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The Role of Human Milk Oligosaccharides and Probiotics on the Neonatal Microbiome and Risk of Necrotizing Enterocolitis: A Narrative Review.
Nolan, LS, Rimer, JM, Good, M
Nutrients. 2020;(10)
Abstract
Preterm infants are a vulnerable population at risk of intestinal dysbiosis. The newborn microbiome is dominated by Bifidobacterium species, though abnormal microbial colonization can occur by exogenous factors such as mode of delivery, formula feeding, and exposure to antibiotics. Therefore, preterm infants are predisposed to sepsis and necrotizing enterocolitis (NEC), a fatal gastrointestinal disorder, due to an impaired intestinal barrier, immature immunity, and a dysbiotic gut microbiome. Properties of human milk serve as protection in the prevention of NEC. Human milk oligosaccharides (HMOs) and the microbiome of breast milk are immunomodulatory components that provide intestinal homeostasis through regulation of the microbiome and protection of the intestinal barrier. Enteral probiotic supplements have been trialed to evaluate their impact on establishing intestinal homeostasis. Here, we review the protective role of HMOs, probiotics, and synbiotic combinations in protecting a vulnerable population from the pathogenic features associated with necrotizing enterocolitis.
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Breast Milk Lipids and Fatty Acids in Regulating Neonatal Intestinal Development and Protecting against Intestinal Injury.
Ramiro-Cortijo, D, Singh, P, Liu, Y, Medina-Morales, E, Yakah, W, Freedman, SD, Martin, CR
Nutrients. 2020;(2)
Abstract
Human breast milk is the optimal source of nutrition for infant growth and development. Breast milk fats and their downstream derivatives of fatty acids and fatty acid-derived terminal mediators not only provide an energy source but also are important regulators of development, immune function, and metabolism. The composition of the lipids and fatty acids determines the nutritional and physicochemical properties of human milk fat. Essential fatty acids, including long-chain polyunsaturated fatty acids (LCPUFAs) and specialized pro-resolving mediators, are critical for growth, organogenesis, and regulation of inflammation. Combined data including in vitro, in vivo, and human cohort studies support the beneficial effects of human breast milk in intestinal development and in reducing the risk of intestinal injury. Human milk has been shown to reduce the occurrence of necrotizing enterocolitis (NEC), a common gastrointestinal disease in preterm infants. Preterm infants fed human breast milk are less likely to develop NEC compared to preterm infants receiving infant formula. Intestinal development and its physiological functions are highly adaptive to changes in nutritional status influencing the susceptibility towards intestinal injury in response to pathological challenges. In this review, we focus on lipids and fatty acids present in breast milk and their impact on neonatal gut development and the risk of disease.
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Bioactive Factors in Human Breast Milk Attenuate Intestinal Inflammation during Early Life.
Thai, JD, Gregory, KE
Nutrients. 2020;(2)
Abstract
Human breast milk is well known as the ideal source of nutrition during early life, ensuring optimal growth during infancy and early childhood. Breast milk is also the source of many unique and dynamic bioactive components that play a key role in the development of the immune system. These bioactive components include essential microbes, human milk oligosaccharides (HMOs), immunoglobulins, lactoferrin and dietary polyunsaturated fatty acids. These factors all interact with intestinal commensal bacteria and/or immune cells, playing a critical role in establishment of the intestinal microbiome and ultimately influencing intestinal inflammation and gut health during early life. Exposure to breast milk has been associated with a decreased incidence and severity of necrotizing enterocolitis (NEC), a devastating disease characterized by overwhelming intestinal inflammation and high morbidity among preterm infants. For this reason, breast milk is considered a protective factor against NEC and aberrant intestinal inflammation common in preterm infants. In this review, we will describe the key microbial, immunological, and metabolic components of breast milk that have been shown to play a role in the mechanisms of intestinal inflammation and/or NEC prevention.
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Dietary Gluten as a Conditioning Factor of the Gut Microbiota in Celiac Disease.
