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1.
The Glutamate and the Immune Systems: New Targets for the Pharmacological Treatment of OCD.
Marazziti, D, Albert, U, Mucci, F, Piccinni, A
Current medicinal chemistry. 2018;(41):5731-5738
Abstract
BACKGROUND In the last decades the pharmacological treatment of obsessivecompulsive disorder (OCD) has been significantly promoted by the effectiveness of selective serotonin (5-HT) reuptake inhibitors (SSRIs) and the subsequent development of the 5-HT hypothesis of OCD. However, since a large majority of patients (between 40% and 60 %) do not respond to SSRIs or strategies based on the modulation of the 5-HT system, it is now essential to search for other possible therapeutic targets. AIMS The aim of this paper was to review current literature through a PubMed and Google Scholar search of novel hypotheses and related compounds for the treatment of OCD, with a special focus on the glutammate and the immune systems. DISCUSSION The literature indicates that glutamate, the main excitatory neurotransmitter, might play an important role in the pathophysiology of OCD. In addition, a series of clinical studies also supports the potential efficacy of drugs modulating the glutamate system. The role of the immune system alterations in OCD in both children and adults needs to be more deeply elucidated. In children, a subtype of OCD has been widely described resulting from infections driven by group A streptococcus β-hemolitic and belonging to the so-called "pediatric autoimmune neuropsychiatric disorders associated with streptococcus" (PANDAS). In adults, available findings are meager and controversial, although interesting. CONCLUSION The glutamate and the immune systems represent two intriguing topics of research that hold promise for the development of open novel treatment strategies in OCD.
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2.
The impact of sport related stressors on immunity and illness risk in team-sport athletes.
Keaney, LC, Kilding, AE, Merien, F, Dulson, DK
Journal of science and medicine in sport. 2018;(12):1192-1199
Abstract
OBJECTIVES Elite team-sport athletes are frequently exposed to stressors that have the potential to depress immunity and increase infection risk. Therefore, the purpose of this review is to describe how team-sport stressors impact upon immune responses, along with exploring whether alterations in these markers have the potential to predict upper respiratory tract illness symptoms. DESIGN Narrative review. METHODS Salivary secretory immunoglobulin A (SIgA) and T-cell markers have been shown to predict infection risk in individual endurance athletes. Papers discussing the impact of team-sport stressors on SIgA and T-cells were discussed in the review, studies discussing other aspects of immunity were excluded. Journal articles were sourced from PubMed, Web of science and Scopus. Key search terms included team-sport athletes, stressors, immunity, T-cells, cytokines, SIgA and upper respiratory illness. RESULTS Most team-sport stressors appear to increase risk for illness. An association between reduced SIgA and increased illness incidence has been demonstrated. Intensive training and competition periods have been shown to reduce SIgA, however, it is less clear how additional stressors including extreme environmental conditions, travel, psychological stress, sleep disturbance and poor nutrition affect immune responses. CONCLUSIONS Monitoring SIgA may provide an assessment of a team-sport athletes risk status for developing upper respiratory tract symptoms, however there is currently not enough evidence to suggest SIgA alone can predict illness. Team-sport stressors challenge immunity and it is possible that the combination of stressors could have a compounding effect on immunodepression and infection risk. Given that illness can disrupt training and performance, further research is required to better elucidate how stressors individually and collectively influence immunity and illness.
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3.
A reverse metabolic approach to weaning: in silico identification of immune-beneficial infant gut bacteria, mining their metabolism for prebiotic feeds and sourcing these feeds in the natural product space.
Michelini, S, Balakrishnan, B, Parolo, S, Matone, A, Mullaney, JA, Young, W, Gasser, O, Wall, C, Priami, C, Lombardo, R, et al
Microbiome. 2018;(1):171
Abstract
BACKGROUND Weaning is a period of marked physiological change. The introduction of solid foods and the changes in milk consumption are accompanied by significant gastrointestinal, immune, developmental, and microbial adaptations. Defining a reduced number of infections as the desired health benefit for infants around weaning, we identified in silico (i.e., by advanced public domain mining) infant gut microbes as potential deliverers of this benefit. We then investigated the requirements of these bacteria for exogenous metabolites as potential prebiotic feeds that were subsequently searched for in the natural product space. RESULTS Using public domain literature mining and an in silico reverse metabolic approach, we constructed probiotic-prebiotic-food associations, which can guide targeted feeding of immune health-beneficial microbes by weaning food; analyzed competition and synergy for (prebiotic) nutrients between selected microbes; and translated this information into designing an experimental complementary feed for infants enrolled in a pilot clinical trial ( http://www.nourishtoflourish.auckland.ac.nz/ ). CONCLUSIONS In this study, we applied a benefit-oriented microbiome research strategy for enhanced early-life immune health. We extended from "classical" to molecular nutrition aiming to identify nutrients, bacteria, and mechanisms that point towards targeted feeding to improve immune health in infants around weaning. Here, we present the systems biology-based approach we used to inform us on the most promising prebiotic combinations known to support growth of beneficial gut bacteria ("probiotics") in the infant gut, thereby favorably promoting development of the immune system.
