Exercise Is Medicine for Immune Function: Implication for COVID-19.

ABSTRACT: This review supports that physical activity improves immunosurveillance and has the potential to counter COVID-19 infection and symptomatology at three prevention levels. At the primary prevention level, several lines of evidence support that physical activity is an immune system adjuvant in combating infectious diseases. Recent epidemiological studies indicate that regular physical activity is associated with a reduced risk for COVID-19, similar to what has been reported for other respiratory infections. Although specific COVID-19-related studies are needed, data from investigations with other types of infectious agents, such as influenza, support the potential role of physical activity in augmenting COVID-19 vaccine efficacy (secondary prevention level). There is a growing awareness that COVID-19 can cause sustained morbidity in some patients, and physical training and rehabilitation (tertiary prevention level) can be directed toward improvement in physical fitness, quality of life, and immune health.

Can exercise affect immune function to increase susceptibility to infection?

Multiple studies in humans and animals have demonstrated the profound impact that exercise can have on the immune system. There is a general consensus that regular bouts of short-lasting (i.e. up to 45 minutes) moderate intensity exercise is beneficial for host immune defense, particularly in older adults and people with chronic diseases. In contrast, infection burden is reported to be high among high performance athletes and second only to injury for the number of training days lost during preparation for major sporting events. This has shaped the common view that arduous exercise (i.e. those activities practiced by high performance athletes/ military personnel that greatly exceed recommended physical activity guidelines) can suppress immunity and increase infection risk. However, the idea that exercise per se can suppress immunity and increase infection risk independently of the many other factors (e.g. anxiety, sleep disruption, travel, exposure, nutritional deficits, environmental extremes, etc.) experienced by these populations has recently been challenged. The purpose of this debate article was to solicit opposing arguments centered around this fundamental question in the exercise immunology field: can exercise affect immune function to increase susceptibility to infection. Issues that were contested between the debating groups include: (i) whether or not athletes are more susceptible to infection (mainly of the upper respiratory tract) than the general population; (ii) whether exercise per se is capable of altering immunity to increase infection risk independently of the multiple factors that activate shared immune pathways and are unique to the study populations involved; (iii) the usefulness of certain biomarkers and the interpretation of in vitro and in vivo data to monitor immune health in those who perform arduous exercise; and (iv) the quality of scientific evidence that has been used to substantiate claims for and against the potential negative effects of arduous exercise on immunity and infection risk. A key point of agreement between the groups is that infection susceptibility has a multifactorial underpinning. An issue that remains to be resolved is whether exercise per se is a causative factor of increased infection risk in athletes. This article should provide impetus for more empirical research to unravel the complex questions that surround this contentious issue in the field of exercise immunology.

Effects Of Exercise Training On Immune Function And Implications For Nutrition Support.

No Abstract Available.

Postexercise Inflammasome Activation and IL-1ß Production Mitigated by Flavonoid Supplementation in Cyclists.

Inflammasomes are multiprotein signaling platforms of the innate immune system that detect markers of physiological stress and promote the maturation of caspase-1 and interleukin 1 beta (IL-1ß), IL-18, and gasdermin D. This randomized, cross-over trial investigated the influence of 2-week mixed flavonoid (FLAV) versus placebo (PL) supplementation on inflammasome activation and IL-1ß and IL-18 production after 75-km cycling in 22 cyclists (42 ± 1.7 years). Blood samples were collected before and after the 2-week supplementation, and then 0 hr, 1.5 hr, and 21 hr postexercise (176 ± 5.4 min, 73.4 ± 2.0 %VO2max). The supplement (678 mg FLAVs) included quercetin, green tea catechins, and bilberry anthocyanins. The pattern of change in the plasma levels of the inflammasome adaptor oligomer ASC (apoptosis-associated speck-like protein containing caspase recruitment domain) was different between the FLAV and PL trials, with the FLAV ASC levels 52% lower (Cohen's d = 1.06) than PL immediately following 75-km cycling (interaction effect, p = .012). The plasma IL-1ß levels in FLAV were significantly lower than PL (23-42%; Cohen's d = 0.293-0.644) throughout 21 hr of recovery (interaction effect, p = .004). The change in plasma gasdermin D levels were lower immediately postexercise in FLAV versus PL (15% contrast, p = .023; Cohen's d = 0.450). The patterns of change in plasma IL-18 and IL-37 did not differ between the FLAV and PL trials (interaction effects, p = .388, .716, respectively). These data indicate that 2-week FLAV ingestion mitigated inflammasome activation, with a corresponding decrease in IL-1ß release in cyclists after a 75-km cycling time trial. The data from this study support the strategy of ingesting high amounts of FLAV to mitigate postexercise inflammation.