Bascuñán, KA, Araya, M, Roncoroni, L, Doneda, L, Elli, L
Advances in nutrition (Bethesda, Md.). 2020;(1):160-174
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Abstract
The gut microbiota plays a relevant role in determining an individual's health status, and the diet is a major factor in modulating the composition and function of gut microbiota. Gluten constitutes an essential dietary component in Western societies and is the environmental trigger of celiac disease. The presence/absence of gluten in the diet can change the diversity and proportions of the microbial communities constituting the gut microbiota. There is an intimate relation between gluten metabolism and celiac disease pathophysiology and gut microbiota; their interrelation defines intestinal health and homeostasis. Environmental factors modify the intestinal microbiota and, in turn, its changes modulate the mucosal and immune responses. Current evidence from studies of young and adult patients with celiac disease increasingly supports that dysbiosis (i.e., compositional and functional alterations of the gut microbiome) is present in celiac disease, but to what extent this is a cause or consequence of the disease and whether the different intestinal diseases (celiac disease, ulcerative colitis, Crohn disease) have specific change patterns is not yet clear. The use of bacterial-origin enzymes that help completion of gluten digestion is of interest because of the potential application as coadjuvant in the current treatment of celiac disease. In this narrative review, we address the current knowledge on the complex interaction between gluten digestion and metabolism, celiac disease, and the intestinal microbiota.
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The Immunomodulatory Properties of Extracellular Vesicles Derived from Probiotics: A Novel Approach for the Management of Gastrointestinal Diseases.
Molina-Tijeras, JA, Gálvez, J, Rodríguez-Cabezas, ME
Nutrients. 2019;(5)
Abstract
Probiotics, included in functional foods, nutritional supplements, or nutraceuticals, exhibit different beneficial effects on gut function. They are extensively used to improve the digestive processes as well as reduce the symptoms and progression of different diseases. Probiotics have shown to improve dysbiosis and modulate the immune response of the host by interacting with different cell types. Probiotics and the host can interact in a direct way, but it is becoming apparent that communication occurs also through extracellular vesicles (EVs) derived from probiotics. EVs are key for bacteria-bacteria and bacteria-host interactions, since they carry a wide variety of components that can modulate different signaling pathways, including those involved in the immune response. Interestingly, EVs are recently starting to be considered as an alternative to probiotics in those cases for which the use of live bacteria could be dangerous, such as immunocompromised individuals or situations where the intestinal barrier is impaired. EVs can spread through the mucus layer and interact with the host, avoiding the risk of sepsis. This review summarizes the existing knowledge about EVs from different probiotic strains, their properties, and their potential use for the prevention or treatment of different gastrointestinal diseases.
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Coeliac disease: beyond genetic susceptibility and gluten. A narrative review.
Pes, GM, Bibbò, S, Dore, MP
Annals of medicine. 2019;(1):1-16
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Abstract
Coeliac disease (CD) is an immune-mediated disorder triggered by the ingestion of gluten in genetically susceptible individuals. However, only a small proportion of subjects harbouring CD-related genetic risk develop the disease. Among the environmental factors that may influence CD risk, pre- and perinatal factors, delivery methods, parental lifestyle, infant feeding practices, seasonality, dietary factors, drug use, childhood infections and variability in gut microbiota are those most widely studied regarding the risk to develop CD. Although for many of these external factors the exact mechanism of action is unknown, most of them are thought to act by disrupting the intestinal barrier, facilitating contact between potential antigens and the immune system effector cells. Management of CD is relatively easy in patients with a definite diagnosis and requires a strict, lifelong, gluten-free diet. Better knowledge of environmental exposures apart from gluten can facilitate understanding of the pathogenesis of the disorder and the wide heterogeneity of its clinical spectrum. The purpose of this review is to discuss current knowledge on environmental CD risk factors, as well as possible interaction between them, on the grounds of the reliable scientific evidence available. Key messages The risk of developing CD is influenced not only by gluten ingestion but also by a number of environmental factors including childhood infections and variability in gut microbiota, pre- and perinatal factors, infant feeding practices, delivery methods, parental lifestyle, seasonality, dietary factors and drug use, acting mainly by disrupting intestinal permeability. Better knowledge of exposure to these factors can facilitate their identification, and subsequent elimination, in the individual patient.
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Taming the Beast: Interplay between Gut Small Molecules and Enteric Pathogens.