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4.
The Biological Activities of Vitamin D and Its Receptor in Relation to Calcium and Bone Homeostasis, Cancer, Immune and Cardiovascular Systems, Skin Biology, and Oral Health.
Khammissa, RAG, Fourie, J, Motswaledi, MH, Ballyram, R, Lemmer, J, Feller, L
BioMed research international. 2018;:9276380
Abstract
Vitamin D plays an important role in calcium homeostasis and bone metabolism, with the capacity to modulate innate and adaptive immune function, cardiovascular function, and proliferation and differentiation of both normal and malignant keratinocytes. 1,25(OH)2D, the biologically active form of vitamin D, exerts most of its functions through the almost universally distributed nuclear vitamin D receptor (VDR). Upon stimulation by 1,25(OH)2D, VDR forms a heterodimer with the retinoid X receptor (RXR). In turn, VDR/RXR binds to DNA sequences termed vitamin D response elements in target genes, regulating gene transcription. In order to exert its biological effects, VDR signalling interacts with other intracellular signalling pathways. In some cases 1,25(OH)2D exerts its biological effects without regulating either gene expression or protein synthesis. Although the regulatory role of vitamin D in many biological processes is well documented, there is not enough evidence to support the therapeutic use of vitamin D supplementation in the prevention or treatment of infectious, immunoinflammatory, or hyperproliferative disorders. In this review we highlight the effects of 1,25(OH)2D on bone and calcium homeostasis, on cancer, and refer to its effects on the cardiovascular and immune systems.
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5.
Regulation of the intestinal immune system by flavonoids and its utility in chronic inflammatory bowel disease.
Hoensch, HP, Weigmann, B
World journal of gastroenterology. 2018;(8):877-881
Abstract
Flavonoids are phytochemicals which can regulate the activity of the intestinal immune system. In patients with chronic inflammatory bowel disease (IBD) there is an overexpression and imbalance of the components of the inflammatory immune reactions which are chronically activated. Suppression of inflammation can be achieved by anti-inflammatory drugs which are used in clinical medicine but these can cause serious side effects. Flavonoids can have natural immunosuppressive properties and inhibit the activation of immune cells and its effectors (chemokines, TNF-, cytokines). Phytochemicals such as flavonoids bind to the nuclear Ah (aryl hydrocarbon) -receptor thereby stimulating protective enzyme activities. As shown by clinical evidence in patients and by experimental work some flavonoids (apigenin, epigallocatechin gallate) were effective in the inhibition of inflammation. Instead of or additionally to anti-inflammatory drugs flavonoids can be used in IBD patients to treat the over-reactive immunologic system. This is accomplished by upregulation of the Ah-receptor. Flavonoids interact with toll-like receptors expressing on the surface of immune cells, then they were internalized to the cytosol and transferred into the nucleus, where they were attached to the Ah-receptor. The Ah-receptor binds to the Ah-R nuclear translocator and via Ah response element beneficial protective enzymes and cytokines are induced, leading to upregulation of the anti-inflammatory system.
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6.
The Microbiotic Highway to Health-New Perspective on Food Structure, Gut Microbiota, and Host Inflammation.
