PDF(Pubmed)
Abstract：
BACKGROUND: Colostrum is the first milk for a newborn. Its high content in microbiota shaping compounds and its intake at the time of gut microbiota seeding suggests colostrum may be critical in the establishment of a healthy microbiota. There is also accumulating evidence on the importance of the gut microbiota for healthy growth. Here, we aimed to investigate the contribution of colostrum, and colostrum-induced microbiota to growth promotion. Addressing this question is highly significant because (1) globally, less than half of the newborns are fully colostrum fed (2) the evidence for the importance of the microbiota for the prevention of undernutrition has only been demonstrated in juvenile or adult pre-clinical models while stunting already starts before weaning.
RESULTS: To address the importance of diet at birth in growth failure, we developed a unique mouse model in which neonates are breastfed by mothers at an advanced stage of lactation who no longer provide colostrum. Feeding newborn mice with mature milk instead of colostrum resulted in significant growth retardation associated with the biological features of chronic undernutrition, such as low leptin levels, dyslipidemia, systemic inflammation, and growth hormone resistance. We next investigated the role of colostrum in microbiota shaping. At the end of the lactation period, we found a major difference in gut microbiota alpha diversity, beta diversity, and taxa distribution in control and colostrum-deprived mice. To determine the causal relationship between changes in microbiota and growth trajectories, we repeated our experiment in germ-free mice. The beneficial effect of colostrum on growth remained in the absence of microbiota.
CONCLUSIONS: Our data suggest that colostrum may play an important role in the prevention of growth failure. They highlight that the interplay between neonatal gut microbiome assembly and diet may not be as crucial for growth control in the developing newborn as described in young adults. This opens a paradigm shift that will foster research for colostrum\'s bioactives that may exert a similar effect to microbiota-derived ligands in promoting growth and lead to new avenues of translational research for newborn-tailored prevention of stunting. Video Abstract.
RESULTS: To address the importance of diet at birth in growth failure, we developed a unique mouse model in which neonates are breastfed by mothers at an advanced stage of lactation who no longer provide colostrum. Feeding newborn mice with mature milk instead of colostrum resulted in significant growth retardation associated with the biological features of chronic undernutrition, such as low leptin levels, dyslipidemia, systemic inflammation, and growth hormone resistance. We next investigated the role of colostrum in microbiota shaping. At the end of the lactation period, we found a major difference in gut microbiota alpha diversity, beta diversity, and taxa distribution in control and colostrum-deprived mice. To determine the causal relationship between changes in microbiota and growth trajectories, we repeated our experiment in germ-free mice. The beneficial effect of colostrum on growth remained in the absence of microbiota.
CONCLUSIONS: Our data suggest that colostrum may play an important role in the prevention of growth failure. They highlight that the interplay between neonatal gut microbiome assembly and diet may not be as crucial for growth control in the developing newborn as described in young adults. This opens a paradigm shift that will foster research for colostrum\'s bioactives that may exert a similar effect to microbiota-derived ligands in promoting growth and lead to new avenues of translational research for newborn-tailored prevention of stunting. Video Abstract.
摘要：
背景：初乳是新生儿的第一口乳汁。它在微生物群形成化合物中的高含量及其在肠道微生物群接种时的摄入量表明初乳可能对建立健康的微生物群至关重要。也有越来越多的证据表明肠道微生物群对健康成长的重要性。这里,我们的目的是调查初乳的贡献，和初乳诱导的微生物群对生长的促进作用。解决这个问题非常重要，因为(1)在全球范围内，不到一半的新生儿完全饲喂初乳(2)微生物群对预防营养不良的重要性的证据仅在青少年或成人临床前模型中得到证实,而发育迟缓在断奶前就已经开始.
结果：为了解决出生时饮食在生长障碍中的重要性，我们开发了一种独特的小鼠模型，其中新生儿由哺乳期晚期不再提供初乳的母亲母乳喂养。用成熟的牛奶代替初乳喂养新生小鼠会导致与慢性营养不良的生物学特征相关的显着生长迟缓。如低瘦素水平，血脂异常,全身性炎症,和生长激素抗性。接下来，我们研究了初乳在微生物群形成中的作用。哺乳期结束时,我们发现了肠道微生物群α多样性的主要差异，β多样性,和类群在对照和初乳剥夺小鼠中的分布。为了确定微生物群变化与生长轨迹之间的因果关系，我们在无菌小鼠中重复了我们的实验。在没有微生物群的情况下，初乳对生长的有益作用仍然存在。
结论：我们的数据表明初乳可能在预防生长障碍中起重要作用。他们强调，新生儿肠道微生物组组装和饮食之间的相互作用对于发育中的新生儿的生长控制可能不像年轻人中描述的那样至关重要。这开启了一个范式转变，将促进对初乳生物活性物质的研究，这些生物活性物质可能在促进生长方面与微生物群衍生的配体产生类似的作用，并为新生儿定制预防发育迟缓提供转化研究的新途径。视频摘要。
结果：为了解决出生时饮食在生长障碍中的重要性，我们开发了一种独特的小鼠模型，其中新生儿由哺乳期晚期不再提供初乳的母亲母乳喂养。用成熟的牛奶代替初乳喂养新生小鼠会导致与慢性营养不良的生物学特征相关的显着生长迟缓。如低瘦素水平，血脂异常,全身性炎症,和生长激素抗性。接下来，我们研究了初乳在微生物群形成中的作用。哺乳期结束时,我们发现了肠道微生物群α多样性的主要差异，β多样性,和类群在对照和初乳剥夺小鼠中的分布。为了确定微生物群变化与生长轨迹之间的因果关系，我们在无菌小鼠中重复了我们的实验。在没有微生物群的情况下，初乳对生长的有益作用仍然存在。
结论：我们的数据表明初乳可能在预防生长障碍中起重要作用。他们强调，新生儿肠道微生物组组装和饮食之间的相互作用对于发育中的新生儿的生长控制可能不像年轻人中描述的那样至关重要。这开启了一个范式转变，将促进对初乳生物活性物质的研究，这些生物活性物质可能在促进生长方面与微生物群衍生的配体产生类似的作用，并为新生儿定制预防发育迟缓提供转化研究的新途径。视频摘要。
