Education > Article > Optimising Your Immune System

Optimising Your Immune System

To help optimise immunity, it is imperative that we nourish the immune system from the outside-in and inside-out with an emphasis on nurturing our relationship with the microbial colonies with which we co-exist. Thankfully, there is much we can do through nutritional and lifestyle medicine to support this.

beach and ocean

It is reassuring to see that general awareness of the importance of nutrition and lifestyle for a healthy immune system is steadily growing. This was exemplified by the decision of the UK Health Secretary, Matt Hancock, to offer a four-month supply of vitamin D supplements to millions of vulnerable individuals given the wealth of research demonstrating the clinical significance of this nutrient in relation to the COVID-19 pandemic1,2. Zinc3 and vitamin C4 are also receiving well-deserved attention for a similar reason.

For optimal immune function, we must nourish the immune system from the ‘outside-in’ as well as from the ‘inside-out’. The ‘outside-in’ approach involves strengthening the system of barriers, which help to protect us from bacteria, viruses, fungi, and/or parasites, which may be pathogenic, as soon as we are exposed to them. This is largely regulated by the colonies of microbes living within and on us. The ‘inside-out’ approach involves direct enhancement of the inner workings of the innate and adaptive immune system to ensure it is primed for a co-ordinated and appropriate response to a microbial threat. This requires ample nourishment of the body with the nutrients it needs to produce adequate, well-functioning white blood cells. When looking to increase the resilience of the immune system, we need to simultaneously support the immune system in both directions.

Importantly, research is revealing a bi-directional relationship between us, the host, and our microbial residents, not least when it comes to our immune system. For instance, host vitamin D status has been associated with the composition of the gut microbiota5, while the composition of the gut microbiota has been associated with variations in circulating neutrophil, lymphocyte, and monocyte counts6. There is much to learn, but what is clear is that when it comes to supporting the immune system, we must nurture the host-microbiome relationship. This is the intention of the outside-in/inside-out approach.

‘Outside-In’ Immune Support

Our bodies are constantly exposed to a plethora of microbes from the environment, particularly from the air we breathe, the food and drink we consume, the surfaces we touch and the people and animals we come into contact with. To help us adapt to this constant environmental challenge and minimise the chance of infection, our body has evolved a remarkable system of barriers to protect us as early as possible following exposure.

One of our earliest points of contact with a potential pathogen, whether a bacteria, virus, parasite, or fungus, is our mucosal barrier, the layer of mucus which covers the epithelial lining of our oral cavity and gastrointestinal, reproductive, and respiratory tracts. It provides us with a barrier between the immune-provoking contents of the outside world and the large population of immune cells that reside in the cellular lining of these organs. As such, it is our first line of defence against pathogen invasion7,8. This is followed by the epithelial barrier which lies underneath the mucus. This is comprised of cells that should be firmly held together by structures called tight junctions9. The true ‘inside’ of the body is therefore the other side of this epithelial barrier. Our goal is to maintain a healthy cross-talk between our microbial parts and ourself while keeping pathogens on the outside wherever possible before they have a chance to cause an infection. As Benjamin Franklin said, “An ounce of prevention is worth a pound of cure.”

To this end, the integrity of our mucosal and epithelial barriers is a cornerstone of a healthy immune system. However, the integrity of these barriers is all too often compromised due to a damaging combination of host, microbiome, and environmental factors. These include an excessive intake of alcohol10, non-steroid anti-inflammatory drugs (NSAIDs)11, and dietary components such as gluten12, as well as emotional stress13 intensive exercise14, environmental pollutants15, and an overabundance of mucin-degrading bacteria in the gut such as Ruminococcus gnavus and –torques16,17. Once impaired, our mucosal barriers become permeable to microbes, which can then interact with the epithelial barrier and trigger the immune system to mount a defensive inflammatory response. If the immune system is already dysregulated and prone to generating chronic inflammation, which often arises in the case of long-term hyperpermeability of the intestinal mucosal and epithelial barrier (so-called ‘leaky gut’) and gut dysbiosis18,19, obesity20, and low vitamin D21, there might be an increased risk of severe infection. Research indicates that poor health of the oral microbiome and mucosa might increase the risk of infections too, including COVID-1922,23.

