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A randomized, phase 1, placebo-controlled trial of APG-157 in oral cancer demonstrates systemic absorption and an inhibitory effect on cytokines and tumor-associated microbes.
Basak, SK, Bera, A, Yoon, AJ, Morselli, M, Jeong, C, Tosevska, A, Dong, TS, Eklund, M, Russ, E, Nasser, H, et al
Cancer. 2020;126(8):1668-1682
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APG-157 is a botanical drug containing multiple polyphenols that delivers the active components to oromucosal tissues near the tumour target. APG-157 slowly disintegrates in the oral cavity over 15 to 20 minutes to release the drug substance. The drug substance is a precise, rational combination of multiple molecules derived from Curcuma longa wherein curcumin is the principal component. The main aim of this study was to determine the pharmacokinetics and safety of the orally delivered pastille (APG-157) when used by normal subjects and patients with cancer. This study is a randomised, double-blind, placebo-controlled trial. A total of 32 subjects were enrolled, and 25 completed the study (13 normal individuals and 12 patients with oral cancer). Results demonstrated that transoral APG-157 treatment leads to systemic absorption of curcumin and its analogs. There was a statistically significant concentration reduction in inflammatory cytokines and Bacteroides species noted in the salivary cells. Pre-treatment and post-treatment tumour samples from patients with cancer demonstrated T-cell recruitment to the tumour microenvironment. Authors conclude that APG-157 is absorbed well, reduces inflammation, and attracts T-cells to the tumour thus, it can be potentially used in combination with immunotherapy drugs. Furthermore, a long-term evaluation of immune checkpoint blockade with and without APG-157 could provide a clear understanding of the usefulness of APG-157 as either an adjuvant or neoadjuvant therapeutic agent for patients with advanced or recurrent head and neck cancer.
Abstract
BACKGROUND Although curcumin's effect on head and neck cancer has been studied in vitro and in vivo, to the authors' knowledge its efficacy is limited by poor systemic absorption from oral administration. APG-157 is a botanical drug containing multiple polyphenols, including curcumin, developed under the US Food and Drug Administration's Botanical Drug Development, that delivers the active components to oromucosal tissues near the tumor target. METHODS A double-blind, randomized, placebo-controlled, phase 1 clinical trial was conducted with APG-157 in 13 normal subjects and 12 patients with oral cancer. Two doses, 100 mg or 200 mg, were delivered transorally every hour for 3 hours. Blood and saliva were collected before and 1 hour, 2 hours, 3 hours, and 24 hours after treatment. Electrocardiograms and blood tests did not demonstrate any toxicity. RESULTS Treatment with APG-157 resulted in circulating concentrations of curcumin and analogs peaking at 3 hours with reduced IL-1β, IL-6, and IL-8 concentrations in the salivary supernatant fluid of patients with cancer. Salivary microbial flora analysis showed a reduction in Bacteroidetes species in cancer subjects. RNA and immunofluorescence analyses of tumor tissues of a subject demonstrated increased expression of genes associated with differentiation and T-cell recruitment to the tumor microenvironment. CONCLUSIONS The results of the current study suggested that APG-157 could serve as a therapeutic drug in combination with immunotherapy. LAY SUMMARY Curcumin has been shown to suppress tumor cells because of its antioxidant and anti-inflammatory properties. However, its effectiveness has been limited by poor absorption when delivered orally. Subjects with oral cancer were given oral APG-157, a botanical drug containing multiple polyphenols, including curcumin. Curcumin was found in the blood and in tumor tissues. Inflammatory markers and Bacteroides species were found to be decreased in the saliva, and immune T cells were increased in the tumor tissue. APG-157 is absorbed well, reduces inflammation, and attracts T cells to the tumor, suggesting its potential use in combination with immunotherapy drugs.
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Brown Adipose Crosstalk in Tissue Plasticity and Human Metabolism.
