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Weight reduction improves immune system and inflammatory cytokines in obese asthmatic patients.
Al-Sharif, FM, Abd El-Kader, SM, Neamatallah, ZA, AlKhateeb, AM
African health sciences. 2020;20(2):897-902
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Asthma is a common condition characterised by attacks of obstruction, chronic inflammation and hyper-responsiveness of the airways. Obesity increases severity of asthmatic symptoms through mechanical, anatomical and/or inflammatory mechanisms. 80 adults with asthma were randomly allocated to a weight reduction programme, including aerobic exercise and a calorie reduced diet, or control group with no intervention. After 3 months, body mass index (BMI) reduced significantly in the intervention group (from 31.7 to 27.9). This was associated with significant reductions in the pro-inflammatory markers TNF-alpha, interleukin-6 and interleukin-8, and significant increases in CD4 and CD8 cell counts (important immune cells). There were no changes in the control group in any of the parameters and the results were statistically significantly better in the intervention compared to the control group. The authors conclude that weight reduction improved immunological and inflammatory markers in obese asthma patients.
Abstract
BACKGROUND Activation of immunological and systemic inflammation markers are common in obesity and asthma. OBJECTIVE The target of this study was to assess impact of weight reduction on immunological and systemic inflammation markers in obese asthma patients. MATERIAL AND METHODS Eighty asthmatic patients of both sex; their age and body mass index (BMI) mean were 38.72 ± 7.14 year and 32.65 ± 3.18 Kg/m2 respectively. Exclusion criteria included smokers, infections, vaccinations, cancer, surgery, immune system disorders and medications that may influence immune system function as anti-inflammatory medications, analgesics and anti-depressant. All subjects were randomly enrolled in weight reduction group (group A) or control group (group B). RESULTS The main findings in the present study indicated that weight reducing program in group (A) was associated with significant reduction in the mean values of IL6, TNF-α, and IL8 in addition to significant increase in the mean values of CD4 and CD8 cell count . However, findings of group (B) showed no significant changes. Moreover, Comparison between both groups at the end of the study revealed significant differences. CONCLUSION Weight reduction improved immunological and systemic inflammation markers in obese asthma patients.
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The Effect of a Multivitamin and Mineral Supplement on Immune Function in Healthy Older Adults: A Double-Blind, Randomized, Controlled Trial.
Fantacone, ML, Lowry, MB, Uesugi, SL, Michels, AJ, Choi, J, Leonard, SW, Gombart, SK, Gombart, JS, Bobe, G, Gombart, AF
Nutrients. 2020;12(8)
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Vitamins and minerals are essential for a healthy immune system. The prevalence of vitamin and mineral deficiencies increases with age, and this may contribute to age-related decline of the immune system. The aim of this study was to investigate whether a daily multivitamin and mineral (MVM) supplement could improve the immune function of older people. 42 healthy adults aged between 55 and 75 took part in this single-centre, two-armed, parallel, randomised, double-blinded study. Half of the group was given a MVM supplement called Redoxon Vita Immune (VI) containing the vitamins A, D, E, C, B6, B12 and folate plus iron, copper, zinc and selenium daily for 12 weeks, whilst the other half was given placebo tablets for 12 weeks. Participants were instructed to avoid certain foods high in vitamins and minerals such as oily fish, red meat, liver, and citrus fruits during the study period. Blood and saliva samples were taken from all participants at the beginning and end of the study period, to measure vitamin and mineral status and markers of immune function. Participants also kept a diary to record any illnesses or symptoms. At the end of the study, participants given the MVM supplement had increased their blood levels of vitamin C by 126% and zinc by 43%. There was no significant change in blood levels of vitamin D. There was no significant difference in the potential of blood to kill the introduced bacteria Staphylococcus aureus, or in neutrophil activity, nor were there any significant changes in blood levels of cytokines and chemokines. Participants taking the supplement did however report a shorter length, and lower severity of illnesses compared to those taking the placebo. The authors concluded that their findings support further research to test whether MVM supplementation can improve immune outcomes in older adults.
