scholarly journals Restoring Bifidobacterium Infantis EVC001 to the Infant Gut Microbiome Significantly Reduces Intestinal Inflammation (OR12-01-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Bethany Henrick ◽  
Stephanie Chew ◽  
Ryan Mitchell ◽  
Lindsey Contreras ◽  
Giorgio Casaburi ◽  
...  
Keyword(s):  
Immune System ◽  
Gut Microbiome ◽  
Intestinal Inflammation ◽  
System Development ◽  
Fecal Calprotectin ◽  
Breastfed Infants ◽  
Gut Dysbiosis ◽  
Immune System Development ◽  
Infant Gut Microbiome ◽  
Chronic Intestinal Inflammation

Abstract Objectives Several seminal publications identify that Bifidobacterium longum subsp. infantis (B. infantis) has uniquely evolved to be the predominant strain in the breastfed infant gut; however, recent cohort studies indicate it is now far less abundant in infants born in industrialized nations, along with increased abundance of potentially pathogenic bacteria and gut dysbiosis. Importantly, recent clinical studies show enteric dysbiosis during the first 100 days of life can lead to higher risk of allergic and autoimmune-mediated disorders later in life. Given the importance of the microbiome for immune system development, we investigated the effect of B. infantis EVC001 consumption on intestinal inflammation in a cohort of healthy, term infants. Methods Forty (n = 40) infants were randomly selected from the previously conducted clinical study in which healthy, exclusively breastfed infants were either fed B. infantis EVC001 daily for 21 days, starting at day 7 postpartum, or received breastmilk alone. Stool samples were collected at multiple times postnatally and analyzed for cytokine production using a multiplex system and calprotectin ELISA. Results Baseline analysis indicated infants randomized to the EVC001 group produced naturally higher levels of IL2, IL5, IL6, IL10, TNFa and IFNg and lower levels of IL1b (all P < 0.01); however, by day 40, infants fed EVC001 produced significantly decreased cytokines, IL1b, IL6, IL8, IL22, TNFa and IFNg (all P < 0.0001) and IL-5 (P = 0.024), and at day 60 postpartum (all P < 0.001) and IL5 (P = 0.013). Fecal calprotectin concentration was significantly decreased in infants whose gut microbiome contained Bifidobacterium (P = 9.61e-05). Conclusions This study is the first to demonstrate a significant impact of B. infantis EVC001 on immune homeostasis in breastfed infants during a critical window of immune system development. Infants fed EVC001 produced significantly less proinflammatory cytokines and fecal calprotectin compared to control infants. Notably, TNFa, IL1b, and IFNg, which increase intestinal permeability, were significantly elevated in control infants. This may play an important mechanistic role in explaining the chronic intestinal inflammation observed in infants not colonized with B. infantis. These critical data provide a new understanding of the role of the infant gut microbiome in immune system development and provide novel applications to address chronic inflammation through modulation of gut dysbiosis. Funding Sources Industry funded.

scholarly journals Metagenomic insights of the infant microbiome community structure and function across multiple sites in the United States

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Giorgio Casaburi ◽  
Rebbeca M. Duar ◽  
Heather Brown ◽  
Ryan D. Mitchell ◽  
Sufyan Kazi ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
System Development ◽  
Antibiotic Resistance Genes ◽  
The United States ◽  
Microbiome Composition ◽  
Immune System Development ◽  
The Us ◽  
The Status ◽  
Infant Gut Microbiome ◽  
And Function

AbstractThe gut microbiome plays an important role in early life, protecting newborns from enteric pathogens, promoting immune system development and providing key functions to the infant host. Currently, there are limited data to broadly assess the status of the US healthy infant gut microbiome. To address this gap, we performed a multi-state metagenomic survey and found high levels of bacteria associated with enteric inflammation (e.g. Escherichia, Klebsiella), antibiotic resistance genes, and signatures of dysbiosis, independent of location, age, and diet. Bifidobacterium were less abundant than generally expected and the species identified, including B. breve, B. longum and B. bifidum, had limited genetic capacity to metabolize human milk oligosaccharides (HMOs), while B. infantis strains with a complete capacity for HMOs utilization were found to be exceptionally rare. Considering microbiome composition and functional capacity, this survey revealed a previously unappreciated dysbiosis that is widespread in the contemporary US infant gut microbiome.

scholarly journals Human Milk Oligosaccharides and Immune System Development

Nutrients ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 1038 ◽  
Author(s):  
Julio Plaza-Díaz ◽  
Luis Fontana ◽  
Angel Gil
Keyword(s):  
Immune System ◽  
Human Milk ◽  
Intestinal Mucosa ◽  
System Development ◽  
Controlled Trials ◽  
Human Milk Oligosaccharides ◽  
Milk Oligosaccharides ◽  
Maternal Milk ◽  
Breastfed Infants ◽  
Immune System Development