Mixed Flavonoid Supplementation Attenuates Postexercise Plasma Levels of 4-Hydroxynonenal and Protein Carbonyls in Endurance Athletes.

This double-blinded, placebo controlled, randomized crossover trial investigated the influence of 2-week mixed flavonoid versus placebo supplementation on oxinflammation markers after a 75-km cycling time trial in 22 cyclists (42.3 ± 1.7 years). Blood samples were collected before and after the 2-week supplementation, and then 0 hr, 1.5 hr, and 21 hr post 75-km cycling (176 ± 5.4 min, 73.4 ±2.0% maximal oxygen consumption). The supplement provided 678-mg flavonoids with quercetin (200 mg), green tea catechins (368 mg, 180-mg epigallocatechin gallate), and anthocyanins (128 mg) from bilberry extract, with caffeine, vitamin C, and omega-3 fatty acids added as adjuvants. Blood samples were analyzed for blood leukocyte counts, oxinflammation biomarkers, including 4-hydroxynonenal, protein carbonyls, and peripheral blood mononuclear mRNA expression for cyclooxygenease-2 and glutathione peroxidase. Each of the blood biomarkers was elevated postexercise (time effects, all ps < .01), with lower plasma levels for 4-hydroxynonenal (at 21-hr postexercise) in flavonoid versus placebo (interaction effect, p = .008). Although elevated postexercise, no trial differences for the neutrophil/lymphocyte ratio (p = .539) or peripheral blood mononuclear mRNA expression for cyclooxygenease-2 (p = .322) or glutathione peroxidase (p = .839) were shown. Flavonoid supplementation prior to intensive exercise decreased plasma peroxidation and oxidative damage, as determined by 4-hydroxynonenal. Postexercise increases were similar between the flavonoid and placebo trials for peripheral blood mononuclear mRNA expression for cyclooxygenease-2 and the nuclear factor erythroid 2-related factor 2 related gene glutathione peroxidase (NFE2L2). The data support the strategy of flavonoid supplementation to mitigate postexercise oxidative stress in endurance athletes.

Exercise-Induced Illness and Inflammation: Can Immunonutrition and Iron Help?

The main focus of this review is illness among elite athletes, how and why it occurs, and whether any measures can be taken to combat it or to prevent its onset. In particular, there is particular interest in exercise-induced immunodepression, which is a result of the immune system regarding exercise (e.g., prolonged, exhaustive exercise) as a challenge to its function. This promotes the inflammatory response. There is often a high incidence of illness in athletes after undertaking strenuous exercise, particularly among those competing in endurance events, not only mainly in terms of upper respiratory tract illness, but also involving gastrointestinal problems. It may well be that this high incidence is largely due to insufficient recovery time being allowed after, for example, a marathon, a triathlon, or other endurance events. Two examples of the incidence of upper respiratory tract illness in moderate versus endurance exercise are provided. In recent years, increasing numbers of research studies have investigated the origins, symptoms, and incidence of these bouts of illness and have attempted to alleviate the symptoms with supplements, sports foods, or immunonutrition. One aspect of the present review discusses iron deficiency, which has been primarily suggested to have an impact upon cell-mediated immunity. Immunonutrition is also discussed, as are new techniques for investigating links between metabolism and immune function.