Kumar, A, Ellermann, M, Sperandio, V
Infection and immunity. 2019;(9)
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Abstract
The overuse of antibiotics has led to the evolution of drug-resistant bacteria that are becoming increasingly dangerous to human health. According to the Centers for Disease Control and Prevention, antibiotic-resistant bacteria cause at least 2 million illnesses and 23,000 deaths in the United States annually. Traditionally, antibiotics are bactericidal or bacteriostatic agents that place selective pressure on bacteria, leading to the expansion of antibiotic-resistant strains. In addition, antibiotics that are effective against some pathogens can also exacerbate their pathogenesis and may lead to severe progression of the disease. Therefore, alternative strategies are needed to treat antibiotic-resistant bacterial infections. One novel approach is to target bacterial virulence to prevent or limit pathogen colonization, while also minimizing tissue damage and disease comorbidities in the host. This review focuses on the interactions between enteric pathogens and naturally occurring small molecules in the human gut as potential therapeutic targets for antivirulence strategies. Individual small molecules in the intestines modulate enteric pathogen virulence and subsequent intestinal fitness and colonization. Targeted interruption of pathogen sensing of these small molecules could therefore attenuate their virulence. This review highlights the paths of discovery for new classes of antimicrobials that could potentially mitigate the urgent problem of antibiotic resistance.
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Improvements in intestine transplantation.
Celik, N, Stanley, K, Rudolph, J, Al-Issa, F, Kosmach, B, Ashokkumar, C, Sun, Q, Brown-Bakewell, R, Zecca, D, Soltys, K, et al
Seminars in pediatric surgery. 2018;(4):267-272
Abstract
Transplantation of the intestine in children has presented significant challenges even as it has become a standard to treat nutritional failure due to short gut syndrome. These challenges have been addressed in part by significant improvements in short and long-term care. Noteworthy enhancements include reduced need for intestine transplantation, drug-sparing immunosuppressive regimens, immune monitoring, and improved surveillance and management of PTLD and non-adherence.
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Factors influencing the infant gut microbiome at age 3-6 months: Findings from the ethnically diverse Vitamin D Antenatal Asthma Reduction Trial (VDAART).
Sordillo, JE, Zhou, Y, McGeachie, MJ, Ziniti, J, Lange, N, Laranjo, N, Savage, JR, Carey, V, O'Connor, G, Sandel, M, et al
The Journal of allergy and clinical immunology. 2017;(2):482-491.e14
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Abstract
BACKGROUND The gut microbiome in infancy influences immune system maturation, and may have an important impact on allergic disease risk. OBJECTIVE We sought to determine how prenatal and early life factors impact the gut microbiome in a relatively large, ethnically diverse study population of infants at age 3 to 6 months, who were enrolled in Vitamin D Antenatal Asthma Reduction Trial, a clinical trial of vitamin D supplementation in pregnancy to prevent asthma and allergies in offspring. METHODS We performed 16S rRNA gene sequencing on 333 infants' stool samples. Microbial diversity was computed using the Shannon index. Factor analysis applied to the top 25 most abundant taxa revealed 4 underlying bacterial coabundance groups; the first dominated by Firmicutes (Lachnospiraceae/Clostridiales), the second by Proteobacteria (Klebsiella/Enterobacter), the third by Bacteriodetes, and the fourth by Veillonella. Scores for coabundance groups were used as outcomes in regression models, with prenatal/birth and demographic characteristics as independent predictors. Multivariate analysis, using all microbial community members, was also conducted. RESULTS White race/ethnicity was associated with lower diversity but higher Bacteroidetes coabundance scores. C-section birth was associated with higher diversity, but decreased Bacteroidetes coabundance scores. Firmicutes scores were higher for infants born by C-section. Breast-fed infants had lower proportions of Clostridiales. Cord blood vitamin D was linked to increased Lachnobacterium, but decreased Lactococcus. CONCLUSIONS The findings presented here suggest that race, mode of delivery, breast-feeding, and cord blood vitamin D levels are associated with infant gut microbiome composition, with possible long-term implications for immune system modulation and asthma/allergic disease incidence.