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Recent Advances in Psoriasis Research; the Clue to Mysterious Relation to Gut Microbiome.
Komine, M
International journal of molecular sciences. 2020;21(7)
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Psoriasis is a chronic inflammatory disease where the skin forms bumpy red patches covered with white scales. There is no cure, but medications have focused on supressing the immune response. There is a link between the gut microbiome and psoriasis but it is poorly understood. This review includes the current understanding of how psoriasis develops and discusses the recent findings to support further research in this area. The composition of the gut microbiome affects inflammation in the whole body. This inflammation is associated with cardiovascular disease, diabetes mellitus and other inflammatory disorders. Recent studies have linked cardiovascular disease, insulin resistance, and metabolic syndrome to an imbalance in the gut microbiome. Psoriasis is often found alongside these conditions with similar abnormalities in gut bacteria. An imbalance in gut microbiome could cause certain people to develop psoriasis. The role of the gut microbiome needs to be further clarified but mounting evidence for this gut/skin link means that other therapeutic options may be available for treatment in the future.
Abstract
Psoriasis is a chronic inflammatory cutaneous disease, characterized by activated plasmacytoid dendritic cells, myeloid dendritic cells, Th17 cells, and hyperproliferating keratinocytes. Recent studies revealed skin-resident cells have pivotal roles in developing psoriatic skin lesions. The balance in effector T cells and regulatory T cells is disturbed, leading Foxp3-positive regulatory T cells to produce proinflammatory IL-17. Not only acquired but also innate immunity is important in psoriasis pathogenesis, especially in triggering the disease. Group 3 innate lymphoid cell are considered one of IL-17-producing cells in psoriasis. Short chain fatty acids produced by gut microbiota stabilize expression of Foxp3 in regulatory T cells, thereby stabilizing their function. The composition of gut microbiota influences the systemic inflammatory status, and associations been shown with diabetes mellitus, cardiovascular diseases, psychomotor diseases, and other systemic inflammatory disorders. Psoriasis has been shown to frequently comorbid with diabetes mellitus, cardiovascular diseases, psychomotor disease and obesity, and recent report suggested the similar abnormality in gut microbiota as the above comorbid diseases. However, the precise mechanism and relation between psoriasis pathogenesis and gut microbiota needs further investigation. This review introduces the recent advances in psoriasis research and tries to provide clues to solve the mysterious relation of psoriasis and gut microbiota.
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COVID-19 infection: the perspectives on immune responses.
Shi, Y, Wang, Y, Shao, C, Huang, J, Gan, J, Huang, X, Bucci, E, Piacentini, M, Ippolito, G, Melino, G
Cell death and differentiation. 2020;27(5):1451-1454
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The SARS-CoV-2 infection triggers an immune response which varies greatly from one person to another. It can be roughly divided into three stages: stage I, an asymptomatic incubation period with or without detectable virus; stage II, non-severe symptomatic period with the presence of virus; stage III, severe respiratory symptomatic stage with high viral load. Currently around 15% of people infected end up in severe stage III. There appears to be a two-phase immune response; an early protective phase and a second inflammation-driven damaging phase. In phase one the adaptive immune system responds to the virus. Being in good general health is important in this phase to limiting the progression of the disease to a more severe stage. In phase two the innate immune system response to tissue damage caused by the virus could lead to widespread inflammation of the lungs and acute respiratory distress syndrome or respiratory failure. Therapeutically this raises the question of whether the immune response should be boosted in phase one and suppressed in phase two. There also appears to be an element of viral relapse in some patients discharged from hospital indicating that a virus-eliminating immune response may be difficult to achieve naturally. These same patients may also not respond to vaccines. Overall, it is still unclear why some people develop severe disease, whilst others do not. Overall immunity alone does not explain the differences in disease presentation.
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Beta Glucan: Supplement or Drug? From Laboratory to Clinical Trials.