Abstract
Older adults are at increased risk for vitamin and mineral deficiencies that contribute to age-related immune system decline. Several lines of evidence suggest that taking a multi-vitamin and mineral supplement (MVM) could improve immune function in individuals 55 and older. To test this hypothesis, we provided healthy older adults with either an MVM supplement formulated to improve immune function (Redoxon® VI, Singapore) or an identical, inactive placebo control to take daily for 12 weeks. Prior to and after treatment, we measured (1) their blood mineral and vitamin status (i.e., vitamin C, zinc and vitamin D); (2) immune function (i.e., whole blood bacterial killing activity, neutrophil phagocytic activity, and reactive oxygen species production); (3) immune status (salivary IgA and plasma cytokine/chemokine levels); and (4) self-reported health status. MVM supplementation improved vitamin C and zinc status in blood and self-reported health-status without altering measures of immune function or status or vitamin D levels, suggesting that healthy older adults may benefit from MVM supplementation. Further development of functional assays and larger study populations should improve detection of specific changes in immune function after supplementation in healthy older adults. Clinical Trials Registration: ClinicalTrials.gov #NCT02876315.
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Stratifying cellular metabolism during weight loss: an interplay of metabolism, metabolic flexibility and inflammation.
Tareen, SHK, Kutmon, M, de Kok, TM, Mariman, ECM, van Baak, MA, Evelo, CT, Adriaens, ME, Arts, ICW
Scientific reports. 2020;10(1):1651
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Obesity is a public health concern as it has been linked to cardiovascular diseases, type 2 diabetes and metabolic syndrome. The aim of this study was to identify and analyse expression profiles of individuals clustered by cellular metabolism centring on metabolic flexibility. This study clustered gene expression samples from a weight loss study (Yoyo study’ - Clinical Trial ID: NCT01559415) into two clusters, based on 291 genes associated with cellular metabolic fexibility. The study covers two diets: a low-calorie diet (LCD) and a very low-calorie diet (VLCD). All the participants of the study were Caucasian with a BMI between 28kg/m2 and 35 kg/m2, aged between 32 and 67 years old. Findings showed that the majority of the individuals had their metabolism associated genes downregulated after weight loss and weight maintenance, but also had an upregulation of immune system associated genes. Furthermore, individuals who had changed their metabolic profiles in response to caloric restriction had a significant retention of lost weight compared to individuals which had not changed their cluster membership. Authors conclude that their findings indicate possible cross-talk between cellular metabolism and inflammation.
Abstract
Obesity is a global epidemic, contributing significantly to chronic non-communicable diseases, such as type 2 diabetes mellitus, cardiovascular diseases and metabolic syndrome. Metabolic flexibility, the ability of organisms to switch between metabolic substrates, is found to be impaired in obesity, possibly contributing to the development of chronic illnesses. Several studies have shown the improvement of metabolic flexibility after weight loss. In this study, we have mapped the cellular metabolism of the adipose tissue from a weight loss study to stratify the cellular metabolic processes and metabolic flexibility during weight loss. We have found that for a majority of the individuals, cellular metabolism was downregulated during weight loss, with gene expression of all major cellular metabolic processes (such as glycolysis, fatty acid β-oxidation etc.) being lowered during weight loss and weight maintenance. Parallel to this, the gene expression of immune system related processes involving interferons and interleukins increased. Previously, studies have indicated both negative and positive effects of post-weight loss inflammation in the adipose tissue with regards to weight loss or obesity and its co-morbidities; however, mechanistic links need to be constructed in order to determine the effects further. Our study contributes towards this goal by mapping the changes in gene expression across the weight loss study and indicates possible cross-talk between cellular metabolism and inflammation.
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Time-restricted eating effects on performance, immune function, and body composition in elite cyclists: a randomized controlled trial.