Maternal milk contains compounds that may affect newborn immunity. Among these are a group of oligosaccharides that are synthesized in the mammary gland from lactose; these oligosaccharides have been termed human milk oligosaccharides (HMOs). The amount of HMOs present in human milk is greater than the amount of protein. In fact, HMOs are the third-most abundant solid component in maternal milk after lactose and lipids, and are thus considered to be key components. The importance of HMOs may be explained by their inhibitory effects on the adhesion of microorganisms to the intestinal mucosa, the growth of pathogens through the production of bacteriocins and organic acids, and the expression of genes that are involved in inflammation. This review begins with short descriptions of the basic structures of HMOs and the gut immune system, continues with the beneficial effects of HMOs shown in cell and animal studies, and it ends with the observational and randomized controlled trials carried out in humans to date, with particular emphasis on their effect on immune system development. HMOs seem to protect breastfed infants against microbial infections. The protective effect has been found to be exerted through cell signaling and cell-to-cell recognition events, enrichment of the protective gut microbiota, the modulation of microbial adhesion, and the invasion of the infant intestinal mucosa. In addition, infants fed formula supplemented with selected HMOs exhibit a pattern of inflammatory cytokines closer to that of exclusively breastfed infants. Unfortunately, the positive effects found in preclinical studies have not been substantiated in the few randomized, double-blinded, multicenter, controlled trials that are available, perhaps partly because these studies focus on aspects other than the immune response (e.g., growth, tolerance, and stool microbiota).

scholarly journals Osteopontin Levels in Human Milk Are Related to Maternal Nutrition and Infant Health and Growth

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2670
Author(s):  
Aysegül Aksan ◽  
Izzet Erdal ◽  
Siddika Songül Yalcin ◽  
Jürgen Stein ◽  
Gülhan Samur
Keyword(s):  
Immune System ◽  
Breast Milk ◽  
Infant Health ◽  
Maternal Nutrition ◽  
System Development ◽  
Maternal Factors ◽  
Immune System Development ◽  
The Mean ◽  
Pregnancy Weight

Background: Osteopontin (OPN) is a glycosylated phosphoprotein found in human tissues and body fluids. OPN in breast milk is thought to play a major role in growth and immune system development in early infancy. Here, we investigated maternal factors that may affect concentrations of OPN in breast milk, and the possible associated consequences for the health of neonates. Methods: General characteristics, health status, dietary patterns, and anthropometric measurements of 85 mothers and their babies were recorded antenatally and during postnatal follow-up. Results: The mean concentration of OPN in breast milk was 137.1 ± 56.8 mg/L. Maternal factors including smoking, BMI, birth route, pregnancy weight gain, and energy intake during lactation were associated with OPN levels (p < 0.05). Significant correlations were determined between body weight, length, and head circumference, respectively, and OPN levels after one (r = 0.442, p = < 0.001; r = −0.284, p = < 0.001; r = −0.392, p = < 0.001) and three months (r = 0.501, p = < 0.001; r = −0.450, p = < 0.001; r = −0.498, p = < 0.001) of lactation. A negative relation between fever-related infant hospitalizations from 0–3 months and breast milk OPN levels (r = −0.599, p < 0.001) was identified. Conclusions: OPN concentrations in breast milk differ depending on maternal factors, and these differences can affect the growth and immune system functions of infants. OPN supplementation in infant formula feed may have benefits and should be further investigated.

scholarly journals Dynamic Associations of Milk Components With the Infant Gut Microbiome and Fecal Metabolites in a Mother–Infant Model by Microbiome, NMR Metabolomic, and Time-Series Clustering Analyses

2022 ◽  
Vol 8 ◽  
Author(s):  
Yosuke Komatsu ◽  
Daiki Kumakura ◽  
Namiko Seto ◽  
Hirohisa Izumi ◽  
Yasuhiro Takeda ◽  
...  
Keyword(s):  
Breast Milk ◽  
Gut Microbiome ◽  
Lactation Period ◽  
Bioactive Components ◽  
Fecal Microbiome ◽  
Breastfed Infants ◽  
H Nmr ◽  
Milk Components ◽  
Infant Gut Microbiome ◽  
Infant Feces

Background: The gut microbiome and fecal metabolites of breastfed infants changes during lactation, and are influenced by breast milk components. This study aimed to investigate dynamic associations of milk components with the infant gut microbiome and fecal metabolites throughout the lactation period in a mother–infant model.Methods: One month after delivery, breast milk and subsequent infant feces were collected in a pair for 5 months from a mother and an exclusively breastfed infant. Composition of the fecal microbiome was determined with 16S rRNA sequencing. Low-molecular-weight metabolites, including human milk oligosaccharides (HMOs), and antibacterial proteins were measured in feces and milk using 1H NMR metabolomics and enzyme-linked immunosorbent assays. The association of milk bioactive components with the infant gut microbiome and fecal metabolites was determined with Python clustering and correlation analyses.Results: The HMOs in milk did not fluctuate throughout the lactation period. However, they began to disappear in infant feces at the beginning of month 4. Notably, at this time-point, a bifidobacterium species switching (from B. breve to B. longum subsp. infantis) occurred, accompanied by fluctuations in several metabolites including acetate and butyrate in infant feces.Conclusions: Milk bioactive components, such as HMOs, might play different roles in the exclusively breastfed infants depending on the lactation period.