Vetvicka, V, Vannucci, L, Sima, P, Richter, J
Molecules (Basel, Switzerland). 2019;24(7)
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Beta glucans, β-1,3-glucans (glucans) are chains of sugars (polysaccharides) naturally occurring in the cell walls of plants such as cereals, bacteria and fungi. They are gaining attention not only as an important food supplement but also as an immunostimulant and potential drug. It has been known since prehistoric times that mushrooms have medicinal properties. Glucans effect various branches of the immune system and there are numerous animal and human studies showing remarkable activity against a wide variety of tumours. This paper represents an up-to-date review of glucans and their role in various immune reactions and the treatment of cancer. It also cites studies showing their potential use for wound healing and skin health, chronic respiratory problems in children, alleviation of allergic problems and reducing cholesterol levels. Additional lesser-known effects of glucan include improvements in colitis, obesity, or Lyme disease The authors conclude that glucans are an important immunomodulator. They believe that glucans will soon move from food supplement to widely accepted drug.
Abstract
Glucans are part of a group of biologically active natural molecules and are steadily gaining strong attention not only as an important food supplement, but also as an immunostimulant and potential drug. This paper represents an up-to-date review of glucans (β-1,3-glucans) and their role in various immune reactions and the treatment of cancer. With more than 80 clinical trials evaluating their biological effects, the question is not if glucans will move from food supplement to widely accepted drug, but how soon.
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A pilot, open labelled, randomised controlled trial of hypertonic saline nasal irrigation and gargling for the common cold.
Ramalingam, S, Graham, C, Dove, J, Morrice, L, Sheikh, A
Scientific reports. 2019;9(1):1015
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The common cold is a viral upper respiratory tract infection which affects adults and children worldwide, often multiple times a year. A large number of viruses cause these infections, making targeted antiviral treatment impractical. This small, randomised, controlled pilot trial (not blinded) of 68 adults aimed to assess the impact of salt-water nasal washing and throat gargling as many times as required (on average 3 times a day for 5 days) within 48 hours of symptom on-set on study recruitment and retention, as well as acceptability, symptom duration and viral shedding. The researchers found that nasal irrigation and gargling with a saline solution was acceptable to study participants. Illness duration was shortened by 1.9 days in the intervention arm, with significant reductions in the duration of runny nose, blocked nose, sneezing, cough and hoarseness of voice. The average quality of life score was also higher in the intervention arm, although this failed to reach significance. Viral shedding was higher in the intervention arm, with over the counter medication use 36% lower. There was also a lower rate of infection spread within households for the intervention arm. The authors call for a larger, placebo controlled trial to confirm these findings. Nutrition Practitioners supporting immunity in relation to the common cold virus may want to discuss the use of saline nasal irrigation with their clients as a simple measure to reduce symptoms and spread.
Abstract
There are no antivirals to treat viral upper respiratory tract infection (URTI). Since numerous viruses cause URTI, antiviral therapy is impractical. As we have evidence of chloride-ion dependent innate antiviral response in epithelial cells, we conducted a pilot, non-blinded, randomised controlled trial of hypertonic saline nasal irrigation and gargling (HSNIG) vs standard care on healthy adults within 48 hours of URTI onset to assess recruitment (primary outcome). Acceptability, symptom duration and viral shedding were secondary outcomes. Participants maintained a symptom diary until well for two days or a maximum of 14 days and collected 5 sequential mid-turbinate swabs to measure viral shedding. The intervention arm prepared hypertonic saline and performed HSNIG. We recruited 68 participants (2.6 participants/week; November 2014-March 2015). A participant declined after randomisation. Another was on antibiotics and hence removed (Intervention:32, Control:34). Follow up data was available from 61 (Intervention:30, Control:31). 87% found HSNIG acceptable, 93% thought HSNIG made a difference to their symptoms. In the intervention arm, duration of illness was lower by 1.9 days (p = 0.01), over-the-counter medications (OTCM) use by 36% (p = 0.004), transmission within household contacts by 35% (p = 0.006) and viral shedding by ≥0.5 log10/day (p = 0.04). We hence need a larger trial to confirm our findings.
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Gut Microbiota Modulation on Intestinal Mucosal Adaptive Immunity.