Moro, T, Tinsley, G, Longo, G, Grigoletto, D, Bianco, A, Ferraris, C, Guglielmetti, M, Veneto, A, Tagliabue, A, Marcolin, G, et al
Journal of the International Society of Sports Nutrition. 2020;17(1):65
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Adequate nutrition is important for elite athletes, as nutrient availability influences energy expenditure, body composition, performance and exercise-induced immune responses. Time-restricted eating (TRE) is a form of intermittent fasting that has received much interest in recent years. Previous research of TRE suggested beneficial effects on performance in untrained individuals, by allowing weight loss whilst maintaining muscle functions. These qualities are of interest for endurance cyclists hence the authors of this study sought to investigate the impact of TRE in elite cyclists. Sixteen under-23 year old, elite cyclists were randomly assigned to eat within a TRE window of 8-hr or 15hr window during a 4-week, high-level endurance training phase. Both groups consumed their full estimated energy needs and markers such as fat and fat-free mass, VO2 max, basal metabolism, blood counts, anabolic hormones and inflammatory markers were measured. As a result, TRE produced weight loss, improved body composition and increased peak power output in relation to body weight without compromising aerobic performance. Furthermore, the TRE pattern proved helpful in mitigating some of the exercise-induced suppressions of the immune system. The authors concluded that TRE could be considered as part of a performance nutrition plan in endurance athletes. Particularly where there is a need to reduce body fat mass or for the management of training-induced depression of the immune system and associated respiratory infection susceptibility. This can be of clinical relevance in the support of endurance athletes.
Abstract
BACKGROUND Although there is substantial interest in intermittent fasting as a dietary approach in active individuals, information regarding its effects in elite endurance athletes is currently unavailable. The present parallel randomized trial investigated the effects of a particular intermittent fasting approach, called time-restricted eating (TRE), during 4 weeks of high-level endurance training. METHODS Sixteen elite under-23 cyclists were randomly assigned either to a TRE group or a control group (ND). The TRE group consumed 100% of its estimated daily energy needs in an 8-h time window (from 10:00 a.m. to 6:00 p.m.) whilst energy intake in the ND group was distributed in 3 meals consumed between 7:00 a.m. and 9:00 p.m. Fat and fat-free mass were estimated by bioelectrical impedance analysis and VO2max and basal metabolism by indirect gas analyzer. In addition, blood counts, anabolic hormones (i.e. free testosterone, IGF-1) and inflammatory markers (i.e. IL-6, TNF-α) were assessed. RESULTS TRE reduced body weight (- 2%; p = 0.04) and fat mass percentage (- 1.1%; p = 0.01) with no change in fat-free mass. Performance tests showed no significant differences between groups, however the peak power output/body weight ratio (PPO/BW) improved in TRE group due to weight loss (p = 0.02). Free testosterone and IGF-1 decreased significantly (p = 0.01 and p = 0.03 respectively) in TRE group. Leucocyte count decreased in ND group (p = 0.02) whilst the neutrophils-to-lymphocytes ratio (NLR) decreased significantly (p = 0.03) in TRE group. CONCLUSIONS Our results suggest that a TRE program with an 8-h feeding window elicits weight loss, improves body composition and increases PPO/BW in elite cyclists. TRE could also be beneficial for reducing inflammation and may have a protective effect on some components of the immune system. Overall, TRE could be considered as a component of a periodized nutrition plan in endurance athletes. TRIAL REGISTRATION This trial was retrospectively registered at clinicaltrials.gov as NCT04320784 on 25 March 2020.
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The Specific Carbohydrate Diet and Diet Modification as Induction Therapy for Pediatric Crohn's Disease: A Randomized Diet Controlled Trial.
Suskind, DL, Lee, D, Kim, YM, Wahbeh, G, Singh, N, Braly, K, Nuding, M, Nicora, CD, Purvine, SO, Lipton, MS, et al
Nutrients. 2020;12(12)
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Crohn’s disease is a painful chronic lifelong condition where the digestive tract gets inflamed. Environmental insults and gut microbial changes may contribute to immune dysregulation by activating and upregulating the immune system in Crohn’s disease. During this single-centre, randomised, double-blind, diet-controlled study, ten male active Crohn's disease patients aged seven to eighteen were randomly assigned to either a specific carbohydrate diet, a modified specific carbohydrate diet, or a whole food diet. All diet groups showed a reduction in symptoms, inflammation, and a positive change in the gut microbial composition after 12 weeks, depending on the degree of variability in the dietary regimen. Based on the results of this study, an exclusionary diet eliminating grains, sugar, dairy, and processed foods may have a positive impact on reducing Crohn's disease symptoms, inflammation, and improving gut microbial composition and biochemical markers. In the future, robust studies with a larger sample size will be needed to figure out better dietary strategies for Crohn's disease. Healthcare professionals can, however, use these results to identify dietary choices that can reduce Crohn's disease symptoms.
