至悉生小鼠（gnotobiotic mice）体内，并为其喂食高饱和脂肪、低果蔬膳食（HiSF-LoFV）。研究人员通过特征降维方法，鉴定出细菌类群、碳水化合物活性酶基因（carbohydrate active enzyme genes, CAZymes）以及代谢通路对膳食纤维的特异性应答反应。在一项针对超重及肥胖成人的临床研究中，受试者在摄入受控的HiSF-LoFV膳食期间，分别连续2周食用含有1种、2种或4种膳食纤维的零食原型样品。通过对连续采样的微生物组数据集、同步检测的1300种血浆蛋白以及粪便聚糖的质谱分析结果应用特征降维方法，研究人员鉴定出膳食纤维特异性的CAZymes丰度变化，该变化与血浆蛋白质组的改变相关，提示宿主代谢与免疫状态得到改善。本研究结果证实了悉生小鼠实验结果向人类研究转化的可行性，并为解析食物、微生物群与宿主生理功能各维度之间的结构-功能关联提供了可行方法。