Hansen, NW, Sams, A
Nutrients. 2018;(11)
Abstract
This review provides evidence that not only the content of nutrients but indeed the structural organization of nutrients is a major determinant of human health. The gut microbiota provides nutrients for the host by digesting food structures otherwise indigestible by human enzymes, thereby simultaneously harvesting energy and delivering nutrients and metabolites for the nutritional and biological benefit of the host. Microbiota-derived nutrients, metabolites, and antigens promote the development and function of the host immune system both directly by activating cells of the adaptive and innate immune system and indirectly by sustaining release of monosaccharides, stimulating intestinal receptors and secreting gut hormones. Multiple indirect microbiota-dependent biological responses contribute to glucose homeostasis, which prevents hyperglycemia-induced inflammatory conditions. The composition and function of the gut microbiota vary between individuals and whereas dietary habits influence the gut microbiota, the gut microbiota influences both the nutritional and biological homeostasis of the host. A healthy gut microbiota requires the presence of beneficial microbiotic species as well as vital food structures to ensure appropriate feeding of the microbiota. This review focuses on the impact of plant-based food structures, the "fiber-encapsulated nutrient formulation", and on the direct and indirect mechanisms by which the gut microbiota participate in host immune function.
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7.
Intrauterine infection, immune system and premature birth.
Helmo, FR, Alves, EAR, Moreira, RAA, Severino, VO, Rocha, LP, Monteiro, MLGDR, Reis, MAD, Etchebehere, RM, Machado, JR, Corrêa, RRM
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2018;(9):1227-1233
Abstract
Preterm birth accounts for nearly one million deaths among children under five years of age, and although its etiopathogenesis is not fully elucidated, ascending intrauterine infection and fetal inflammatory response seem to be the main triggers. The intense inflammatory response mediated by IL-1β, TNF-α, PAF, IFN-γ and IL-6, PGE2 and MMP-1 and MMP-9 causes fetal membrane damage and rupture, increased uterine contractions and biochemical and structural changes in the cervix. Furthermore, preterm neonates have deficient innate and adaptive immune responses characterized by reduced levels of IgG, opsonization and phagocytosis, as well as increased activation of Th1 cells in relation to Th2 cells. Therefore, this triad is favors the occurrence of neonatal complications, such as respiratory distress syndrome, necrotizing enterocolitis, retinopathy of prematurity and bronchopulmonary dysplasia. Due to serious maternal and child health complications of intrauterine infection, several studies have tried to identify biomarkers for the early diagnosis of this entity. This literature review aims to discuss the main scientific findings regarding the association between ascending intrauterine infection, immune system and preterm birth.
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8.
Neuro-, Cardio-, and Immunoplasticity: Effects of Early Adversity.
Pakulak, E, Stevens, C, Neville, H
Annual review of psychology. 2018;:131-156
Abstract
The relationship between early adversity and outcomes across the lifespan is apparent in a striking range of measures. Evidence suggests that many of these outcomes can be traced to the impacts of early adversity on multiple and integrated biological systems mediated by the brain. In this review, we integrate empirical and theoretical advances in the understanding of relationships among the brain and the functions of the endocrine, autonomic, and immune systems. We emphasize the effects of environmental experiences related to caregiver relationships because it is these experiences, in particular, that shape regulatory and threat response systems in ways that increase vulnerability and may underlie the wide range of poor outcomes associated with early adversity. Thus, we metaphorically extend the concept of plasticity to highlight our goal of a broader consideration of these interconnected mechanisms. We conclude by discussing implications for neurobiologically informed interventions that can potentially ameliorate the broad and costly effects of early adversity.
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9.
Diet, the intestinal microbiota, and immune health in aging.
Clements, SJ, R Carding, S
Critical reviews in food science and nutrition. 2018;(4):651-661
Abstract
Many countries are facing aging populations, with those over 65 years of age likely to represent the largest population over the next 10-20 years. Living longer often comes with poor health and, in particular, a decline in the immune function characterized by poor vaccine responses and increased risk of infection and certain cancers. Aging and diet represent major intrinsic and extrinsic factors that influence the makeup and activity of resident intestinal microbes, the microbiota, the efficient functioning of which is essential for sustaining overall health and the effectiveness of the immune system. The provision of elderly specific dietary recommendations appears to be lacking but is necessary since this population has an altered microbiota and immune response and may not respond in the same way as their healthy and younger counterparts. We have reviewed the evidence supporting the role of diet and, in particular, dietary carbohydrate, protein, and fat in influencing the microbiota and its generation of key metabolites that influence the efficient functioning of immune cells during aging, and how dietary intervention might be of benefit in improving the intestinal health and immune status in the elderly.
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10.
Stress and Immune Function: There is a Role for the Gut Microbiota?
Castellazzi, A, Tagliacarne, SC, Soldi, S, Perna, S, Ziviani, L, Milleri, S, Montagna, L, Valsecchi, C
Journal of clinical gastroenterology. 2018;:S66-S67