Flavonoid Mixture Inhibits Mycobacterium tuberculosis Survival and Infectivity.

BACKGROUND: Flavonoids have been shown to exert anti-pathogenic potential, but few studies have investigated their effects on Mycobacterium tuberculosis (Mtb) infectivity. We hypothesized that a flavonoid mixture would have a favorable influence on cell death and the resolution of Mtb infection in THP-1 macrophages and in granulomas derived from both healthy participants and those with type 2 diabetes mellitus (T2DM). METHODS: THP-1 macrophages, and in vitro granulomas from healthy participants (N = 8) and individuals with T2DM (N = 5) were infected with Mtb. A mixed flavonoid supplement (MFS) at a concentration of 0.69 mg per ml was added as treatment to Mtb infected THP-1 macrophages and granulomas for 8 to 15 days. RESULTS: MFS treatment significantly reduced the intracellular Mtb survival, increased cell density, aggregation, and granuloma formation, and increased glutathione (GSH) levels. IL-12 and IFN-γ levels tended to be higher and IL-10 lower when Mtb infected THP-1 macrophages and granulomas obtained from healthy subjects were treated with MFS compared to control. CONCLUSIONS: MFS treatment exerted a strong influence against Mtb infectivity in THP-1 macrophages and in granulomas including antimycobacterial effects, GSH enrichment, cytokine regulation, and augmented granuloma formation. Our data support the strategy of increased flavonoid intake for managing tuberculosis.

Identification of a select metabolite panel for measuring metabolic perturbation in response to heavy exertion.

INTRODUCTION AND OBJECTIVE: Databases from three global metabolomics-based studies (N = 59) (PMID: 25409020, 26561314, 29566095) were evaluated for metabolite shifts following heavy exertion (75-km cycling) to generate a representative, select panel of metabolites identified by variable importance in projection (VIP) scores. METHODS AND RESULTS: OPLS-DA was used to separate samples at pre- and post-exercise during the water-only trial in one of the studies (PMID: 26561314), and of 590 metabolites, 26 (all but one from the lipid pathway) had a VIP > 2 and were selected for the panel. A second OPLS-DA based on the 26 metabolites was performed to separate pre- and post-exercise samples, and this model performed as well as the one with 590 metabolites (Q2Y = 0.923, 0.925 respectively); this model also showed a complete separation using OPLS-DA plots between pre- and post-exercise samples for the other two studies. A latent variable t1 (a linear combination of the 26 metabolites), was generated and the metabolite data at each time point were projected to t1 with the relative distance on t1 and area under the curve (AUC) determined from the three databases. Acute carbohydrate compared to water-only ingestion was linked to a 28-47% reduction in AUCs following exercise depending on the carbohydrate source and recovery time period. CONCLUSIONS: These data support that a panel of 26 metabolites can be used to represent global metabolite increases induced by prolonged, intensive exercise. This select panel includes metabolites primarily from the lipid super pathway, and exercise-induced increases are sensitive to the moderating effect of acute carbohydrate ingestion.

Influence of 2-Weeks Ingestion of High Chlorogenic Acid Coffee on Mood State, Performance, and Postexercise Inflammation and Oxidative Stress: A Randomized, Placebo-Controlled Trial.

