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Factors affecting early-life intestinal microbiota development
Abstract
Objectives
To review the published evidence on early-life intestinal microbiota development, the different factors influencing its development prenatally, at birth and post-natally.
Results
A growing body of evidence indicates that the intrauterine environment is not sterile as once presumed, but that maternal-foetal transmission of microbiota occurs during pregnancy. The genetic background of the infant may also strongly influence microbial colonization of the gastrointestinal (GI) tract. The consecutive order of bacteria with which the GI tract is colonized will influence the outcome of community assembly and the ecological success of individual colonizers. The composition and development of infant gut microbiota can be influenced by many prenatal factors such as maternal diet, obesity, smoking and use of antibiotics during pregnancy. Mode of delivery is generally accepted as a major factor determining the initial colonisation, which persists for months, if not for years. Breastfeeding, mainly because of its high content of unique oligosaccharides, stimulates the most balanced microbiome development for the infant. Feeding is, in general, another important factor determining intestinal colonization. Compared with breastfed infants, formula-fed infants have an increased richness of species. Initial clinical studies show that infant formulas supplemented with specific human milk oligosaccharides (HMO) -2´-FL alone or in combination with LNnT, structurally identical to those in breast milk-, increase the proportion of infants with a high bifidobacteria dominated gut microbiota typical of that observed in breastfed infants, lead to plasma immune marker profiles similar to those of breast-fed infants, and to lower morbidity and antibiotics use. Further clinical studies with the same, others or more HMOs are needed to confirm these clinical effects.
Conclusions
A growing number of studies have reported on how the composition and development of the microbiota during early life will affect risk factors related to health up to and during adulthood. If exclusive breastfeeding is not possible, the composition of infant formula should be adapted to stimulate the development of a bifidobacteria dominated gut microbiota typical of that observed in breastfed infants. The main components in breast milk that stimulate the growth of specific bifidobacteria are HMOs.
... Formula feeding has also been associated with a more rapid maturation of the microbiome towards an adult state and a higher abundance of inflammatory-type microbiota [26]. The microbiome is also affected by other environmental factors including geographical location and gestational age, as well as genetics [33][34][35]. ...
... A neonate's gut microbiota is originally unstable, lacking diversity, and is predominantly colonized by Bifidobacterium [33,34]. During the first few years of life, the microbiota matures and diversifies, leading to an intestinal microbiota that is functionally and structurally comparable to an adult's, typically by the age of 3 [26]. ...
... However, antibiotic exposure in early life can trigger intestinal dysbiosis through disruption of the commensal bacteria, in addition to harmful bacteria [99]. The impact of antibiotics on the microbiome depends on the duration, dosage, frequency, and age at the time of treatment [33]. The largest disruptions in the development of the microbiota occur when antibiotics are prescribed more frequently and in early life, which is also when antibiotic usage is most strongly correlated with becoming overweight [100]. ...
Obesity is a major public health problem that continues to be one of the leading risk factors for premature death. Early life is a critical period of time when the gut microbiota and host metabolism are developing in tandem and significantly contribute to long-term health outcomes. Dysbiosis of the gut microbiota, particularly in early life, can have detrimental effects on host health and increase the susceptibility of developing obesity later in life. Antibiotics are an essential lifesaving treatment; however, their use in early life may not be without risk. Antibiotics are a leading cause of intestinal dysbiosis, and early life administration is associated with obesity risk. The following review explores the relevant literature that simultaneously examines antibiotic-induced dysbiosis and obesity risk. Current evidence suggests that disruptions to the composition and maturation of the gut microbiota caused by antibiotic use in early life are a key mechanism linking the association between antibiotics and obesity. Without compromising clinical practice, increased consideration of the long-term adverse effects of antibiotic treatment on host health, particularly when used in early life is warranted. Novel adjunct interventions should be investigated (e.g., prebiotics) to help mitigate metabolic risk when antibiotic treatment is clinically necessary.
... It also can effectively prevent the colonization of pathogenic microorganisms. 33 The development of the gut microbiota profile in early life depends on mode of delivery, type of feeding (human milk or infant formula) and other environmental factors to which the newborn is exposed. 34,35 It is often assumed that fetal development in utero is sterile; however, much evidence suggests that bacterial colonization of the gut begins before birth. ...
... 34,35 It is often assumed that fetal development in utero is sterile; however, much evidence suggests that bacterial colonization of the gut begins before birth. 33 The intestine of infants delivered vaginally is initially colonized by microorganisms from the maternal vagina, such as Lactobacillus and Prevotella. 34 In contrast, infants born by caesarean section are primarily colonized by microorganisms from the maternal skin and the hospital environment, including Streptococcus, Corynebacterium and Propionibacterium. ...
... The different types of milk consumed by infants have different effects on the composition and distribution of the intestinal microbiota. 33 A large number of undigested nutrients (mainly oligosaccharides and polysaccharides) in the ileum enter the colon where they are transformed into short chain fatty acids (SCFAs) and other metabolites through bacterial fermentation. 36 The main glycolytic bacteria are Bacteroides, Bifidobacterium, Clostridium, Lactobacillus and Lactococcus, while Bifidobacterium, Bacteroides, Clostridium and Propionibacterium can hydrolyze undigested proteins. ...
Food digestion and absorption in infants are closely related to early growth and long-term health. Human milk and infant formula are the main food sources for 0-6 month-old infants. Due to the immature gastrointestinal tract of newborns, mild digestive problems, such as inefficient digestion and impaired absorption of proteins, lipids and lactose, and gut dysbiosis, are often seen in infancy. The differences in composition between infant formula and human milk make mild digestive problems more likely to occur in formula-fed infants. In recent years, several types of infant formulas have been developed to treat or reduce gastrointestinal digestive problems in infants. This review summarizes the gastrointestinal environment of infants and the digestion of human milk and different infant formulas. We particularly focus on the common digestive problems and appropriate nutritional solutions that may occur in healthy term infants during the first six months of life.
... Animal studies have shown that a high-fat diet in pregnancy can lead to decreased microbial diversity within the offspring for up to one year [40]. These changes may persist longer [41,42]. Additional evidence suggests that maternal obesity and extent of weight gain during pregnancy may also alter the neonatal microbiome compared to mothers without obesity [43]. ...
... The neonatal microbiome is suddenly exposed to potential maternal antibiotic use, vaginal vs. caesarean section delivery, breastmilk, formula, solids, and multiple environmental exposures [42,50]. It is estimated that only 9% of the intestinal microbiome is affected by the host's genetic background; the majority of bacterial colonization is therefore derived from external sources [32,41]. ...
... There are significant differences in the intestinal microbiome of term infants (≥37 weeks gestational age) compared to preterm infants (<37 weeks gestational age). In particular, preterm infants have decreased levels of Lactobacillus and Bifidobacteria and relatively greater abundance of Escherichia, Klebsiella, and Enterobacter [41,97]. Very premature infants (<32 weeks) have increased levels of Gram positive bacteria, including Staphylococcus, Clostridia and Enterococcus during their first month of life [98,99]. ...
The neonatal microbiome offers a valuable model for studying the origins of human health and disease. As the field of metagenomics expands, we also increase our understanding of early life influences on its development. In this review we will describe common techniques used to define and measure the microbiome. We will review in utero influences, normal perinatal development, and known risk factors for abnormal neonatal microbiome development. Finally, we will summarize current evidence that links early life microbial impacts on the development of chronic in-flammatory diseases, obesity, and atopy.
... Mode of delivery is generally accepted as a significant factor associated with initial gut colonization. However, results are still inconclusive, and some research suggests that infant microbiota undergoes substantial reorganization during the first months of life [42]. The colonization of the newborn intestine begins with the microbiota of the birth canal in vaginal delivery, or nosocomial microbiota in cesarean section, as well as the bacteria transferred from mother's milk. ...
... HMOs resist gastric acidity, hydrolysis by host enzymes, and gastrointestinal absorption and due to their probiotic activity can be used by infant gut beneficial microorganisms as an energy source [45]. Among the bioactive compounds of human milk, HMOs have been reported to have the greatest influence on the infant's gut microbiota shaping [42]. ...
... longum, B.bifidum, B. breve) and Bacteroides (particularly B. fragilis) strains commonly present in the babies gut [49]. Children born by cesarean section generally have a lower abundance of these bacterial species [42]. In the Korpela cohort [23], newborns vaginally delivered, from Se+ and Se-mothers, did not present differences in their microbiota. ...
Human milk oligosaccharides (HMOs) are the third most abundant solid component of breast milk. However, the newborn cannot assimilate them as nutrients. They are recognized prebiotic agents (the first in the newborn diet) that stimulate the growth of beneficial microorganisms, mainly the genus Bifidobacterium, dominant in the gut of breastfed infants. The structures of the oligosaccharides vary mainly according to maternal genetics, but also other maternal factors such as parity and mode of delivery, age, diet, and nutritional status or even geographic location and seasonality cause different breast milk oligosaccharides profiles. Differences in the profiles of HMO have been linked to breast milk microbiota and gut microbial colonization of babies. Here, we provide a review of the scope of reports on associations between HMOs and the infant gut microbiota to assess the impact of HMO composition.
... On the other hand, several other previous studies FIGURE 1 | Factors influencing the gut microbiota composition in the fetal period and infancy. Some factors like maternal diet, obesity, cigarette smoking, and the use of antibiotics influence the maternal microbiota composition and, consequently, fetal microbiome (25). The fetal microbiome probably originates both from the vagina through ascendant colonization and from the maternal oral cavity/gut, through the bloodstream (5,11). ...
... It has previously been shown that many prenatal factors, such as maternal diet, obesity, cigarette smoking and the use of antibiotics, may influence maternal microbiota composition, and in turn that of the neonate as well (25). Besides the "still controversial" hypothesis of "in utero colonization, " it should be emphasized that fetal development, including gut maturation, is definitely regulated by maternal microbial metabolites, transported to the fetus through the placenta [(24, 26); Figure 1]. ...
Differentiation of the digestive tube and formation of the gut unit as a whole, are regulated by environmental factors through epigenetic modifications which enhance cellular plasticity. The critical period of DNA imprinting lasts from conception until approximately the 1,000th day of human life. During pregnancy, besides agents that may directly promote epigenetic programming (e.g., folate, zinc, and choline supplementation), some factors (e.g., antibiotic use, dietary components) can affect the composition of the mother's microbiota, in turn affecting the fetal microbiome which interacts with the offspring's intestinal epithelial cells. According to available literature that confirms intrauterine microbial colonization, the impact of the microbiome and its metabolites on the genome seems to be key in fetal development, including functional gut maturation and the general health status of the offspring, as well as later on in life. Although the origin of the fetal microbiome is still not well-understood, the bacteria may originate from both the vagina, as the baby is born, as well as from the maternal oral cavity/gut, through the bloodstream. Moreover, the composition of the fetal gut microbiota varies depending on gestational age, which in turn possibly affects the regulation of the immune system at the barrier between mother and fetus, leading to differences in the ability of microorganisms to access and survive in the fetal environment. One of the most important local functions of the gut microbiota during the prenatal period is their exposure to foreign antigens which in turn contributes to immune system and tissue development, including fetal intestinal Innate Lymphoid Cells (ILCs). Additional factors that determine further infant microbiome development include whether the infant is born premature or at term, the method of delivery, maternal antibiotic use, and the composition of the mother's milk, among others. However, the latest findings highlight the fact that a more diverse infant gut microbiome at birth facilitates the proliferation of stem cells by microbial metabolites and accelerates infant development. This phenomenon confirms the unique role of microbiome. This review emphasizes the crucial perinatal and postnatal factors that may influence fetal and neonatal microbiota, and in turn gut maturation.
... On the other hand, several other previous studies FIGURE 1 | Factors influencing the gut microbiota composition in the fetal period and infancy. Some factors like maternal diet, obesity, cigarette smoking, and the use of antibiotics influence the maternal microbiota composition and, consequently, fetal microbiome (25). The fetal microbiome probably originates both from the vagina through ascendant colonization and from the maternal oral cavity/gut, through the bloodstream (5,11). ...
... It has previously been shown that many prenatal factors, such as maternal diet, obesity, cigarette smoking and the use of antibiotics, may influence maternal microbiota composition, and in turn that of the neonate as well (25). Besides the "still controversial" hypothesis of "in utero colonization, " it should be emphasized that fetal development, including gut maturation, is definitely regulated by maternal microbial metabolites, transported to the fetus through the placenta [(24, 26); Figure 1]. ...
... The microbial colonization process is an orchestrated phenomenon resulting in specialized microbial ecosystems in the different gut compartments. However, this colonization process can be influenced by numerous environmental factors (4). One of the preponderant factors is neonatal diet, and it is largely accepted that human milk (HM) is the optimal diet that stimulates the most adequate microbiota development for the infant. ...
... Of note, although some species were shared between HM and infant feces, their relative abundance within microbiota strongly differs. This is the case for Bifidobacterium whose abundance was low in HM but which became dominant in the infant gut, due to modifications of growth conditions and to their ability to metabolize HMOs (4,90). ...
The assembly of the newborn's gut microbiota during the first months of life is an orchestrated process resulting in specialized microbial ecosystems in the different gut compartments. This process is highly dependent upon environmental factors, and many evidences suggest that early bacterial gut colonization has long-term consequences on host digestive and immune homeostasis but also metabolism and behavior. The early life period is therefore a “window of opportunity” to program health through microbiota modulation. However, the implementation of this promising strategy requires an in-depth understanding of the mechanisms governing gut microbiota assembly. Breastfeeding has been associated with a healthy microbiota in infants. Human milk is a complex food matrix, with numerous components that potentially influence the infant microbiota composition, either by enhancing specific bacteria growth or by limiting the growth of others. The objective of this review is to describe human milk composition and to discuss the established or purported roles of human milk components upon gut microbiota establishment. Finally, the impact of maternal diet on human milk composition is reviewed to assess how maternal diet could be a simple and efficient approach to shape the infant gut microbiota.
