Plasma Endogenous Endotoxin Core Antibody Response to Exercise in Endurance Athletes

Abstract

The study aimed to investigate the impact of laboratory-controlled exertional and exertional-heat stress on concentrations of plasma endogenous endotoxin core antibody (EndoCAb). Forty-four (males n=26 and females n=18) endurance trained (V̇ O _2max 56.8min/kg/min) participants completed either: P1–2h high intensity interval running in 23°C ambient temperature (T_amb), P2–2h running at 60% V̇ O_2max in 35°C T_amb, or P3–3h running at 60% V̇ O_2max in 23°C T_amb. Blood samples were collected pre- and post-exercise to determine plasma IgM, IgA, and IgG concentrations. Overall resting pre-exercise levels for plasma Ig were 173MMU/ml, 37AMU/ml, and 79GMU/ml, respectively. Plasma IgM concentration did not substantially change pre- to post-exercise in all protocols, and the magnitude of pre- to post-exercise change for IgM was not different between protocols (p=0.135). Plasma IgA and IgG increased pre- to post-exercise in P2 only (p=0.017 and p=0.016, respectively), but remained within normative range (35–250MU/ml). P2 resulted in greater disturbances to plasma IgA (p=0.058) and IgG (p=0.037), compared with P1 and P3. No substantial differences in pre-exercise and exercise-associated change was observed for EndoCAb between biological sexes. Exertional and exertional-heat stress resulted in modest disturbances to systemic EndoCAb responses, suggesting EndoCAb biomarkers presents a low sensitivity response to controlled-laboratory experimental designs within exercise gastroenterology.

Key words

gastrointestinal - epithelium - endotoxin - inflammatory cytokine - immunoglobulin - exercise