Abstract
BACKGROUND Crohn's disease (CD) is a chronic inflammatory intestinal disorder associated with intestinal dysbiosis. Diet modulates the intestinal microbiome and therefore has a therapeutic potential. The aim of this study is to determine the potential efficacy of three versions of the specific carbohydrate diet (SCD) in active Crohn's Disease. METHODS 18 patients with mild/moderate CD (PCDAI 15-45) aged 7 to 18 years were enrolled. Patients were randomized to either SCD, modified SCD(MSCD) or whole foods (WF) diet. Patients were evaluated at baseline, 2, 4, 8 and 12 weeks. PCDAI, inflammatory labs and multi-omics evaluations were assessed. RESULTS Mean age was 14.3 ± 2.9 years. At week 12, all participants (n = 10) who completed the study achieved clinical remission. The C-reactive protein decreased from 1.3 ± 0.7 at enrollment to 0.9 ± 0.5 at 12 weeks in the SCD group. In the MSCD group, the CRP decreased from 1.6 ± 1.1 at enrollment to 0.7 ± 0.1 at 12 weeks. In the WF group, the CRP decreased from 3.9 ± 4.3 at enrollment to 1.6 ± 1.3 at 12 weeks. In addition, the microbiome composition shifted in all patients across the study period. While the nature of the changes was largely patient specific, the predicted metabolic mode of the organisms increasing and decreasing in activity was consistent across patients. CONCLUSIONS This study emphasizes the impact of diet in CD. Each diet had a positive effect on symptoms and inflammatory burden; the more exclusionary diets were associated with a better resolution of inflammation.
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A Large Randomized Trial: Effects of Mindfulness-Based Stress Reduction (MBSR) for Breast Cancer (BC) Survivors on Salivary Cortisol and IL-6.
Lengacher, CA, Reich, RR, Paterson, CL, Shelton, M, Shivers, S, Ramesar, S, Pleasant, ML, Budhrani-Shani, P, Groer, M, Post-White, J, et al
Biological research for nursing. 2019;21(1):39-49
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Breast cancer survivors (BCS) often experience physiological and psychological stressors related to their diagnosis and treatment, and a disruption of cortisol function can affect cancer risk and progression. Increased levels of the stress hormone cortisol and interleukin-6 (IL-6), a pro-inflammatory immune mediator, have been associated with acute and chronic stress levels. Mindfulness-Based Stress Reduction (MBSR) is a clinical stress-reducing program, which has been found to decrease psychological and physical symptoms associated with stress. The purpose of this randomised study, involving 299 BCS, was to evaluate the efficacy of MBSR in reducing cortisol and IL-6 levels, compared to a usual-care control treatment. Statistically significant reductions in cortisol levels were seen after the delivery of the MBSR program at both time points (week 1 and 6), and at week 6 only for IL-6. There was no significant difference in change in cortisol or IL6 levels over time between the MBSR and the usual-care groups. An association was observed between levels of IL-6 and psychological and physical symptoms and quality of life, but not for cortisol. The authors conclude that MBSR can alleviate the stress response in the short term for breast cancer survivors.
Abstract
Breast cancer survivors (BCS) often experience psychological and physiological symptoms after cancer treatment. Mindfulness-based stress reduction (MBSR), a complementary and alternative therapy, has reduced subjective measures of stress, anxiety, and fatigue among BCS. Little is known, however, about how MBSR affects objective markers of stress, specifically the stress hormone cortisol and the pro-inflammatory cytokine interleukin-6 (IL-6). In the present study, BCS ( N = 322) were randomly assigned to a 6-week MBSR program for BC or usual-care control. Measurements of cortisol, IL-6, symptoms, and quality of life were obtained at orientation and 6 weeks. Cortisol and IL-6 were also measured prior to and after the MBSR(BC) class Weeks 1 and 6. The mean age of participants was 56.6 years and 69.4% were White non-Hispanic. Most had Stage I (33.8%) or II (35.7%) BC, and 35.7% had received chemotherapy and radiation. Cortisol levels were reduced immediately following MBSR(BC) class compared to before the class Weeks 1 and 6 (Wilcoxon-signed rank test; p < .01, d = .52-.56). IL-6 was significantly reduced from pre- to postclass at Week 6 (Wilcoxon-signed rank test; p < .01, d = .21). No differences were observed between the MBSR(BC) and control groups from baseline to Week 6 using linear mixed models. Significant relationships with small effect sizes were observed between IL-6 and both symptoms and quality of life in both groups. Results support the use of MBSR(BC) to reduce salivary cortisol and IL-6 levels in the short term in BCS.
