Influence of diet and a healthy gut on the immune response Parveen Yaqoob

Transcription

1 Influence of diet and a healthy gut on the immune response Parveen Yaqoob Professor of Nutritional Physiology Director of Research & Deputy Head of Department Food & Nutritional Sciences

2 Early life events Nutrient status Diet Gut flora? Obesity Genetics Alcohol consumption Gender Immune function Smoking Age Hormonal status Exposure to pathogens (Infections) - Presence - History Vaccination history Exercise - Acute - Chronic Stress - Environmental - Physiological - Psychological 2

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4 NUTRIENT INTAKE & ABSORPTION NUTRIENT LOSSES Anorexia Malabsorption Intestinal damage Diarrhoea Activation of immune & inflammatory response NUTRIENT REQUIREMENT 4

5 Contributes to normal function of the immune system Vitamin A Vitamin C Vitamin D (and healthy inflammatory response) Zinc Selenium and others. plays a role and supports normal function is acceptable, but stimulates or optimises normal function is not.

6 Vitamin A Deficiency associated with increased susceptibility to infection Deficiency associated with breakdown of gut barrier and skin infections Replenishment of vitamin A in deficient individuals: decreases mortality in children 6mo-5y by 30% frequent, small doses are better than infrequent high doses promotes regeneration of damaged gut tissue, reducing incidence and duration of diarrhea 6

7 Malnutrition in older people (From Stratton et al 2003; Disease-related malnutrition) 7

8 Ageing and influenza vaccination Vaccine effectiveness declines sharply after age 65y. Immunization of the elderly provides only 30-50% protection against infection. Older people more likely to develop complications such as pneumonia following infection. 8

9 Nutrition & response to influenza vaccination in elderly subjects Nutrient Subjects Findings Reference Vitamin A (plasma) Fe + Vit C supplements Plasma Fe levels Healthy elderly (70-95y) from retirement community No association Gardner, 2000 Institutionalized >65y No effect of supplementation Crogan, 2005 Institutionalized (62-98y) Positive relationship between Fe and response to vaccination Fulop, 1999 Zn supplements Institutionalized (<80y) No effect Remarque, 1993 Zn supplements Institutionalized (64-100y) No effect Provinciali, 1998 Zn + Se or Vit A,C,E or both Long-term institutionalized (65-103y) Zn + Se and Zn/Se/Vit ACE increased seroprotection vs placebo and Vit ACE Girodon, 1999 Serum Zn Hemodialysis patients >65y No association Kreft, 2000 Dietary and serum Zn Serum Zn Women 67-96y, institutionalized and free-living Healthy elderly (70-95y) from retirement community No association Stiedemann, 1980 No association Gardner,

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11 Gut microbiota composition correlates with diet and health in elderly subjects Death sits in the bowel; a bad digestion is the root of all evil. Hippocrates, ca 400 BC Community Long-stay Claesson et al., (2012) Nature 488,

12 Intestinal putrefaction Production of carcinogens Ps. aeruginosa Proteus sp. Candida sp. Sulphate reducers Clostridia Diarrhoea, constipation, infections, liver damage, cancer, toxigenesis, encephalopathy Enterococci E. coli Streptococci Bacteroides Lactobacilli Bifidobacteria Inhibition of growth of exogenous and harmful bacteria Digestion/ absorption nutrients Stimulate immune function Vitamin synthesis 12

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14 iotics for preventing acute upper respiratory tract Probiotics infections for preventing (Review) acute upper respiratory tract infections (Review) Hao Q, Lu Z, Dong BR, Huang CQ, Wu T [Intervention Review] Hao Q, Lu Z, Dong BR, Huang CQ, Wu T Probiotics for preventing acute upper respiratory tract infections Qiukui Hao 1, Zhenchan Lu 1,Bi Rong Dong 1,Chang Quan Huang 1,Taixiang Wu 2 27 RCTs 10 included in meta-analysis 3451 participants Probiotics better than placebo in reducing: Number of participants experiencing at least 1 episode acute URTI (42%) Number of participants experiencing 3 or more episodes acute URTI (47%) 1 Department of Geriatrics, West ChinaHospital, Sichuan University, Chengdu, China. 2 ChineseCochraneCentre, ChineseClinical Trial Registry, Chinese Evidence-Based Medicine Centre, INCLEN Resource and Training Centre, West China Hospital, Sichuan Antibiotic use (33%) University, Chengdu, China Contact address: Bi RongDong, Department of Geriatrics, West ChinaHospital, Sichuan University, No. 37, GuoXueXiang, Chengdu, No effect on mean duration URTI Sichuan, , China. birongdong@163.com. Editorial group: CochraneAcuteRespiratory InfectionsGroup. Publication statusand date: New, published in Issue9, Review content assessed asup-to-date: 17 May f acochranereview, prepared and maintained by TheCochraneCollaboration and published in TheCochraneLibrary No data for older people Citation: Hao Q, Lu Z, Dong BR, Huang CQ, Wu T. Probiotics for preventing acute upper respiratory tract infections. Cochrane Databaseof SystematicReviews2011, Issue9. Art. No.: CD DOI: / CD pub2. 14

15 Probiotics and immune function; parameters subject to modulation Natural killer cell activity Phagocytosis by macrophages and neutrophils T lymphocyte proliferation Number of antibody-secreting cells in the circulation post-infection or vaccination Antibody response to infection Antibody response to vaccination

16 Criteria for evaluation of markers: Differentially expressed Correlate with clinical endpoint Linked to causal pathway (backed by human data) Biologically sensitive (taking variation into account) Technically feasible Robust 16

17 Group A marker Group B marker Group C marker Group D marker Indicative of clinical relevance and involvement of immune function Response to natural or experimental infection Response to vaccination Delayed type hypersensitivity Mucosal IgA (saliva, tears etc) Indicative of clinical relevance, but not necessarily involvement of immune function (ie clinical symptom) Incidence, duration and severity of natural or experimental infection Pathogen load Indicative of involvement of immune function and associated with clinical relevance in specific( sub)populations Ex vivo pathogen-specific B cell function Ex vivo pathogen-specific T cell function Ex vivo phagocytic function Ex vivo NK cell function Provides mechanistic insights but not necessarily into clinical relevance Markers of the acute phase response Phenotypes of immune cell subsets Circulating or ex vivo produced antibodies Circulating or ex vivo produced cytokines.and others 17

18 EFSA discussion paper 2014 Claims that are insufficiently defined for scientific evaluation (eg gut health, natural defences, maintenance of normal immune function). Claims which are not considered beneficial per se (eg increasing numbers of lactobacilli/bifidobacteria, stimulation of markers of the immune system, changes in inflammatory markers). Claims on immune defence against pathogens (relevant immune markers need to be measured, appropriate outcomes related to vaccination will be clarified).

19 Summary Relationship between malnutrition and immunity Specific micronutrients contribute to normal function of the immune system Immunity and response to vaccination declines significantly in older people. Theoretical basis for gut microbiota modulation to influence immunity. Promising data relating to effects of probiotics on respiratory infections. Relevance of immune biomarkers is an issue.