Publikationsverlauf

Eingereicht: 23. Januar 2022

Angenommen: 05. April 2022

Accepted Manuscript online:
14. April 2022

Artikel online veröffentlicht:
22. Juli 2022

• References

• 1 Costa RJS, Gaskell SK, McCubbin AJ. et al. Exertional-heat stress associated gastrointestinal perturbations-management strategies for athletes preparing for and competing in the 2020 Tokyo Olympic Games. Temperature (Austin) 2020; 7: 58-88
• 2 Costa RJ, Snipe RM, Kitic CM. et al. Systematic review: exercise- induced gastrointestinal syndrome-implications for health and intestinal disease. Aliment Pharmacol Ther 2017; 46: 246-265
• 3 Gaskell SK, Costa RJS, Lis D. Gaskell SK, Costa RJS, Lis D. Chapter 21: Exercise-induced gastrointestinal syndrome, gastrointestinal disorders, food intolerance and allergies. In: Burke L, Deakin V, Minehan M (Eds.). Clinical Sports Nutrition, 6e. McGraw-Hill Education. Sydney, NSW, Australia: 2021
• 4 Gaskell SK, Rauch CE, Costa RJS. Gastrointestinal assessment and therapeutic intervention for the management of exercise-associated gastrointestinal symptoms: a case series translational and professional practice approach. Front Physiol 2021; 12: 719142
• 5 Peake JM, Della Gatta P, Suzuki K. et al. Cytokine expression and secretion by skeletal muscle cells: regulatory mechanisms and exercise effects. Exerc Immunol Rev 2015; 21: 8-25
• 6 Suzuki K, Tominaga T, Ruhee RT. et al. Characterization and modulation of systemic inflammatory response to exhaustive exercise in relation to oxidative stress. Antioxidants 2020; 9: 401
• 7 Gaskell SK, Taylor B, Muir J. et al. Impact of 24-hour low and high fermentable oligo-di-mono-saccharide polyol diets on markers of exercise-induced gastrointestinal syndrome in response to exertional-heat stress. Appl Physiol Nutr Metab 2020; 45: 569-580
• 8 Snipe R, Costa RJS. Does the temperature of water ingested during exertional-heat stress influence gastrointestinal injury, symptoms, and systemic inflammatory profile?. J Sci Med Sport 2018; 21: 771-776
• 9 Snipe R, Khoo A, Kitic C. et al. The impact of exertional-heat stress on gastrointestinal integrity, gastrointestinal symptoms, systemic endotoxin and cytokine profile. Eur J Appl Physiol 2018; 118: 389-400
• 10 Snipe R, Khoo A, Kitic C. et al. Mild Heat stress during prolonged running results in exacerbated intestinal epithelial injury and gastrointestinal symptoms. Int J Sports Med 2018; 39: 255-263
• 11 Gaskell SK, Parr A, Rauch C. et al. Diurnal versus nocturnal exercise-impact on the gastrointestinal tract. Med Sci Sports Exerc 2021; 53: 1056-1067
• 12 Gill SK, Hankey J, Wright A. et al. The impact of a 24-hour ultra-marathon on circulatory endotoxin and cytokine profile. Int J Sports Med 2015; 36: 688-695
• 13 Gill SK, Teixeira A, Rama L. et al. Circulatory endotoxin concentration and cytokine profile in response to exertional-heat stress during a multi-stage ultra-marathon competition. Exerc Immunol Rev 2015; 21: 114-128
• 14 Laitano O, Leon LR, Roberts WO. et al. Controversies in exertional heat stroke diagnosis, prevention, and treatment. J Appl Physiol (1985) 2019; 127: 1338-1348
• 15 Roberts WO, Armstrong LE, Sawka MN. et al. ACSM expert consensus statement on exertional heat illness: recognition, management, and return to activity. Curr Sports Med Rep 2021; 20: 470-484
• 16 Robson-Ansley P, Toit GD. Pathophysiology, diagnosis and management of exercise-induced anaphylaxis. Curr Opin Allergy Clin Immunol 2010; 10: 312-317
• 17 Costa RJ, Miall A, Khoo A. et al. Gut-training: the impact of two weeks repetitive gut-challenge during exercise on gastrointestinal status, glucose availability, fuel kinetics, and running performance. Appl Physiol Nutr Metab 2017; 42: 547-557
• 18 Costa RJ, Snipe R, Camões-Costa V. et al. The impact of gastrointestinal symptoms and dermatological injuries on nutritional intake and hydration status during ultramarathon events. Sports Med Open 2016; 2: 16
• 19 Miall A, Khoo A, Rauch C. et al. Two weeks of repetitive gut-challenge reduces exercise associated gastrointestinal symptoms and malabsorption. Scand J Med Sci Sports 2018; 28: 630-640