This study measured the influence of 2-weeks ingestion of high chlorogenic acid (CQA) coffee on postexercise inflammation and oxidative stress, with secondary outcomes including performance and mood state. Cyclists (N = 15) were randomized to CQA coffee or placebo (300 ml/day) for 2 weeks, participated in a 50-km cycling time trial, and then crossed over to the opposite condition with a 2-week washout period. Blood samples were collected pre- and postsupplementation, and immediately postexercise. CQA coffee was prepared using the Turkish method with 30 g lightly roasted, highly ground Hambela coffee beans in 300 ml boiling water, and provided 1,066 mg CQA and 474 mg caffeine versus 187 mg CQA and 33 mg caffeine for placebo. Plasma caffeine was higher with CQA coffee versus placebo after 2-weeks (3.3-fold) and postexercise (21.0-fold) (interaction effect, p < .001). Higher ferric reducing ability of plasma (FRAP) levels were measured after exercise with CQA coffee versus placebo (p = .01). No differences between CQA coffee and placebo were found for postexercise increases in plasma IL-6 (p = .74) and hydroxyoctadecadienoic acids (9 + 13 HODEs) (p = .99). Total mood disturbance (TMD) scores were lower with CQA coffee versus placebo (p = .04). 50-km cycling time performance and power did not differ between trials, with heart rate and ventilation higher with CQA coffee, especially after 30 min. In summary, despite more favorable TMD scores with CQA coffee, these data do not support the chronic use of coffee highly concentrated with chlorogenic acids and caffeine in mitigating postexercise inflammation or oxidative stress or improving 50-km cycling performance.

Effect of 4-Week Ingestion of Tomato-Based Carotenoids on Exercise-Induced Inflammation, Muscle Damage, and Oxidative Stress in Endurance Runners.

This double-blind, randomized, placebo-controlled crossover trial determined if ingestion of a supplement containing a tomato complex with lycopene, phytoene, and phytofluene (T-LPP) and other compounds for 4 weeks would attenuate inflammation, muscle damage, and oxidative stress postexercise and during recovery from a 2-hr running bout that included 30 min of -10% downhill running. Study participants ingested the T-LPP supplement or placebo with the evening meal for 4 weeks prior to running 2 hr at high intensity. Blood samples and delayed onset muscle soreness ratings were taken pre- and post-4-week supplementation, and immediately following the 2-hr run, and then 1-hr, 24-hr, and 48-hr postrun. After a 2-week washout period, participants crossed over to the opposite treatment and repeated all procedures. Plasma lycopene, phytoene, and phytofluene increased significantly in T-LPP compared with placebo (p < .001 for each). Significant time effects were shown for serum creatine kinase, delayed onset muscle soreness, C-reactive protein, myoglobin, 9- and 13-hydroxyoctadecadienoic acids, ferric reducing ability of plasma, and six plasma cytokines (p < .001 for each). The pattern of increase for serum myoglobin differed between T-LPP and placebo (interaction effect, p = .016, with lower levels in T-LPP), but not for creatine kinase, delayed onset muscle soreness, C-reactive protein, the six cytokines, 9- and 13-hydroxyoctadecadienoic acids, and ferric reducing ability of plasma. No significant time or interaction effects were measured for plasma-oxidized low-density lipoprotein or serum 8-hydroxy-2'-deoxyguanosine. In summary, supplementation with T-LPP over a 4-week period increased plasma carotenoid levels 73% and attenuated postexercise increases in the muscle damage biomarker myoglobin, but not inflammation and oxidative stress.

IL-6 Linkage to Exercise-Induced Shifts in Lipid-Related Metabolites: A Metabolomics-Based Analysis.

Metabolomics profiling and bioinformatics technologies were used to determine the relationship between exercise-induced increases in IL-6 and lipid-related metabolites. Twenty-four male runners (age 36.5 ± 1.8 y) ran on treadmills to exhaustion (2.26 ± 0.01 h, 24.9 ± 1.3 km, 69.7 ± 1.9% VO2max). Vastus lateralis muscle biopsy and blood samples were collected before and immediately after running and showed a 33.7 ± 4.2% decrease in muscle glycogen, 39.0 ± 8.8-, 2.4 ± 0.3-, and 1.4 ± 0.1-fold increases in plasma IL-6, IL-8, and MCP-1, respectively, and 95.0 ± 18.9 and 158 ± 20.6% increases in cortisol and epinephrine, respectively (all, P < 0.001). The metabolomics analysis revealed changes in 209 metabolites, especially long- and medium-chain fatty acids, fatty acid oxidation products (dicarboxylate and monohydroxy fatty acids, acylcarnitines), and ketone bodies. OPLS-DA modeling supported a strong separation in pre- and post-exercise samples (R2Y = 0.964, Q2Y = 0.902). OPLSR analysis failed to produce a viable model for the relationship between IL-6 and all lipid-related metabolites (R2Y = 0.76, Q2Y = -0.0748). Multiple structure equation models were evaluated based on IL-6, with the best-fit pathway model showing a linkage of exercise time to IL-6, then carnitine, and 13-methylmyristic acid (a marker for adipose tissue lipolysis) and sebacate. These metabolomics-based data indicate that the increase in plasma IL-6 after long endurance running has a minor relationship to increases in lipid-related metabolites.

