Early-life Microbiota Research Articles

Architecture Insight of Bifidobacterial α-L-Fucosidases.

Fucosylated carbohydrates and glycoproteins from human breast milk are essential for the development of the gut microbiota in early life because they are selectively metabolized by bifidobacteria. In this regard, α-L-fucosidases play a key role in this successful bifidobacterial colonization allowing the utilization of these substrates. Although a considerable number of α-L-fucosidases from bifidobacteria have been identified by computational analysis, only a few of them have been characterized. Hitherto, α-L-fucosidases are classified into three families: GH29, GH95, and GH151, based on their catalytic structure. However, bifidobacterial α-L-fucosidases belonging to a particular family show significant differences in their sequence. Because this fact could underlie distinct phylogenetic evolution, here extensive similarity searches and comparative analyses of the bifidobacterial α-L-fucosidases identified were carried out with the assistance of previous physicochemical studies available. This work reveals four and two paralogue bifidobacterial fucosidase groups within GH29 and GH95 families, respectively. Moreover, Bifidobacterium longum subsp. infantis species exhibited the greatest number of phylogenetic lineages in their fucosidases clustered in every family: GH29, GH95, and GH151. Since α-L-fucosidases phylogenetically descended from other glycosyl hydrolase families, we hypothesized that they could exhibit additional glycosidase activities other than fucosidase, raising the possibility of their application to transfucosylate substrates other than lactose in order to synthesis novel prebiotics.

Environmentally enriched housing conditions affect pig welfare, immune system and gut microbiota in early life

BackgroundConventional pig housing and management conditions are associated with gastrointestinal pathophysiology and disease susceptibility in early life. Developing new strategies to reduce both therapeutic and prophylactic antibiotic use is urgent for the sustainable swine production globally. To this end, housing methodology providing effective environmental enrichment could be a promising alternative approach to reduce antibiotic usage, as it has been proven to positively influence pig welfare and immune status and reduce susceptibility to infections. It is, however, poorly understood how this enriched housing affects systemic and local pulmonary immune status and gut microbiota colonization during early life. In the present study, we compared the effects of two housing conditions, i.e., conventional housing: (CH) versus enriched housing (EH), on immune status and gut microbiota from birth until 61 days of age.ResultsThe expected benefits of enrichment on pig welfare were confirmed as EH pigs showed more positive behaviour, less aggression behaviour during the weaning transition and better human animal relation during the post weaning phase. Regarding the pigs’ immune status, EH pigs had higher values of haemoglobin and mean corpuscular volume in haematological profiles and higher percentages of T cells and cytotoxic T cells in peripheral blood. Furthermore, EH pigs showed higher ex vivo secretion of IL1ß and TNF-α after lipopolysaccharide stimulation of whole blood than CH pigs. The structure of the developing faecal microbiota of CH and EH pigs significantly differed as early as day 12 with an increase in the relative abundance of several bacterial groups known to be involved in the production of short chain fatty acids, such as Prevotella_2, Christensenellaceae_R_7_group and Ruminococcus gauvreauii group. Furthermore, the main difference between both housing conditions post weaning was that on day 61, CH pigs had significantly larger inter-individual variation of ileal and colonic microbiota than EH pigs. In addition to housing, other intrinsic factors (e.g., sex) were associated with gut microbiota development and immune competence.ConclusionsIn addition to the known welfare benefits for pigs, environmentally enriched housing also positively drives important aspects of the development of the immune system and the establishment of gut microbiota in early life. Consequently, EH may contribute to increasing productivity of pigs and reducing antibiotic use.

Altered IgA Response to Gut Bacteria Is Associated with Childhood Asthma in Peru.