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The Effect of Olive Leaf Extract on Upper Respiratory Illness in High School Athletes: A Randomised Control Trial.
Somerville, V, Moore, R, Braakhuis, A
Nutrients. 2019;11(2)
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When an individual exercises, there is a 3 to 72 hour subsequent period known as the ‘open window’ where they are susceptible to illness due to altered immune function and activity. The aim of this study was to determine the effect of olive leaf extract (OLE) supplementation on upper respiratory illness (URI) incidence and duration in high school athletes. The study was a two-month parallel double-blind randomised controlled trial. The study recruited 32 students (females n = 22) aged between 16 and 19 years. The participants were randomly allocated to one of the two groups: OLE or placebo tablets group. Results indicate that there were 17 participants who experienced a total of 26 URI episodes. There was no significant difference in incidence; however, there was a significant 28% reduction in sick days. Authors conclude that OLE supplementation could be used to alleviate the effect of URI on high school athletes.
Abstract
Upper respiratory illness (URI) has a major impact on both training and competition in an athletic setting. High school athletes are a sub-category who have reported higher illness rates than professional and sub-elite high school athletes of the same sport. Olive leaf extract (OLE) is an over-the-counter supplement that contains polyphenols, notably oleuropein and hydroxytyrosol, that have antiviral, antibacterial, anti-inflammatory and antioxidant properties that may reduce URI rates. Thirty-two high school students who play sport for the elite team at their school were recruited to a randomised controlled trial and allocated to a daily placebo or OLE (extent equivalent to 20 g of olive leaf, containing 100 mg oleuropein) supplementation for nine weeks during their competitive season. Twice weekly measures of wellbeing, training load and respiratory illness (sporting upper respiratory illness (SUPPRESS) questionnaire) were recorded at trainings, meetings or games. There was no significant difference in illness incidence (odds ratio (OR): 1.02 (95% confidence interval (CI) 0.21⁻4.44)), but there was a significant 28% reduction in sick days (OR: 0.72 (95% CI 0.56⁻0.93) p-value = 0.02) when supplemented with OLE. The dietary intakes of the athletes were sub-optimal with regard to immune support. OLE supplementation over a season did not significantly reduce URI incidence, but did decrease duration in high school athletes, potentially aiding return to play.
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The effects of bovine colostrum supplementation on in vivo immunity following prolonged exercise: a randomised controlled trial.
Jones, AW, March, DS, Thatcher, R, Diment, B, Walsh, NP, Davison, G
European journal of nutrition. 2019;58(1):335-344
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Upper respiratory tract symptoms (URS) are the most common ailment reported by athletes to medicine clinics at major sporting events. The main aim of this study was to investigate the effects of bovine colostrum (COL) supplementation on the induction of invivo immune responses to a novel antigen, diphenylcyclopropenone (DPCP) [a topically administered experimental drug], following prolonged exercise. The study is a double-blind randomised placebo-controlled trial which recruited 34 healthy male participants aged between 18 and 45 years. The participants were randomly assigned to one of the two groups: COL group (n = 17) or placebo group (n = 17). Results indicate that COL did not significantly affect the overall response to the novel antigen, DPCP, but COL supplementation induced greater sensitivity of antigen-specific memory recalled 4 weeks following the initial sensitisation. Authors conclude that their findings may suggest a nutritional strategy to counter exercise-induced immunodepression assessed via an established, clinically relevant in vivo marker of immunity.