The microbiota of our oral cavity, gastrointestinal, reproductive, and respiratory tracts are vital in the upkeep of quality mucosal and epithelial barriers and thus, in maintaining these vital first lines of defence. Short-chain fatty acids (SCFAs), such as butyrate, made by our commensal microbiome provide a dual benefit to the immune system. They both enhance the production of the glycoprotein mucins (specifically MUC2) by the Goblet cells in the epithelial barrier24, as well as support the structural integrity of the underlying epithelial barrier25. Our commensal microbiome can also upregulate the production of other vital components of the mucosal barrier, notably secretory IgA (SIgA)26 and beta-defensins27,28 which assist its defensive function by keeping it gently primed and ready for action. A healthy colony of Bifidobacterium spp. in the gut microbiome is vital for a strong, balanced immune system29, namely through its ability to stimulate the production of butyrate by other colonic bacteria via the process of cross-feeding30, increase host SIgA production31, and balance inflammatory cytokines32.

Good levels of mucins in the mucosal barrier provide a substrate for the growth, adhesion, and protection of the commensal microbes, creating an alliance between us, the host, and the microbial cells living within and on us33. This alliance can have far-reaching consequences for our immunity, not least by regulating the dynamics of our white blood cells as mentioned above and making the respiratory tract more resilient to infection via the emerging ‘gut-lung axis’34. It is therefore fitting that the gut microbiota is being discussed in relation to the current pandemic35,36.

In the meantime, it is our responsibility to be diligent stewards of our microbial residents by providing them with the environment they need to thrive. In turn, they hold immense potential for improving our immune resilience.

How you can support your microbiome:
  • An increased intake of prebiotic fibre and polyphenols is a fundamental starting point. A range of prebiotics, including galactoligosaccharides (GOS) and the polyphenols present in aronia berry and pomegranate, can stimulate the growth of commensal bacteria colonies in the gut, including Lactobacilli spp., Bifidobacterium spp., as well as Akkermansia muciniphila which is especially important for the health of the mucosal barrier37.
  • When therapeutic support for the intestinal mucosal and/or epithelial barrier is required, an increased intake of probiotic bacteria alongside prebiotics is prudent. Specific strains of probiotic bacteria have been shown to improve gut integrity, such as the Barrier probiotics blend of Lactobacilli and Bifidobacterium strains38. Interestingly, this blend has also been shown to reduce vulnerability to depression39, which might confer additional benefits for the immune system given the connection between poor mental health and risk of infection40. This approach can work well in practice alongside an increased intake of nutrients that support gut integrity, such as vitamin A and D41 and zinc42.
  • When SIgA has been shown to be low in a stool test, supplementation with colostrum, a source of SIgA, lactoferrin, and other immune factors, or the probiotic yeast, Saccharomyces boulardii, which can stimulate our ability to make SIgA, can be helpful to further improve immune resilience43,44. Research shows that colostrum can also support intestinal hyperpermeability, conferring additional immune benefits45.
Inside-Out Immune Support

Should a pathogen evade these early lines of defence, we need to make sure that the systemic immune system is ready to mount an appropriate, effective response. A decent oral intake of vitamins and minerals, especially vitamin A, C, D, and zinc, is essential here. There is an extensive body of research showing how instrumental these nutrients are to innate and adaptive immune system function and in reducing the risk of infection. Vitamin A, for example, can confer additional immune benefits by assisting the transport of SIgA into the mucosal barrier47.

A range of botanicals and medicinal mushrooms can be directly immune-supportive too, not least Andrographis (Andrographis paniculata)48, Echinacea (Echinacea purpurea)49, and medicinal mushrooms such as maitake (Grifola frondosa)50. With regards to Andrographis, a review of 33 randomised clinical trials showed significant improvement in coughs and a reduction in sore throats and in overall symptoms and duration of acute upper respiratory tract symptoms51.