Alterations in gut microbiota in early life have been associated with the development of asthma; however, the role of gut bacteria or the IgA response to gut bacteria in school-aged children with asthma is unclear. To address this question, we profiled the microbial populations in fecal and nasal swab samples by 16S rRNA sequencing from 40 asthma and 40 control children aged 9-17 y from Peru. Clinical history and laboratory evaluation of asthma and allergy were obtained. Fecal samples were analyzed by flow cytometry and sorted into IgA+ and IgA- subsets for 16S rRNA sequencing. We found that the fecal or nasal microbial 16S rRNA diversity and frequency of IgA+ fecal bacteria did not differ between children with or without asthma. However, the α diversity of fecal IgA+ bacteria was decreased in asthma compared with control. Machine learning analysis of fecal bacterial IgA-enrichment data revealed loss of IgA binding to the Blautia, Ruminococcus, and Lachnospiraceae taxa in children with asthma compared with controls. In addition, this loss of IgA binding was associated with worse asthma control (Asthma Control Test) and increased odds of severe as opposed to mild to moderate asthma. Thus, despite little to no change in the microbiota, children with asthma exhibit an altered host IgA response to gut bacteria compared with control participants. Notably, the signature of altered IgA responses is loss of IgA binding, in particular to members of Clostridia spp., which is associated with greater severity of asthma.

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.

Cardiovascular Diseases of Developmental Origins: Preventive Aspects of Gut Microbiota-Targeted Therapy

Cardiovascular diseases (CVDs) can originate from early life. Accumulating evidence suggests that gut microbiota in early life is linked to CVDs in later life. Gut microbiota-targeted therapy has gained significant importance in recent decades for its health-promoting role in the prevention (rather than just treatment) of CVDs. Thus far, available gut microbiota-based treatment modalities used as reprogramming interventions include probiotics, prebiotics, and postbiotics. The purpose of this review is, first, to highlight current studies that link dysbiotic gut microbiota to the developmental origins of CVD. This is followed by a summary of the connections between the gut microbiota and CVD behind cardiovascular programming, such as short chain fatty acids (SCFAs) and their receptors, trimethylamine-N-oxide (TMAO), uremic toxins, and aryl hydrocarbon receptor (AhR), and the renin-angiotensin system (RAS). This review also presents an overview of how gut microbiota-targeted reprogramming interventions can prevent the developmental origins of CVD from animal studies. Overall, this review reveals that recent advances in gut microbiota-targeted therapy might provide the answers to reduce the global burden of CVDs. Still, additional studies will be needed to put research findings into practice.

Transformation pathways and metabolic activity of free chlorophyll compounds from chloroplast thylakoid membrane under in vitro gastrointestinal digestion and colonic fermentation in early life

Thylakoid membrane was subjected for the first time to an in vitro gastrointestinal digestion and colonic fermentation process in early life to investigate transformation pathways and metabolic activity of free chlorophyll compounds. Volume-mean diameters proved that the thylakoid membrane was digested, releasing free chlorophylls. The released chlorophylls favored the pheophytinisation reaction under in vitro gastrointestinal digestion, leading to the formation of pheophytin a and pheophytin b. Gut microbiota in early life of Blautia, Bacteroides and Enterococcus utilized a wide range of pheophytin-types derivatives, which stimulated the production of pheophorbide a, pheophorbide b, 151-hydroxy-lactone pheophorbide a and 132-hydroxy pheophorbide a. Accordingly, a high increase in the concentration of acetic acid, propionic acid, butyric acid and valeric acid was observed due to fermentation of pheophytins by the intestinal microbiota. We believe that this systematic investigation will be extended to in vivo to better understand health benefits of chlorophylls.

Dietary Lipid Effects on Gut Microbiota of First Feeding Atlantic Salmon (Salmo salar L.)