• 20 Bosenberg AT, Brock-Utne JG. et al. Strenuous exercise causes systemic endotoxemia. J Appl Physiol (1985) 1988; 65: 106-108
• 21 Brock-Utne JG, Gaffin SL, Wells MT. et al. Endotoxemia in exhausted runners after a long-distance race. S Afr Med J 1988; 73: 533-536
• 22 Camus G, Nys M, Poortmans JR. et al. Endotoxaemia, production of tumour necrosis factor alpha and polymorphonuclear neutrophil activation following strenuous exercise in humans. Eur J Appl Physiol Occup Physiol 1998; 79: 62-68
• 23 Camus G, Poortmans J, Nys M. et al. Mild endotoxaemia and the inflammatory response induced by a marathon race. Clin Sci 1997; 92: 415-422
• 24 Camus G, Nys M, Poortmans JR. et al. Possible in vivo tolerance of human polymorphonuclear neutrophil to low-grade exercise-induced endotoxaemia. Mediators Inflamm 1998; 7: 413-415
• 25 Snipe R, Khoo A, Kitic C. et al. Carbohydrate and protein intake during exertional-heat stress ameliorates intestinal epithelial injury and small intestine permeability. Appl Physiol Nutr Metab 2017; 42: 1283-1292
• 26 Basauri A, González-Fernández C, Fallanza M. et al. Biochemical interactions between LPS and LPS-binding molecules. Crit Rev Biotechnol 2020; 40: 292-305
• 27 Cao Y, Zhang Y, Qiu F. Low endotoxin recovery and its impact on endotoxin detection. Biopolymers 2021; 112: e23470
• 28 Gnauck A, Lentle RG, Kruger MC. The Limulus Amebocyte Lysate assay may be unsuitable for detecting endotoxin in blood of healthy female subjects. J Immunol Methods 2015; 416: 146-156
• 29 Gnauck A, Lentle RG, Kruger MC. Chasing a ghost? Issues with the determination of circulating levels of endotoxin in human blood. Crit Rev Clin Lab Sci 2016; 53: 197-215
• 30 Gnauck A, Lentle RG, Kruger MC. The characteristics and function of bacterial lipopolysaccharides and their endotoxic potential in humans. Int Rev Immunol 2016; 35: 189-218
• 31 Guerville M, Boudry G. Gastrointestinal and hepatic mechanisms limiting entry and dissemination of lipopolysaccharide into the systemic circulation. Am J Physiol Gastrointest Liver Physiol 2016; 311: G1-G15
• 32 Hurley JC, Nowak P, Öhrmalm L. et al. Endotoxemia as a diagnostic tool for patients with suspected bacteremia caused by gram-negative organisms: a meta-analysis of 4 decades of studies. J Clin Microbiol 2015; 53: 1183-1191
• 33 Irving AT, Mimuro H, Kufer TA. et al. The immune receptor NOD1 and kinase RIP2 interact with bacterial peptidoglycan on early endosomes to promote autophagy and inflammatory signaling. Cell Host Microbe 2014; 15: 623-635
• 34 Kaparakis-Liaskos M, Ferrero RL. Immune modulation by bacterial outer membrane vesicles. Nat Rev Immunol 2015; 15: 375-387
• 35 Kulp A, Kuehn MJ. Biological functions and biogenesis of secreted bacterial outer membrane vesicles. Annu Rev Microbiol 2010; 64: 163-184
• 36 Barclay GR. Endogenous endotoxin-core antibody (EndoCAb) as a marker of endotoxin exposure and a prognostic indicator: a review. Prog Clin Biol Res 1995; 392: 263-272
• 37 Scott BB, Barclay GR. IgG antibodies to Gram-negative endotoxin in human sera. II. Opsonic activity of cross reactive antibodies to endotoxin core for rough and smooth bacteria. Serodiag Immun Inf D 1990; 4: 39-51
• 38 Scott BB, Barclay GR, Smith DGE. et al. IgG antibodies to Gram-negative endotoxin in human sera. I. Lipopolysaccharide (LPS) cross-reactivity due to antibodies to LPS core. Serodiag Immun Inf D 1990; 4: 25-38
• 39 Barclay GR. Antibodies to endotoxin in health and disease. Rev Med Microbiol 1990; 1: 133-142
• 40 Barclay GR, Scott BB, Wright IH. et al. Changes in anti-endotoxin-IgG antibody and endotoxaemia in three cases of Gram-negative septic shock. Circ Shock 1989; 29: 93-106
• 41 Bennett C, Snipe R, Henry R. et al. Is the gut microbiota bacterial abundance and composition associated with intestinal epithelial injury, systemic inflammatory profile, and gastrointestinal symptoms in response to exertional-heat stress?. J Sci Med Sport 2020; 23: 1141-1153
• 42 Harriss DJ, Macsween A, Atkinson G. Ethical standards in sport and exercise science research: 2020 update . Int J Sports Med 2019; 40: 813-817
• 43 Snipe RMJ, Costa RJS. Does biological sex influence intestinal epithelial injury, small intestine permeability, gastrointestinal symptoms and systemic cytokine profile in response to exertional-heat stress?. J Sports Sci 2018; 36: 2827-2835
