Nutrition and immunity: Better understanding and biomarkers still needed

While the fact that there is a significant link between what we eat and how well our immune system works is not disputed, the science linking different aspects of immune functions and nutritional states is complex and sometimes controversial. 

According to a World Health Organisation (WHO) Report by David Thurnham and George McCabe, many plasma nutrients are influenced by immune responses to infection or tissue damage. In addition, such infection and tissue damage can be recognised by the clinical effects on the body, said the authors. However, research in the nutrition arena often deals with subclinical infection or inflammation that can only be recognised by measuring inflammation biomarkers in the blood.

“It is therefore important to measure biomarkers of inflammation as well as of nutrition in prevalence surveys of nutritional status in apparently healthy people,”​ stated the WHO report.​​

Yet, the wide range of possible biomarkers, and sometimes muddy science that connects them to nutrition, means that knowing exactly which biomarkers to track in a study can be akin to pinning the tail on the donkey. 

Immune biomarkers 

According to Thurnham and McCabe, the most commonly used biomarkers of inflammation are cytokines and acute phase proteins such as C-reactive protein (CRP) and alpha1-acid glycoprotein (AGP).

Indeed, a recent guidance document, supported the International Life Sciences Institute Europe (ILSI Europe), defined criteria to evaluate the usefulness of immune function markers - before scoring over seventy-five markers within the context of three distinct immune system functions: defence against pathogens; avoidance or mitigation of allergy; control of low-grade (metabolic) inflammation.

The report, published in The British Journal of Nutrition​​​ found markers that involve the standardised assessment of relevant symptoms (like symptoms of common infections or allergies) or in vivo​ responses to a defined challenge with antigens or allergens (like response to vaccination or allergen provocation) “provide the most useful indication to interpret the modulation of immune function.” ​

“Other useful markers include selected ex vivo markers of particular immune functions (e.g. NK-cell activity, phagocytosis and responsiveness of specific T-cell subpopulations) and selected basal markers essential in the exertion of critical immune functions, such as mucosal IgA for infection resistance, allergen-sIgE and tryptase for avoidance or mitigation of allergy, and CRP and inflammatory mediators to indicate low-grade inflammation,”​ the report said.

The group further classified a selection of the most useful biomarkers depending on whether a change in the markers by itself conclusively indicated clinical relevance and/or involvement of altered immune function.

The report added that there is clearly ‘no gold standard of immune function’ that can be recommended for all studies assessing the effects of nutrition on immune function in the general population. 

“It is, therefore, proposed to first define the functional domain of interest and then select (combinations of) markers that indicate clinical relevance and for which a plausible hypothesis explaining how they could be related is available,”​ wrote the team.

According to work published by Professor Philip Calder and colleagues, (British Journal of Nutrition), in order to monitor inflammation in a meaningful way, the biomarkers used must be valid and reflect inflammatory process under study and they must be predictive of future health status.

However, a lack of agreement over what markers reliably indicate different inflammatory processes causes confusion: 

“Currently, there is no consensus as to which markers of inflammation best represent low-grade inflammation or differentiate between acute and chronic inflammation or between the various phases of inflammatory responses,”​ wrote the team – adding that there are a number of modifying factors that affect the concentration of an inflammatory marker at a given time, including age, diet and body fatness, among others.

“It is likely that a combination of multiple inflammatory markers and integrated readouts based upon kinetic analysis following defined challenges will be the most informative biomarker of inflammation,”​ they concluded.