Decline in fish oil and fish meal availability has forced the aquaculture sector to investigate alternative and sustainable aquafeed ingredients. Despite that several studies have evaluated the effect of fish oil replacement in aquaculture fish species, there is a knowledge gap on the effects of alternative dietary lipid sources on the gut microbiota in early life stages of Salmo salar. The present study evaluated the influence of dietary administration of two different lipid sources (fish oil and vegetable oil) on the intestinal microbiota of first feeding Atlantic salmon (S. salar) up to 93 days post first feeding (dpff). The two diets used in this study, FD (fish oil diet) and VD (blend of rapeseed, linseed and palm oils diet), were formulated to cover the fish nutritional requirements. Apart from the lipid source, the rest of the feed components were identical in the two diets. Hindgut samples were collected at 0, 35, 65, and 93 dpff. Moreover, fertilized eggs, yolk sac larvae, rearing water and feed were also collected in order to assess a possible contribution of their microbiota to the colonization and bacterial succession of the fish intestines. To analyze the bacterial communities, amplicon sequencing was used targeting the V3–V4 region of the 16S rRNA gene. The findings indicate that feeding on either fish oil or vegetable oil-based diet, fish growth variables (mean wet weight and total length) did not differ significantly during the experiment (p > 0.05). No significant differences were also found between the two dietary groups, regarding their gut bacteria composition, after the analysis of the 16S rRNA sequencing data. Instead, gut microbiota changed with age, and each stage was characterized by different dominant bacteria. These operational taxonomic units (OTUs) were related to species that provide different functions and have been isolated from a variety of environments. The results also show little OTUs overlap between the host and rearing environment microbiota. Overall, this study revealed the occurrence of a core microbiota in early life of Atlantic salmon independent of the feed-contained oil origin.

Maternal Microbiota, Early Life Colonization and Breast Milk Drive Immune Development in the Newborn.

The innate immune system is the oldest protection strategy that is conserved across all organisms. Although having an unspecific action, it is the first and fastest defense mechanism against pathogens. Development of predominantly the adaptive immune system takes place after birth. However, some key components of the innate immune system evolve during the prenatal period of life, which endows the newborn with the ability to mount an immune response against pathogenic invaders directly after birth. Undoubtedly, the crosstalk between maternal immune cells, antibodies, dietary antigens, and microbial metabolites originating from the maternal microbiota are the key players in preparing the neonate’s immunity to the outer world. Birth represents the biggest substantial environmental change in life, where the newborn leaves the protective amniotic sac and is exposed for the first time to a countless variety of microbes. Colonization of all body surfaces commences, including skin, lung, and gastrointestinal tract, leading to the establishment of the commensal microbiota and the maturation of the newborn immune system, and hence lifelong health. Pregnancy, birth, and the consumption of breast milk shape the immune development in coordination with maternal and newborn microbiota. Discrepancies in these fine-tuned microbiota interactions during each developmental stage can have long-term effects on disease susceptibility, such as metabolic syndrome, childhood asthma, or autoimmune type 1 diabetes. In this review, we will give an overview of the recent studies by discussing the multifaceted emergence of the newborn innate immune development in line with the importance of maternal and early life microbiota exposure and breast milk intake.

A rich meconium metabolome in human infants is associated with early-life gut microbiota composition and reduced allergic sensitization

SummaryMicrobiota maturation and immune development occur in parallel with, and are implicated in, allergic diseases, and research has begun to demonstrate the importance of prenatal influencers on both. Here, we investigate the meconium metabolome, a critical link between prenatal exposures and both early microbiota and immune development, to identify components of the neonatal gut niche that contribute to allergic sensitization. Our analysis reveals that newborns who develop immunoglobulin E (IgE)-mediated allergic sensitization (atopy) by 1 year of age have a less-diverse gut metabolome at birth, and specific metabolic clusters are associated with both protection against atopy and the abundance of key taxa driving microbiota maturation. These metabolic signatures, when coupled with early-life microbiota and clinical factors, increase our ability to accurately predict whether or not infants will develop atopy. Thus, the trajectory of both microbiota colonization and immune development are significantly affected by metabolites present in the neonatal gut at birth.

Early Life Microbiota Colonization at Six Months of Age: A Transitional Time Point.

