Intestinal Microbiota In Early Life Research Articles

The Effect of Nutrient Deprivation on Early Life Small Intestinal Mucosal Microbiome and Host Proteome

BackgroundNutrition plays a vital role in shaping the intestinal microbiome. However, many hospitalized children undergo periods of fasting during medical treatment. Changes to the small intestinal microbiota in early life in the setting of enteral deprivation have not been well described. ObjectiveThe aim of this study was to investigate the impact of enteral deprivation on the small intestinal mucosal microbiome and to identify factors that shape this interaction in infancy. MethodsIntestinal biopsies were collected from proximal (fed) and distal (unfed) small bowel at the time of ostomy closure in children with a small intestinal enterostomy. Mucosal and luminal microbiome comparisons were performed including β-diversity and differential abundance and correlations with clinical factors were analyzed. Host proteomics were compared between fed and unfed samples and correlated with microbiome parameters. Finally, microbial results were validated in another cohort of pediatric patients. ResultsSamples from 13 children (median age 84 d) were collected. Mucosal microbiome communities in the fed and unfed segments were strikingly similar [paired UniFrac distance (β-diversity)], whereas luminal effluent differed significantly from fed samples (PERMANOVA, P = 0.003). Multivariate analysis revealed patient as the strongest predictor of the UniFrac distance. Environmental variables did not influence the intrapatient microbial dissimilarity. Host proteomics were similar intrapatient (paired fed–unfed Euclidian distance) and showed a correlation with the UniFrac distance (Spearman rho = 0.71, P < 0.001). Specific proteins and functional clusters were significantly different between paired samples, including lipid metabolism and intracellular trafficking, whereas no difference was seen in innate immune proteins. The microbiome results were validated in a different cohort with similar characteristics. ConclusionWe found the host to be the most dominant factor in the structure of the early life small intestinal mucosal microbiome. Nutrient deprivation was associated with specific changes in the host proteome. Further research is needed to better understand this host–microbe–nutrition interaction.

Early life stress induces irritable bowel syndrome from childhood to adulthood in mice.

Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorder. Traditionally, early life stress (ELS) is predisposed to IBS in adult. However, whether ELS induces IBS in early life remains unclear. Separated cohort studies were conducted in neonatal male pups of C57BL/6 mice by maternal separation (MS) model. MS and non-separation mice were scheduled to be evaluated for prime IBS-phenotypes, including visceral hypersensitivity, intestinal motility, intestinal permeability, and anxiety-like behavior. Ileal contents and fecal samples were collected and analyzed by 16S rRNA gene sequencing and bacterial community analyses. Subcellular structures of intestinal epithelial, such as epithelial tight junctions and mitochondria, were observed under transmission electron microscopy. MS induced visceral hypersensitivity and decreased total intestinal transit time from childhood to adulthood. In addition, MS induced intestinal hyperpermeability and anxiety-like behavior from adolescence to adulthood. Besides, MS affected intestinal microbial composition from childhood to adulthood. Moreover, MS disrupted intestinal mitochondrial structure from childhood to adulthood. The study showed for the first time that MS induced IBS from early life to adulthood in mice. The disrupted intestinal mitochondrial structure and the significant dysbiosis of intestinal microbiota in early life may contribute to the initiation and progress of IBS from early life to adulthood.

The concept of endothelial transcytosis as a theoretical prerequisite for the development of prevention and treatment of atherosclerosis

This part of the review focuses on the proposed involvement of the gut microbiota in the realization of the genetic risk of multiple sclerosis, the formation of the intestinal microbiome in early life, and provides data supporting the hypothesis that aberrant formation of the intestinal microbiota in early life may be a predisposing factor to multiple sclerosis.

Role of the intestinal microbiota in the pathogenesis of multiple sclerosis. Part 2. Gut microbiota as a predisposition factor for the multiple sclerosis development

This part of the review focuses on the proposed involvement of the gut microbiota in the realization of the genetic risk of multiple sclerosis, the formation of the intestinal microbiome in early life, and provides data supporting the hypothesis that aberrant formation of the intestinal microbiota in early life may be a predisposing factor to multiple sclerosis.

The nutritional and functional properties of 1-oleoyl-2-palmitoyl-3-linoleoylglycerol-rich oil: promoting early-life growth and intestinal health with alterations in the intestinal microbiota of Micropterus salmoides.