Coupling such nutritional and botanical interventions with targeted support for stress management52 and sleep53 can be formative for improving immune resilience.

To help optimise immunity, it is imperative that we nourish the immune system from the outside-in and inside-out with an emphasis on nurturing our relationship with the microbial colonies with which we co-exist. Thankfully, there is much we can do through nutritional and lifestyle medicine to support this.


  1. Maghbooli Z, Sahraian MA, Ebrahimi M, Pazoki M, Kafan S, Tabriz HM, et al. Vitamin D sufficiency, a serum 25-hydroxyvitamin D at least 30 ng/mL reduced risk for adverse clinical outcomes in patients with COVID-19 infection. PLoS One [Internet]. 2020 Sep 1 [cited 2020 Dec 21];15(9 September).
  2. Grant WB, Lahore H, McDonnell SL, Baggerly CA, French CB, Aliano JL, et al. Evidence that vitamin d supplementation could reduce risk of influenza and covid-19 infections and deaths [Internet]. Vol. 12, Nutrients. MDPI AG; 2020 [cited 2020 Dec 21].
  3. Jothimani D, Kailasam E, Danielraj S, Nallathambi B, Ramachandran H, Sekar P, et al. COVID-19: Poor outcomes in patients with zinc deficiency. Int J Infect Dis. 2020 Nov 1;100:343–9.
  4. Feyaerts AF, Luyten W. Vitamin C as prophylaxis and adjunctive medical treatment for COVID-19? Nutrition [Internet]. 2020 Nov 1 [cited 2020 Dec 15];79–80:110948.
  5. Thomas RL, Jiang L, Adams JS, Xu ZZ, Shen J, Janssen S, et al. Vitamin D metabolites and the gut microbiome in older men. Nat Commun [Internet]. 2020 Dec 26 [cited 2020 Dec 15];11(1):5997.
  6. Schluter J, Peled JU, Taylor BP, Markey KA, Smith M, Taur Y, et al. The gut microbiota is associated with immune cell dynamics in humans. Nature [Internet]. 2020 Dec 10 [cited 2020 Dec 15];588(7837).
  7. Pelaseyed T, Bergström JH, Gustafsson JK, Ermund A, Birchenough GMH, Schütte A, et al. The mucus and mucins of the goblet cells and enterocytes provide the first defense line of the gastrointestinal tract and interact with the immune system. Immunol Rev. 2014;260(1):8–20.
  8. Cornick S, Tawiah A, Chadee K. Roles and regulation of the mucus barrier in the gut. Tissue Barriers. 2015;3(1).
  9. Fasano A. Intestinal Permeability and Its Regulation by Zonulin: Diagnostic and Therapeutic Implications. Clin Gastroenterol Hepatol. 2012 Oct;10(10):1096–100.
  10. Bishehsari F, Magno E, Swanson G, Desai V, Voigt RM, Forsyth CB, et al. Alcohol and gut-derived inflammation. Alcohol Res Curr Rev [Internet]. 2017 [cited 2020 Dec 21];38(2):e-1-e-9.
  11. Utzeri E, Usai P. Role of non-steroidal anti-inflammatory drugs on intestinal permeability and nonalcoholic fatty liver disease [Internet]. Vol. 23, World Journal of Gastroenterology. Baishideng Publishing Group Co., Limited; 2017 [cited 2020 Dec 21]. p. 3954–63.
  12. Fasano A. Zonulin and its regulation of intestinal barrier function: The biological door to inflammation, autoimmunity, and cancer [Internet]. Vol. 91, Physiological Reviews. Physiol Rev; 2011 [cited 2020 Dec 21]. p. 151–75.
  13. Kelly JR, Kennedy PJ, Cryan JF, Dinan TG, Clarke G, Hyland NP. Breaking down the barriers: The gut microbiome, intestinal permeability and stress-related psychiatric disorders [Internet]. Vol. 9, Frontiers in Cellular Neuroscience. Frontiers Media S.A.; 2015 [cited 2020 Dec 21]. p. 392.