• 44 Costa RJ, Oliver SJ, Laing SJ. et al. Influence of timing of postexercise carbohydrate-protein ingestion on selected immune indices. Int J Sport Nutr Exerc Metab 2009; 19: 366-384
• 45 Ong DK, Mitchell SB, Barrett JS. et al. Manipulation of dietary short chain carbohydrates alters the pattern of gas production and genesis of symptoms in irritable bowel syndrome. J Gastroenterol Hepatol 2010; 25: 1366-1373
• 46 Thomas DT, Erdman KA, Burke LM. American college of sports medicine joint position statement. Nutrition and athletic performance. Med Sci Sports Exerc 2016; 48: 543-568
• 47 Costa RJ, Gill SK, Hankey J. et al. Perturbed energy balance and hydration status in ultra-endurance runners during a 24 h ultra-marathon. Br J Nutr 2014; 112: 428-437
• 48 Costa RJ, Swancott A, Gill S. et al. Compromised energy and macronutrient intake of ultra-endurance runners during a multi-stage ultra-marathon conducted in a hot ambient environment. Int J Sports Sci 2013; 3: 51-61
• 49 Russo I, Della Gatta PA, Garnham A. et al. Assessing overall exercise recovery processes using carbohydrate and carbohydrate-protein containing recovery beverages. Front Physiol 2021; 12: 628863
• 50 Russo I, Della Gatta PA, Garnham A. et al. Does the nutritional composition of dairy milk based recovery beverages influence post-exercise gastrointestinal and immune status, and subsequent markers of recovery optimisation in response to high intensity interval exercise?. Front Nutr 2021; 7: 622270
• 51 Russo I, Della Gatta PA, Garnham A. et al. The effects of an acute “train-low” nutritional protocol on markers of recovery optimization in endurance-trained male athletes. Int J Sports Physiol Perform 2021; 16: 1764–1776
• 52 Costa RJS, Camões-Costa V, Snipe RMJ. et al. The impact of exercise-induced hypohydration on intestinal integrity, function, symptoms, and systemic endotoxin and inflammatory responses. J Appl Physiol (1985) 2019; 126: 1281-1291
• 53 Snipe R, Costa RJS. Does the temperature of water ingested during exertional-heat stress influence gastrointestinal injury, symptoms, and systemic inflammatory profile?. J Sci Med Sport 2018; 21: 771-776
• 54 Gonzalez-Quintela A, Alende R, Gude F. et al. Serum levels of immunoglobulins (IgG, IgA, IgM) in a general adult population and their relationship with alcohol consumption, smoking and common metabolic abnormalities. Clin Exp Immunol 2008; 151: 42-50
• 55 Hurley JC, Nowak P, Öhrmalm L. et al. Endotoxemia as a diagnostic tool for patients with suspected bacteremia caused by gram-negative organisms: a meta-analysis of 4 decades of studies. J Clin Microbiol 2015; 53: 1183-1191
• 56 Cavaillon JM, Adib-Conquy M. Bench-to-bedside review: endotoxin tolerance as a model of leukocyte reprogramming in sepsis. Crit Care 2006; 10: 233
• 57 Keyt BA, Baliga R, Sinclair AM. et al. Structure, function, and therapeutic use of IgM antibodies. Antibodies 2020; 9: 53
• 58 López-Collazo E, del Fresno C. Pathophysiology of endotoxin tolerance: mechanisms and clinical consequences. Crit Care 2012; 17: 242
• 59 Allan E, Poxton IR, Barclay GR. Anti-bacteroides lipopolysaccharide IgG levels in healthy adults and sepsis patients. FEMS Immunol Med Microbiol 1995; 11: 5-12
• 60 Bemark M, Angeletti D. Know your enemy or find your friend? Induction of IgA at mucosal surfaces. Immunol Rev 2021; 303: 83-102
• 61 Hoffman MD, Snipe RMJ, Costa RJS. Ad libitum drinking adequately supports hydration during 2 h of running in different ambient temperatures. Eur J Appl Physiol 2018; 118: 2687-2697
• 62 Nehlsen-Cannarella SL, Nieman DC, Jessen J. et al. The effects of acute moderate exercise on lymphocyte function and serum immunoglobulin levels. Int J Sports Med 1991; 12: 391-398
• 63 Sawka MN, Young AJ, Dennis RC. et al. Human intravascular immunoglobulin responses to exercise-heat and hypohydration. Aviat Space Environ Med 1989; 60: 634-638
• 64 Valizadeh R, Karampour S, Saiiari A. et al. The effect of one bout submaximal endurance exercise on the innate and adaptive immune responses of hypertensive patients. J Sports Med Phys Fitness 2022; 62: 244–249