Science:促进肠道菌群成熟的辅食或可治疗营养不良儿童
  • 严重急性营养不良患儿接受标准治疗后转为持续中度急性营养不良(MAM),伴随持续的肠道菌群发育滞后(不成熟),血浆蛋白、代谢物、生理指标和年龄相关的肠道菌群成员间有显著关联;
  • 在人源化悉生动物中筛选旨在促进菌群成熟的辅食(MDCF)成分,并在定植MAM菌群的悉生动物模型中验证其功效;
  • 在临床试验中,含鹰嘴豆粉、香蕉、大豆粉和花生粉的MDCF,明显改善了MAM患儿的菌群以及与生长、发育和免疫功能等相关的血浆蛋白质组标志物。
主编推荐语
mildbreeze
儿童营养不良导致生长迟缓和不成熟的肠道菌群,现有的治疗干预措施结果不尽如人意。最新一期《Science》背靠背发表了来自菌群领域大牛Jeffrey Gordon团队的两项研究(另一项研究见查看文章),揭示了健康儿童肠道菌群的发育特征,以及营养不良儿童的菌群发育滞后及其与血液标志物的关联,以限菌动物为模型筛选出可促进菌群成熟的辅食成分,并在一项初步临床试验中显示出该策略治疗儿童营养不良的潜力。这两项研究为菌群导向的饮食干预提供了一个很好的范例,鉴定反映菌群发育程度的共变“生态群”的方法,也值得微生态领域的研究者参考借鉴。
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Science [IF:41.845]

Effects of microbiota-directed foods in gnotobiotic animals and undernourished children

菌群导向的食物对限菌动物和营养不良儿童的影响

10.1126/science.aau4732

2019-07-12, Article

Abstract & Authors:展开

Abstract:收起
INTRODUCTION: There is a dimension to postnatal human development that involves assembly of microbial communities in different body habitats, including the gut. Children with acute malnutrition have impaired development of their gut microbiota, leaving them with communities that appear younger (more immature) than those of chronologically age-matched healthy individuals. Current therapeutic foods given to children with acute malnutrition have not been formulated based on knowledge of how they affect the developmental biology of the gut microbiota. Moreover, they are largely ineffective in ameliorating the long-term sequelae of malnutrition that include persistent stunting, neurodevelopmental abnormalities, and immune dysfunction.
RATIONALE: Repairing microbiota immaturity and determining the degree to which such repair restores healthy growth requires identification of microbial targets that are not only biomarkers of community assembly but also mediators of various aspects of growth. Identifying ingredients in complementary foods, consumed during the transition from exclusive milk feeding to a fully weaned state, that increase the representation and expressed beneficial functions of growth-promoting bacterial taxa in the developing microbiota could provide an effective, affordable, culturally acceptable, and sustainable approach to treatment.
RESULTS: Metabolomic and proteomic analyses of serially collected plasma samples were combined with metagenomic analyses of serially collected fecal samples from Bangladeshi children with severe acute malnutrition (SAM) treated with standard therapy. The results provided a readout of their biological features as they transitioned from SAM to a state of persistent moderate acute malnutrition (MAM) with accompanying persistent microbiota immaturity. Significant correlations were identified between levels of plasma proteins, anthropometry, plasma metabolites, and the representation of bacteria in their microbiota. Gnotobiotic mice were subsequently colonized with a defined consortium of bacterial strains that represent various phases of microbiota development in healthy Bangladeshi children. Administration of different combinations of Bangladeshi complementary food ingredients to colonized mice and germ-free controls revealed diet-dependent increases in the abundance and changes in the metabolic activities of targeted weaning-phase strains as well as diet- and colonization-dependent augmentation of growth-promoting host signaling pathways. Host and microbial effects of microbiota-directed complementary food (MDCF) prototypes were subsequently examined in gnotobiotic mice colonized with immature microbiota from children with post-SAM MAM and in gnotobiotic piglets colonized with a defined consortium of targeted age- and growth-discriminatory taxa. A randomized, double-blind study of standard therapy versus various MDCF prototypes emerging from these preclinical models, conducted in Bangladeshi children with MAM, identified a lead MDCF that increased levels of biomarkers and mediators of growth, bone formation, neurodevelopment, and immune function toward a state resembling healthy children. Using an approach inspired by statistical methods applied to financial markets, we show in the accompanying paper by Raman et al. that this lead MDCF was most effective in repairing the microbiota.
CONCLUSION: These findings demonstrate the translatability of results obtained from preclinical gnotobiotic animal models to humans, directly support the hypothesis that healthy microbiota development is causally linked to healthy growth, illustrate an approach for treating childhood undernutrition, and with the capacity to deliberately reconfigure immature microbiota, suggest a means to decipher how elements of the gut microbial community operate to regulate various host systems involved in healthy growth.

First Authors:
Jeanette L Gehrig,Siddarth Venkatesh,Hao-Wei Chang

Correspondence Authors:
Jeffrey I Gordon

All Authors:
Jeanette L Gehrig,Siddarth Venkatesh,Hao-Wei Chang,Matthew C Hibberd,Vanderlene L Kung,Jiye Cheng,Robert Y Chen,Sathish Subramanian,Carrie A Cowardin,Martin F Meier,David O'Donnell,Michael Talcott,Larry D Spears,Clay F Semenkovich,Bernard Henrissat,Richard J Giannone,Robert L Hettich,Olga Ilkayeva,Michael Muehlbauer,Christopher B Newgard,Christopher Sawyer,Richard D Head,Dmitry A Rodionov,Aleksandr A Arzamasov,Semen A Leyn,Andrei L Osterman,Md Iqbal Hossain,Munirul Islam,Nuzhat Choudhury,Shafiqul Alam Sarker,Sayeeda Huq,Imteaz Mahmud,Ishita Mostafa,Mustafa Mahfuz,Michael J Barratt,Tahmeed Ahmed,Jeffrey I Gordon

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Science期刊

A sparse covarying unit that describes healthy and impaired human gut microbiota development

Arjun S Raman,Jeanette L Gehrig,Siddarth Venkatesh,Hao-Wei Chang,Matthew C Hibberd,Sathish Subramanian,Gagandeep Kang,Pascal O Bessong,Aldo AM Lima,Margaret N Kosek,William A Petri Jr,Dmitry A Rodiono,2019-07-12

点评:Science期刊同期背靠背发表的来自Jeffrey Gordon实验室的另一项研究。

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Science期刊

Gut microbes may help malnourished children

Elizabeth Pennisi,2019-07-12

点评:Science期刊配发的新闻评论文章

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学术经纬微信公众号

同期两篇《科学》:这份专为肠道细菌设计的营养餐,帮助儿童健康成长

学术经纬,2019-07-15

点评:对研究的中文解读。

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Genetic Engineering and Biotechnology News期刊

Microbiome Repairing Food for Malnourished Children Beats Current Therapy

GENews,2019-07-12

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Cell Host and Microbe期刊

Turning the “Phage” on Malnutrition and Stunting

2020-02-12

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Developmental Cell期刊

Packing in the Proteins

2019-10-07

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Cell Host and Microbe期刊

Fueling the Optimal Microbiome: Interventions for Severe Acute Malnutrition

Josef Neu,2019-09-11

点评:Cell Host and Microbe发表的评论解读文章。

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