Scheele, C, Wolfrum, C
Endocrine reviews. 2020;41(1)
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Brown adipose tissue (BAT) is an important contributor to the regulation of metabolism via cellular communication with organs such as liver, muscle, gut and central nervous system. BAT is important for heat generation and is at high levels in human infants. Levels of activation of BAT decline as we age and it has been shown that the amount of BAT is smaller and its activity reduced in those with obesity and type 2 diabetes. To date, there is no answer to efficiently restore functional BAT in aging and obese subjects. This review looks at experiments done on the factors secreted from active BAT (batokines). The review aims to provide a structure for the processes and cell types involved in BAT and the recent findings of BAT whole-body communication are discussed. Altogether, these findings demonstrate that BAT has an adaptive capacity. Studying batokines, offers an alternative approach to identify novel drug targets for metabolic regulation.
Abstract
Infants rely on brown adipose tissue (BAT) as a primary source of thermogenesis. In some adult humans, residuals of brown adipose tissue are adjacent to the central nervous system and acute activation increases metabolic rate. Brown adipose tissue (BAT) recruitment occurs during cold acclimation and includes secretion of factors, known as batokines, which target several different cell types within BAT, and promote adipogenesis, angiogenesis, immune cell interactions, and neurite outgrowth. All these processes seem to act in concert to promote an adapted BAT. Recent studies have also provided exciting data on whole body metabolic regulation with a broad spectrum of mechanisms involving BAT crosstalk with liver, skeletal muscle, and gut as well as the central nervous system. These widespread interactions might reflect the property of BAT of switching between an active thermogenic state where energy is highly consumed and drained from the circulation, and the passive thermoneutral state, where energy consumption is turned off. (Endocrine Reviews 41: XXX - XXX, 2020).
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Unusual Early Recovery of a Critical COVID-19 Patient After Administration of Intravenous Vitamin C.
Waqas Khan, HM, Parikh, N, Megala, SM, Predeteanu, GS
The American journal of case reports. 2020;21:e925521
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Coronavirus disease (Covid-19) continues to spread globally and to date there are no proven treatments. Current treatment focuses on the management of the associated acute respiratory distress syndrome (ARDS). There are many studies demonstrating that in severe sepsis and ARDS; Vitamin C reduces systemic inflammation, prevents lung damage, reduces the duration of mechanical ventilation (MV) and the length of intensive care unit (ICU) stay in patients. This is a case report where a critically ill patient received high-dose Vitamin C intravenous (IV) infusions and recovered. A 74 year-old woman with Covid-19, developed ARDS and septic shock. Usual medications were given. She needed MV and deteriorated rapidly. On Day 7 she was administered Vitamin C (11g per 24 hours as a continuous IV infusion). Her clinical condition improved slowly after this. In this case, high dose IV Vitamin C was associated with fewer days on mechanical intervention, a shorter ICU stay and earlier recovery. These results show the importance of further investigation of IV Vitamin C to assess its efficacy in critically ill Covid-19 patients requiring mechanical ventilation and ICU care.
Abstract
BACKGROUND Coronavirus disease 2019 (COVID-19) continues to spread, with confirmed cases now in more than 200 countries. Thus far there are no proven therapeutic options to treat COVID-19. We report a case of COVID-19 with acute respiratory distress syndrome who was treated with high-dose vitamin C infusion and was the first case to have early recovery from the disease at our institute. CASE REPORT A 74-year-old woman with no recent sick contacts or travel history presented with fever, cough, and shortness of breath. Her vital signs were normal except for oxygen saturation of 87% and bilateral rhonchi on lung auscultation. Chest radiography revealed air space opacity in the right upper lobe, suspicious for pneumonia. A nasopharyngeal swab for severe acute respiratory syndrome coronavirus-2 came back positive while the patient was in the airborne-isolation unit. Laboratory data showed lymphopenia and elevated lactate dehydrogenase, ferritin, and interleukin-6. The patient was initially started on oral hydroxychloroquine and azithromycin. On day 6, she developed ARDS and septic shock, for which mechanical ventilation and pressor support were started, along with infusion of high-dose intravenous vitamin C. The patient improved clinically and was able to be taken off mechanical ventilation within 5 days. CONCLUSIONS This report highlights the potential benefits of high-dose intravenous vitamin C in critically ill COVID-19 patients in terms of rapid recovery and shortened length of mechanical ventilation and ICU stay. Further studies will elaborate on the efficacy of intravenous vitamin C in critically ill COVID-19.