1-Oleoyl-2-palmitoyl-3-linoleoylglycerol (OPL), a key structural lipid in the breast milk fat, plays a critical role in providing nutrients and energy for infants. OPL is more abundant in Chinese breast milk fat and might be better for Chinese infants' growth. However, few studies have investigated the effect of OPL on the growth and intestinal health of the organism in early life. OPL-rich oil with 45.77% OPL was prepared by immobilized lipase-catalyzed synthesis and purification. The effects of OPL on the nutritional properties and the regulation of intestinal microbiota in early life were further investigated in vivo (Micropterus salmoides). Dietary OPL-rich oil significantly increased the juvenile fish weight gain rate, protein content, and muscular polyunsaturated fatty acids, which in turn markedly altered the muscle texture in springiness and cohesiveness. Dietary OPL-rich oil could also protect intestinal tissues by significantly increasing fish intestinal fold height, mucosal thickness, and intestinal wall thickness. Furthermore, dietary OPL-rich oil regulated intestinal microbiota. Particularly, OPL significantly increased the probiotics (Cetobacterium_sp014250685, Streptomyces_mutabilis, Saccharopolyspora_spinosa, and Nocardiopsis_kunsanensis) and reduced the potential pathogens (Staphylococcus_nepalensis, Salmonella_enterica, the Candidatus_berkiella). The structured OPL significantly promoted fish growth and improved nutritional composition due to its higher bioavailability relative to tripalmitate (PPP). Moreover, OPL significantly improved the growth, cholesterol metabolism, and intestinal health than the mixed oil (MO), which was attributed to the higher palmitic acid content in the sn-2 position. Overall, the structure of triacylglycerols and its distribution of fatty acids affected early growth and intestinal health, and OPL was more effective in the improvement of juvenile growth and intestinal health.

Dysbiosis of intestinal microbiota in early life aggravates high-fat diet induced dysmetabolism in adult mice

BackgroundAccumulating evidence have shown that the intestinal microbiota plays an important role in prevention of host obesity and metabolism disorders. Recent studies also demonstrate that early life is the key time for the colonization of intestinal microbes in host. However, there are few studies focusing on possible association between intestinal microbiota in the early life and metabolism in adulthood. Therefore the present study was conducted to examine whether the short term antibiotic and/or probiotic exposure in early life could affect intestinal microbes and their possible long term effects on host metabolism.ResultsA high-fat diet resulted in glucose and lipid metabolism disorders with higher levels of visceral fat rate, insulin-resistance indices, and leptin. Exposure to ceftriaxone in early life aggravated the negative influences of a high-fat diet on mouse physiology. Orally fed TMC3115 protected mice, especially those who had received treatment throughout the whole study, from damage due to a high-fat diet, such as increases in levels of fasting blood glucose and serum levels of insulin, leptin, and IR indices. Exposure to ceftriaxone during the first 2 weeks of life was linked to dysbiosis of the fecal microbiota with a significant decrease in the species richness and diversity. However, the influence of orally fed ceftriaxone on the fecal microbiota was limited to 12 weeks after the termination of treatment. Of note, at week 12 there were still some differences in the composition of intestinal microbiota between mice provided with high fat diet and antibiotic exposure and those only fed a high fat diet.ConclusionsThese results indicated that exposure to antibiotics, such as ceftriaxone, in early life may aggravate the negative influences of a high-fat diet on the physiology of the host animal. These results also suggest that the crosstalk between the host and their intestinal microbiota in early life may be more important than that in adulthood, even though the same intestinal microbes are present in adulthood.

Antibiotics-Induced Dysbiosis of Intestinal Microbiota Aggravates Atopic Dermatitis in Mice by Altered Short-Chain Fatty Acids.

PurposeAlterations in the intestinal microbiota in early life affects the development of atopic dermatitis (AD) in humans. This study aimed to further investigate the effects of gut dysbiosis in early life in an ovalbumin (OVA)-induced mouse model of AD.MethodsThe AD mouse model was developed by serial OVA sensitization and mice were treated with an antibiotic cocktail in their drinking water for 2 weeks before primary sensitization. Probiotics (Lactobacillus rhamnosus, 1 × 109 CFU) or 100 µL of fresh fecal supernatant were orally administered daily from 1 week before the first sensitization until the end of the study.ResultsThe AD mice which received antibiotics had significantly aggravated phenotypes, including clinical score, transepidermal water loss, and histopathology, compared to those treated with healthy feces or probiotics. Total systemic immunoglobulin E production and skin interleukin (IL) 4 levels were significantly increased in the antibiotic-treated mice compared to the other groups. Antibiotic treatment also increased the levels of IL17 and group 3 innate lymphoid cells (ILC3) in the gut and significantly suppressed the production of short-chain fatty acids (SCFAs) and decreased the number FOXP3+ cells.ConclusionsOur results suggest that the status of the gut microbiota in early life in the mouse may play a crucial role in AD development through intestinal SCFA production through regulate the numbers of CD4+IL17+/CD4+FOXP3+ regulatory T cells and ILC3s.

