The assembly of microbial communities within the gastrointestinal tract during early life plays a critical role in immune, endocrine, metabolic, and other host developmental pathways. Environmental insults during this period, such as food insecurity and infections, can disrupt this optimal microbial succession, which may contribute to lifelong and intergenerational deficits in growth and development. Here, we review the human microbiome in the first 1000 daysreferring to the period from conception to 2 years of ageand using a developmental model, we examine the role of early microbial succession in growth and development. We propose that an 'undernourished' microbiome is intergenerational, thereby perpetuating growth impairments into successive generations. We also identify and discuss the intertwining host-microbe-environment interactions occurring prenatally and during early infancy, which may impair the trajectories of healthy growth and development, and explore their potential as novel microbial targets for intervention. Growth and Development: A Microbial PerspectiveThe first 1000 daysthe period from conception to 2 years of agerepresents a critical window of early childhood growth and development. This prenatal and early postnatal period is defined by rapid maturation of metabolic, endocrine, neural, and immune pathways, which strongly influence and support child growth and development. These pathways develop in tandem and are highly interdependent, with a complex program of assembly reliant on internal and external cues. When these developmental pathways are challenged by adverse environmental insults, such as infection or suboptimalfeeding,thetrajectoryofchildgrowthcanbeperturbed,leadingtomalnutrition,whichcan manifest as overnutrition (overweight or obesity) or as undernutritionstunting (see Glossary) or wasting.Anemergingperspectiveofhumandevelopmentalbiology includesthetrillionsofmicrobes (microbiota) and their genes (microbiome) that reside within the human body, and which assemble and stabilize during the first 2 years of life [1]. Emerging evidence suggests that the colonization of microbes in the human body during early life plays a critical role in theestablishmentand maturation of developmental pathways [2] and that disruptionof this optimalmicrobialsuccession may contribute to lifelong and intergenerational deficits in growth and development (Figure 1).Here, we review the role of the human microbiota in healthy growth and development during the first 1000 days. We focus on undernutrition, which remains an enormous public health challenge: 155 million children are stunted (low height-for-age), and 52 million children are wasted (low weight-for-height); global targets to end malnutrition in all its forms by 2030 are unlikely to be achieved (https://sustainabledevelopment.un.org/sdg2). We identify and discuss the intertwining host-microbe-environment interactions that occur prenatally and during early infancy that may impair the trajectories of healthy growth and development, and we explore their p...

BackgroundUnderstanding the mechanism of the sexual dimorphism in susceptibility to obesity and metabolic syndrome (MS) is important for the development of effective interventions for MS.ResultsHere we show that gut microbiome mediates the preventive effect of estrogen (17β-estradiol) on metabolic endotoxemia (ME) and low-grade chronic inflammation (LGCI), the underlying causes of MS and chronic diseases. The characteristic profiles of gut microbiome observed in female and 17β-estradiol-treated male and ovariectomized mice, such as decreased Proteobacteria and lipopolysaccharide biosynthesis, were associated with a lower susceptibility to ME, LGCI, and MS in these animals. Interestingly, fecal microbiota-transplant from male mice transferred the MS phenotype to female mice, while antibiotic treatment eliminated the sexual dimorphism in MS, suggesting a causative role of the gut microbiome in this condition. Moreover, estrogenic compounds such as isoflavones exerted microbiome-modulating effects similar to those of 17β-estradiol and reversed symptoms of MS in the male mice. Finally, both expression and activity of intestinal alkaline phosphatase (IAP), a gut microbiota-modifying non-classical anti-microbial peptide, were upregulated by 17β-estradiol and isoflavones, whereas inhibition of IAP induced ME and LGCI in female mice, indicating a critical role of IAP in mediating the effects of estrogen on these parameters.ConclusionsIn summary, we have identified a previously uncharacterized microbiome-based mechanism that sheds light upon sexual dimorphism in the incidence of MS and that suggests novel therapeutic targets and strategies for the management of obesity and MS in males and postmenopausal women.Electronic supplementary materialThe online version of this article (10.1186/s40168-018-0587-0) contains supplementary material, which is available to authorized users.