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Increased Colonic Permeability and Lifestyles as Contributing Factors to Obesity and Liver Steatosis.
Di Palo, DM, Garruti, G, Di Ciaula, A, Molina-Molina, E, Shanmugam, H, De Angelis, M, Portincasa, P
Nutrients. 2020;12(2)
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Intestinal permeability (IP) is dependent on the structure and function of the intestinal barrier. The gut barrier integrity is the result of ongoing equilibrium and crosstalk involving the microbiome, the mucus, the enterocytes [intestinal absorptive cells], the gut immune system, and the gut–vascular barrier. The main aim of this study was to explore the pan-enteric IP (stomach, small intestine, and colon) with respect to size and fat distribution, as well as the presence of liver steatosis. The study is a cohort study that examined 120 subjects (obese n = 45, overweight n=30, normal weight n = 45). Groups were gender-matched except for the prevalence of males in the overweight group. Results highlight the existence of an association between colonic (but not stomach and small intestinal) permeability, obesity, and liver steatosis. Findings show that: - liver steatosis was detected in 69 (57.5%) subjects, of which 36 (52%) were males. The prevalence of liver steatosis increased from 4% in normal weight subjects to 77%, and to 98% in overweight and obese subjects, respectively. - gastrointestinal permeability changed between age groups at every tract, whereas stomach and small intestine IP decreased with age. Furthermore, this finding also occurred in subjects aged over or equal to 65 years, with respect to colonic permeability. Authors conclude that further studies must evaluate the possibility of modulating colonic permeability to allow both primary prevention measures and new therapeutic strategies in metabolic and liver diseases.
Abstract
Intestinal permeability (IP) is essential in maintaining gut-metabolic functions in health. An unequivocal evaluation of IP, as marker of intestinal barrier integrity, however, is missing in health and in several diseases. We aimed to assess IP in the whole gastrointestinal tract according to body mass index (BMI) and liver steatosis. In 120 patients (61F:59M; mean age 45 ± SEM 1.2 years, range: 18-75), IP was distinctively studied by urine recovery of orally administered sucrose (SO, stomach), lactulose/mannitol ratio (LA/MA, small intestine), and sucralose (SA, colon). By triple quadrupole mass-spectrometry and high-performance liquid chromatography, we measured urinary recovery of saccharide probes. Subjects were stratified according to BMI as normal weight, overweight, and obesity, and answered questionnaires regarding dietary habits and adherence to the Mediterranean Diet. Liver steatosis was assessed by ultrasonography. IP at every gastrointestinal tract was similar in both sexes and decreased with age. Stomach and small intestinal permeability did not differ according to BMI. Colonic permeability increased with BMI, waist, neck, and hip circumferences and was significantly higher in obese than in lean subjects. As determined by logistic regression, the odds ratio (OR) of BMI increment was significantly higher in subjects in the highest tertile of sucralose excretion, also after adjusting for age and consumption of junk food. The presence of liver steatosis was associated with increased colonic permeability. Patients with lower score of adherence to Mediterranean diet had a higher score of 'junk food'. Intestinal permeability tended to increase in subjects with a lower adherence to Mediterranean diet. In conclusion, colonic (but not stomach and small intestinal) permeability seems to be linked to obesity and liver steatosis independently from dietary habits, age, and physical activity. The exact role of these last factors, however, requires specific studies focusing on intestinal permeability. Results should pave the way to both primary prevention measures and new therapeutic strategies in metabolic and liver diseases.
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The study evaluating the effect of probiotic supplementation on the mental status, inflammation, and intestinal barrier in major depressive disorder patients using gluten-free or gluten-containing diet (SANGUT study): a 12-week, randomized, double-blind, and placebo-controlled clinical study protocol.