Wang, L, Zhu, L, Qin, S
Journal of immunology research. 2019;2019:4735040
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The mammalian intestine plays host to a vast microbiota, which is essential for the development and maintenance of the host’s immune system. This highly technical review highlights the results of recent studies on the effects and cellular and molecular mechanisms of the intestinal microbiota, and their metabolites and signals, on the development of intestinal immune cells and their functions. When the balance of the microbiota and their effects on intestinal immunity is disrupted (dysbiosis) this can lead to chronic local and systemic inflammatory and autoimmune disorders. The authors conclude that identifying microorganisms and their metabolites that can affect immunity, and the underlying mechanisms, is crucial for the development of microbiota based therapeutics.
Abstract
The mammalian intestine harbors a remarkable number of microbes and their components and metabolites, which are fundamental for the instigation and development of the host immune system. The intestinal innate and adaptive immunity coordinate and interact with the symbionts contributing to the intestinal homeostasis through establishment of a mutually beneficial relationship by tolerating to symbiotic microbiota and retaining the ability to exert proinflammatory response towards invasive pathogens. Imbalance between the intestinal immune system and commensal organisms disrupts the intestinal microbiological homeostasis, leading to microbiota dysbiosis, compromised integrity of the intestinal barrier, and proinflammatory immune responses towards symbionts. This, in turn, exacerbates the degree of the imbalance. Intestinal adaptive immunity plays a critical role in maintaining immune tolerance towards symbionts and the integrity of intestinal barrier, while the innate immune system regulates the adaptive immune responses to intestinal commensal bacteria. In this review, we will summarize recent findings on the effects and mechanisms of gut microbiota on intestinal adaptive immunity and the plasticity of several immune cells under diverse microenvironmental settings.
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Tryptophan Metabolism in Inflammaging: From Biomarker to Therapeutic Target.
Sorgdrager, FJH, Naudé, PJW, Kema, IP, Nollen, EA, Deyn, PP
Frontiers in immunology. 2019;10:2565
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Inflammation is a normal physiological process activated by the immune system in response to injury or infection. As we age, the immune system changes and the balance between pro- and anti-inflammatory agents can shift. This causes a chronic inflammatory state referred to as inflammaging. The rate of inflammaging is strongly associated with age-related disability, disease and mortality. The way in which the essential amino acid tryptophan (Trp) is broken down affects inflammation. If it is converted to kynurenine (Kyn) and its metabolites, inflammation is modulated. Studies have shown that the Kyn/Trp ratio, measured in blood, is strongly associated with ageing in humans. It could therefore be a useful marker to predict the onset of age-related diseases. This review discusses the metabolism of Trp and the links to inflammation. The authors hypothesize how intervening in these pathways could impact health- and lifespan. Future studies are needed to confirm the value of Trp metabolism as a biomarker for (un)healthy ageing and as drug target for inflammaging-related disease.
Abstract
Inflammation aims to restore tissue homeostasis after injury or infection. Age-related decline of tissue homeostasis causes a physiological low-grade chronic inflammatory phenotype known as inflammaging that is involved in many age-related diseases. Activation of tryptophan (Trp) metabolism along the kynurenine (Kyn) pathway prevents hyperinflammation and induces long-term immune tolerance. Systemic Trp and Kyn levels change upon aging and in age-related diseases. Moreover, modulation of Trp metabolism can either aggravate or prevent inflammaging-related diseases. In this review, we discuss how age-related Kyn/Trp activation is necessary to control inflammaging and alters the functioning of other metabolic faiths of Trp including Kyn metabolites, microbiota-derived indoles and nicotinamide adenine dinucleotide (NAD+). We explore the potential of the Kyn/Trp ratio as a biomarker of inflammaging and discuss how intervening in Trp metabolism might extend health- and lifespan.
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Gut Microbiota-Immune System Crosstalk and Pancreatic Disorders.