Multi-population cohort meta-analysis of human intestinal microbiota in early life reveals the existence of infant community state types (ICSTs)

Appropriate development of the intestinal microbiota during infancy is known to be important for human health. In fact, aberrant alterations of the microbial composition during childhood may cause short- and/or long-term negative health effects. Many factors influence the initial assembly and subsequent progression of the gut microbiota of a neonate, such as feeding type, delivery mode, gestational age, maternal metabolic status and antibiotic exposure.In the current study, the composition of the infant gut core-microbiota was explored, revealing particular variations of this core-microbiota during the first three years as influenced by delivery mode and feeding type. A multi-population cohort meta-analysis was performed by selecting 15 publicly available datasets pertaining to taxonomic profiles of 1035 fecal samples of healthy infants, as obtained by means of a 16S rRNA gene-based profiling approach. Interestingly, this multi-population cohort meta-analysis revealed great microbial complexity and specific taxonomic shifts in children older than six months, suggesting a major impact by the introduction of solid foods which prompts progression of infant gut microbiota towards that typical of adults. The taxonomic data sets employed in this multi-population cohort meta-analysis possess the statistical robustness to allow the identification of infant community state types (ICSTs). Our analysis therefore reveals the existence of specific taxonomic patterns that correspond to particular nutritional and developmental stages of early life, and that had previously been obscured by the high variability typical of such infant gut microbiota.

Intestinal microbiota and infant health in early life

The establishment and development of the intestinal microbiota in early life is critical to the development of intestinal immune system, digestive function, metabolic function, and central nervous system function in infants.The first 1000 days of life is a critical period for the establishment of intestinal microbiota, which is susceptible to many factors.The disorder of intestinal microbiota in this period will increase the risk of some diseases in the long-term life.In this review, we will describe the main physiological functions of the early-life microbiota and its role in programming future health of infants.We also will describe the establishment and development of the intestinal microbiota in early life and its main drivers. Key words: Early life; Intestinal microbiota; Health; Factors; Physiological function

Gastroenteritis during infancy is a novel risk factor for allergic disease.

Antibiotics during infancy, delivery, and breastfeeding affect the intestinal microbiota in early life and is associated with allergic disease. Gastroenteritis (GE) during infancy also affects intestinal microbiota in early life, however, its relationship to allergic disease has not been investigated.Data of 45,499 males and 49,430 females, from birth to 5 years of age, were collected from a national database in Taiwan. Subjects were categorized into early GE (GE within 0–6 months) and non-early GE group (no GE within 0–6 months). The rates of asthma (AS), allergic rhinitis (AR), and atopic dermatitis (AD) over 5 years were evaluated and compared between the groups. In patients with AS, AR, and AD, the number of clinical visits and drug prescriptions for the allergic disease was also evaluated to assess the effect of early GE on allergic disease.After adjusting for the effect of GE in later life and other factors, the rates of AS [OR (odds ratio) 1.54, 95% confidence interval (CI) 1.48–1.60], AR [OR 1.49, 95% CI 1.45–1.54], and AD [OR 1.40, 95% CI 1.33–1.47] were higher in the early GE group than in the non-early GE group. The magnitude of the increase was higher in females than in males. In those with AS, AR, and AD, the number of clinical visits and drug prescriptions was not different between the early GE and non-early GE groups. In children with early GE, good control of GE in the following years lowered the rate of allergic disease.Early-life GE was associated with increased rates of AS, AR, and AD in later life and this was trend more prominent in females.