Karakula-Juchnowicz, H, Rog, J, Juchnowicz, D, Łoniewski, I, Skonieczna-Żydecka, K, Krukow, P, Futyma-Jedrzejewska, M, Kaczmarczyk, M
Nutrition journal. 2019;18(1):50
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Major depressive disorder (MDD) has historically been recognised as a brain disease, however more recently it is being recognised as a whole-body disorder. The immune system and the gut microbiota have been implicated in MDD with particular focus on the gut wall integrity and the resultant immune reaction and its influence on the brain. Gluten may incite an immune reaction in certain individuals and a gluten free diet may be of benefit to symptoms of depression in those who have gluten-related disorders. This randomised prospective control trial of 120 patients with MDD aims to determine the effect of a gluten free diet and probiotic supplementation in symptom management over 12 weeks. As this was a prospective study, no results were achieved. However, the study does indicate that randomised control trials on the effect of diet in MDD are advancing and there may be scientifically proven avenues to support standard therapies.
Abstract
BACKGROUND Current treatment of major depressive disorder (MDD) often does not achieve full remission of symptoms. Therefore, new forms of treatment and/or adjunct therapy are needed. Evidence has confirmed the modulation of the gut-brain-microbiota axis as a promising approach in MDD patients. The overall purpose of the SANGUT study-a 12-week, randomized, double-blind, and placebo-controlled Study Evaluating the Effect of Probiotic Supplementation on the Mental Status, Inflammation, and Intestinal Barrier in Major Depressive Disorder Patients Using Gluten-free or Gluten-containing Diet - is to determine the effect of interventions focused on the gut-brain-microbiota axis in a group of MDD patients. METHODS A total of 120 outpatients will be equally allocated into one of four groups: (1) probiotic supplementation+gluten-free diet group (PRO-GFD), (2) placebo supplementation+ gluten-free diet group (PLA-GFD), (3) probiotic supplementation+ gluten containing diet group (PRO-GD), and (4) placebo supplementation+gluten containing diet group (PLA-GD). PRO groups will receive a mixture of psychobiotics (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175), and GFD groups will follow a gluten-free diet. The intervention will last 12 weeks. The primary outcome measure is change in wellbeing, whereas the secondary outcome measures include physiological parameters. DISCUSSION Microbiota and its metabolites have the potential to influence CNS function. Probiotics may restore the eubiosis within the gut while a gluten-free diet, via changes in the microbiota profile and modulation of intestinal permeability, may alter the activity of microbiota-gut-brain axis previously found to be associated with the pathophysiology of depression. It is also noteworthy that microbiota being able to digest gluten may play a role in formation of peptides with different immunogenic capacities. Thus, the combination of a gluten-free diet and probiotic supplementation may inhibit the immune-inflammatory cascade in MDD course and improve both psychiatric and gut barrier-associated traits. TRIAL REGISTRATION NCT03877393 .
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The Role of Dietary Fiber in Rheumatoid Arthritis Patients: A Feasibility Study.
Häger, J, Bang, H, Hagen, M, Frech, M, Träger, P, Sokolova, MV, Steffen, U, Tascilar, K, Sarter, K, Schett, G, et al
Nutrients. 2019;11(10)
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Rheumatoid arthritis (RA) is a chronic, autoimmune inflammatory musculoskeletal disorder, affecting around 1% of the world population. Risk factors are genetic and environmental, with diet appearing to be an important environmental trigger. The impacts of diet on the gut microbiota are well studied, including the ability of the gut microbiome to manipulate the immune system. This small feasibility study of 36 patients with RA aimed to examine the effect of short-term high fibre dietary supplementation on T-reg cell numbers (cells which regulate the immune system). A high fibre bar was provided to study subjects for 28 days and measurements taken of immune and inflammation markers, bone erosion, gut bacterial changes and quality of life. The authors found a positive improvement to patient immune systems at the end of the intervention, as well as decreased markers of bone erosion. Physical functioning and quality of life were also reported as significantly improved. Whilst this is a small uncontrolled trial, the results support increasing the fibre intake when working with RA clients.