... The lower consumption of breast milk stopped at 4 months of age, and the use of an infant formula containing a source of Limosilactobacillus reuteri DSM 17,938 and 2 -FL, initially in combination with maternal milk and then as the main source of protein of the diet, surely affected the growth and numerousness of bifidobacteria in the gut of the young patient. In fact, human milk impacts gut microbiota mainly due to its human milk oligosaccharides and endogenous bifidobacteria [43]; furthermore, it has been observed that infant formulas enriched of 2 -FL showed initial evidence on promoting Bifidobacterium spp. in the gut microbiota of children [44]. ...
Propionic Acidemia (PA) is a rare inherited metabolic disorder caused by the enzymatic block of propionyl-CoA carboxylase with the consequent accumulation of propionic acid, which is toxic for the brain and cardiac cells. Since a considerable amount of propionate is produced by intestinal bacteria, interest arose in the attempt to reduce propionate-producing bacteria through a monthly antibiotic treatment of metronidazole. In the present study, we investigated the gut microbiota structure of an infant diagnosed at 4 days of life through Expanded Newborn Screening (NBS) and treated the child following international guidelines with a special low-protein diet, specific medications and strict biochemical monitoring. Microbiota composition was assessed during the first month of life, and the presence of Bacteroides fragilis, known to be associated with propionate production, was effectively decreased by metronidazole treatment. After five antibiotic therapy cycles, at 4 months of age, the infant was supplemented with a daily mixture of three bifidobacterial strains, known not to be propionate producers. The supplementation increased the population of bifidobacteria, with Bifidobacterium breve as the dominating species; Ruminococcus gnavus, an acetate and formate producer, was also identified. Metabarcoding analysis, compared with low coverage whole metagenome sequencing, proved to capture all the microbial biodiversity and could be the elected tool for fast and cost-effective monitoring protocols to be implemented in the follow up of rare metabolic disorders such as PA. Data obtained could be a possible starting point to set up tailored microbiota modification treatment studies in the attempt to improve the quality of life of people affected by propionic acidemia.
... It is highly dependent on the term of pregnancy, the mode of delivery, the type of feeding [breast feeding (BF) or formula feeding (FF)] and the use of antibiotics or proton pump inhibitors [1,2]. Postnatal immune maturation is, as well, highly dependent on the intestinal microbiome implementation and composition [1][2][3]. Type of feeding is a key issue in the human gut development, the diversity of microbiome, and the intestinal function at any age in life [4,5]. By providing bioactive components, human milk (HM) protects the infant against pathogenic infections. ...
Intestinal colonization of the neonate is highly dependent on the term of pregnancy, the mode of delivery, the type of feeding [breast feeding or formula feeding]. Postnatal immune maturation is dependent on the intestinal microbiome implementation and composition and type of feeding is a key issue in the human gut development, the diversity of microbiome, and the intestinal function. It is well established that exclusive breastfeeding for 6 months or more has several benefits with respect to formula feeding. The composition of the new generation of infant formulas aims in mimicking HM by reproducing its beneficial effects on intestinal microbiome and on the gut associated immune system (GAIS). Several approaches have been developed currently for designing new infant formulas by the addition of bioactive ingredients such as human milk oligosaccharides (HMOs), probiotics, prebiotics [fructo-oligosaccharides (FOSs) and galacto-oligosaccharides (GOSs)], or by obtaining the so-called post-biotics also known as milk fermentation products. The aim of this article is to guide the practitioner in the understanding of these different types of Microbiota Influencing Formulas by listing and summarizing the main concepts and characteristics of these different models of enriched IFs with bioactive ingredients.
... Three groups of infant-fed mice clustered together, showing that feeding infant formula affected their fecal microbiota composition. Similar results have been reported regarding differences in gut microbiota abundance between formula-fed and breast-fed infants (61). Furthermore, our results confirmed that the pHIF mice and eHIF mice were similar, suggesting that hydrolyzed infant formula, and standard infant formula had different effects on the gut microbiota abundance in mice. ...
Infant formula, an important food for babies, is convenient and nutritious, and hydrolyzed formulas have attracted much attention due to their non-allergicity. However, it is uncertain whether hydrolyzed formulars cause obesity and other side effects in infants. Herein, three infant formulas, standard (sIF), partially hydrolyzed (pHIF), and extensively hydrolyzed (eHIF), were analyzed in an in vitro gastrointestinal digestion model. With increasing degree of hydrolysis, the protein moleculars, and allergenicity of the proteins decreased and the long-chain polyunsaturated fatty acid content increased. Moreover, the digestion model solutions quickly digested the small fat globules and proteins in the hydrolyzed formula, allowing it to become electrostatically stable sooner. The eHIF-fed mice presented larger body sizes, and exhibited excellent exploratory and spatial memory abilities in the maze test. Based on villus height and crypt depth histological characterizations and amplicon sequencing, eHIF promoted mouse small intestine development and changed the gut microbiota composition, eventually favoring weight gain. The mouse spleen index showed that long-term infant formula consumption might be detrimental to immune system development, and the weight-bearing swimming test showed that eHIF could cause severe physical strength decline. Therefore, long-term consumption of infant formula, especially eHIF, may have both positive and negative effects on mouse growth and development, and our results might shed light on feeding formula to infants.
... As described above, the assembly of the gut microbiome is sensitive to various perinatal events; the modulating factors and their impacts have both been described in numerous reviews (Mackie et al., 1999;Penders et al., 2006;Adlerberth and Wold, 2009;Fouhy et al., 2012;Edwards, 2017;Milani et al., 2017;Tun et al., 2017;Vandenplas et al., 2020;Stinson, 2020). The most historically documented modulating factors include mode of delivery [vaginal delivery vs. cesarean section (CS)] and method of early feeding (breast milk vs. formula). ...
Underpinning the theory “developmental origins of health and disease” (DOHaD), evidence is accumulating to suggest that the risks of adult disease are in part programmed by exposure to environmental factors during the highly plastic “first 1,000 days of life” period. An elucidation of the mechanisms involved in this programming is challenging as it would help developing new strategies to promote adult health. The intestinal microbiome is proposed as a long-lasting memory of the neonatal environment. This proposal is supported by indisputable findings such as the concomitance of microbiota assembly and the first 1,000-day period, the influence of perinatal conditions on microbiota composition, and the impact of microbiota composition on host physiology, and is based on the widely held but unconfirmed view that the microbiota is long-lastingly shaped early in life. In this review, we examine the plausibility of the gut microbiota being programmed by the neonatal environment and evaluate the evidence for its validity. We highlight that the capacity of the pioneer bacteria to control the implantation of subsequent bacteria is supported by both theoretical principles and statistical associations, but remains to be demonstrated experimentally. In addition, our critical review of the literature on the long-term repercussions of selected neonatal modulations of the gut microbiota indicates that sustained programming of the microbiota composition by neonatal events is unlikely. This does not exclude the microbiota having a role in DOHaD due to a possible interaction with tissue and organ development during the critical windows of neonatal life.
... However, the outcomes of RSV ingestion in pregnant women may differ from those in non-pregnant women. In particular, the intestinal microbiota in the offspring are mainly derived from the maternal microbiota, but the composition of the intestinal microbiota in infants is directly affected by childbirth delivery methods, postnatal diets, and the postnatal environment [74]. Huang et al. [75] showed that RSV supplementation could not alleviate the reduction in the abundance of Lactobacillus in offspring caused by prenatal and postnatal HFDs. ...
Resveratrol butyrate esters (RBE) are derivatives of resveratrol (RSV) and butyric acid and exhibit biological activity similar to that of RSV but with higher bioavailability. The aim of this study was designed as an animal experiment to explore the effects of RBE on the serum biochemistry, and fat deposits in the offspring rats exposed to bisphenol A (BPA), along with the growth and decline of gut microbiota. We constructed an animal model of perinatal Bisphenol A (BPA) exposure to observe the effects of RBE supplementation on obesity, blood lipids, and intestinal microbiota in female offspring rats. Perinatal exposure to BPA led to weight gain, lipid accumulation, high levels of blood lipids, and deterioration of intestinal microbiota in female offspring rats. RBE supplementation reduced the weight gain and lipid accumulation caused by BPA, optimised the levels of blood lipids, significantly reduced the Firmicutes/Bacteroidetes (F/B) ratio, and increased and decreased the abundance of S24-7 and Lactobacillus, respectively. The analysis of faecal short-chain fatty acid (SCFA) levels revealed that BPA exposure increased the faecal concentration of acetate, which could be reduced via RBE supplementation. However, the faecal concentrations of propionate and butyrate were not only significantly lower than that of acetate, but also did not significantly change in response to BPA exposure or RBE supplementation. Hence, RBE can suppress BPA-induced obesity in female offspring rats, and it demonstrates excellent modulatory activity on intestinal microbiota, with potential applications in perinatological research.
... Studies have found the gut microbiome profile of infants to be time dependent, with specific types of microbes enriched at different stages of early-life development (6,10,11). Further, many events in early life, such as delivery by caesarean section, formula feeding, and exposure to antibiotics, can perturb the composition of the gut microbiota (12)(13)(14)(15). For instance, Bifidobacterium and Lactobacillus are enriched in breast-fed infants compared to those who are fed exclusively with formula. ...
Background:
The gut microbiome plays a potential role in clinical events in preterm infants and may affect their lateral development. Understanding the initial colonization of microbes in the gut, their early dynamic changes, and the major factors correlated with these changes would provide crucial information about the developmental process in early life.
Methods:
The present study enrolled 151 preterm infants and examined the longitudinal dynamics of their fecal microbiome profiles during the period of hospitalization using 16S ribosomal RNA gene sequencing. Random forest modeling was used to predict postnatal age (Age), postmenstrual age (PMA), and gestational age (GA), using gut microbiome features.
Results:
Principal coordinate analysis revealed that the gut microbiome of the preterm infants displayed an obvious time-dependent change pattern, which showed the strongest association with Age, followed by PMA, and a much weaker association with (GA). Random forest modeling further evidenced the time-dependent change pattern, with the Pearson's correlation coefficients between the actual values and the gut microbiome-predicted values being 0.68, 0.53, and 0.38 for postnatal, postmenstrual, and gestational age, respectively. The microbiome dynamism could be further divided into four Age stages, each with its own characteristic microbial taxa. The first 1-4 days (T1 stage) represented the meconium microbiome, with colonization of a high diversity of microbes before or during delivery. During 5-15 days (T2 stage), the gut microbiome of the preterm infants underwent a rapid turnover, in which microbial diversity declined, and stabilized afterward. Enterobacteriaceae, Enterococcaceae, Streptococcaceae, Staphylococcaceae, and Clostridiaceae were the major classes in the gut microbiome in the lateral stages of development (T3-T4 stage).
Conclusions:
Postnatal age, rather than the gestational age, is significantly correlated with the gut microbiome of preterm infants, suggesting that clinical interventions contribute more to the early dynamics of gut microbiome in preterm infants than the natural development of the gut.
... The composition and development of infant gut microbiota can be influenced by many factors, such as maternal obesity, smoking status, use of antibiotics, pre/term birth, mode of delivery and infant feeding mode (Vandenplas et al. 2020). Undisputedly, breast milk represents the most suitable nutritional resource for optimal infant growth, but it also harbors a set of bioactive components that drives the establishment and maintenance of early gut microbiota (as e.g. ...
Background
Accumulating evidence indicates that free amino acids (FAA) might be bioactive compounds with potential immunomodulatory capabilities. However, the FAA composition in human milk is still poorly characterized with respect to its correlation to maternal serum levels and its physiological significance for the infant. Studies addressing the relation of human milk FAA to the infants' intestinal microbiota are still missing.
Methods
As part of a pilot study, maternal serum and breast milk FAA concentrations as well as infant intestinal microbiota (16S rRNA) were determined 2 months after birth. The study cohort consisted of 41 healthy mothers and their term delivered, healthy infants with normal birthweight. The relationship between maternal serum and milk FAA was determined by correlation analyses. Associations between (highly correlated) milk FAA and infant intestinal beta diversity were tested using PERMANOVA, LefSe and multivariate regression models adjusted for common confounders.
Results
Seven breast milk FAA correlated significantly with serum concentrations. One of these, threonine showed a negative association with abundance of members of the class Gammaproteobacteria ( R ² adj = 17.1%, p = 0.006; β = − 0.441). In addition, on the level of families and genera, threonine explained 23.2% of variation of the relative abundance of Enterobacteriaceae ( R ² adj; p = 0.001; β = − 0.504) and 11.1% of variability in the abundance of Escherichia/Shigella (R ² adj, p = 0.025; β = − 0.368), when adjusted for confounders.
Conclusion
Our study is the first to suggest potential interactions between breast milk FAA and infant gut microbiota composition during early lactation. The results might be indicative of a potential protective role of threonine against members of the Enterobacteriaceae family in breast-fed infants. Still, results are based on correlation analyses and larger cohorts are needed to support the findings and elucidate possible underlying mechanisms to assess the complex interplay between breast milk FAA and infant intestinal microbiota in detail.
... The fecal microbiota of breastfed infants is not only different in composition than that of formula-fed infants, but it is also more stable and less diverse [15,18]. There are likely many reasons for these differences including HM oligosaccharides (HMOs) indigestible by human enzymes but selectively metabolized by microbes [19]. Even within exclusively breastfed infants, different HMO profiles have been associated with variation in infant fecal microbiomes [20,21]. ...