Pagliari, D, Saviano, A, Newton, EE, Serricchio, ML, Dal Lago, AA, Gasbarrini, A, Cianci, R
Mediators of inflammation. 2018;2018:7946431
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Gut microbiota homeostasis plays a central role in modulating the mucosal immune system. Increasing research has shown a correlation between an imbalanced gut microbiota, called dysbiosis, and various pancreatic disorders. The aim of this review was to analyse current data linking the gut microbiome and several pancreatic disorders. The current evidence demonstrates gut dysbiosis is correlated with the duration and prognosis of pancreatic disorders. While this may lead to early detection of several pancreatic disorders, it remains unclear whether dysbiosis is a cause or effect of pancreatic disorders. Based on these results, the authors conclude future studies are required to better understand the crosstalk between gut microbiota and the immune system to improve diagnostic and treatment strategies for pancreatic disorders.
Abstract
Gut microbiota is key to the development and modulation of the mucosal immune system. It plays a central role in several physiological functions, in the modulation of inflammatory signaling and in the protection against infections. In healthy states, there is a perfect balance between commensal and pathogens, and microbiota and the immune system interact to maintain gut homeostasis. The alteration of such balance, called dysbiosis, determines an intestinal bacterial overgrowth which leads to the disruption of the intestinal barrier with systemic translocation of pathogens. The pancreas does not possess its own microbiota, and it is believed that inflammatory and neoplastic processes affecting the gland may be linked to intestinal dysbiosis. Increasing research evidence testifies a correlation between intestinal dysbiosis and various pancreatic disorders, but it remains unclear whether dysbiosis is the cause or an effect. The analysis of specific alterations in the microbiome profile may permit to develop novel tools for the early detection of several pancreatic disorders, utilizing samples, such as blood, saliva, and stools. Future studies will have to elucidate the mechanisms by which gut microbiota is modulated and how it tunes the immune system, in order to be able to develop innovative treatment strategies for pancreatic disorders.
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The Effect of Bifidobacterium animalis ssp. lactis HN019 on Cellular Immune Function in Healthy Elderly Subjects: Systematic Review and Meta-Analysis.
Miller, LE, Lehtoranta, L, Lehtinen, MJ
Nutrients. 2017;9(3)
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Elderly individuals are more susceptible to infections and cancer, due to lowered immune system function. The gut bacteria play a key role in human immune system function and there is an interest in a potential role for probiotics in strengthening the immune system through manipulation of the microbiome. This systematic review and meta-analysis of 4 randomised controlled trials aimed to examine the efficacy of Bifidobacterium animalis lactis HN019 on the cellular immune activity of healthy elderly adults age 60-70 years. The authors concluded that supplementation with this bacterial strain at a range of potencies for 3-6 weeks duration had a significant positive impact on the part of the immune system that is responsible for removing pathogens and cell debris (phagocytosis) and a lesser but nevertheless significant impact on natural killer cells responsible for tumour destruction.
Abstract
Elderly people have increased susceptibility to infections and cancer that are associated with decline in cellular immune function. The objective of this work was to determine the efficacy of Bifidobacterium (B.) animalis ssp. lactis HN019 (HN019) supplementation on cellular immune activity in healthy elderly subjects. We conducted a systematic review of Medline and Embase for controlled trials that reported polymorphonuclear (PMN) cell phagocytic capacity or natural killer (NK) cell tumoricidal activity following B. lactis HN019 consumption in the elderly. A random effects meta-analysis was performed with standardized mean difference (SMD) and 95% confidence interval between probiotic and control groups for each outcome. A total of four clinical trials were included in this analysis. B. lactis HN019 supplementation was highly efficacious in increasing PMN phagocytic capacity with an SMD of 0.74 (95% confidence interval: 0.38 to 1.11, p < 0.001) and moderately efficacious in increasing NK cell tumoricidal activity with an SMD of 0.43 (95% confidence interval: 0.08 to 0.78, p = 0.02). The main limitations of this research were the small number of included studies, short-term follow-up, and assessment of a single probiotic strain. In conclusion, daily consumption of B. lactis HN019 enhances NK cell and PMN function in healthy elderly adults.