Abstract
Short-chain fatty acids are microbial metabolites that have been shown to be key regulators of the gut-joint axis in animal models. In humans, microbial dysbiosis was observed in rheumatoid arthritis (RA) patients as well as in those at-risk to develop RA, and is thought to be an environmental trigger for the development of clinical disease. At the same time, diet has a proven impact on maintaining intestinal microbial homeostasis. Given this association, we performed a feasibility study in RA patients using high-fiber dietary supplementation with the objective to restore microbial homeostasis and promote the secretion of beneficial immunomodulatory microbial metabolites. RA patients (n = 36) under routine care received daily high-fiber bars or cereals for 28 days. Clinical assessments and laboratory analysis of immune parameters in blood and stool samples from RA patients were done before and after the high-fiber dietary supplementation. We observed an increase in circulating regulatory T cell numbers, favorable Th1/Th17 ratios, as well as decreased markers of bone erosion in RA patients after 28 days of dietary intervention. Furthermore, patient-related outcomes of RA improved. Based on these results, we conclude that controlled clinical studies of high-fiber dietary interventions could be a viable approach to supplement or complement current pharmacological treatment strategies.
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Gut microbiota alterations associated with reduced bone mineral density in older adults.
Das, M, Cronin, O, Keohane, DM, Cormac, EM, Nugent, H, Nugent, M, Molloy, C, O'Toole, PW, Shanahan, F, Molloy, MG, et al
Rheumatology (Oxford, England). 2019;58(12):2295-2304
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Osteoporosis, characterised by reduced bone density or ‘brittle bones’ affects a significant number of individuals over the age of 50 worldwide. Contributing factors include calcium and vitamin D deficiency and the presence of other inflammatory conditions. The composition of gut bacteria, the gut microbiome, plays an important role in immune activity and changes in composition have been associated with other inflammatory conditions. This cohort study of 181 individuals at high risk of reduced bone density and fractures, aimed to determine whether different gut microbiota composition is associated with bone density. Dexa scans and faecal samples were used as part of the assessment and confounding factors of diet, BMI, supplementation and medication were included in the analysis. The authors of the study found 6 species of gut bacteria that were significantly altered in numbers in the groups with osteoporosis and osteopenia, after controlling for confounding factors, and suggest that they could be used as markers of disease risk or progression and as a therapeutic target. Nutrition Practitioners working with bone density can focus on supporting the gut microbiome as part of their nutrition protocols.
Abstract
OBJECTIVE To investigate compositional differences in the gut microbiota associated with bone homeostasis and fractures in a cohort of older adults. METHODS Faecal microbiota profiles were determined from 181 individuals with osteopenia (n = 61) or osteoporosis (n = 60), and an age- and gender-matched group with normal BMD (n = 60). Analysis of the 16S (V3-V4 region) amplicon dataset classified to the genus level was used to identify significantly differentially abundant taxa. Adjustments were made for potential confounding variables identified from the literature using several statistical models. RESULTS We identified six genera that were significantly altered in abundance in the osteoporosis or osteopenic groups compared with age- and gender-matched controls. A detailed study of microbiota associations with meta-data variables that included BMI, health status, diet and medication revealed that these meta-data explained 15-17% of the variance within the microbiota dataset. BMD measurements were significantly associated with alterations in the microbiota. After controlling for known biological confounders, five of the six taxa remained significant. Overall microbiota alpha diversity did not correlate to BMD in this study. CONCLUSION Reduced BMD in osteopenia and osteoporosis is associated with an altered microbiota. These alterations may be useful as biomarkers or therapeutic targets in individuals at high risk of reductions in BMD. These observations will lead to a better understanding of the relationship between the microbiota and bone homeostasis.
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Cashew apple juice supplementation enhances leukocyte count by reducing oxidative stress after high-intensity exercise in trained and untrained men.