Prospects for primary prevention of type 1 diabetes by restoring a disappearing microbe

Prevention of childhood-onset type 1 diabetes has become more urgent with its marked increased incidence in recent decades in the modern world. Temporally associated with the rising incidence of type 1 diabetes, as well as other autoimmune and allergic diseases in childhood in modern times, is the disappearance of Bifidobacterium and specifically Bifidobacterium longum subsp. infantis (B. infantis) predominance in the intestinal microbiota of breastfed, vaginally-delivered infants. B. infantis efficiently metabolizes human milk oligosaccharides (HMOs) without cross-feeding free sugar monomers to other commensals or pathogens and thereby dominates the intestinal microbiota of breastfed infants. Increased levels of short-chain fatty acids (SCFA), which stimulate both immunoregulation and healthy intestinal and pancreatic β-cell function, are generated by B. infantis. Based on recent observations of the intestinal microbiota in early life in young children who develop type 1 diabetes and demonstration of the robust preventive effects of SCFA in animal models of autoimmune diabetes, we hypothesize that restoring a B. infantis-dominant microbiota early in infancy will prevent islet autoimmunity and childhood-onset type 1 diabetes.

Increased prevalence of pathogenic bacteria in the gut microbiota of infants at risk of developing celiac disease: The PROFICEL study

ABSTRACTCeliac disease (CD) is an immune-mediated enteropathy involving genetic and environmental factors, whose interaction influences disease risk. The intestinal microbiota, including viruses and bacteria, could play a role in the pathological process leading to gluten intolerance. In this study, we investigated the prevalence of pathogens in the intestinal microbiota of infants at familial risk of developing CD. We included 127 full-term newborns with at least one first-degree relative with CD. Infants were classified according to milk-feeding practice (breastfeeding or formula feeding) and HLA-DQ genotype (low, intermediate or high genetic risk). The prevalence of pathogenic bacteria and viruses was assessed in the faeces of the infants at 7 days, 1 month and 4 months of age. The prevalence of Clostridium perfringens was higher in formula-fed infants than in breast-fed over the study period, and that of C. difficile at 4 months. Among breastfed infants, a higher prevalence of enterotoxigenic E. coli (ETEC) was found in infants with the highest genetic risk compared either to those with a low or intermediate risk. Among formula-fed infants, a higher prevalence of ETEC was also found in infants with a high genetic risk compared to those of intermediate risk. Our results show that specific factors, such as formula feeding and the HLA-DQ2 genotype, previously linked to a higher risk of developing CD, influence the presence of pathogenic bacteria differently in the intestinal microbiota in early life. Further studies are warranted to establish whether these associations are related to CD onset later in life.

Comparison of the gut microbiota profile in breast-fed and formula-fed Korean infants using pyrosequencing.

BACKGROUND/OBJECTIVESFeeding in infancy is the most significant determinant of the intestinal microbiota in early life. The aim of this study was to determine the gut microbiota of Korean infants and compare the microbiota obtained between breast-fed and formula-fed Korean infants.SUBJECTS/METHODSWe analyzed the microbial communities in fecal samples collected from twenty 4-week old Korean (ten samples in each breast-fed or formula-fed) infants using pyrosequencing.RESULTSThe fecal microbiota of the 4-week-old Korean infants consisted of the three phyla Actinobacteria, Firmicutes, and Proteobacteria. In addition, five species, including Bifidocbacterium longum, Streptococcus salivarius, Strepotococcus lactarius, Streptococcus pseudopneumoniae, and Lactobacillus gasseri were common commensal intestinal microbiota in all infants. The predominant intestinal microbiota in the breast-fed infants (BFI) included the phylum Actinobacteria (average 70.55%), family Bifidobacteriacea (70.12%), genus Bifidobacterium (70.03%) and species Bifidobacterium longum (69.96%). In the microbiota from the formula-fed infants (FFI), the proportion of the phylum Actinobacteria (40.68%) was less, whereas the proportions of Firmicutes (45.38%) and Proteobacteria (13.85%) as well as the diversity of each taxonomic level were greater, compared to those of the BFI. The probiotic species found in the 4-week-old Korean infants were Bifidobacterium longum, Streptococcus salivarius, and Lactobacillus gasseri. These probiotic species accounted for 93.81% of the microbiota from the BFI, while only 63.80% of the microbiota from the FFI. In particular, B. longum was more abundant in BFI (69.96%) than in FFI (34.17%).CONCLUSIONSBreast milk supports the growth of B. longum and inhibits others. To the best of our knowledge, this study was the first attempt to analyze the gut microbiota of healthy Korean infants according to the feeding type using pyrosequencing. Our data can be used as a basis for further studies to investigate the development of intestinal microbiota with aging and disease status.