BackgroundEarly life gut microbiota is involved in several biological processes, particularly metabolism, immunity, and cognitive neurodevelopment. Perturbation in the infant’s gut microbiota increases the risk for diseases in early and later life, highlighting the importance of understanding the connections between perinatal factors with early life microbial composition. The present research paper is aimed at exploring the prenatal and postnatal factors influencing the infant gut microbiota composition at six months of age.MethodsGut microbiota of infants enrolled in the longitudinal, prospective, observational study “A.MA.MI” (Alimentazione MAmma e bambino nei primi MIlle giorni) was analyzed. We collected and analyzed 61 fecal samples at baseline (meconium, T0); at six months of age (T2), we collected and analyzed 53 fecal samples. Samples were grouped based on maternal and gestational weight factors, type of delivery, type of feeding, time of weaning, and presence/absence of older siblings. Alpha and beta diversities were evaluated to describe microbiota composition. Multivariate analyses were performed to understand the impact of the aforementioned factors on the infant’s microbiota composition at six months of age.ResultsDifferent clustering hypotheses have been tested to evaluate the impact of known metadata factors on the infant microbiota. Neither maternal body mass index nor gestational weight gain was able to determine significant differences in infant microbiota composition six months of age. Concerning the type of feeding, we observed a low alpha diversity in exclusive breastfed infants; conversely, non-exclusively breastfed infants reported an overgrowth of Ruminococcaceae and Flavonifractor. Furthermore, we did not find any statistically significant difference resulting from an early introduction of solid foods (before 4 months of age). Lastly, our sample showed a higher abundance of clostridial patterns in firstborn babies when compared to infants with older siblings in the family.ConclusionOur findings showed that, at this stage of life, there is not a single factor able to affect in a distinct way the infants’ gut microbiota development. Rather, there seems to be a complex multifactorial interaction between maternal and neonatal factors determining a unique microbial niche in the gastrointestinal tract.

Neurodevelopmental Outcomes and Gut Bifidobacteria in Term Infants Fed an Infant Formula Containing High sn-2 Palmitate: A Cluster Randomized Clinical Trial.

A few studies suggested high stereo-specifically numbered (sn)-2 palmitate in a formula might favor the gut Bifidobacteria of infants. The initial colonization and subsequent development of gut microbiota in early life might be associated with development and later life functions of the central nervous system via the microbiota–gut–brain axis, such as children with autism. This study aims to assess the hypothesized effect of increasing the amount of palmitic acid esterified in the sn-2 position in infant formula on neurodevelopment in healthy full-term infants and to explore the association of this effect with the altered gut Bifidobacteria. One hundred and ninety-nine infants were enrolled in this cluster randomized clinical trial: 66 breast-fed (BF group) and 133 formula-fed infants who were clustered and randomly assigned to receive formula containing high sn-2 palmitate (sn-2 group, n = 66) or low sn-2 palmitate (control group, n = 67), where 46.3% and 10.3% of the palmitic acid (PA) was sn-2-palmitate, respectively. Infants’ neurodevelopmental outcomes were measured by the Ages and Stages Questionnaire, third edition (ASQ-3). Stool samples were collected for the analysis of Bifidobacteria (Trial registration number: ChiCTR1800014479). At week 16, the risk of scoring close to the threshold for fine motor skills (reference: scoring above the typical development threshold) was significantly lower in the sn-2 group than the control group after adjustment for the maternal education level (p = 0.036) but did not differ significantly versus the BF group (p = 0.513). At week 16 and week 24, the sn-2 group (week 16: 15.7% and week 24: 15.6%) had a significantly higher relative abundance of fecal Bifidobacteria than the control group (week 16: 6.6%, p = 0.001 and week 24:11.2%, p = 0.028) and did not differ from the BF group (week 16: 14.4%, p = 0.674 and week 24: 14.9%, p = 0.749). At week 16, a higher relative abundance of Bifidobacteria was associated with the decreased odds of only one domain scoring close to the threshold in the formula-fed infants group (odds ratio (OR), 95% confidence interval (CI): 0.947 (0.901–0.996)). Elevating the sn-2 palmitate level in the formula improved infants’ development of fine motor skills, and the beneficial effects of high sn-2 palmitate on infant neurodevelopment was associated with the increased gut Bifidobacteria level.

