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1.
Obesity in Humans Is Characterized by Gut Inflammation as Shown by Pro-Inflammatory Intestinal Macrophage Accumulation.
Rohm, TV, Fuchs, R, Müller, RL, Keller, L, Baumann, Z, Bosch, AJT, Schneider, R, Labes, D, Langer, I, Pilz, JB, et al
Frontiers in immunology. 2021;:668654
Abstract
Chronic low-grade inflammation is a hallmark of obesity and associated with cardiovascular complications. However, it remains unclear where this inflammation starts. As the gut is constantly exposed to food, gut microbiota, and metabolites, we hypothesized that mucosal immunity triggers an innate inflammatory response in obesity. We characterized five distinct macrophage subpopulations (P1-P5) along the gastrointestinal tract and blood monocyte subpopulations (classical, non-classical, intermediate), which replenish intestinal macrophages, in non-obese (BMI<27kg/m2) and obese individuals (BMI>32kg/m2). To elucidate factors that potentially trigger gut inflammation, we correlated these subpopulations with cardiovascular risk factors and lifestyle behaviors. In obese individuals, we found higher pro-inflammatory macrophages in the stomach, duodenum, and colon. Intermediate blood monocytes were also increased in obesity, suggesting enhanced recruitment to the gut. We identified unhealthy lifestyle habits as potential triggers of gut and systemic inflammation (i.e., low vegetable intake, high processed meat consumption, sedentary lifestyle). Cardiovascular risk factors other than body weight did not affect the innate immune response. Thus, obesity in humans is characterized by gut inflammation as shown by accumulation of pro-inflammatory intestinal macrophages, potentially via recruited blood monocytes. Understanding gut innate immunity in human obesity might open up new targets for immune-modulatory treatments in metabolic disease.
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2.
Evaluation of a Nutraceutical Product with Probiotics, Vitamin D, Plus Banaba Leaf Extracts (Lagerstroemia speciosa) in Glycemic Control.
Signorini, L, Ballini, A, Arrigoni, R, De Leonardis, F, Saini, R, Cantore, S, De Vito, D, Coscia, MF, Dipalma, G, Santacroce, L, et al
Endocrine, metabolic & immune disorders drug targets. 2021;(7):1356-1365
Abstract
BACKGROUND Dysbiosis is related to changes in the composition and behaviour of intestinal microbiota, which may contribute to an age-related decline in metabolic and immune system functioning (immune-senescence). OBJECTIVE The microbiota-targeted dietary and probiotic interventions have been shown to favorably affect the host health by an enhancement of antioxidant activity, improving immune homeostasis, suppression of chronic inflammation, regulation of metabolism and prevention of insulin resistance. RESULTS In our study, the use of specific probiotics strains improved the serum concentration of glycemic markers, thereby promoting better overall health. CONCLUSION Probiotics may help correct defects in the gut microbial environment improving metabolic parameters, such as blood sugar levels, glycosylated hemoglobin and a decrease in body weight.
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3.
Modulation of Immune Responses by Nutritional Ligands of Aryl Hydrocarbon Receptor.
De Juan, A, Segura, E
Frontiers in immunology. 2021;:645168
Abstract
Accumulating evidence indicates that nutrition can modulate the immune system through metabolites, either produced by host digestion or by microbiota metabolism. In this review, we focus on dietary metabolites that are agonists of the Aryl hydrocarbon Receptor (AhR). AhR is a ligand-activated transcription factor, initially characterized for its interaction with xenobiotic pollutants. Numerous studies have shown that AhR also recognizes indoles and tryptophan catabolites originating from dietary compounds and commensal bacteria. Here, we review recent work employing diet manipulation to address the impact of nutritional AhR agonists on immune responses, both locally in the intestine and at distant sites. In particular, we examine the physiological role of these metabolites in immune cell development and functions (including T lymphocytes, innate-like lymphoid cells, and mononuclear phagocytes) and their effect in inflammatory disorders.
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The Gut‒Breast Axis: Programming Health for Life.
Rodríguez, JM, Fernández, L, Verhasselt, V
Nutrients. 2021;(2)
Abstract
The gut is a pivotal organ in health and disease. The events that take place in the gut during early life contribute to the programming, shaping and tuning of distant organs, having lifelong consequences. In this context, the maternal gut plays a quintessence in programming the mammary gland to face the nutritional, microbiological, immunological, and neuroendocrine requirements of the growing infant. Subsequently, human colostrum and milk provides the infant with an impressive array of nutrients and bioactive components, including microbes, immune cells, and stem cells. Therefore, the axis linking the maternal gut, the breast, and the infant gut seems crucial for a correct infant growth and development. The aim of this article is not to perform a systematic review of the human milk components but to provide an insight of their extremely complex interactions, which render human milk a unique functional food and explain why this biological fluid still truly remains as a scientific enigma.
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5.
The Possible Role of Pathogenic and Non-Pathogenic Bacteria in Initiation and Exacerbation of Celiac Disease; A Comprehensive Review.
Azimi, T, Nasser, A, Shariati, A, Shiadeh, SMJ, Safari, H, Alizade-Sani, M, Taghipour, A, Dehghan, A
Current pharmaceutical biotechnology. 2020;(6):452-466
Abstract
Celiac Disease (CD) is an immune-mediated enteropathy, generally of the proximal intestine, that occurs in genetically susceptible individuals triggered by the ingestion of gluten. The incidence and frequency of CD are increasing, and it is predicted that CD affects approximately 1% of the people worldwide. The common clinical manifestations of CD are divided in two sections, including classic and non-classic symptoms that can be created in childhood and adulthood. The relationship between pathogenic and non-pathogenic bacteria with CD is complex and multidirectional. In previous published studies, results demonstrated the triggering impact of bacteria, viruses, and parasites on initiation and development of Inflammatory Bowel Disease (IBD) and Irritable Bowel Syndrome (IBS). Different studies revealed the inducing effect of pathogenic and non-pathogenic bacteria on CD. However, increasing evidence proposes that some of these microorganisms can also play several positive roles in CD process. Although information of the pathogenesis of the CD is quickly expanding, the possible role of bacteria needs further examination. In conclusion, with respect to the possible correlation between different bacteria in CD, the current review-based study aims to discuss the possible relationship between CD and pathogenic and non-pathogenic bacteria and to show various and significant aspects of mechanisms involved in the CD process.
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6.
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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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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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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Preterm neonatal immunology at the intestinal interface.
Van Belkum, M, Mendoza Alvarez, L, Neu, J
Cellular and molecular life sciences : CMLS. 2020;(7):1209-1227
Abstract
Fetal and neonatal development represents a critical window for setting a path toward health throughout life. In this review, we focus on intestinal immunity, how it develops, and its implications for subsequent neonatal diseases. We discuss maternal nutritional and environmental exposures that dictate outcomes for the developing fetus. Although still controversial, there is evidence in support of an in utero microbiome. Specific well-intentioned and routine applications of antibiotics, steroids, and surgical interventions implemented before, during, and after birth skew the neonate towards pro-inflammatory dysbiosis. Shortly after birth, a consortium of maternal and environmentally derived bacteria, through cross-talk with the developing host immune system, takes center stage in developing or disrupting immune homeostasis at the intestinal interface. We also examine subsequent immunological cross-talks, which involve neonatal myeloid and lymphoid responses, and their potential impacts on health and disease such as necrotizing enterocolitis and sepsis, especially critical disease entities for the infant born preterm.
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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.