Influence of Ingesting a Flavonoid-Rich Supplement on the Metabolome and Concentration of Urine Phenolics in Overweight/Obese Women.

This study evaluated the effect of ingesting a flavonoid-rich supplement (329 mg/d) on total urine phenolics and shifts in plasma metabolites in overweight/obese female adults using untargeted metabolomics procedures. Participants (N = 103, 18-65 y, BMI ≥ 25 kg/m2) were randomized to flavonoid (F) or placebo (P) groups for 12 weeks with blood and 24 h urine samples collected prestudy and after 4 and 12 weeks in a parallel design. Supplements were prepared as chewable tablets and included vitamin C, wild bilberry fruit extract, green tea leaf extract, quercetin, caffeine, and omega 3 fatty acids. At 4 weeks, urine total phenolics increased 24% in F versus P with similar changes at 12 weeks (interaction effect, P = 0.041). Groups did not differ in markers of inflammation (IL-6, MCP-1, CRP) or oxidative stress (oxLDL, FRAP). Metabolomics data indicated shifts in 63 biochemicals in F versus P with 70% from the lipid and xenobiotics superpathways. The largest fold changes in F were measured for three gut-derived phenolics including 3-methoxycatechol sulfate, 3-(3-hydroxyphenyl)propanoic acid sulfate, and 1,2,3-benzenetriol sulfate (interaction effects, p ≤ 0.050). This randomized clinical trial of overweight/obese women showed that 12 weeks ingestion of a mixed flavonoid nutrient supplement was associated with a corresponding increase in urine total phenolics and gut-derived phenolic metabolites.

Consensus Statement Immunonutrition and Exercise.

In this consensus statement on immunonutrition and exercise, a panel of knowledgeable contributors from across the globe provides a consensus of updated science, including the background, the aspects for which a consensus actually exists, the controversies and, when possible, suggested directions for future research.

9- and 13-Hydroxy-octadecadienoic acids (9+13 HODE) are inversely related to granulocyte colony stimulating factor and IL-6 in runners after 2h running.

This study utilized a pro-inflammatory exercise mode to explore potential linkages between increases in 9- and 13-hydroxy-octadecadienoic acid (9+13 HODE) and biomarkers for inflammation, oxidative stress, and muscle damage. Male (N=10) and female (N=10) runners ran at ∼70% VO2max for 1.5h followed by 30min of downhill running (-10%). Blood samples were taken pre-run and immediately-, 1-h-, and 24-h post-run, and analyzed for 9+13 HODE, F2-isoprostanes, six cytokines, C-reactive protein (CRP), creatine kinase (CK), and myoglobin (MYO). Gender groups performed at comparable relative heart rate and oxygen consumption levels during the 2-h run. All outcome measures increased post-run (time effects, P⩽0.001), with levels near pre-run levels by 24h except for CRP, CK, MYO, and delayed onset of muscle soreness (DOMS). Plasma 9+13 HODE increased 314±38.4% post-run (P<0.001), 77.3±15.8% 1-h post-run (P<0.001), and 40.6±16.4% 24-h post-exercise (P=0.024), and F2-isoprostanes increased 50.8±8.9% post-run (P<0.001) and 19.0±5.3% 1-h post-run (P=0.006). Post-run increases were comparable between genders for all outcomes except for 9+13 HODE (interaction effect, P=0.024, post-run tending higher in females), IL-10 (P=0.006, females lower), and DOMS (P=0.029, females lower). The pre-to-post-run increase in 9+13 HODEs was not related to other outcomes except for plasma granulocyte colony stimulating factor (GCSF) (r=-0.710, P<0.001) and IL-6 (r=-0.457, P=0.043). Within the context of this study, exercise-induced increases in 9+13 HODEs tended higher in females, and were not related to increases in F2-isoprostanes, muscle damage, or soreness. The negative relationships to GCSF and IL-6 suggest a linkage between 9+13 HODES and exercise-induced neutrophil chemotaxis, degranulation, and inflammation.