Both undernutrition and overnutrition continue to represent enduring global health crises, and with the growing implications of both forms of malnutrition occurring simultaneously in individuals and populations (referred to as the double burden of malnutrition), understanding their biological and environmental causes is a primary research and humanitarian necessity. There is growing evidence of a bidirectional association between variation in the gastrointestinal (GI) microbiome and risk of/resilience to malnutrition during early life. For example, studies of siblings who discordantly do or do not develop severe malnutrition show clear differences in the diversity and composition of fecal microbiomes. These differences are transiently lessened during refeeding but re-emerge thereafter. These findings have been somewhat recapitulated using animal models, but small sample sizes and limited range complicate interpretation of results and applicability to humans. Mechanisms driving these differences are currently unknown but likely involve a combination of inflammatory pathways (and perhaps antioxidant status of the host) and effects on nutrient availability, requirements, and utilization by both host and microbe. A less robust literature also suggests that variation in GI microbiome is associated with risk for obesity during childhood. The putative impact of GI microbiomes on malnutrition is likely modified by a variety of important variables such as genetics (likely driven, in part, by evolution), environmental pathogen exposure and its timing, dietary factors, and cultural/societal pattern (e.g., use of antibiotics). Given the growing double burden of malnutrition, this topic demands a focused interdisciplinary approach that expands from merely characterizing differences and longitudinal changes in fecal microbes to examining their functionality during early life. Understanding the complex composition of human milk and how its components impact establishment and maintenance of the recipient infant’s GI microbiome will also undoubtedly shed important light on this topic.
... Moreover, a recent study reported that formula feeding in the early life of infants small for their gestational age is related to prospective overweight in preschool age, but only among girls [44]. Breastfeeding also modulates the physiological development of the digestive tract [45] and intestinal colonization [46], which might contribute to risk reduction for obesity in later life [47]. However, our results also show significant confounding of the association of breastfeeding and later overweight by low SES that is linked to both less breastfeeding success and more overweight. ...
The benefits of breastfeeding (BF) include risk reduction of later overweight and obesity. We aimed to analyse the association between breastfeeding practices and overweight/obesity among preschool children participating in the ToyBox study. Data from children in the six countries, participating in the ToyBox-study (Belgium, Bulgaria, Germany, Greece, Poland, and Spain) 7554 children/families and their age is 3.5–5.5 years, 51.9% were boys collected cross-sectionally in 2012. The questionnaires included parents’ self-reported data on their weight, height, socio-demographic status, and infant feeding practices. Measurements of preschool children’s weight and height were done by trained researchers using standard protocols and equipment. The ever breastfeeding rate in the total sample was 85.0% (n = 5777). Only 6.3% (n = 428) of the children from the general sample were exclusively breastfed (EBF) for the duration of the first six months. EBF for four to six months was significantly (p < 0.001) less likely among mothers with formal education < 12 years (adjusted Odds Ratio (OR) = 0.61; 95% Confidence interval (CI) 0.44–0.85), smoking throughout pregnancy (adjusted OR = 0.39; 95% CI 0.24–0.62), overweight before pregnancy (adjusted OR = 0.67; 95%CI 0.47–0.95) and ≤25 years old. The median duration of any breastfeeding was five months. The prevalence of exclusive formula feeding during the first five months in the general sample was about 12% (n = 830). The prevalence of overweight and obesity at preschool age was 8.0% (n = 542) and 2.8% (n = 190), respectively. The study did not identify any significant association between breastfeeding practices and obesity in childhood when adjusted for relevant confounding factors (p > 0.05). It is likely that sociodemographic and lifestyle factors associated with breastfeeding practices may have an impact on childhood obesity. The identified lower than desirable rates and duration of breastfeeding practices should prompt enhanced efforts for effective promotion, protection, and support of breastfeeding across Europe, and in particular in regions with low BF rates.
... The vaginally delivered newborns mainly obtain their gut microbiota from the mother's vaginal microbiota, and the gut microbiota is mainly composed of the genera Lactobacillus and Prevotella; on the other hand, the gut microbiota of cesarean section-delivered newborns is similar to the skin microbiota, which is mainly composed of the genera Staphylococcus, Corynebacterium, and Propionibacterium (Dominguez-Bello et al., 2010;Tamburini et al., 2016). After birth, the microorganisms from the mother and the surrounding environments colonize rapidly (Vandenplas et al., 2020) and some opportunistic pathogens might also colonize the infants' gut, causing infections (Shao et al., 2019). The initial gut microbiota subsequently affects child health, and the cesarean section-delivered newborns might have a higher risk of food allergies and other diseases (Arrieta et al., 2015;Rachid and Chatila, 2016). ...
Cow’s milk protein allergy (CMPA) is an immune response to cow’s milk proteins, which is one of the most common food allergies in infants and young children. It is estimated that 2–3% of infants and young children have CMPA. The diet, gut microbiota, and their interactions are believed to be involved in the alterations of mucosal immune tolerance, which might lead to the development of CMPA and other food allergies. In this review, the potential molecular mechanisms of CMPA, including omics technologies used for analyzing microbiota, impacts of early microbial exposures on CMPA development, and microbiota–host interactions, are summarized. The probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and other modulation strategies for gut microbiota and the potential application of microbiota-based design of diets for the CMPA treatment are also discussed. This review not only summarizes the current studies about the interactions of CMPA with gut microbiota but also gives insights into the possible CMPA treatment strategies by modulating gut microbiota, which might help in improving the life quality of CMPA patients in the future.
... Preterm infants treated with antibiotics often exhibit a microbiome colonized with multidrug-resistant bacteria such as Enterobacteriaceae and Enterococcus following treatment (Greenwood et al., 2014; Gibson et al., 2016). Dysbiosis of the microbiome can lead to lesser production of antibacterial compounds and IgG, altered short-chain fatty acids (SCFAs), and elevated levels of inflammatory cytokines making infants susceptible to infection and at a higher risk to immune-mediated diseases (Vandenplas et al., 2020;Francino, 2015). In addition, antibiotics treatment during infancy can also lead to the development of allergies and an increased risk of eczema, especially when there are opportunistic colonizers such as Escherichia coli or Clostridium difficile (Adlerberth et al., 2007). ...
Prenatal and postnatal factors and the human milk (HM) influences infant's gut microbial colonization. HM contains an array of immunomodulatory factors, complex carbohydrates such as human milk oligosaccharides, and microorganisms. These likely contribute to the establishment of the infant's intestinal microbiota, thereby influencing infant immune and metabolic maturation. This article presents the several factors affecting the neonates' gut microbiota and their impact on the overall health.
... Intestinal coloniza- tion and immune regulation in humans are dynamic. The neonate's initial intestinal flora is primarily derived from the mother's delivery process and postnatal exposure (30,31), and B. fragilis, which might be transferred from mother to neonate, is the most abundant bacterium in the newborn's early digestive tract. The shift in intestinal abundance corresponds to the development of the adaptive immune system (32). ...
Background: At present, there is no report that the intestinal flora of pregnant women with mild thalassemia is different from that of healthy pregnant women. Objectives: This study compared the composition and changes of the intestinal flora of pregnant women with mild thalassemia to those of healthy pregnant women using metagenomic sequencing technology and evaluated the potential microecological risk for pregnant women and the fetus. Methods: The present study was carried out on 14 mild thalassemia pregnant women with similar backgrounds in the Affiliated Hospital of Putian University, Fujian, China. In the same period, 6 healthy pregnant women were selected as the control group. The genomic deoxyribonucleic acid was extracted from the sable stool samples of pregnant women. Illumina HiSeq sequencing technology was adopted after library preparation. Prodigal software (ver 2.6.3, Salmon software (ver 1.6.0, and Kraken software (ver 2) were used to analyze the sequence data. Moreover, analysis of variance and Duncan’s multiple-comparison test or Wilcoxon rank-sum test were used as statistical methods. Results: The characteristics of the intestinal flora of pregnant women with mild thalassemia differed significantly from those of healthy pregnant women, showing an increase in some conditionally pathogenic bacteria (e.g., Prevotella stercorea rose and Escherichia coli) and a decrease in some probiotic bacteria, which might affect pregnant women and cause physiological function damage to their offspring by changing metabolic pathways; however, further validation is needed. Conclusions: The diversity and composition of intestinal flora in pregnant women with mild thalassemia vary significantly from those in healthy pregnant women, especially at the genus and species levels, representing more profound alterations in intestinal microecology.
... Additionally, it has an important role on the colonisation of the infant's gut, conferring protection against pathogens and contributing to the maturation of the immune system and to the digestion of nutrients [2]. This is particularly important after birth and during the first months of life, when milk is the main source of microbiota for the breastfed infant [13], with consequences for the long-term too [14]. ...
The objective of this work was to characterize the microbiota of breast milk in healthy Spanish mothers and to investigate the effects of lactation time on its diversity. A total of ninety-nine human milk samples were collected from healthy Spanish women and were assessed by means of next-generation sequencing of 16S rRNA amplicons and by qPCR. Firmicutes was the most abundant phylum, followed by Bacteroidetes, Actinobacteria, and Proteobacteria. Accordingly, Streptococcus was the most abundant genus. Lactation time showed a strong influence in milk microbiota, positively correlating with Actinobacteria and Bacteroidetes, while Firmicutes was relatively constant over lactation. 16S rRNA amplicon sequencing showed that the highest alpha-diversity was found in samples of prolonged lactation, along with wider differences between individuals. As for milk nutrients, calcium, magnesium, and selenium levels were potentially associated with Streptococcus and Staphylococcus abundance. Additionally, Proteobacteria was positively correlated with docosahexaenoic acid (DHA) levels in breast milk, and Staphylococcus with conjugated linoleic acid. Conversely, Streptococcus and trans-palmitoleic acid showed a negative association. Other factors such as maternal body mass index or diet also showed an influence on the structure of these microbial communities. Overall, human milk in Spanish mothers appeared to be a complex niche shaped by host factors and by its own nutrients, increasing in diversity over time.
... During the first days of life, the newborn's intestine is colonized by Gram negative bacteria, which by consuming oxygen, generate an anaerobic environment and the relative abundance of Lactobacillus and Bifidobacterium genera (5). Thus, relatively minor changes occur, maintaining a stability of gut microbiota, although with the possibility of reshaping by the environment, including diet (6). This means that maternal nutritional exposures during pregnancy and breastfeeding could affect the microbial transmission to offspring modifying the microbiota ecosystem and setting health alterations associated with a dysbiotic microbiota (3). ...
Background: There is increasing evidence that gut microbiota in offspring is derived in part from maternal environment such as diet. Thus, sweeteners intake including caloric or non-caloric during perinatal period can induce gut dysbiosis and program the offspring to develop cognitive problems later in life.
Objective: To determine the effect of maternal high-sweeteners intake during gestation and lactation on gut microbiota shifts in adult male offspring rats and the impact on cognitive dysfunction.
Methods: Thirty-four male pups from dams fed standard diet (Control-C, n = 10), high-sucrose diet (HS-C, n = 11), high-honey diet (Ho-C, n = 8), and high-stevia diet (HSt-C, n = 5) were fed standard diet after weaning, and body weight and food intake were recorded once a week for 26 weeks. Learning and memory tests were performed at week 23 of life using the Barnes maze. Fecal samples from the breastfeeding and adulthood periods were collected and analyzed by sequencing the 16S rRNA V3-V4 region of gut microbiota.
Results: Maternal high-sucrose and stevia diets programmed the male offspring, and changes in microbial diversity by Shannon index were observed after weaning ( p < 0.01). Furthermore, maternal high-stevia diet programming lasted into adulthood. The increase of Firmicutes abundance and the decrease in phylum Bacteroidetes were significant in HS-C and HSt-C groups. This led to an increase in the Firmicutes/Bacteroidetes index, although only in HS-C group was statistically significant ( p < 0.05). Of note, the downstream gram-negative Bacteroidales and the upregulation of the gram-positive Clostridiales abundance contribute to cognitive dysfunction.
Conclusion: These results suggest that dams fed a high-sucrose and stevia diets during gestation and lactation favor a deficient memory performance in adult male offspring rats through shifts gut microbiota diversity and relative abundance at several taxa.
... In the present study, at the phylum level, the relative abundance of Proteobacteria and Bacteroidetes fluctuated over time with no significant difference observed between the two groups at each time point, which was consistent with another study on intestinal microbiota and allergy diseases (Shen et al., 2019). At the genus level, the relative abundance of Bifidobacterium increased gradually over time in both groups, which may be related to the fact that human milk HMO can stimulate the growth of Bifidobacterium in the intestinal microbiota of infants (Vandenplas et al., 2020). However, the relative abundance of Bifidobacterium in the NA group was higher than that in the FA group. ...
Regulating the composition of human breastmilk has the potential to prevent allergic diseases early in life. The composition of breastmilk is complex, comprising varying levels of oligosaccharides, immunoactive molecules, vitamins, metabolites, and microbes. Although several studies have examined the relationship between different components of breastmilk and infant food allergies, few have investigated the relationship between microorganisms in breastmilk and infant food allergy. In the present study, we selected 135 healthy pregnant women and their full-term newborns from a cohort of 202 mother–infant pairs. Among them, 69 infants were exclusively breastfed until 6 mo after birth. At follow-up, 11 of the 69 infants developed a food allergy in infancy while 22 showed no signs of allergy. Thirty-three breastmilk samples were collected within 1 mo after delivery, and 123 infant fecal samples were collected at five time points following their birth. These samples were analyzed using microbial 16S rRNA gene sequencing. The abundance and evenness of the milk microbiota and the number of differential bacteria were higher in the breastmilk samples from the non-allergy group than in those from the food allergy group. The non-allergy group showed relatively high abundance of Bifidobacterium , Akkermansia , Clostridium IV, Clostridium XIVa, Veillonella , and butyrate-producing bacteria such as Fusobacterium , Lachnospiraceae incertae sedis , Roseburia , and Ruminococcus . In contrast, the abundance of Proteobacteria , Acinetobacter , and Pseudomonas in breastmilk was higher in the food allergy group. A comparison of the changes in dominant differential breastmilk microbiota in the intestinal flora of the two groups of infants over time revealed that the changes in Bifidobacterium abundance were consistent with those in the breastmilk flora. Functional pathway prediction of breastmilk microflora showed that the enhancement of the metabolic pathways of tyrosine, tryptophan, and fatty acids was significantly different between the groups. We suggest that changes in the breastmilk microbiota can influence the development of food allergies. Breastmilk contains several microbes that have protective effects against food allergies, both by influencing the colonization of intestinal microbiota and by producing butyrate. This study may provide new ideas for improving infant health through early intervention with probiotics.