Comparative analysis of gut microbiota of breast‐ and formula‐fed Korean infants by using pyrosequencing (1017.4)

Infant feeding is one of the significant determinants of the intestinal microbiota in early life. Although numerous researches have performed to investigate the bacteria community in the infant gut, culture‐based methods had showed limited bacteria population. Recently, pyrosequencing, a new high throughtput DNA sequencing technique, has been introduced and applied to explore microbiome. The purpose of this study was to compare the compositions of the fecal microbiota of Korean infants fed breast milk to those of infants fed milk formula. We examined microbial communities in fecal samples collected from 20 Korean infants at 4 weeks of age using pyrosequencing. Diversity analysis of total microbiota sequences revealed that a more diverse collection in milk formula‐fed infants (MFI), whereas, the probiotics, including S. salivarius, L. gasseri, and B. longum were abundant in the microbiota of breast milk‐fed infants (BFI). Moreover, Bifidobacteriaceae were significantly abundant in BFI compared with those of FFI. Our study is the first attempt to analyze gut microbiota in Korean infants by using pyrosequencing, which may provide valuable information to future study of the role of intestinal microbiota affecting in adulthood.Grant Funding Source: Ewha Womans University Research Grant of 2013.

Intestinal microbiology in early life: specific prebiotics can have similar functionalities as human-milk oligosaccharides

Human milk is generally accepted as the best nutrition for newborns and has been shown to support the optimal growth and development of infants. On the basis of scientific insights from human-milk research, a specific mixture of nondigestible oligosaccharides has been developed, with the aim to improve the intestinal microbiota in early life. The mixture has been extensively studied and has been shown to be safe and to have potential health benefits that are similar to those of human milk. The specific mixture of short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides has been found to affect the development of early microbiota and to increase the Bifidobacterium amounts as observed in human-milk-fed infants. The resulting gut ecophysiology is characterized by high concentrations of lactate, a slightly acidic pH, and specific short-chain fatty acid profiles, which are high in acetate and low in butyrate and propionate. Here, we have summarized the main findings of dietary interventions with these specific oligosaccharides on the gut microbiota in early life. The gut ecophysiology in early life may have consequences for the metabolic, immunologic, and even neurologic development of the child because reports increasingly substantiate the important function of gut microbes in human health. This review highlights major findings in the field of early gut colonization and the potential impact of early nutrition in healthy growth and development.

Restricting Microbial Exposure in Early Life Negates the Immune Benefits Associated with Gut Colonization in Environments of High Microbial Diversity

BackgroundAcquisition of the intestinal microbiota in early life corresponds with the development of the mucosal immune system. Recent work on caesarean-delivered infants revealed that early microbial composition is influenced by birthing method and environment. Furthermore, we have confirmed that early-life environment strongly influences both the adult gut microbiota and development of the gut immune system. Here, we address the impact of limiting microbial exposure after initial colonization on the development of adult gut immunity.Methodology/Principal FindingsPiglets were born in indoor or outdoor rearing units, allowing natural colonization in the immediate period after birth, prior to transfer to high-health status isolators. Strikingly, gut closure and morphological development were strongly affected by isolator-rearing, independent of indoor or outdoor origins of piglets. Isolator-reared animals showed extensive vacuolation and disorganization of the gut epithelium, inferring that normal gut closure requires maturation factors present in maternal milk. Although morphological maturation and gut closure were delayed in isolator-reared animals, these hard-wired events occurred later in development. Type I IFN, IL-22, IL-23 and Th17 pathways were increased in indoor-isolator compared to outdoor-isolator animals during early life, indicating greater immune activation in pigs originating from indoor environments reflecting differences in the early microbiota. This difference was less apparent later in development due to enhanced immune activation and convergence of the microbiota in all isolator-reared animals. This correlated with elevation of Type I IFN pathways in both groups, although T cell pathways were still more affected in indoor-reared animals.Conclusions/SignificanceEnvironmental factors, in particular microbial exposure, influence expression of a large number of immune-related genes. However, the homeostatic effects of microbial colonization in outdoor environments require sustained microbial exposure throughout development. Gut development in high-hygiene environments negatively impacts on normal succession of the gut microbiota and promotes innate immune activation which may impair immune homeostasis.