Crosstalk between sIgA-Coated Bacteria in Infant Gut and Early-Life Health.

Gut microbiota transmission from mother to offspring has attracted much interest in recent years. The gut microbiota in the infant plays a potentially significant role in modulating and maintaining the development of infant immunity. Secretory immunoglobulin A (sIgA), the major immunoglobulin in the intestine, can target polysaccharides and flagellin on the bacterial surface, resulting in sIgA-coated bacteria. The presentation of specific bacteria coated with sIgA may be a signal of disease and provide novel insights into the relationship between infant microbiota and disease. Here, we review the composition of sIgA-coated bacteria in the adult intestine, human milk, and the infant intestine, as well as the factors that influence the development of gut microbiota in early life. Then, we highlight the diseases that are related to variations in sIgA-coated bacteria in the infant and adult intestine. Furthermore, we discuss the possibility that sIgA-coated bacteria could play a role in mediating both innate and adaptive immune responses. Finally, we propose directions for future research to promote our understanding within this field.

The Development of Early Life Microbiota in Human Health and Disease

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.

The Association between Early-Life Gut Microbiota and Long-Term Health and Diseases.

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.

Modeling transfer of vaginal microbiota from mother to infant in early life.

Early-life microbiota has been linked to the development of chronic inflammatory diseases. It has been hypothesized that maternal vaginal microbiota is an important initial seeding source and therefore might have lifelong effects on disease risk. To understand maternal vaginal microbiota's role in seeding the child's microbiota and the extent of delivery mode-dependent transmission, we studied 665 mother-child dyads from the COPSAC2010 cohort. The maternal vaginal microbiota was evaluated twice in the third trimester and compared with the children's fecal (at 1 week, 1 month, and 1 year of age) and airway microbiota (at 1 week, 1 month, and 3 months). Based on the concept of weighted transfer ratios (WTRs), we have identified bacterial orders for which the WTR displays patterns indicate persistent or transient transfer from the maternal vaginal microbiome, as well as orders that are shared at later time points independent of delivery mode, indicating a common reservoir.

Disentangling the Relative Roles of Vertical Transmission, Subsequent Colonizations, and Diet on Cockroach Microbiome Assembly.

A multitude of factors affect the assemblies of complex microbial communities associated with animal hosts, with implications for community flexibility, resilience, and long-term stability; however, their relative effects have rarely been deduced. Here, we use a tractable lab model to quantify the relative and combined effects of parental transmission (egg case microbiome present/reduced), gut inocula (cockroach versus termite gut provisioned), and varying diets (matched or unmatched with gut inoculum source) on gut microbiota structure of hatchlings of the omnivorous cockroach Shelfordella lateralis using 16S rRNA gene (rDNA) amplicon sequencing. We show that the presence of a preexisting bacterial community via vertical transmission of microbes on egg cases reduces subsequent microbial invasion, suggesting priority effects that allow initial colonizers to take a strong hold and which stabilize the microbiome. However, subsequent inoculation sources more strongly affect ultimate community composition and their ecological networks, with distinct host-taxon-of-origin effects on which bacteria establish. While this is so, communities respond flexibly to specific diets in ways that consequently impact predicted community functions. In conclusion, our findings suggest that inoculations drive communities toward different stable states depending on colonization and extinction events, through ecological host-microbe relations and interactions with other gut bacteria, while diet in parallel shapes the functional capabilities of these microbiomes. These effects may lead to consistent microbial communities that maximize the extended phenotype that the microbiota provides the host, particularly if microbes spend most of their lives in host-associated environments.IMPORTANCE When host fitness is dependent on gut microbiota, microbial community flexibility and reproducibility enhance host fitness by allowing fine-tuned environmental tracking and sufficient stability for host traits to evolve. Our findings lend support to the importance of vertically transmitted early-life microbiota as stabilizers, through interactions with potential colonizers, which may contribute to ensuring that the microbiota aligns within host fitness-enhancing parameters. Subsequent colonizations are driven by microbial composition of the sources available, and we confirm that host-taxon-of-origin affects stable subsequent communities, while communities at the same time retain sufficient flexibility to shift in response to available diets. Microbiome structure is thus the result of the relative impact and combined effects of inocula and fluctuations driven by environment-specific microbial sources and digestive needs. These affect short-term community structure on an ecological time scale but could ultimately shape host species specificities in microbiomes across evolutionary time, if environmental conditions prevail.