Metabolomics-Based Analysis of Banana and Pear Ingestion on Exercise Performance and Recovery.

Bananas and pears vary in sugar and phenolic profiles, and metabolomics was utilized to measure their influence on exercise performance and recovery. Male athletes (N = 20) cycled for 75 km while consuming water (WATER), bananas (BAN), or pears (PEAR) (0.6 g carbohydrate/kg each hour) in randomized order. UPLC-MS/MS and the library of purified standards maintained by Metabolon (Durham, NC) were used to analyze metabolite shifts in pre- and postexercise (0-h, 1.5-h, 21-h) blood samples. Performance times were 5.0% and 3.3% faster during BAN and PEAR versus WATER (P = 0.018 and P = 0.091, respectively), with reductions in cortisol, IL-10, and total leukocytes, and increases in blood glucose, insulin, and FRAP. Partial Least Square Discriminant Analysis (PLS-DA) showed a distinct separation between trials immediately (R(2)Y = 0.877, Q(2)Y = 0.457) and 1.5-h postexercise (R(2)Y = 0.773, Q(2)Y = 0.441). A total of 107 metabolites (primarily lipid-related) increased more than 2-fold during WATER, with a 48% and 52% reduction in magnitude during BAN and PEAR recovery (P < 0.001). Increases in metabolites unique to BAN and PEAR included fructose and fruit constituents, and sulfated phenolics that were related to elevated FRAP. These data indicate that BAN and PEAR ingestion improves 75-km cycling performance, attenuates fatty acid utilization and oxidation, and contributes unique phenolics that augment antioxidant capacity.

Cytokine expression and secretion by skeletal muscle cells: regulatory mechanisms and exercise effects.

Cytokines are important mediators of various aspects of health and disease, including appetite, glucose and lipid metabolism, insulin sensitivity, skeletal muscle hypertrophy and atrophy. Over the past decade or so, considerable attention has focused on the potential for regular exercise to counteract a range of disease states by modulating cytokine production. Exercise stimulates moderate to large increases in the circulating concentrations of interleukin (IL)-6, IL-8, IL- 10, IL-1 receptor antagonist, granulocyte-colony stimulating factor, and smaller increases in tumor necrosis factor-α, monocyte chemotactic protein-1, IL-1ß, brain-derived neurotrophic factor, IL-12p35/p40 and IL-15. Although many of these cytokines are also expressed in skeletal muscle, not all are released from skeletal muscle into the circulation during exercise. Conversely, some cytokines that are present in the circulation are not expressed in skeletal muscle after exercise. The reasons for these discrepant cytokine responses to exercise are unclear. In this review, we address these uncertainties by summarizing the capacity of skeletal muscle cells to produce cytokines, analyzing other potential cellular sources of circulating cytokines during exercise, and discussing the soluble factors and intracellular signaling pathways that regulate cytokine synthesis (e.g., RNA-binding proteins, microRNAs, suppressor of cytokine signaling proteins, soluble receptors).

Metabolomics approach to assessing plasma 13- and 9-hydroxy-octadecadienoic acid and linoleic acid metabolite responses to 75-km cycling.