Abstract
BACKGROUND Bovine colostrum (COL) has been advocated as a nutritional countermeasure to exercise-induced immune dysfunction, but there is a lack of research with clinically relevant in vivo measures. AIM: To investigate the effects of COL supplementation on in vivo immunity following prolonged exercise using experimental contact hypersensitivity (CHS) with the novel antigen diphenylcyclopropenone (DPCP). METHODS In a double-blind design, 31 men were randomly assigned to COL (20 g/day) or placebo (PLA) for 58 days. Participants ran for 2 h at 60% maximal aerobic capacity on day 28 and received a primary DPCP exposure (sensitisation) 20 min after. On day 56, participants received a low-dose-series DPCP challenge to elicit recall of in vivo immune-specific memory (quantified by skinfold thickness 24 and 48 h later). Analysis of the dose-response curves allowed determination of the minimum dose required to elicit a positive response (i.e., sensitivity). RESULTS There was no difference in summed skinfold thickness responses between COL and PLA at 24 h (p = 0.124) and 48 h (p = 0.405). However, sensitivity of in vivo immune responsiveness was greater with COL at 24 h (p < 0.001) and 48 h (p = 0.023) with doses ~ twofold greater required to elicit a positive response in PLA. CONCLUSIONS COL blunts the prolonged exercise-induced decrease in clinically relevant in vivo immune responsiveness to a novel antigen, which may be a mechanism for reduced illness reports observed in the previous studies. These findings also suggest that CHS sensitivity is highly relevant to host defence.
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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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Dietary supplementation with inulin-propionate ester or inulin improves insulin sensitivity in adults with overweight and obesity with distinct effects on the gut microbiota, plasma metabolome and systemic inflammatory responses: a randomised cross-over trial.
Chambers, ES, Byrne, CS, Morrison, DJ, Murphy, KG, Preston, T, Tedford, C, Garcia-Perez, I, Fountana, S, Serrano-Contreras, JI, Holmes, E, et al
Gut. 2019;68(8):1430-1438
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Literature shows that higher intakes of dietary fibre are associated with a reduced risk of type 2 diabetes. The main aim of this study was to elucidate the underlying mechanisms behind improvements in glucose homeostasis following long-term delivery of propionate (a short-chain fatty acid produced by human gut microbiota in response to dietary fibre) to the human colon. The study is a randomised, double-blind, placebo-controlled cross over trial. Fourteen participants randomly received 20 g/day of a low-fermentable fibre control, a high-fermentable fibre control and inulin-propionate ester (IPE) for 42 days each. Results indicate that stool concentrations of short-chain fatty acids were not different following the three supplementation periods. Furthermore, dietary supplementation with 20 g/day IPE promoted no superior impacts on measures of glucose homeostasis compared with inulin (high-fermentable fibre), yet both IPE and inulin improved insulin resistance relative to cellulose (low-fermentable fibre). Authors conclude that manipulating the colonic fermentation profile of a dietary fibre in favour of propionate promotes selective effects on the mechanisms that contribute to metabolic dysregulation.
Abstract
OBJECTIVE To investigate the underlying mechanisms behind changes in glucose homeostasis with delivery of propionate to the human colon by comprehensive and coordinated analysis of gut bacterial composition, plasma metabolome and immune responses. DESIGN Twelve non-diabetic adults with overweight and obesity received 20 g/day of inulin-propionate ester (IPE), designed to selectively deliver propionate to the colon, a high-fermentable fibre control (inulin) and a low-fermentable fibre control (cellulose) in a randomised, double-blind, placebo-controlled, cross-over design. Outcome measurements of metabolic responses, inflammatory markers and gut bacterial composition were analysed at the end of each 42-day supplementation period. RESULTS Both IPE and inulin supplementation improved insulin resistance compared with cellulose supplementation, measured by homeostatic model assessment 2 (mean±SEM 1.23±0.17 IPE vs 1.59±0.17 cellulose, p=0.001; 1.17±0.15 inulin vs 1.59±0.17 cellulose, p=0.009), with no differences between IPE and inulin (p=0.272). Fasting insulin was only associated positively with plasma tyrosine and negatively with plasma glycine following inulin supplementation. IPE supplementation decreased proinflammatory interleukin-8 levels compared with cellulose, while inulin had no impact on the systemic inflammatory markers studied. Inulin promoted changes in gut bacterial populations at the class level (increased Actinobacteria and decreased Clostridia) and order level (decreased Clostridiales) compared with cellulose, with small differences at the species level observed between IPE and cellulose. CONCLUSION These data demonstrate a distinctive physiological impact of raising colonic propionate delivery in humans, as improvements in insulin sensitivity promoted by IPE and inulin were accompanied with different effects on the plasma metabolome, gut bacterial populations and markers of systemic inflammation.