Exposure to p40 in Early Life Prevents Intestinal Inflammation in Adulthood Through Inducing a Long-Lasting Epigenetic Imprint on TGFβ.

Background & AimsColonization by gut microbiota in early life confers beneficial effects on immunity throughout the host’s lifespan. We sought to elucidate the mechanisms whereby neonatal supplementation with p40, a probiotic functional factor, reprograms intestinal epithelial cells for protection against adult-onset intestinal inflammation.Methodsp40 was used to treat young adult mouse colonic (YAMC) epithelial cells with and without deletion of a methyltransferase, su(var)3-9, enhancer-of-zeste and trithorax domain–containing 1β (Setd1β), and mice in early life or in adulthood. Anti–transforming growth factor β (TGFβ)-neutralizing antibodies were administered to adult mice with and without colitis induced by 2,4,6-trinitrobenzenesulfonic acid or dextran sulfate sodium. We examined Setd1b and Tgfb gene expression, TGFβ production, monomethylation and trimethylation of histone H3 on the lysine 4 residue (H3K4me1/3), H3K4me3 enrichment in Tgfb promoter, differentiation of regulatory T cells (Tregs), and the inflammatory status.Resultsp40 up-regulated expression of Setd1b in YAMC cells. Accordingly, p40 enhanced H3K4me1/3 in YAMC cells in a Setd1β-dependent manner. p40-regulated Setd1β mediated programming the TGFβ locus into a transcriptionally permissive chromatin state and promoting TGFβ production in YAMC. Furthermore, transient exposure to p40 during the neonatal period and in adulthood resulted in the immediate increase in Tgfb gene expression. However, only neonatal p40 supplementation induced the sustained H3K4me1/3 and Tgfb gene expression that persisted into adulthood. Interfering with TGFβ function by neutralizing antibodies diminished the long-lasting effects of neonatal p40 supplementation on differentiation of Tregs and protection against colitis in adult mice.ConclusionsExposure to p40 in early life enables an epigenetic imprint on TGFβ, leading to long-lasting production of TGFβ by intestinal epithelial cells to expand Tregs and protect the gut against inflammation.

Evaluation of the effect of antibiotics on gut microbiota in early life based on culturomics, SMRT sequencing and metagenomics sequencing methods.

Symbiotic gut microbiota in early life plays a vital role in human health, and changes in its communication and function are associated with various complex disorders. In this study, we analyzed the gut flora communication of 6 infants at 4 months of age and determined the disturbances related to antibiotic treatment. By the culturomics and Single Molecule Real-time sequencing methods, a total of 6234 strains were divided into 16 genera and 45 species. The alpha diversity of culturable microorganisms in amoxicillin-treated infants was significantly less than that in healthy infants (p <0.05), as indicated by Chao 1, observed species and Faith's PD index. According to metagenomics, the dominant genus and species were Bifidobacterium and B. longum in the healthy group. After treatment with amoxicillin, the dominant genus and species shifted to Enterococcus and E. faecium. Based on the functional annotation of metagenomics, amoxicillin affected the metabolic function of the gut microbiome by activating carbohydrate and lipid metabolism and inhibiting amino acid metabolism. Besides, the intake of antibiotics in early life increased the risk of neurodegenerative disease, virus infectious disease and antimicrobial resistance. The Antibiotic Resistance Genes Database annotation result indicated that the abundance of drug-resistance genes in the antibiotic group was higher than that in the healthy group. These genes were associated with resistance to bacitracin, most of which were associated with K. pneumonia. These findings can provide guidance in the clinic on the proper usage of antibiotics.