... The gut microbiota is another important variable affecting the metabolism of naringin [24]. It is the prominent inhabitant of the gastrointestinal tract, and is influenced by diets, antibiotics, and other environmental factors [25]. The gut microbiota is deeply involved in the degradation of exogenous compounds in the digestive tract by secreting a mass of metabolic enzymes [26]. ...
Naringin is a dietary flavonoid glycoside with multiple bioactivities. It has been involved in numerous metabolism and excretion studies, and its metabolic properties are clear. However, information concerning the excretion profile of its original metabolites are still scarce, and few methods for simultaneous determination of multiple original metabolites of naringin in biological samples have been reported so far. In this study, a rapid and sensitive method for simultaneous determination of ten flavonoid metabolites of naringin in rat urine was developed with an UHPLC-Q-Trap-MS/MS system. One-step protein precipitation method with acetonitrile was used to extract analytes. A rapid chromatographic separation within 11 min was performed on an ACQUITY UPLC® BEH C18 column (2.1 mm × 50 mm, 1.7 μm) using gradient elution with a mobile phase of water and methanol, both with 0.1% formic acid (v/v). MS/MS detection was conducted in negative ion mode and multiple reactions monitoring scanning mode. The analytical method was fully validated and successfully applied to monitor the excretion profiles of naringin in rat urine. Quantitative results revealed the visible individual difference and low urinary recovery of flavonoid metabolites in the excretion of naringin, which may be helpful for further study to understand the in vivo behavior and action mechanism of naringin.
... Following birth, colonization of the infant gut is majorly determined by the early feeding mode, with distinguishable microbial compositions between breast-and formula-fed infants (254,255). Generally, breast-fed infants harbor a less diverse and species-rich microbiota that is dominated by Bifidobacterium species, whereas the microbiota of formulafed infants is functionally more similar to that of an adult and is often enriched in microbial taxa such as Klebsiella, Enterococcus, Peptostreptococcaceae, Akkermansia, Veillonella, and C. difficile (256,257). Thus, various intrinsic factors of breast milk influence the developing microbiota. Human milk harbors a unique microbial community, including commensal, mutualistic, and probiotic bacteria, some of which can be found as first colonizers of the neonatal gut (258,259). ...
Over the past decade, the gut microbiota has emerged as a key component in regulating brain processes and behavior. Diet is one of the major factors involved in shaping the gut microbiota composition across the lifespan. However, whether and how diet can affect the brain via its effects on the microbiota is only now beginning to receive attention. Several mechanisms for gut-to-brain communication have been identified, including microbial metabolites, immune, neuronal, and metabolic pathways, some of which could be prone to dietary modulation. Animal studies investigating the potential of nutritional interventions on the microbiota–gut–brain axis have led to advancements in our understanding of the role of diet in this bidirectional communication. In this review, we summarize the current state of the literature triangulating diet, microbiota, and host behavior/brain processes and discuss potential underlying mechanisms. Additionally, determinants of the responsiveness to a dietary intervention and evidence for the microbiota as an underlying modulator of the effect of diet on brain health are outlined. In particular, we emphasize the understudied use of whole-dietary approaches in this endeavor and the need for greater evidence from clinical populations. While promising results are reported, additional data, specifically from clinical cohorts, are required to provide evidence-based recommendations for the development of microbiota-targeted, whole-dietary strategies to improve brain and mental health.
... Interestingly, plenty of research studies have proved the transmission of gut microbiota between mothers and offspring in utero. Studies [39,41,42] involving maternal diet, gestational weight gain (GWG), and antibiotic treatment have reinforced that point of view. Accordingly, several hypotheses [42] were proposed about transmission routes (e.g., vagina, placenta, amniotic fluid, cord blood, and fetal membranes) which means that maternal prenatal factors can alter the initial newborns' gut microbiota. ...
Background: Individualized maternal diet and alcohol consumption can influence both maternal and infant’s gut microbiota. These relationships are still unknown in Chinese population. The purpose of this study was to explore the effect of alcohol consumption and diet during pregnancy on maternal and infant’s gut microbiota.
Methods: Twenty-nine mother-child dyads were enrolled in Central China. Fecal samples of mothers during late pregnancy and of newborns within 48 hours were collected. The V3-V4 regions of 16S rRNA sequences were analyzed. A self-administrated questionnaire about simple diet frequency in the past week was completed by mothers before childbirth. The general demographic information was finished by mothers at 24 hours after childbirth.
Results: Among these 29 mothers, 10 mothers reported alcohol consumption during pregnancy. The PCoA (β-diversity) showed significant difference in maternal gut microbiota between the alcohol consumption group vs the non-alcohol consumption group (Jaccard, R = 0.2, P = 0.006). The same phenomenon was observed in newborns (unweighted-UniFrac full tree ,R = 0.174，P = 0.031). Maternal alcohol consumption frequency showed positive associations with maternal Phascolarctobacterium (P = 0.032) and Blautia (P = 0.019); maternal Faecalibacterium (P = 0.013) was negatively correlated with frequency of alcohol consumption. A positive relationship between Megamonas and maternal alcohol consumption (P = 0.035). The diet was not associated with both maternal and infant’s gut microbiota.
Conclusions: Maternal alcohol consumption during pregnancy influenced the gut microbiota on both mothers and the newborns. Future research is needed to explore these relationships in a lager birth cohort. Understanding the long-term effect of alcohol consumption on maternal and newborns’ gut microbiota is needed.
... During pregnancy and lactation, the mothers share gut microbes and microbial metabolites with their offspring, which highlights the importance of maternal influences in the development of early-life gut microbiota [76]. A diversity of early-life factors governs the establishment of the gut microbiota, such as maternal medical conditions, gestational age, types of delivery, antibiotic exposure, formula feeding, and ecological factors [74][75][76][77]. ...
Hypertension is the leading cause of global disease burden. Hypertension can arise from early life. Animal models are valuable for giving cogent evidence of a causal relationship between various environmental insults in early life and the hypertension of developmental origins in later life. These insults consist of maternal malnutrition, maternal medical conditions, medication use, and exposure to environmental chemicals/toxins. There is a burgeoning body of evidence on maternal insults can shift gut microbiota, resulting in adverse offspring outcomes later in life. Emerging evidence suggests that gut microbiota dysbiosis is involved in hypertension of developmental origins, while gut microbiota-targeted therapy, if applied early, is able to help prevent hypertension in later life. This review discusses the innovative use of animal models in addressing the mechanisms behind hypertension of developmental origins. We will also highlight the application of animal models to elucidate how the gut microbiota connects with other core mechanisms, and the potential of gut microbiota-targeted therapy as a novel preventive strategy to prevent hypertension of developmental origins. These animal models have certainly enhanced our understanding of hypertension of developmental origins, closing the knowledge gap between animal models and future clinical translation.
... Subjects with type 1 diabetes are known to exhibit differences in composition of the intestinal microbiome and a decrease in its diversity [16]. Early life factors which are known to affect the gut microbiome include infant feeding, mode of delivery, hygiene practices and parental smoking [16,17]. Gestational age and birth weight have also been implicated as risk factors in type 1 diabetes [18] through undetermined mechanisms. ...
Background
The prevalence of type 1 diabetes is increasing worldwide, suggesting that unknown environmental factors are becoming increasingly important in its pathogenesis.
Aim
The aim of the study was to investigate the possible role of a number of prenatal and perinatal factors in the aetiology of type 1 diabetes.
Methods
Mothers of patients diagnosed with type 1 diabetes (cases) and mothers of children born on the same day and of the same sex as type 1 diabetes patients (controls) were interviewed on a number of prenatal and perinatal factors of interest.
Results
Hand washing prior to eating, frequency of bathing and total stress score were found to be positively associated with the development of type 1 diabetes on univariate analyses. Hand-washing prior to eating and frequency of house cleaning were independently associated with an increased risk of type 1 diabetes, whilst getting dirty was associated with a reduced risk in multivariate analyses. There was no association of type 1 diabetes to removing of outdoor shoes indoors or to the age of first attendance to school or pre-school. There were also no significant associations to parental smoking, parental age, birth order, infant feeding, antibiotic use, mode of delivery or birth weight.
Conclusion
Our data suggest that factors that affect the skin or gut microbiome might be more important than infections or factors affecting the microbiome at other sites.
... Animals stressed due to environmental temperature are found to impair gastrointestinal (GI) function and increase GI permeability (Karl et al., 2018). Environmental factors affecting gut microbiota populations have been investigated in humans and animals (Cholewinska et al., 2021;Moeller et al., 2020;Vandenplas et al., 2020). Moreover, cold stress induced vasoconstriction, which results in an increase in efferent sympathetic activity and a reduction in parasympathetic activity (Manou-Stathopoulou et al., 2015, Greaney et al., 2015. ...
Background: Cold temperature is a common environmental stressor that has a great impact on the poultry industries, inducing pathophysiological stress in birds with profound economic losses. Current methods used for preventing cold stress, such as reducing ventilation and using gas heaters, are facing challenges due to poor indoor air quality and its deleterious effects on bird and caretaker health. The aim of this study was to examine if the novelly designed warmed perch system, as a thermal device, can reduce cold stress-associated adverse effects on laying hens.
Methods: Seventy-two 32-week-old DeKalb hens were randomly assigned to 36 cages arranged to 3 banks. The banks were assigned to 1 of 3 treatments: cages with warmed perches (WP; perches with circulating water at 30 oC), air perches (AP, regular perches only) or no perches (NP) for a 21- day trial. The room temperature was set at 10 oC during the entire experimental period. Rectal temperature and body weight were measured from the same bird of each cage at day 1, 8, 15, and 21 during the cold exposure. Egg production was recorded daily. Feed intake, egg and eggshell quality were determined during the 1st and 3rd week of cold stress. Plasma levels of corticosterone, thyroid hormones (3, 3’, 5-triiodothyronine and thyroxine), interleukin (IL)-6 and IL-10, were determined at day 1 and 21 post initiation of cold exposure.
Results: Compared to both AP and NP hens, WP hens were able to maintain their body temperature without increasing feed intake and losing body weight. The eggs laid by WP hens had thicker eggshell during the 3rd week of cold exposure. Warmed perch hens also had a lower thyroxine conversion rate (3, 3’, 5-triiodothyronine/thyroxine) at day 1, while higher plasma concentrations of IL-6 at day 21. Plasma levels of corticosterone, 3, 3’, 5-triiodothyronine, and IL-10 were not different among treatments.
Conclusions: Our results indicate that the warmed perch system can be used as a novel thermal device for preventing cold stress-induced negative effects on hen health and welfare through regulating innate immunity and metabolic hormonal homeostasis.
... Different microbiota colonization patterns of infants and children affect the subsequent regulation of immune responses and potential disease incidence in their lifetime [54][55][56]. A growing body of evidence has shown that, during the establishment stage (2.5-3 years) of a child, certain factors can shape the structure and composition of the gut microbiota, including maternal prenatal condition, delivery mode, breast or bottle feeding, early diet, and postnatal medical interventions [19,35,57]. ...
The colonization of the human microbiota in early life has long-lasting health implications. The status of the initial intestinal microbiota determines human growth and development from infancy to adulthood, and thus represents a crucial window in our long-term development. This review aims to summarize the latest findings on the symbiotic gut microbiota early in life and its vital role in metabolic-, allergic-, and auto-immune-disorder-related diseases, including obesity, diabetes, allergy, autism, inflammatory bowel disease, and stunting. It discusses the development process and various factors shaping the gut microbiota, as well as the crosstalk between the gut microbiota and the host’s physiological systems (especially intestinal immune development and homeostasis, and the central nervous system in the course of neurodevelopment), during the early life establishment of the gut microbiota, in order to decipher the mechanisms of diseases associated with the intestinal microbiome of early life. In addition, it examines microbiota-targeted therapeutic methods that show promising effects in treating these diseases. The true process of gut microbiome maturation, which depends on genetics, nutrition, and environmental factors, must be scrutinized in order to monitor healthy gut microbiome development and potentially correct unwanted courses by means of intervention via methods such as novel probiotics or fecal microbiota transplantation.
... It is associated with infant growth, and its total amount in breast milk seems not to be affected by maternal diet [47,48]. On the other hand, the amount and quality composition of human milk oligosaccharides (HMOs) vary substantially between women in accordance to different factors such as enzymatic activity, which determine the synthesis of fucosylated HMOs and other genetic and environmental factors, which are not completely understood nowadays [48][49][50][51][52]. A better understanding of the maternal factors that influence this variability could be important in terms of health prevention. ...
The benefits of human milk for both mother and infant are widely acknowledged. Human milk could represent a link between maternal and offspring health. The triad mother-breast milk-infant is an interconnected system in which maternal diet and lifestyle might have effects on infant’s health outcome. This link could be in part explained by epigenetics, even if the underlining mechanisms have not been fully clarified yet. The aim of this paper is to update the association between maternal diet and human milk, pointing out how maternal diet and lifestyle could be associated with breast-milk composition, hence with offspring’s health outcome.