  14. van Wijck K, Lenaerts K, van Loon LJC, Peters WHM, Buurman WA, Dejong CHC. Exercise-Induced splanchnic hypoperfusion results in gut dysfunction in healthy men. PLoS One [Internet]. 2011 [cited 2020 Dec 21];6(7).
  15. Gillois K, Lévêque M, Théodorou V, Robert H, Mercier-Bonin M. Mucus: An Underestimated Gut Target for Environmental Pollutants and Food Additives. Microorganisms. 2018;6(2):53.
  16. Crost EH, Tailford LE, Le Gall G, Fons M, Henrissat B, Juge N. Utilisation of Mucin Glycans by the Human Gut Symbiont Ruminococcus gnavus Is Strain-Dependent. PLoS One [Internet]. 2013 Oct 25 [cited 2020 Dec 21];8(10).
  17. Png CW, Lindén SK, Gilshenan KS, Zoetendal EG, McSweeney CS, Sly LI, et al. Mucolytic bacteria with increased prevalence in IBD mucosa augment in vitro utilization of mucin by other bacteria. Am J Gastroenterol [Internet]. 2010 Nov [cited 2020 Dec 21];105(11):2420–8.
  18. Iacob S, Iacob DG. Infectious Threats, the Intestinal Barrier, and Its Trojan Horse: Dysbiosis. Front Microbiol [Internet]. 2019 Aug 7 [cited 2020 Dec 21];10.
  19. Kumar M, Leon Coria A, Cornick S, Petri B, Mayengbam S, Jijon HB, et al. Increased intestinal permeability exacerbates sepsis through reduced hepatic SCD-1 activity and dysregulated iron recycling. Nat Commun [Internet]. 2020 Dec 1 [cited 2020 Dec 21];11(1).
  20. Malhotra A, Kamepalli RK, Bamrah JS. Perspective: Poor metabolic health is a major issue for increased COVID-19 mortality in BAME groups. The Physician [Internet]. 2020 Jul 8 [cited 2020 Dec 21];6(2).
  21. Martineau AR, Forouhi NG. Vitamin D for COVID-19: a case to answer? [Internet]. Vol. 8, The Lancet Diabetes and Endocrinology. Lancet Publishing Group; 2020 [cited 2020 Dec 21]. p. 735–6.
  22. Sampson V, Kamona N, Sampson A. Could there be a link between oral hygiene and the severity of SARS-CoV-2 infections? Br Dent J [Internet]. 2020 Jun 1 [cited 2020 Dec 21];228(12):971–5.
  23. Hayata M, Watanabe N, Tamura M, Kamio N, Tanaka H, Nodomi K, et al. The periodontopathic bacterium Fusobacterium nucleatum induced proinflammatory cytokine production by human respiratory epithelial cell lines and in the lower respiratory organs in mice. Cell Physiol Biochem [Internet]. 2019 [cited 2020 Dec 21];53(1):49–61.
  24. Willemsen LEM, Koetsier MA, Van Deventer SJH, Van Tol EAF. Short chain fatty acids stimulate epithelial mucin 2 expression through differential effects on prostaglandin E1 and E2 production by intestinal myofibroblasts. Gut [Internet]. 2003 Oct 1 [cited 2020 Dec 21];52(10):1442–7.
  25. Canani RB, Costanzo M Di, Leone L, Pedata M, Meli R, Calignano A. Potential beneficial effects of butyrate in intestinal and extraintestinal diseases. World J Gastroenterol [Internet]. 2011 Mar 28 [cited 2020 Dec 21];17(12):1519–28.
  26. Mantis NJ, Rol N, Corthésy B. Secretory IgA’s complex roles in immunity and mucosal homeostasis in the gut. Mucosal Immunol. 2011 Nov;4(6):603–11.
  27. Cheng HY, Ning MX, Chen DK, Ma WT. Interactions between the gut microbiota and the host innate immune response against pathogens [Internet]. Vol. 10, Frontiers in Immunology. Frontiers Media S.A.; 2019 [cited 2020 Dec 21]. p. 607.
