美国国立卫生研究院Jonathan Krakoff、Alessio Basolo和加州大学Peter J. Turnbaugh研究组合作取得一项新成果。经过不懈努力，他们揭示了营养不足和口服万古霉素对人体肠道菌群和营养吸收的影响。相关论文发表在2020年3月23日出版的《自然-医学》杂志上。

研究人员进行了一项扩展的住院研究；在该研究中，研究人员使用了两种他们认为会改变肠道菌群和营养吸收的干预措施。每组都测量了其粪便卡路里流失，这是营养吸收的直接表征。第一阶段是随机的交叉饮食干预，其中所有参与者均以过量和节食三天的随机顺序进行饮食。第二种是使用万古霉素或配套安慰剂（NCT02037295）进行的随机、双盲、安慰剂对照药理干预。

研究人员选取了除葡萄糖耐受和肥胖症以外的27名健康志愿者（男17名，女10名，年龄35.1±7.3，BMI 32.3±8.0），其中25名完成了整个试验。该研究的主要节点是饮食和药理干预对大便热量损失的影响。研究人员假设与过量饮食相比，以粪便卡路里为代表的卡路里吸收百分比在节食组会增加，并且在万古霉素治疗期间也会增加。最终这两个主要节点都得以证实。与过量饮食以及安慰剂相比，营养不足和万古霉素治疗导致的粪便热量损失更大。该研究的次要节点是评估肠道微生物群落结构的变化，如扩增子测序和宏基因组学所证明的那样。

研究人员观察到肠道微生物群落结构受正常饮食、营养不良和过量饮食的影响较小，但口服万古霉素引起群落结构多样性更为广泛的降低。两种干预措施均导致嗜黏蛋白阿克曼氏菌增多以及大便热量损失增加。这些结果表明营养吸收对环境扰动敏感，并与临床前模型相关；这表明肠道微生物组在饮食能量吸收中可能起因果作用。

据了解，尚无直接证据表明微生物组对营养吸收有影响。

附：英文原文

Title: Effects of underfeeding and oral vancomycin on gut microbiome and nutrient absorption in humans

Author: Alessio Basolo, Maximilian Hohenadel, Qi Yan Ang, Paolo Piaggi, Sascha Heinitz, Mary Walter, Peter Walter, Shannon Parrington, Donovan D. Trinidad, Reiner Jumpertz von Schwartzenberg, Peter J. Turnbaugh, Jonathan Krakoff

Issue&Volume: 2020-03-23

Abstract: Direct evidence in humans for the impact of the microbiome on nutrient absorption is lacking. We conducted an extended inpatient study using two interventions that we hypothesized would alter the gut microbiome and nutrient absorption. In each, stool calorie loss, a direct proxy of nutrient absorption, was measured. The first phase was a randomized cross-over dietary intervention in which all participants underwent in random order 3d of over- and underfeeding. The second was a randomized, double-blind, placebo-controlled pharmacologic intervention using oral vancomycin or matching placebo (NCT02037295). Twenty-seven volunteers (17 men and 10 women, age 35.1±7.3, BMI 32.3±8.0), who were healthy other than having impaired glucose tolerance and obesity, were enrolled and 25 completed the entire trial. The primary endpoints were the effects of dietary and pharmacological intervention on stool calorie loss. We hypothesized that stool calories expressed as percentage of caloric intake would increase with underfeeding compared with overfeeding and increase during oral vancomycin treatment. Both primary endpoints were met. Greater stool calorie loss was observed during underfeeding relative to overfeeding and during vancomycin treatment compared with placebo. Key secondary endpoints were to evaluate the changes in gut microbial community structure as evidenced by amplicon sequencing and metagenomics. We observed only a modest perturbation of gut microbial community structure with under- versus overfeeding but a more widespread change in community structure with reduced diversity with oral vancomycin. Increase in Akkermansia muciniphila was common to both interventions that resulted in greater stool calorie loss. These results indicate that nutrient absorption is sensitive to environmental perturbations and support the translational relevance of preclinical models demonstrating a possible causal role for the gut microbiome in dietary energy harvest.

DOI: 10.1038/s41591-020-0801-z

Source: https://www.nature.com/articles/s41591-020-0801-z