... If the antibiotic treatment is given at an earlier stage of infancy, it affects the microbiome to a greater extent. Similarly, more frequent administration causes more damage to the microbiome and leads to lesser production of antibacterial compounds and IgG, making the infants susceptible to infections [69,70]. Antibiotic resistant microbes might become pathogenic at some stage. ...
Early life gut microbiota have been increasingly recognized as major contributors to short and/or long-term human health and diseases. Numerous studies have demonstrated that human gut microbial colonization begins at birth, but continues to develop a succession of taxonomic abundances for two to three years until the gut microbiota reaches adult-like diversity and proportions. Several factors, including gestational age (GA), delivery mode, birth weight, feeding types, antibiotic exposure, maternal microbiome, and diet, influence the diversity, abundance, and function of early life gut microbiota. Gut microbial life is essential for assisting with the digestion of food substances to release nutrients, exerting control over pathogens, stimulating or modulating the immune system, and influencing many systems such as the liver, brain, and endocrine system. Microbial metabolites play multiple roles in these interactions. Furthermore, studies provide evidence supporting that imbalances of the gut microbiota in early life, referred to as dysbiosis, are associated with specific childhood or adult disease outcomes, such as asthma, atopic dermatitis, diabetes, allergic diseases, obesity, cardiovascular diseases (CVD), and neurological disorders. These findings support that the human gut microbiota may play a fundamental role in the risk of acquiring diseases that may be programmed during early life. In fact, it is critical to explore the role of the human gut microbiota in early life.
... The human gut microbes are easily affected by the toxic environment agents that we intake from food [37]. Intermediate fasting, unhealthy eating habits, ph and water quality also disfigured the composition of gut micro biota [38]. In breast feeding the main component that is taken by the infant from the outside environment (HMO) human milk oligosaccaride which is, responsible for increase in the abundance of bifidobacteria in gut community [39]. ...
Increasing evidence shows that gut microbiota plays a critical role in host immune system development and immune regulation, thus the composition of gut microbiota may affect how individuals respond to immunizations. Currently, little evidence is available on the correlation between porcine gut microbiota and vaccine immune response. Here, we investigated the influence of gut microbiota on immune response in pigs to porcine reproductive and respiratory syndrome virus (PRRSV) vaccine. Based on the antibody levels for PRRSV, the immunized pigs were divided into three groups (high, low, and others), and followed by virulent PRRSV challenge. The comprehensive analysis of microbial composition revealed that gut microbiota was similar in the richness and diversity among different groups before immunization. After immunization, the richness and diversity of gut microbial community in the high group were still similar to the low group, although there was a decrease in community diversity overtime. Interestingly, the antibody titers were positively correlated with the abundance of Lactobacillus in gut microbiota in immunized pigs. Further analysis indicated that gut microbial composition might be correlated to the clinical parameters such as body weight and rectal temperature after virus challenge. Taken together, our findings suggest that certain specific members of gut microbiota, such as Lactobacillus may serve as a mechanism for regulating the immune response following immunization in pigs.
The review summarizes the results of experimental and clinical studies aimed at elucidating the causes and pathophysiological mechanisms of the development of endocrine pathology in children. The modern data on the role of epigenetic influences in the early ontogenesis of unfavorable factors that violate the patterns of the formation of regulatory mechanisms during periods of critical development of fetal organs and systems and contribute to the delayed development of pathological conditions are considered. The mechanisms of the participation of melatonin in the regulation of metabolic processes and the key role of maternal melatonin in the formation of the circadian system of regulation in the fetus and in the protection of the genetic program of its morphofunctional development during pregnancy complications are presented. Melatonin, by controlling DNA methylation and histone modification, prevents changes in gene expression that are directly related to the programming of endocrine pathology in offspring. Deficiency and absence of the circadian rhythm of maternal melatonin underlies violations of the genetic program for the development of hormonal and metabolic regulatory mechanisms of the functional systems of the child, which determines the programming and implementation of endocrine pathology in early ontogenesis, contributing to its development in later life. The significance of this factor in the pathophysiological mechanisms of endocrine disorders determines a new approach to risk assessment and timely prevention of offspring diseases even at the stage of family planning.
ABSTRACT
Background: Immature immune system in preterm infants is associated with gut dysbiosis and poses significant health risks to their growth and development. Current guidelines for managing preterm infants focuses solely on macro- and micronutrients, whereas preterm infants’ gastrointestinal system requires optimalization to support nutrient absorption. Studies on the positive impacts of prebiotics as supplements have been conducted, but has not been implemented in Indonesia. Indonesian pediatricians’ perspective on these findings needs to be assessed. Objectives: To describe the perspectives of Indonesian pediatricians on the role of gut microbiota balance in supporting immunity, growth, and development of preterm infants, and the role of breastmilk and prebiotic-supplemented formula in optimizing gut microbiota balance. Methods: A cross-sectional study was conducted on 114 Indonesian pediatricians using a previously-validated and previously-used questionnaire on the role of gut microbiota balance on preterm infants, as well as the role of breastmilk and prebiotic-supplemented formula in optimizing gut microbiota balance. Results: Most respondents agreed that gut microbiota balance supports immunity, growth, and development of preterm infants. Respondents also agreed that breastmilk contains nutrients that support gut microbiota balance and when breastmilk becomes unavailable, prebiotic-supplemented formula can be given as substitute. Conclusions: Indonesian pediatricians considered gut microbiota balance to be important for immunity, growth, and development of preterm infants, and breastmilk to be the most ideal source of nutrition for preterm infants in optimizing gut microbiota balance. When breastmilk is unavailable, prebiotic-supplemented formula can be considered as an alternative.
Background
Maturation of the infant gut microbiota has lifelong implications on health, which has been proposed as the major events during the first year of life. However, little was known about dynamic colonization of the gut microbiota and its influencing elements among the two-year infancy as well as into the adulthood.
Results
Based on the 16S rRNA sequencing data in the V3-V4 regions among 30 healthy mother-infant pairs with the normal range of the growth and development index from birth to two years old, the diversity of the gut microbiota was significantly increased from Six-month to Two-year subgroups. Furthermore, the dynamic colonization of gut microbiota was that the significant trends of Firmicutes (Faecalibacterium, Blautia, Enterococcus, Subdoligranulum, Agathobacter, Unidentified_Erysipelotrichaceae, Staphylococcus, Acinetobacillus, Unidentified_ Ruminococcaceae and Fusicatenibacter), Bacteroidetes and Verrucomicrobia were increased, while Actinobacteria (Bifidobacterium) and Proteobacteria (Enterobacteriaceae and Klebsiella) were decreased with the increased age at the phylum and genus levels. These above results revealed that certain bacteria might modulate the host pathways, such as Chemoheterotrophy, Fermentation, Parasites_or _symbionts, Nitrate_reduction and Aerobic_chemoheterotrophy metabolism. Moreover, there were significant associations between maternal (gut microbiota in the milk, Pre-pregnancy BMI-M.BMI, BMI gain during the pregnancy-I.BMI) and infant characteristics (BMI at birth-B.BMI and increment of BMI-G.BMI), and the compositions of gut microbiota in the faeces, but not differences were shown between the different sex and mode of productive subgroups.
Conclusion
Overall, the gut microbial community was significantly matured into adulthood with the increased age subgroups. It also identified that there were significant correlations between the features of gut microbiota and maternal (gut microbiota in the milk, M.BMI and I.BMI) and infant characteristics (B.BMI and G.BMI), which will provide a new direction for the host-gut microbiota interplay during the two years of life.
Breast milk is the optimal food choice for infant growth and development. Among breast milk components, fructooligosaccharides (FOSs) are being actively studied because of their role in microbiota development. In particular, 2'-fucosyllactose is being proposed as a potential supplement/nutraceutical or component of infant formula. In this systematic review, we critically summarize the available information on FOSs and we discuss their future use in infant nutrition. We searched the main electronic databases (PubMed, Embase, and Scopus), with a final check in May 2021. Search terms were inserted individually and using the Boolean tools AND and OR. Relevant articles were identified using the following words: ("fructooligosaccharides" OR "FOS") AND ("human milk" OR "breast milk" OR "donor milk" OR "bank milk"). The search retrieved 1814 articles. After removal of duplicates, we screened 1591 articles based on title, abstract, and exclusive use of the English language. We included articles describing the concentration of FOSs in human milk and assessed the relevant ones. We excluded reviews, studies on animals, and studies exclusively carried out on adults. Also, we excluded studies that have not reported evidence either on FOSs or on galactooligosaccharides from human milk. The resulting publications were reviewed, and 10 studies were included in the systematic review. We conclude that human milk FOSs are, indeed, crucial to infant gut development and their addition to infant formula is safe, well-tolerated, and might provide immune benefits to newborns. However, we would like to underscore the scantiness of human data and the need to avoid the immediate translation of infant research to the commercialization of supplements marketed to adults.
In Chapter 1, the anatomical, physiological, and embryological bases of the gastrointestinal system are reviewed.
Background: Gut microbiota, a complex ecosystem consisting of abundant microorganisms, plays a role in preterm infants’ immunity, growth, and development. Dysbiosis or disruption of the gut microbiota can precipitate various diseases, such as allergy or autoimmune disorders in premature infants. Purpose: This study aimed to review gut microbiota in preterm infants and its role in supporting the infants’ immunity, growth, and development. Discussion: Bifidobactericeae is the predominant microbiota in GI tract of preterm infants. However, various factors can influence this gut microbiota e.g., genetics, lifestyle of the mothers (smoking, diet, use of antibiotic, obesity), birth mode, type of feeding, and environmental factors. Gut dysbiosis can result in impaired immune system which predisposes the preterm infants to infections, even fatal adverse event. Furthermore, the growth and development might be affected as well as lead to various neurodevelopmental and psychiatric disorders. Human milk is a prebiotic source which can stimulate the growth of Baifidobactericeae and Bacteroidetes. If the human milk is inadequate or unavailable, the recommended interventions for gut dysbiosis in premature infants are probiotics, prebiotics, or both supplementations (synbiotics). The administration of prebiotics and probiotics associates with lower morbidity and death rates in preterm infants, as well as shorter duration of hospital stay and duration to achieve full enteral feeding. Conclusions: Immunity as well as growth and development of preterm infants are affected greatly by gut microbiota The less diverse microbiota in preterm infants’ gut predispose them to various health problems. Hence, this problem should be managed properly, one of which is prebiotic and probiotic supplementation Keywords: Gastrointestinal Microbiome, Premature, Immunity, Growth, Development
Objective
The changes of microbial community in pregnant women, let alone those of patients with recurrent spontaneous abortion (RSA), remain unclear. We analyzed the differences of gut mircobiota (GM) between RSA patients and pregnant women to find the possible mechanism of RSA.
Methods
We enrolled 30 RSA patients (RSA group) and 30 pregnant women who terminated their pregnancy and did not have a history of spontaneous abortion (NR group) in our hospital from June 2020 to August 2020, and fecal samples were obtained to analyze the GM using 16S rDNA V3–V4 sequencing.
Results
At the phylum level, we found that there is no significant difference in composition of GM between RSA and NR. But at the genus level, compared with NR, Roseburia significantly decreased (P<0.01), and Ruminococcus significantly increased in RSA patients (P<0.05). Further analysis indicated that Klebsiella (P<0.05) was significantly increased, Prevotella.9 (P<0.05) and Roseburia (P<0.05) were significantly decreased in RSA2 group (BMI>23.9 in RSA). Moreover, Agathobacter (P<0.01) was significantly increased in NR2 group (no delivery in NR). Functional prediction indicated that GM may interfere with RSA through membrane transport, carbohydrate metabolism, amino acid metabolism and other pathways.
Conclusion
Decreased Roseburia in GM of pregnant women maybe related to RSA. Our results provide the basis for in-depth studies of the composition of gut microbial communities in RSA.
Microbiomes are transmitted between generations by a variety of different vertical and/or horizontal modes, including vegetative reproduction (vertical), via female germ cells (vertical), coprophagy and regurgitation (vertical and horizontal), physical contact starting at birth (vertical and horizontal), breast-feeding (vertical), and via the environment (horizontal). Analyses of vertical transmission can result in false negatives (failure to detect rare microbes) and false positives (strain variants). In humans, offspring receive most of their initial gut microbiota vertically from mothers during birth, via breast-feeding and close contact. Horizontal transmission is common in marine organisms and involves selectivity in determining which environmental microbes can colonize the organism’s microbiome. The following arguments are put forth concerning accurate microbial transmission: First, the transmission may be of functions, not necessarily of species; second, horizontal transmission may be as accurate as vertical transmission; third, detection techniques may fail to detect rare microbes; lastly, microbiomes develop and reach maturity with their hosts. In spite of the great variation in means of transmission discussed in this paper, microbiomes and their functions are transferred from one generation of holobionts to the next with fidelity. This provides a strong basis for each holobiont to be considered a unique biological entity and a level of selection in evolution, largely maintaining the uniqueness of the entity and conserving the species from one generation to the next.
The obesity epidemic has become a global public health crisis in recent years and is continuing to worsen at an alarming rate. However, the pathophysiological mechanisms involved in the development of obesity and obesity-related diseases are still being unraveled. In the past ten years, the gut microbiota has been identified as a crucial player affecting the onset and progression of obesity and obesity-related diseases, especially with respect to changes in its composition and metabolites during obesity progression. Herein, we summarize the roles and mechanisms of gut microbiota’s composition and metabolite changes in the gut play in obesity and obesity related diseases. Furthermore, we discuss potential therapeutic treatments that can be used to modulate the gut microbiome composition and target the relevant metabolic pathways of obesity and obesity-related metabolic diseases.