scholarly journals 398 Towards new feeding approaches for optimizing nutritional status, immunity and host-microbiota interactions in neonatal and weaned piglets

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 181-181
Author(s):  
Martin Lessard ◽  
Mylène Blais ◽  
Guylaine Talbot ◽  
J Jacques Matte ◽  
Ann Letellier ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Intestinal Microbiota ◽  
System Development ◽  
Feed Additives ◽  
Epithelial Cell Line ◽  
Host Immune System ◽  
Gut Health ◽  
Weaned Piglets ◽  
Immune System Development

Abstract Lactation, feeding conditions, microbial interventions and piglet growth in the first few weeks of life have important impact on the intestinal microbiota establishment and immune system development of piglets. Indeed, colostrum and milk contain various bioactive components such as immune factors, antimicrobial peptides and oligosaccharides that contribute to maintain intestinal homeostasis and regulate interactions between microbiota and host immune system. Recent results revealed that low birth weight piglet (LBWP) with poor weight gain during the first two weeks of life develop different intestinal microbiota and immune response profiles compared to high BWP (HBWP) littermates. Consequently, piglets within litters may have different resilience to infections after weaning and benefit from feed additives in a specific manner. A study has been performed to evaluate the potential of bovine colostrum extract (BC) as replacement to plasma proteins for improving gut health and resilience to Salmonella infection in piglets. Results revealed that in weaned piglets fed BC, intestinal microbiota was differently modulated and bacterial dysbiosis induced by Salmonella was restored faster. Moreover, expression of genes involved in innate immunity such as β-defensin-2 and glutathione peroxidase-2 was respectively down- and up-regulated in BC fed piglets. A combination of dietary supplementation with BC, cupper and vitamins A and D has also been tested in LBWP and HBWP, and there is clear evidence that BC in combination with other feed additives promote growth and gut health in both LBWP and HBWP. The porcine intestinal epithelial cell line IPEC-J2 was used to better understand the functional properties of BC. Results indicated that BC improves wound healing, enhances barrier function and modulates the expression of several genes involved in innate immune response. Finally, as microbial intervention, the potential of fecal transplantation to modulate intestinal microbiota and immune system development of piglets is under investigation and will be discussed.

scholarly journals VOLARE: Visual analysis of disease-associated microbiome-immune system interplay

2018 ◽  
Author(s):  
Janet C. Siebert ◽  
Charles Preston Neff ◽  
Jennifer M. Schneider ◽  
EmiLie H. Regner ◽  
Neha Ohri ◽  
...  
Keyword(s):  
Immune System ◽  
Web Application ◽  
Visual Analysis ◽  
System Development ◽  
Patient Specific ◽  
Domain Experts ◽  
Immune System Development ◽  
Interactive Environment ◽  
System Logs ◽  
Linear Regressions

AbstractBackgroundRelationships between specific microbes and proper immune system development, composition, and function have been reported in a number of studies. However, researchers have discovered only a fraction of the likely relationships. High-dimensional “omic” methodologies such as 16S ribosomal RNA (rRNA) sequencing and Time-of-flight mass cytometry (CyTOF) immunophenotyping generate data that support generation of hypotheses, with the potential to identify additional relationships at a level of granularity ripe for further experimentation. Pairwise linear regressions between microbial and host immune features is one approach for quantifying relationships between “omes”, and the differences in these relationships across study cohorts or arms. This approach yields a top table of candidate results. However, the top table alone lacks the detail that domain experts need to vet candidate results for follow-up experiments.ResultsTo support this vetting, we developed VOLARE (Visualization Of LineAr Regression Elements), a web application that integrates a searchable top table, small in-line graphs illustrating the fitted models, a network summarizing the top table, and on-demand detailed regression plots showing full sample-level detail. We applied VOLARE to three case studies—microbiome:cytokine data from fecal samples in HIV, microbiome:cytokine data in inflammatory bowel disease and spondyloarthritis, and microbiome:immune cell data from gut biopsies in HIV. We present both patient-specific phenomena and relationships that differ by disease state. We also analyzed interaction data from system logs to characterize usage scenarios. This log analysis revealed that, in using VOLARE, domain experts frequently generated detailed regression plots, suggesting that this detail aids the vetting of results.ConclusionsSystematically integrating microbe:immune cell readouts through pairwise linear regressions and presenting the top table in an interactive environment supports the vetting of results for scientific relevance. VOLARE allows domain experts to control the analysis of their results, screening dozens of candidate relationships with ease. This interactive environment transcends the limitations of a static top table.

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