The effect of a single, early-life administration of a probiotic on piglet growth performance and faecal microbiota until weaning

The establishment and maintenance of a balanced gut microbiota in early life play a pivotal role in pigs. This study aims to evaluate the effect of the administration of a single early-life probiotic on piglet faecal microbiota and growth performance until weaning. Forty-eight hours after birth (d0), 820 piglets were allocated into 4 groups (205 piglets/16 litters/group) and orally inoculated as follows: 1) Control (CO: 4 mL of pure water); 2) Saccharomyces (SA: 4 mL containing a total of 1 × 1010 CFU of Saccharomyces cerevisiae var. boulardii CNCM-1079; 3) Enterococcus (EF: 4 mL containing a total of 1 × 1010 CFU of Enterococcus faecium lactiferm WS200); 4) a mix of the two probiotics at the same doses (SAEF). At d7 and d18, the piglets were weighed, and faeces from the piglets (18 piglets/group from 6 sows/group) and their mothers were analysed for a microbial profile by sequencing the v3-v4 regions of the 16S rRNA gene. Data were arranged in a 2x2 factorial design. The probiotic supplement improved piglet ADG in the periods d7-d18 (p < .0001) and d0-d18 (p < .05). From d7 to d18, the SA group tended to have lower mortality than the CO group (p = .08). The probiotic supplement significantly affected the microbial beta diversity at d7 (p < .05). The SA probiotic favoured the colonisation of Erysipelatoclostridium and Christensenella, and the EF probiotic the colonisation of Lachnospiraceae. These results highlighted that the administration of a single early-life probiotic supplement could improve piglet performance and shape the faecal microbial profile. Highlights A single dose of E. faecium or S. cerevisiae improved piglet performance in the pre-weaning period. The early administration of probiotics shaped the faecal microbial profile of the piglets and contributed to improved growth performance.

Vitamin A Deficiency in the Early-Life Periods Alters a Diversity of the Colonic Mucosal Microbiota in Rats.

Vitamin A deficiency (VAD) remains a public health issue worldwide, affecting pregnant women and children. The early-life microbiota is a potentially effective intervention target for modulating immune and metabolic development of the host. This paper investigates the effects of VAD during different life periods on the structure of the colonic mucosa microbiota in adolescent rats. The results showed that the concentrations of serum retinol were > ~1.05 μmol/L in maternal VA normal (VAN)rats and < 0.7 μmol/L in maternal VAD rats, while the serum retinol levels were higher than 0.7 μmol/L in the pups of the VAN group and below 0.5 μmol/L in the pups of the VAD group. Compared to the offspring persistent with VAN from embryonic stage (group A), all the remaining groups exhibited an increased ratio of Firmicutes/Bacteroidetes abundance. A metagenome analysis (LEfSe) and a differentially abundant features approach using Metastats for genus abundances revealed that Diaphorobacter and Psychrobacter were increased in the offspring persistent with VAD from embryonic stage (group B);Bifidobacterium was decreased and Staphylococcus was increased in the offspring with VAD after weaning (group C); Propionibacterium and Enterobacter were increased significantly in the offspring with VAD during gestation(group E); and Ochrobactrum was increased in group B and the offspring with VAD during gestation and lactation(group D). Faecalibacterium abundance was significantly and positively related to serum retinol levels, while that of Staphylococcus was significantly and negatively correlated with serum retinol levels. VAD in different life periods can alter the gut microbiome in rats, but VAD in the early-life periods (especially gestation and/or lactation) leads to a diversity of the colonic mucosal microbiota in adolescent rats as well as an imbalance of the ratio between Firmicutes and Bacteroidetes. The early-life period may become a time window of VA intervention to improve intestinal microbiota caused by VA deficiency, but the specific mechanism requires more in-depth research.