Bioactive oxidized linoleic acid metabolites (OXLAMs) include 13- and 9-hydroxy-octadecadienoic acid (13-HODE + 9-HODE) and have been linked to oxidative stress, inflammation, and numerous pathological and physiological states. The purpose of this study was to measure changes in plasma 13-HODE + 9-HODE following a 75-km cycling bout and identify potential linkages to linoleate metabolism and established biomarkers of oxidative stress (F2-isoprostanes) and inflammation (cytokines) using a metabolomics approach. Trained male cyclists (N = 19, age 38.0 ± 1.6 yr, wattsmax 304 ± 10.5) engaged in a 75-km cycling time trial on their own bicycles using electromagnetically braked cycling ergometers (2.71 ± 0.07 h). Blood samples were collected preexercise, immediately post-, 1.5 h post-, and 21 h postexercise, and analyzed for plasma cytokines (IL-6, IL-8, IL-10, tumor necrosis factor-α, monocyte chemoattractant protein-1, granulocyte colony-stimulating factor), F2-isoprostanes, and shifts in metabolites using global metabolomics procedures with gas chromatography mass spectrometry (GC-MS) and liquid chromatography mass spectrometry (LC-MS). 13-HODE + 9-HODE increased 3.1-fold and 1.7-fold immediately post- and 1.5 h postexercise (both P < 0.001) and returned to preexercise levels by 21-h postexercise. Post-75-km cycling plasma levels of 13-HODE + 9-HODE were not significantly correlated with increases in plasma cytokines but were positively correlated with postexercise F2-isoprostanes (r = 0.75, P < 0.001), linoleate (r = 0.54, P = 0.016), arachidate (r = 0.77, P < 0.001), 12,13-dihydroxy-9Z-octadecenoate (12,13-DiHOME) (r = 0.60, P = 0.006), dihomo-linolenate (r = 0.57, P = 0.011), and adrenate (r = 0.56, P = 0.013). These findings indicate that prolonged and intensive exercise caused a transient, 3.1-fold increase in the stable linoleic acid oxidation product 13-HODE + 9-HODE and was related to increases in F2-isoprostanes, linoleate, and fatty acids in the linoleate conversion pathway. These data support the use of 13-HODE + 9-HODE as an oxidative stress biomarker in acute exercise investigations.

The effects of moderate exercise on chronic stress-induced intestinal barrier dysfunction and antimicrobial defense.

The purpose of this study was to examine the effect of moderate exercise on repeated restraint stress (RRS)-induced intestinal barrier dysfunction and explore possible mechanisms in a mouse model. Male Balb/c mice (6weeks) were randomized into 7 groups: CON functioned as controls with no intervention; RRS was subjected to 6h per day RRS for 7 consecutive days; RRS+SWIM received 30min per day of swimming prior to RRS; CON+SWIM only received 30min per day of swimming; and the other groups received one session of 30min swimming prior to sacrifice at 1-, 3- and 6h recovery. Intestinal permeability was quantified with FITC-dextran. Bacterial translocation was determined by quantification of bacterial colony forming units (CFUs) in cultured mesenteric lymph nodes (MLN), and with fluorescence in situ hybridization (FISH). Antimicrobial related gene expression at baseline and 1h after one session of 30min swimming was tested by quantitative real-time polymerase chain reaction (Q-PCR) in small intestinal segments. Protein expression of 5 genes with statistically significant increase was measured at baseline, and 1-, 3- and 6h post-swimming using enzyme-linked immunosorbent assay (ELISA). Thirty minutes per day of swimming before RRS attenuated bacterial translocations and maintained intestinal permeability. Gene expression and protein levels for four antimicrobial peptides (α-defensin 5, ß-defensin 1, RegIIIß and RegIIIγ) were significantly increased after one 30min swimming session. In conclusion, moderate exercise attenuated chronic stress-induced intestinal barrier dysfunction in mice, possibly due to augmentation of antimicrobial responses in the small intestine.