Prasertsri, P, Roengrit, T, Kanpetta, Y, Tong-Un, T, Muchimapura, S, Wattanathorn, J, Leelayuwat, N
Journal of the International Society of Sports Nutrition. 2019;16(1):31
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High-intensity aerobic training has been shown to suppress leukocyte counts in moderately fit athletes. The aim of this study to explore possible advantageous effects of cashew apple juice (CAJ) supplementation, and, if present, to identify the possible mechanisms underlying those effects. The study is a double-blind randomised cross-over design with two treatment arms: CAJ supplementation and placebo. Ten moderately (endurance) trained and untrained men were randomized to one of the two groups for four weeks, with a four-week wash out period. Results showed that CAJ supplementation for four weeks increased leukocyte (a type of blood cell) counts, while simultaneously decreasing oxidative stress, following an acute bout of high-intensity exercise in trained men. Furthermore, the CAJ supplementation increased neutrophil (a type of white blood cell) counts while simultaneously reducing oxidative stress and stress hormone concentrations in untrained men. The antioxidant effects following exercise were observed in both endurance-trained and untrained men. Authors conclude that CAJ supplementation is beneficial to men, both in resting states and in response to an acute bout of high-intensity aerobic exercise.
Abstract
BACKGROUND Cashew apple juice (CAJ) was shown to improve immunological mechanisms by regulating a balance between reactive oxygen species and antioxidant concentrations. However, no study exploring the effects of the CAJ and training status on the immune system and oxidative stress induced by exercise. Therefore, we investigated the effects of CAJ supplementation primarily on leukocyte counts and secondary on oxidative stress and cortisol changes after high-intensity exercise in trained and untrained men. METHODS Ten moderately (endurance) trained (Age = 21.5 ± 0.97 yr., VO2max = 45.6 ± 4.12 mL/kgBM/min) and ten sedentary men (Age = 20.4 ± 2.72 yr., VO2peak = 32.2 ± 7.26 mL/kgBM/min) were randomized to ingest either daily CAJ or a placebo at 3.5 mL/kgBM/day for 4 weeks, with a four-week washout period. Before and after each period, they performed 20-min, high-intensity cycling (85% VO2max), with blood samples collected immediately preceding and the following exercise. Samples were analyzed to determine leukocyte counts, malondialdehyde, 8-isoprostane, and cortisol concentrations. A repeated measures analysis of variance was used to examine the effects of supplement and training status over time with an alpha level of 0.05. RESULTS There was no interaction between supplement and training status on those variables before and after exercise. However, CAJ raised resting neutrophil counts and exercise-induced leukocyte counts in the trained group (all p < 0.05). Besides, CAJ significantly reduced plasma malondialdehyde concentrations at rest and after exercise and reduced the post-exercise plasma 8-isoprostane concentration in both groups of subjects (p < 0.05). Moreover, CAJ reduced plasma cortisol after exercise in the untrained subjects. CONCLUSIONS We suggest that 4-week CAJ supplementation can enhance exercise-induced leukocyte and resting neutrophil counts in trained men. The possible mechanism is a reduction in oxidative stress. However, the supplementation did not change the immune responses of untrained men, but it did reduce stress hormone concentrations. TRIAL REGISTRATION NUMBER TCTR20181127002 Registered 26 November 2018 "retrospectively registered".
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Daily Intake of Fermented Milk Containing Lactobacillus casei Shirota (Lcs) Modulates Systemic and Upper Airways Immune/Inflammatory Responses in Marathon Runners.