Preeclampsia (PE) is a unique complication of pregnancy that affects the health of the mother and the infant. Intestinal flora plays an important regulatory role in human body's metabolism and immunity and is associated with many diseases. Studies have shown that the development and progression of PE can lead to alterations in intestinal flora in the mother and are even closely associated with the colonization and development of intestinal flora in the offspring. This article reviews related studies on the effect of PE on maternal-infant intestinal flora, so as to provide new ideas for the prevention and treatment of maternal and infant complications associated with PE.
Early-life gastrointestinal microbiota development is crucial for physiological development and immunological homeostasis. In the current study, perinatal microbiota and the development of gastrointestinal microbiota in different early-life periods (perinatal, lactation, and postweaning nutrition periods) were explored by using an antibiotic-interfered mouse model and a dextran sulfate sodium-induced colitis mouse model. Gut microbiota samples were collected from mother mice and litters. The results of 16S rRNA gene sequences suggested that microbiota in the gastrointestinal system were present in prenatal fetal mice, and microbiota structures in different parts of the gastrointestinal system of the fetal mice were similar to those in the corresponding gut parts of maternal mice. Microbiota in mucus samples from different regions exhibited higher diversity at birth than at other periods and varied substantially over time with diet change. Moreover, antibiotic treatment in early life affected the composition and diversity of gastrointestinal microbiota in adult mice and enhanced susceptibility to experimental colitis in mice, particularly in the lactation period. This approach of exploring gut microbiota evolution is hoped to provide an enhanced view of how resident microbiota develop in early life, which in turn might facilitate understanding of gut microbiota and related diseases. IMPORTANCE This study investigated resident microbiota in the whole gastrointestinal (GI) tract to explore gut microbiota development in early life and found that early-life antibiotic exposure exacerbated alterations in gut microbiota and murine dextran sulfate sodium (DSS)-induced colitis. Furthermore, the presence of bacteria in the GI tract of mice before birth and the importance of the lactation period in GI microbiota development were confirmed.
Background:
Maternal emotional symptoms during pregnancy increase the risk of neurodevelopmental problems in offspring, and microbiota have been shown to be a potential mechanism underlying the link. However, the associations among maternal prenatal emotional symptoms, the meconium microbiota, and offspring neurodevelopment have yet to be fully elucidated. The aim of this prospective cohort study was to assess the relationship between maternal prenatal emotional symptoms and neurodevelopment of the child at 24 months of age, and to investigate the potential role of the neonatal meconium microbiota in the relationship.
Methods:
A total of 410 mother-child pairs (152 women in the Symptoms group vs. 258 women in the No-symptoms group) were recruited from the ongoing Shanghai Maternal-Child Pairs Cohort. This study included a subgroup of women who were assessed for maternal anxiety and depressive symptoms at 32-36 weeks of gestation. Neonatal meconium samples were collected after birth for 16 S sequencing. Children's neurodevelopment was measured using the Ages and Stages Questionnaire, Third Edition (ASQ-3) and Strengths and Difficulties Questionnaire (SDQ) at 24 months postnatally (n = 287).
Results:
Compared with the No-symptoms group, children in the Symptoms group had a higher degree of hyperactivity and total difficulties at 24 months of age. Increases in alpha diversity, distinct overall composition, enriched relative abundance of Proteobacteria, and different predicted microbial functions were observed in the meconium of neonates exposed to maternal prenatal emotional symptoms. The neonatal gut microbiota alpha diversity and relative abundance of genera from the Proteobacteria phylum and Lactobacillus were negatively correlated with children's degree of prosocial behavior, tendency toward hyperactivity, and poor fine motor development. In addition, mediating effects of neonatal meconium microbial richness and the relative abundance of Lactobacillus were observed between maternal emotional symptoms and children's prosocial behavior.
Conclusions:
Maternal prenatal emotional symptoms are associated with alterations in the offspring meconium microbiota and children's neurodevelopment at 24 months of age, and the microbial richness indices and Lactobacillus may play a mediating role. Future research is needed to identify and understand the biological pathways and metabolisms linking the relationships among maternal emotional symptoms, meconium microbiota, and neurodevelopment of children.
Bisphenol F (BPF) is becoming the main substitute for bisphenol A (BPA) in plastics for food and beverage applications. Previous studies have demonstrated the neurotoxicity of BPF; however, its lifecycle toxicity and the underlying mechanisms remain poorly understood. In the current study, zebrafish were continuously exposed to BPF for four months from the embryo to adult stages in order to assess its neurotoxicity. Locomotor behaviors significantly decreased after BPF exposure, which was accompanied by a decrease in body weight, length, and hatching rate. Additionally, BPF increased the expression of inflammatory genes in the brain and destroyed the zebrafishes' intestinal integrity. Meanwhile, the 16S rRNA gene sequence results showed a significantly decreased microbiota abundance and diversity following BPF treatment. Neurotransmitter metabolites were also altered by BPF. Notably, the correlation analysis between microbiota and neurotransmitter metabolism verified that gut microbiota dysbiosis was closely related to the disturbance of neurotransmitter metabolites. Therefore, the present study evaluated the neurotoxicity of lifecycle exposure to BPF and unraveled a novel mechanism involving disturbance of neurotransmitter metabolism and gut dysbiosis, which may provide potential targets for BPF-mediated neurotoxicity.
The maturation of infant gut microbiota has lifelong implications on health, which has been proposed as the major events during the first year of life. However, little is known about their dynamic colonization and influencing elements among the first two-year infancy as well as into the adulthood. So based on the 16S rRNA sequencing data among 30 healthy breast-feeding mother-infant pairs with normal ranges of growth and development indicators from birth to two years old, the dynamic colonization of gut microbiota and its influencing factors were discussed using this birth cohort. Among these, we identified that the diversity of gut microbiota was significantly increased from six-month to two-year subgroups. The significantly dynamic trends of gut microbiota at the phylum (genus) level were that the percents of Firmicutes (Faecalibacterium, Blautia, Enterococcus, Subdoligranulum, Agathobacter, unidentified_Erysipelotrichaceae, Staphylococcus, unidentified_Ruminococcaceae, and Fusicatenibacter), Bacteroidetes and Verrucomicrobia were increased, while Actinobacteria (Bifidobacterium) and Proteobacteria (unidentified-Enterobacteriaceae and Klebsiella) were decreased with the increased ages from six months to two years old, which might simultaneously modulate the host pathways, such as the higher percents of chemoheterotrophy and fermentation, and lower percentages of nitrate_reduction, aerobic_chemoheterotrophy and so on. Furthermore, there were significant associations between maternal (milk microbiota, pre-pregnancy BMI, BMI increment during the pregnancy)/infant characteristics (BMI at birth and BMI gain), and the compositions of gut microbiota. However, no differences of gut microbiota were shown between the different sex and productive mode subgroups. Overall, the colonization of gut microbiota is significantly matured into the adulthood with the increased ages to two-years old and regulated by the above maternal/infant characteristics, which will provide a new direction for the host-gut microbiota interplay during the first two years of life.
The gut microbiome of neonates, infants, and toddlers (NITs) is very dynamic, and only begins to stabilize towards the third year of life. Within this period, exposure to xenobiotics may perturb the gut environment, thereby driving or contributing to microbial dysbiosis, which may negatively impact health into adulthood. Despite exposure of NITs globally, but especially in Africa, to copious amounts and types of xenobiotics – such as mycotoxins, pesticide residues, and heavy metals – little is known about their influence on the early-life microbiome or their effects on acute or long-term health. Within the African context, the influence of fermented foods, herbal mixtures, and the delivery environment on the early-life microbiome are often neglected, despite being potentially important factors that influence the microbiome. Consequently, data on in-depth understanding of the microbiome–exposome interactions is lacking in African cohorts. Collecting and evaluating such data is important because exposome-induced gut dysbiosis could potentially favor disease progression.
Allergic diseases are becoming a major healthcare issue in many developed nations, where living environment and lifestyle are most predominantly distinct. Such differences include urbanized, industrialized living environments, overused hygiene products, antibiotics, stationary lifestyle, and fast-food-based diets, which tend to reduce microbial diversity and lead to impaired immune protection, which further increase the development of allergic diseases. At the same time, studies have also shown that modulating a microbiocidal community can ameliorate allergic symptoms. Therefore, in this paper, we aimed to review recent findings on the potential role of human microbiota in the gastrointestinal tract, surface of skin, and respiratory tract in the development of allergic diseases. Furthermore, we addressed a potential therapeutic or even preventive strategy for such allergic diseases by modulating human microbial composition.
Background
Gut microbiota promote and maintain infant health. Vertical transmission of bacteria from the maternal gut through breast milk to an infant is an important source of microbial colonisation in human offspring. However, the causative active/culturable bacteria and mechanisms responsible for their mother-neonate vertical transfer via breastfeeding remain unclear. Secretory immunoglobulin A (sIgA) may mediate this vertical transmission; however, evidence supporting this hypothesis is required. In this study, we aimed to investigate whether sIgA-coated bacteria in the maternal intestine may migrate to breast milk and colonise the infant gut.
Results
Maternal faeces, breast milk, and neonatal faeces were collected from 19 mother-infant dyads during lactation stages specific to colostrum, transitional, and mature milk. sIgA-coated bacteria were enriched using magnetic-activated cell sorting, and live bacteria were cultured in lactic acid bacteria- and gut bacteria-specific medium. 16S ribosomal RNA gene amplicon sequencing showed that microbiota diversity in maternal faeces, breast milk, and infant faeces decreased sequentially from colostrum to transitional milk to mature milk. Significant beta diversity existed between sample types (p < 0.05). However, high similarity was found between sIgA-coated microbiota of the three types of samples at the mature milk stage. Source track analysis showed that sIgA-coated microbiota in breast milk and maternal gut are major contributors of sIgA-coated microbiota in infant gut. Genera with co-occurrence in sample types included Bifidobacterium, Enterococcus, Streptococcus, Lactobacillus, Klebsiella, Escherichia-Shigella, and an unclassified genus of Enterobacteriaceae. Shotgun sequencing of three dyads identified co-occurring species Lactobacillus and Bifidobacterium, including Lactobacillus salivarius, Lactobacillus reuteri, Lactobacillus gasseri, Lactobacillus jonsonii, Lactobacillus oris, Bifidobacterium longum, and Bifidobacterium breve.
Conclusions
Breastmilk and infant faeces samples showed unique microbial composition and diversity in the three lactation stages. The fractions of sIgA-coated microbiota in maternal faeces, breast milk, and infant gut showed similar bacterial abundance patterns. This study will facilitate development of strategies to adjust aberrant microbial establishment and reduce the risk of disease by providing essential information for effective probiotic administration to the neonate and/or breastfeeding mother.
Human milk is the sole and recommended nutrition for the newborn infant and contains one of the largest constituents of diverse oligosaccharides, dubbed human milk oligosaccharides (HMOs). Preclinical and clinical association studies indicate that HMOs have multiple physiological functions largely mediated through the establishment of the gut microbiome. Until recently, HMOs were not available to investigate their role in randomized controlled intervention trials. To our knowledge, this is the first report on the effects of 2 HMOs on establishing microbiota in newborn infants. We provide a detailed description of the microbiota changes observed upon feeding a formula with 2 HMOs in comparison to breastfed reference infants' microbiota. Then, we associate the microbiota to long-term health as assessed by prescribed antibiotic use.
Background
Microbial invasion of the amniotic cavity resulting in intra-amniotic infection is associated with obstetrical complications such as preterm labor with intact or ruptured membranes, cervical insufficiency, as well as clinical and histological chorioamnionitis. The most widely accepted pathway for intra-amniotic infection is the ascension of microorganisms from the lower genital tract. However, hematogenous dissemination of microorganisms from the oral cavity or intestine, retrograde seeding from the peritoneal cavity through the fallopian tubes, and introduction through invasive medical procedures have also been suggested as potential pathways for intra-amniotic infection. The primary reason that an ascending pathway is viewed as most common is that the microorganisms most often detected in the amniotic fluid are those that are typical inhabitants of the vagina. However, thus far, no studies have shown that microorganisms in the amniotic cavity are simultaneously present in the vagina of the woman from which they were isolated. The objective of the study was to determine the frequency with which microorganisms isolated from women with intra-amniotic infection are also present in the lower genital tract.
Methods
This was a cross-sectional study of women with intra-amniotic infection with intact membranes. Intra-amniotic infection was defined as a positive culture and elevated concentrations of interleukin-6 (IL-6) (>2.6 ng/mL) in amniotic fluid and/or acute histologic chorioamnionitis and funisitis. Microorganisms isolated from bacterial cultures of amniotic fluid were taxonomically identified through matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF) and 16S ribosomal RNA (rRNA) gene sequencing. Vaginal swabs were obtained at the time of amniocentesis for the identification of microorganisms in the lower genital tract. The overall bacterial profiles of amniotic fluids and vaginal swabs were characterized through 16S rRNA gene sequencing. The bacterial profiles of vaginal swabs were interrogated for the presence of bacteria cultured from amniotic fluid and for the presence of prominent (>1% average relative abundance) operational taxonomic units (OTUs) within the overall 16S rRNA gene bacterial profiles of amniotic fluid.
Results
(1) A total of 75% (6/8) of women had bacteria cultured from their amniotic fluid that are typical residents of the vaginal ecosystem. (2) A total of 62.5% (5/8) of women with bacteria cultured from their amniotic fluid also had these bacteria present in their vagina. (3) The microorganisms cultured from amniotic fluid and also detected in the vagina were Ureaplasma urealyticum , Escherichia coli , and Streptococcus agalactiae . (4) 16S rRNA gene sequencing revealed that the amniotic fluid of women with intra-amniotic infection had bacterial profiles dominated by Sneathia , Ureaplasma , Prevotella , Lactobacillus , Escherichia , Gardnerella , Peptostreptococcus , Peptoniphilus , and Streptococcus , many of which had not been cultured from the amniotic fluid samples. (5) Seventy percent (7/10) of the prominent (>1% average relative abundance) OTUs found in amniotic fluid were also prominent in the vagina.
