一则对马拉维的年幼双胞胎的研究揭示，一种叫做夸休可尔症（kwashiorkor）的严重、急性形式的营养不良与某些肠道细菌有关，而不是仅仅与营养有关。这些结果表明，对世界上某些营养不良的儿童来说，仅仅让他们摄入更多的卡路里将不足以让他们变得健康。更令人乐观的是，在一则相关的《观点栏目》中，David Relman写道，这些发现“带来了希望，即通过理解肠道微生物群在营养不足中所扮演的作用，我们可以设计新的受到生态学启发的策略来纠正这一问题。”
不幸的是，营养不良在马拉维是常见的，而夸休可尔症的病儿除了消瘦外还会有水肿、肝损害、皮肤溃疡及厌食症等问题。Michelle Smith及其同事对马拉维的317对双胞胎进行了研究，研究的时间为双胞胎长到3岁以前的这段时间。在这一时期中，有一半的双胞胎保持着良好的营养状态，而在其他的双胞胎中，他们中有一人或两人出现了夸休可尔症。患有该疾患的孩子及他们的双胞胎按照标准护理给予了以花生为基础的治疗性食疗。对他们肠道微生物群的随着时间推移而做的研究揭示，严重营养不良的孩子有着不同的微生物概貌，而该微生物概貌在治疗过程中会日趋与营养状态良好的孩子的微生物概貌相似。然而，当治疗停止时，其微生物组合会回复至其较早前的状态。为了做进一步的调查，研究人员将每位健康及患病双胞胎的粪便菌群转移到无菌小鼠的体内。那些接受了夸休可尔症双胞胎肠道微菌群的小鼠会像有这种肠道微菌群的人类一样出现营养不良的症状。尽管夸休可尔症患者的肠道微菌群一般在饮食治疗时会成熟，但它会在恢复当地村庄饮食时又回复到夸休可尔症时的状态。代谢概貌的变化及异常硫代谢的迹象伴随着这些微生物组成的改变。
DOI: 10.1126/science.1229000
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Gut Microbiomes of Malawian Twin Pairs Discordant for Kwashiorkor
M.I. Smith; T. Yatsunenko; M.J. Manary; I. Trehan; J. Cheng; A.L. Kau; J.I. Gordon at Washington University in St. Louis in St. Louis, MO; M.J. Manary; I. Trehan at University of Malawi College of Medicine in Blantyre, Malawi; M.J. Manary at U.S. Department of Agriculture Children’s Nutrition Research Center in Houston, TX; M.J. Manary at Baylor College of Medicine in Houston, TX; R. Mkakosya at University of Malawi in Chichiri, Malawi; S.S. Rich; P. Concannon; J.C. Mychaleckyj; J. Liu; E. Houpt at University of Virginia in Charlottesville, VA; J.V. Li; E. Holmes; J. Nicholson at Imperial College London in London, UK; D. Knights; L.K. Ursell; R. Knight at University of Colorado in Boulder, CO; R. Knight at Howard Hughes Medical Institute in Boulder, CO; D. Knights at University of Minnesota in Minneapolis, MN; D. Knights at University of Minnesota in Saint Paul, MN.
Kwashiorkor, an enigmatic form of severe acute malnutrition, is the consequence of inadequate nutrient intake plus additional environmental insults. To investigate the role of the gut microbiome, we studied 317 Malawian twin pairs during the first 3 years of life. During this time, half of the twin pairs remained well nourished, whereas 43% became discordant, and 7% manifested concordance for acute malnutrition. Both children in twin pairs discordant for kwashiorkor were treated with a peanut-based, ready-to-use therapeutic food (RUTF). Time-series metagenomic studies revealed that RUTF produced a transient maturation of metabolic functions in kwashiorkor gut microbiomes that regressed when administration of RUTF was stopped. Previously frozen fecal communities from several discordant pairs were each transplanted into gnotobiotic mice. The combination of Malawian diet and kwashiorkor microbiome produced marked weight loss in recipient mice, accompanied by perturbations in amino acid, carbohydrate, and intermediary metabolism that were only transiently ameliorated with RUTF. These findings implicate the gut microbiome as a causal factor in kwashiorkor.