Vaisberg, M, Paixão, V, Almeida, EB, Santos, JMB, Foster, R, Rossi, M, Pithon-Curi, TC, Gorjão, R, Momesso, CM, Andrade, MS, et al
Nutrients. 2019;11(7)
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Athletes undergoing high-intensity efforts show increased incidence of upper respiratory tract infections (URTI), both in the context of competitions and during strenuous training. The aim of this study was to evaluate the influence of the daily intake of fermented milk (containing Lactobacillus casei Shirota) on the systemic and upper airway immune/inflammatory responses before and after a race in marathon runners who previously reported upper respiratory symptoms (URS) after an exhaustive physical exercise session. The study is a double-blind randomised clinical study which recruited 42 male amateur marathon runners with an average age of 39 years. The participants were randomly separated into two groups: Lactobacillus casei Shirota group (n=20) or the placebo group (n=22). Results indicate that daily ingestion of fermented milk (containing Lactobacillus casei Shirota) was able to control both immunological and inflammatory responses in the blood and also in the upper airways mucosal of amateurs´ runners after a marathon. Authors conclude that Lactobacillus casei Shirota is able to modulate the systemic and airways immune responses post-marathon, presenting protective effects.
Abstract
BACKGROUND Although Lactobacillus casei Shirota (LcS) can benefit the immune status, the effects of LcS in the immune/inflammatory responses of marathon runners has never been evaluated. Therefore, here we evaluated the effect of daily ingestion of fermented milk containing or not LcS in the systemic and upper airway immune/inflammatory responses before and after a marathon. METHODS Forty-two male marathon runners ingested a fermented milk containing 40 billion of LcS/day (LcS group, n = 20) or placebo (unfermented milk, n = 22) during 30 days pre-marathon. Immune/inflammatory parameters in nasal mucosa and serum, as well as concentrations of secretory IgA (SIgA) and antimicrobial peptides in saliva, were evaluated before and after fermented milk ingestion, immediately, 72 h, and 14 d post-marathon. RESULTS Higher proinflammatory cytokine levels in serum and nasal mucosa, and also lower salivary levels of SIgA and antimicrobial peptides, were found immediately post-marathon in the placebo group compared to other time points and to LcS group. In opposite, higher anti-inflammatory levels and reduced neutrophil infiltration on nasal mucosa were found in the LcS group compared to other time points and to the placebo group. CONCLUSION For the first time, it is shown that LcS is able to modulate the systemic and airways immune responses post-marathon.
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A clinically meaningful metric of immune age derived from high-dimensional longitudinal monitoring.
Alpert, A, Pickman, Y, Leipold, M, Rosenberg-Hasson, Y, Ji, X, Gaujoux, R, Rabani, H, Starosvetsky, E, Kveler, K, Schaffert, S, et al
Nature medicine. 2019;25(3):487-495
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The human immune system changes with age, ultimately leading to a clinically evident, profound deterioration resulting in high morbidity and mortality rates attributed to infectious and chronic diseases. The aim of this study was to assess at high resolution the dynamics of older adults’ immune systems. The study uses multiple ‘omics’ technologies in a cohort of 135 adults (63 young adults and 72 older adults) of different ages who were sampled longitudinally over the course of 9 years to comprehensively capture population- and individual-level changes in the immune system over time. Results indicate that immune-cell frequencies changed at substantially different rates; some cell subsets show no directionality of change yet differ between young and old individuals, whereas other cell subsets continued changing (either increasing or decreasing) throughout the course of the study. Authors postulate that an individual’s immune age is a function of life history, namely environmental exposure coupled with genetic background. Thus, immune modulators may one day be identified that affect the position of an individual’s immune system along the immunological landscape.
Abstract
Immune responses generally decline with age. However, the dynamics of this process at the individual level have not been characterized, hindering quantification of an individual's immune age. Here, we use multiple 'omics' technologies to capture population- and individual-level changes in the human immune system of 135 healthy adult individuals of different ages sampled longitudinally over a nine-year period. We observed high inter-individual variability in the rates of change of cellular frequencies that was dictated by their baseline values, allowing identification of steady-state levels toward which a cell subset converged and the ordered convergence of multiple cell subsets toward an older adult homeostasis. These data form a high-dimensional trajectory of immune aging (IMM-AGE) that describes a person's immune status better than chronological age. We show that the IMM-AGE score predicted all-cause mortality beyond well-established risk factors in the Framingham Heart Study, establishing its potential use in clinics for identification of patients at risk.