Conclusion
The majority of women with intra-amniotic infection had bacteria cultured from their amniotic fluid that were typical vaginal commensals, and these bacteria were detected within the vagina at the time of amniocentesis. Molecular microbiological interrogation of amniotic fluid from women with intra-amniotic infection revealed that the bacterial profiles of amniotic fluid were largely consistent with those of the vagina. These findings indicate that ascension from the lower genital tract is the primary pathway for intra-amniotic infection.
Human breast milk contains numerous biomolecules. Human milk oligosaccharides (HMOs) are the third most abundant component of breast milk, after lactose and lipids. Amongst the synthetized HMOs, 2′-fucosyllactose (2′-FL) and lacto-N-neotetraose (LNnT) are widely studied and are considered safe for infant nutrition. Several studies have reported the health benefits of HMOs, which include modulation of the intestinal microbiota, anti-adhesive effect against pathogens, modulation of the intestinal epithelial cell response, and development of the immune system. The amount and diversity of HMOs are determined by the genetic background of the mothers (HMO secretors or non-secretors). The non-secretor mothers secrete lower HMOs than secretor mothers. The breastfed infants of secretor mothers gain more health benefit than those of non-secretor mothers. In conclusion, supplementation of infant formula with 2′-FL and LNnT is a promising innovation for infant nutrition.
This study evaluated the effect of a partly fermented infant formula (using the bacterial strains Bifidobacterium breve C50 and Streptococcus thermophilus 065) with a specific prebiotic mixture (short-chain galacto-oligosaccharides (scGOS) and long-chain fructo-oligosaccharides (lcFOS; 9:1)) on the incidence of gastrointestinal symptoms, stool characteristics, sleeping and crying behaviour, growth adequacy and safety. Two-hundred infants ≤28 days of age were assigned either to experimental infant formula containing 30% fermented formula and 0.8 g/100 mL scGOS/lcFOS or to non-fermented control infant formula without scGOS/lcFOS. A group of breastfed infants served as a reference. No relevant differences in parent-reported gastrointestinal symptoms were observed. Stool consistency was softer in the experimental versus control group with values closer to the breastfed reference group. Daily weight gain was equivalent for both formula groups (0.5 SD margins) with growth outcomes close to breastfed infants. No clinically relevant differences in adverse events were observed, apart from a lower investigator-reported prevalence of infantile colic in the experimental versus control group (1.1% vs. 8.7%; p < 0.02). Both study formulae are well-tolerated, support an adequate infant growth and are safe for use in healthy term infants. Compared to the control formula, the partly fermented formula with prebiotics induces stool consistencies closer to breastfed infants.
Human milk oligosaccharides (HMOs) are a major component of human milk, and play an important role in protecting the infant from infections. Preterm infants are particularly vulnerable, but have improved outcomes if fed with human milk. This study aimed to determine if the HMO composition of preterm milk differed from that of term milk at equivalent stage of lactation and equivalent postmenstrual age. In all, 22 HMOs were analyzed in 500 samples of milk from 25 mothers breastfeeding very preterm infants (< 32 weeks of gestational age, < 1500 g of birthweight) and 28 mothers breastfeeding term infants. The concentrations of most HMOs were comparable at equivalent postpartum age. However, HMOs containing α-1,2-linked fucose were reduced in concentration in preterm milk during the first month of lactation. The concentrations of a number of sialylated oligosaccharides were also different in preterm milk, in particular 3′-sialyllactose concentrations were elevated. At equivalent postmenstrual age, the concentrations of a number of HMOs were significantly different in preterm compared to term milk. The largest differences manifest around 40 weeks of postmenstrual age, when the milk of term infants contains the highest concentrations of HMOs. The observed differences warrant further investigation in view of their potential clinical impact.
Human milk oligosaccharides (HMOs) signify a unique group of oligosaccharides in breast milk, which is of major importance for infant health and development. The functional benefits of HMOs create an enormous impetus for biosynthetic production of HMOs for use as additives in infant formula and other products. HMO molecules can be synthesized chemically, via fermentation, and by enzymatic synthesis. This treatise discusses these different techniques, with particular focus on harnessing enzymes for controlled enzymatic synthesis of HMO molecules. In order to foster precise and high-yield enzymatic synthesis, several novel protein engineering approaches have been reported, mainly concerning changing glycoside hydrolases to catalyze relevant transglycosylations. The protein engineering strategies for these enzymes range from rationally modifying specific catalytic residues, over targeted subsite −1 mutations, to unique and novel transplantations of designed peptide sequences near the active site, so-called loop engineering. These strategies have proven useful to foster enhanced transglycosylation to promote different types of HMO synthesis reactions. The rationale of subsite −1 modification, acceptor binding site matching, and loop engineering, including changes that may alter the spatial arrangement of water in the enzyme active site region, may prove useful for novel enzyme-catalyzed carbohydrate design in general.
Objectives
Establishment and development of the infant gastrointestinal microbiome (GIM) varies cross‐culturally and is thought to be influenced by factors such as gestational age, birth mode, diet, and antibiotic exposure. However, there is little data as to how the composition of infants' households may play a role, particularly from a cross‐cultural perspective. Here, we examined relationships between infant fecal microbiome (IFM) diversity/composition and infants' household size, number of siblings, and number of other household members.
Materials and methods
We analyzed 377 fecal samples from healthy, breastfeeding infants across 11 sites in eight different countries (Ethiopia, The Gambia, Ghana, Kenya, Peru, Spain, Sweden, and the United States). Fecal microbial community structure was determined by amplifying, sequencing, and classifying (to the genus level) the V1–V3 region of the bacterial 16S rRNA gene. Surveys administered to infants' mothers identified household members and composition.
Results
Our results indicated that household composition (represented by the number of cohabitating siblings and other household members) did not have a measurable impact on the bacterial diversity, evenness, or richness of the IFM. However, we observed that variation in household composition categories did correspond to differential relative abundances of specific taxa, namely: Lactobacillus, Clostridium, Enterobacter, and Klebsiella.
Discussion
This study, to our knowledge, is the largest cross‐cultural study to date examining the association between household composition and the IFM. Our results indicate that the social environment of infants (represented here by the proxy of household composition) may influence the bacterial composition of the infant GIM, although the mechanism is unknown. A higher number and diversity of cohabitants and potential caregivers may facilitate social transmission of beneficial bacteria to the infant gastrointestinal tract, by way of shared environment or through direct physical and social contact between the maternal–infant dyad and other household members. These findings contribute to the discussion concerning ways by which infants are influenced by their social environments and add further dimensionality to the ongoing exploration of social transmission of gut microbiota and the “old friends” hypothesis.
Gestation is accompanied by alterations in the microbial repertoire; however, the mechanisms driving these changes are unknown. Here, we demonstrate a dramatic shift in the gut microbial composition of women and mice during late pregnancy, including an increase in the relative abundance of Bifidobacterium. Using in-vivo-transplanted pellets, we found that progesterone, the principal gestation hormone, affects the microbial community. The effect of progesterone on the richness of several bacteria species, including Bifidobacterium, was also demonstrated in vitro, indicating a direct effect. Altogether, our results delineate a model in which progesterone promotes Bifidobacterium growth during late pregnancy. : Nuriel-Ohayon et al. demonstrate a dramatic shift in the gut microbial composition of women and mice during late pregnancy, including an increase in the relative abundance of Bifidobacterium. Using in vitro and in vivo experiments, they show that supplementation of progesterone affects the microbial communities, including increasing the relative abundance of Bifidobacterium. Keywords: progesterone, Bifidobacterium, pregnancy, gut microbiota, 16S rRNA, microbiome
The mode of delivery has been suggested to modulate the bacterial composition of breast milk but the impact of intrapartum antibiotic use on the milk microbiota is currently not known. The aim of this study was to analyze the effects of the mode of the delivery and intrapartum antibiotic administration on the microbial composition of breast milk. Breast milk samples were collected from 84 healthy mothers 1 month after the delivery. In total, 61 mothers had delivered vaginally, 23 of which had received intrapartum antibiotics, 13 women had delivered with non-elective cesarean section, 7 of which had received antibiotics, and 10 mothers had delivered with elective cesarean section without intrapartum antibiotic treatment. Both mode of delivery and intrapartum antibiotic exposure were significantly associated with changes in the milk microbial composition as assessed by analysis of similarities (ANOSIM) test (p = 0.001). The mode of delivery had a more profound effect on the milk microbiota composition as compared to intrapartum antibiotic exposure. Although the clinical significance of breast milk microbiota is currently poorly understood, this study shows that cesarean section delivery has an independent effect on breast milk microbiota composition. The dysbiosis observed in infants born by cesarean section delivery may be aggravated by the aberrant breast milk microbiota.
There has been a striking generational increase in life-threatening food allergies in Westernized societies1,2. One hypothesis to explain this rising prevalence is that twenty-first century lifestyle practices, including misuse of antibiotics, dietary changes, and higher rates of Caesarean birth and formula feeding have altered intestinal bacterial communities; early-life alterations may be particularly detrimental3,4. To better understand how commensal bacteria regulate food allergy in humans, we colonized germ-free mice with feces from healthy or cow’s milk allergic (CMA) infants⁵. We found that germ-free mice colonized with bacteria from healthy, but not CMA, infants were protected against anaphylactic responses to a cow’s milk allergen. Differences in bacterial composition separated the healthy and CMA populations in both the human donors and the colonized mice. Healthy and CMA colonized mice also exhibited unique transciptome signatures in the ileal epithelium. Correlation of ileal bacteria with genes upregulated in the ileum of healthy or CMA colonized mice identified a clostridial species, Anaerostipes caccae, that protected against an allergic response to food. Our findings demonstrate that intestinal bacteria are critical for regulating allergic responses to dietary antigens and suggest that interventions that modulate bacterial communities may be therapeutically relevant for food allergy. © 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.
The factors that govern assembly of the gut microbiota are insufficiently understood. Here, we test the hypothesis that inter-individual microbiota variation can arise solely from differences in the order and timing by which the gut is colonized early in life. Experiments in which mice were inoculated in sequence either with two complex seed communities or a cocktail of four bacterial strains and a seed community revealed that colonization order influenced both the outcome of community assembly and the ecological success of individual colonizers. Historical contingency and priority effects also occurred in Rag1-/- mice, suggesting that the adaptive immune system is not a major contributor to these processes. In conclusion, this study established a measurable effect of colonization history on gut microbiota assembly in a model in which host and environmental factors were strictly controlled, illuminating a potential cause for the high levels of unexplained individuality in host-associated microbial communities. Supplemental figures attached below.
Background
Dietary changes are suggested to play a role in the increasing prevalence of allergic diseases and asthma. Short‐chain fatty acids (SCFAs) are metabolites present in certain foods and are produced by microbes in the gut following fermentation of fibers. SCFAs have been shown to have anti‐inflammatory properties in animal models. Our objective was to investigate the potential role of SCFAs in the prevention of allergy and asthma.
Methods
We analysed SCFAs levels by HPLC (High Performance Liquid Chromatography) in fecal samples from 301 one‐year old children from a birth cohort and examined their association with early life exposures, especially diet, and allergy and asthma later in life. Data on exposures and allergic diseases were collected by questionnaires. In addition, we treated mice with SCFAs to examine their effect on allergic airway inflammation.
Results
Significant associations between the levels of SCFAs and the infant's diet were identified. Children with the highest levels of butyrate and propionate (≥95th percentile) in feces at the age of one year had significantly less atopic sensitization and were less likely to have asthma between 3 and 6 years. Children with the highest levels of butyrate were also less likely to have a reported diagnosis of food allergy or allergic rhinitis. Oral administration of SCFAs to mice significantly reduced the severity of allergic airway‐inflammation.
Conclusion
Our results suggest that strategies to increase SCFAs levels could be a new dietary preventive option for allergic diseases in children.
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Maternal obesity is associated with increased risk for offspring obesity and non-alcoholic fatty liver disease (NAFLD), but the causal drivers of this association are unclear. Early colonization of the infant gut by microbes plays a critical role in establishing immunity and metabolic function. Here, we compare germ-free mice colonized with stool microbes (MB) from 2-week-old infants born to obese (Inf-ObMB) or normal-weight (Inf-NWMB) mothers. Inf-ObMB-colonized mice demonstrate increased hepatic gene expression for endoplasmic reticulum stress and innate immunity together with histological signs of periportal inflammation, a histological pattern more commonly reported in pediatric cases of NAFLD. Inf-ObMB mice show increased intestinal permeability, reduced macrophage phagocytosis, and dampened cytokine production suggestive of impaired macrophage function. Furthermore, exposure to a Western-style diet in Inf-ObMB mice promotes excess weight gain and accelerates NAFLD. Overall, these results provide functional evidence supporting a causative role of maternal obesity-associated infant dysbiosis in childhood obesity and NAFLD.
The development of the microbiome from infancy to childhood is dependent on a range of factors, with microbial–immune crosstalk during this time thought to be involved in the pathobiology of later life diseases1–9 such as persistent islet autoimmunity and type 1 diabetes10–12. However, to our knowledge, no studies have performed extensive characterization of the microbiome in early life in a large, multi-centre population. Here we analyse longitudinal stool samples from 903 children between 3 and 46 months of age by 16S rRNA gene sequencing (n = 12,005) and metagenomic sequencing (n = 10,867), as part of the The Environmental Determinants of Diabetes in the Young (TEDDY) study. We show that the developing gut microbiome undergoes three distinct phases of microbiome progression: a developmental phase (months 3–14), a transitional phase (months 15–30), and a stable phase (months 31–46). Receipt of breast milk, either exclusive or partial, was the most significant factor associated with the microbiome structure. Breastfeeding was associated with higher levels of Bifidobacterium species (B. breve and B. bifidum), and the cessation of breast milk resulted in faster maturation of the gut microbiome, as marked by the phylum Firmicutes. Birth mode was also significantly associated with the microbiome during the developmental phase, driven by higher levels of Bacteroides species (particularly B. fragilis) in infants delivered vaginally. Bacteroides was also associated with increased gut diversity and faster maturation, regardless of the birth mode. Environmental factors including geographical location and household exposures (such as siblings and furry pets) also represented important covariates. A nested case–control analysis revealed subtle associations between microbial taxonomy and the development of islet autoimmunity or type 1 diabetes. These data determine the structural and functional assembly of the microbiome in early life and provide a foundation for targeted mechanistic investigation into the consequences of microbial–immune crosstalk for long-term health.
Research on the neonatal microbiome has been performed mostly on hospital-born infants, who often undergo multiple birth-related interventions. Both the hospital environment and interventions around the time of birth may affect the neonate microbiome. In this study, we determine the structure of the microbiota in feces from babies born in the hospital or at home, and from vaginal samples of their mothers. We included 35 vaginally-born, breast-fed neonates, 14 of whom delivered at home (4 in water), and 21 who delivered in the hospital. Feces from babies and mothers and maternal vaginal swab samples were collected at enrollment, the day of birth, followed by days 1, 2, 7, 14, 21, and 28. At the time of birth, the diversity of the vaginal microbiota of mothers delivering in the hospital was higher than in mothers delivering at home, and showed higher proportion of Lactobacillus. Among 20 infants not exposed to perinatal maternal antibiotics or water birth, fecal beta diversity differed significantly by birth site, with hospital-born infants having lower Bacteroides, Bifidobacterium, Streptococcus, and Lactobacillus, and higher Clostridium and Enterobacteriaceae family (LDA > 3.0), than babies born at home. At 1 month of age, feces from infants born in the hospital also induced greater pro-inflammatory gene expression (TLR4, IL-8, occludin and TGFβ) in human colon epithelial HT-29 cells. The results of this work suggest that hospitalization (perinatal interventions or the hospital environment) may affect the microbiota of the vaginal source and the initial colonization during labor and birth, with effects that could persist in the intestinal microbiota of infants 1 month after birth. More research is needed to determine specific factors that alter bacterial transmission between mother and baby and the long-term health implications of these differences for the developing infant.
This review focuses on the evidence for health benefits of human milk oligosaccharides (HMOs) for preterm infants to stimulate gut adaptation and reduce the incidence of necrotizing enterocolitis (NEC) in early life. The health benefits of breastfeeding are partly explained by the abundant HMOs that serve as prebiotics and immunomodulators. Gut immaturity in preterm infants leads to difficulties in tolerating enteral feeding and bacterial colonization and a high sensitivity to NEC, particularly when breast milk is insufficient. Due to the immaturity of the preterm infants, their response to HMOs could be different from that in term infants. The concentration of HMOs in human milk is highly variable and there is no evidence to support a specifically adapted high concentration in preterm milk. Further, the gut microbiota is not only different but also highly variable after preterm birth. Studies in pigs as models for preterm infants indicate that HMO supplementation to formula does not mature the gut or prevent NEC during the first weeks after preterm birth and the effects may depend on a certain stage of gut maturity. Supplemented HMOs may become more important for gut protection in the preterm infants when the gut has reached a more mature phase.
Background:
Human milk oligosaccharides (HMOs) shape the developing gut microbiome and influence immune function. Aside from genetic Secretor status, the factors influencing HMO synthesis and secretion are largely unknown.
Objective:
We aimed to identify modifiable and nonmodifiable factors associated with HMO concentrations.
Methods:
This prospective observational study included a representative subset of 427 mothers participating in the CHILD birth cohort (mean age: 33 y, 73% Caucasian). Breast milk was collected at 3-4 mo postpartum. Concentrations of 19 predominant HMOs were measured by rapid high-throughput HPLC. Secretor status was defined by the presence of 2'-fucosylactose. Associations with maternal, infant, and environmental factors were explored using multivariable regression. Breastfeeding duration was explored as a secondary outcome.
Results:
Overall, 72% of mothers were Secretors and the mean ± SD duration of any breastfeeding was 12.8 ± 5.7 mo. HMO profiles were highly variable; total HMO concentrations varied 3.7-fold and individual HMOs varied 20- to >100-fold. Secretor mothers had higher total HMO concentrations than did non-Secretors (mean: 15.91 ± 2.80 compared with 8.94 ± 1.51 μmol/mL, P < 0.001) and all individual HMOs differed by Secretor status, except for disialyllacto-N-tetraose (DSLNT). Most HMO concentrations were lower in milk collected later in lactation, although some were higher including DSLNT and 3'-sialyllactose. Independent of Secretor status and lactation stage, seasonal and geographic variation was observed for several HMOs. Parity, ethnicity, and breastfeeding exclusivity also emerged as independent factors associated with some HMOs, whereas diet quality and mode of delivery did not. Together, these factors explained between 14% (for 6'-sialyllactose) and 92% (for 2'-fucosyllactose) of the observed variation in HMO concentrations. Lower concentrations of lacto-N-hexaose or fucodisialyllacto-N-hexaose were associated with earlier breastfeeding cessation.
Conclusions:
HMO concentrations vary widely between mothers and are associated with multiple characteristics beyond genetic Secretor status, as well as feeding practices and environmental factors. Further research is warranted to determine how these associations affect infant health. This study was registered at clinicaltrials.gov as NCT03225534.
One of the most abundant components in human milk is formed by oligosaccharides, which are poorly digested by the infant. The oligosaccharide composition of breast milk varies between mothers, and is dependent on maternal secretor (FUT2) genotype. Secretor mothers produce milk containing α1-2 fucosylated human milk oligosaccharides, which are absent in the milk of non-secretor mothers. Several strains of bacteria in the infant gut have the capacity to utilise human milk oligosaccharides (HMOs). Here we investigate the differences in infant gut microbiota composition between secretor (N = 76) and non-secretor (N = 15) mothers, taking into account birth mode. In the vaginally born infants, maternal secretor status was not associated with microbiota composition. In the caesarean-born, however, many of the caesarean-associated microbiota patterns were more pronounced among the infants of non-secretor mothers compared to those of secretor mothers. Particularly bifidobacteria were strongly depleted and enterococci increased among the caesarean-born infants of non-secretor mothers. Furthermore, Akkermansia was increased in the section-born infants of secretor mothers, supporting the suggestion that this organism may degrade HMOs. The results indicate that maternal secretor status may be particularly influential in infants with compromised microbiota development, and that these infants could benefit from corrective supplementation.
The authors reviewed the published evidence on the presence of oligosaccharides in human milk (HMO) and their benefits in in vitro and in vivo studies. The still limited data of trials evaluating the effect of mainly 2′-fucosyllactose (2′-FL) on the addition of some of HMOs to infant formula were also reviewed. PubMed was searched from January 1990 to April 2018. The amount of HMOs in mother’s milk is a dynamic process as it changes over time. Many factors, such as duration of lactation, environmental, and genetic factors, influence the amount of HMOs. HMOs may support immune function development and provide protection against infectious diseases directly through the interaction of the gut epithelial cells or indirectly through the modulation of the gut microbiota, including the stimulation of the bifidobacteria. The limited clinical data suggest that the addition of HMOs to infant formula seems to be safe and well tolerated, inducing a normal growth and suggesting a trend towards health benefits. HMOs are one of the major differences between cow’s milk and human milk, and available evidence indicates that these components do have a health promoting benefit. The addition of one or two of these components to infant formula is safe, and brings infant formula closer to human milk. More prospective, randomized trials in infants are need to evaluate the clinical benefit of supplementing infant formula with HMOs.
Background:
Early life microbiota is an important determinant of immune and metabolic development and may have lasting consequences. The maternal gut microbiota during pregnancy or breastfeeding is important for defining infant gut microbiota. We hypothesized that maternal gut microbiota during pregnancy and breastfeeding is a critical determinant of infant immunity. To test this, pregnant BALB/c dams were fed vancomycin for 5 days prior to delivery (gestation; Mg), 14 days postpartum during nursing (Mn), or during gestation and nursing (Mgn), or no vancomycin (Mc). We analyzed adaptive immunity and gut microbiota in dams and pups at various times after delivery.
Results:
In addition to direct alterations to maternal gut microbial composition, pup gut microbiota displayed lower α-diversity and distinct community clusters according to timing of maternal vancomycin. Vancomycin was undetectable in maternal and offspring sera, therefore the observed changes in the microbiota of stomach contents (as a proxy for breastmilk) and pup gut signify an indirect mechanism through which maternal intestinal microbiota influences extra-intestinal and neonatal commensal colonization. These effects on microbiota influenced both maternal and offspring immunity. Maternal immunity was altered, as demonstrated by significantly higher levels of both total IgG and IgM in Mgn and Mn breastmilk when compared to Mc. In pups, lymphocyte numbers in the spleens of Pg and Pn were significantly increased compared to Pc. This increase in cellularity was in part attributable to elevated numbers of both CD4+ T cells and B cells, most notable Follicular B cells.
Conclusion:
Our results indicate that perturbations to maternal gut microbiota dictate neonatal adaptive immunity.
Background:
The gut microbiome has an important role in infant health and immune development and may be affected by early-life exposures. Maternal diet may influence the infant gut microbiome through vertical transfer of maternal microbes to infants during vaginal delivery and breastfeeding. We aimed to examine the association of maternal diet during pregnancy with the infant gut microbiome 6 weeks post-delivery in mother-infant dyads enrolled in the New Hampshire Birth Cohort Study. Infant stool samples were collected from 145 infants, and maternal prenatal diet was assessed using a food frequency questionnaire. We used targeted sequencing of the 16S rRNA V4-V5 hypervariable region to characterize infant gut microbiota. To account for differences in baseline and trajectories of infant gut microbial profiles, we stratified analyses by delivery mode.
Results:
We identified three infant gut microbiome clusters, characterized by increased abundance of Bifidobacterium, Streptococcus and Clostridium, and Bacteroides, respectively, overall and in the vaginally delivered infant stratum. In the analyses stratified to infants born vaginally and adjusted for other potential confounders, maternal fruit intake was associated with infant gut microbial community structure (PERMANOVA, p < 0.05). In multinomial logistic regression analyses, increased fruit intake was associated with an increased odds of belonging to the high Streptococcus/Clostridium group among infants born vaginally (OR (95% CI) = 2.73 (1.36, 5.46)). In infants delivered by Cesarean section, we identified three clusters that differed slightly from vaginally delivered infants, which were characterized by a high abundance of Bifidobacterium, high Clostridium and low Streptococcus and Ruminococcus genera, and high abundance of the family Enterobacteriaceae. Maternal dairy intake was associated with an increased odds of infants belonging to the high Clostridium cluster in infants born by Cesarean section (OR (95% CI) = 2.36 (1.05, 5.30)). Linear models suggested additional associations between maternal diet and infant intestinal microbes in both delivery mode strata.
Conclusions:
Our data indicate that maternal diet influences the infant gut microbiome and that these effects differ by delivery mode.
Objective
The initial colonisation of the human microbiota and the impact of maternal health on neonatal microbiota at birth remain largely unknown. The aim of our study is to investigate the possible dysbiosis of maternal and neonatal microbiota associated with gestational diabetes mellitus (GDM) and to estimate the potential risks of the microbial shift to neonates.
Design
Pregnant women and neonates suffering from GDM were enrolled and 581 maternal (oral, intestinal and vaginal) and 248 neonatal (oral, pharyngeal, meconium and amniotic fluid) samples were collected. To avoid vaginal bacteria contaminations, the included neonates were predominantly delivered by C-section, with their samples collected within seconds of delivery.
Results
Numerous and diverse bacterial taxa were identified from the neonatal samples, and the samples from different neonatal body sites were grouped into distinct clusters. The microbiota of pregnant women and neonates was remarkably altered in GDM, with a strong correlation between certain discriminatory bacteria and the oral glucose tolerance test. Microbes varying by the same trend across the maternal and neonatal microbiota were observed, revealing the intergenerational concordance of microbial variation associated with GDM. Furthermore, lower evenness but more depletion of KEGG orthologues and higher abundance of some viruses (eg, herpesvirus and mastadenovirus) were observed in the meconium microbiota of neonates associated with GDM.
Conclusion
GDM can alter the microbiota of both pregnant women and neonates at birth, which sheds light on another form of inheritance and highlights the importance of understanding the formation of early-life microbiome.
A few commonly used non-antibiotic drugs have recently been associated with changes in gut microbiome composition, but the extent of this phenomenon is unknown. Here, we screened more than 1,000 marketed drugs against 40 representative gut bacterial strains, and found that 24% of the drugs with human targets, including members of all therapeutic classes, inhibited the growth of at least one strain in vitro. Particular classes, such as the chemically diverse antipsychotics, were overrepresented in this group. The effects of human-targeted drugs on gut bacteria are reflected on their antibiotic-like side effects in humans and are concordant with existing human cohort studies. Susceptibility to antibiotics and human-targeted drugs correlates across bacterial species, suggesting common resistance mechanisms, which we verified for some drugs. The potential risk of non-antibiotics promoting antibiotic resistance warrants further exploration. Our results provide a resource for future research on drug-microbiome interactions, opening new paths for side effect control and drug repurposing, and broadening our view of antibiotic resistance.