  28. Meade KG, O’Farrelly C. Β-Defensins: Farming the microbiome for homeostasis and health. Front Immunol. 2019;10(JAN):1–20.
  29. Arboleya S, Watkins C, Stanton C, Ross RP. Gut bifidobacteria populations in human health and aging. Front Microbiol. 2016;7(AUG):1–9.
  30. Rivière A, Selak M, Lantin D, Leroy F, De Vuyst L. Bifidobacteria and butyrate-producing colon bacteria: Importance and strategies for their stimulation in the human gut. Front Microbiol. 2016;7(JUN).
  31. Macfarlane GT, Steed H, Macfarlane S. Bacterial metabolism and health-related effects of galacto-oligosaccharides and other prebiotics. J Appl Microbiol. 2008;104(2):305–44.
  32. Vulevic J, Juric A, Walton GE, Claus SP, Tzortzis G, Toward RE, et al. Influence of galacto-oligosaccharide mixture (B-GOS) on gut microbiota, immune parameters and metabonomics in elderly persons. Br J Nutr. 2015;114(4):586–95.
  33. Tailford LE, Crost EH, Kavanaugh D, Juge N. Mucin glycan foraging in the human gut microbiome. Front Genet. 2015 Mar 19;5(FEB):81.
  34. Enaud R, Prevel R, Ciarlo E, Beaufils F, Wieërs G, Guery B, et al. The Gut-Lung Axis in Health and Respiratory Diseases: A Place for Inter-Organ and Inter-Kingdom Crosstalks [Internet]. Vol. 10, Frontiers in Cellular and Infection Microbiology. Frontiers Media S.A.; 2020 [cited 2020 Dec 21].
  35. Dhar D, Mohanty A. Gut microbiota and Covid-19- possible link and implications. Vol. 285, Virus Research. Elsevier B.V.; 2020. p. 198018.
  36. Gohil K, Samson R, Dastager S, Dharne M. Probiotics in the prophylaxis of COVID-19: something is better than nothing [Internet]. Vol. 11, 3 Biotech. Springer Science and Business Media Deutschland GmbH; 2021 [cited 2020 Dec 21].
  37. Neri-Numa IA, Pastore GM. Novel insights into prebiotic properties on human health: A review. Food Res Int [Internet]. 2020;131(December 2019):108973.
  38. Hemert S Van, Ormel G. Influence of the Multispecies Probiotic Ecologic® BARRIER on Parameters of Intestinal Barrier Function. Food Nutr Sci [Internet]. 2014 Sep 22 [cited 2020 Dec 21];05(18):1739–45.
  39. Steenbergen L, Sellaro R, van Hemert S, Bosch JA, Colzato LS. A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to sad mood. Brain Behav Immun [Internet]. 2015 [cited 2020 Dec 21];48:258–64.
  40. Wang QQ, Xu R, Volkow ND. Increased risk of COVID-19 infection and mortality in people with mental disorders: analysis from electronic health records in the United States. World Psychiatry [Internet]. 2020 [cited 2020 Dec 21];
  41. Cantorna MT, Snyder L, Arora J. Vitamin A and vitamin D regulate the microbial complexity, barrier function, and the mucosal immune responses to ensure intestinal homeostasis. Crit Rev Microbiol [Internet]. 2018 [cited 2020 Mar 20];54(2):184–12.
  42. Ohashi W, Fukada T. Contribution of Zinc and Zinc Transporters in the Pathogenesis of Inflammatory Bowel Diseases. 2019 [cited 2020 Mar 20];
  43. Główka N, Woźniewicz M. Potential use of Colostrum Bovinum supplementation in athletes – A review. Acta Sci Pol Technol Aliment. 2019 Jul 1;18(2):115–23.
  44. Qamar A, Aboudola S, Warny M, Michetti P, Pothoulakis C, LaMont JT, et al. Saccharomyces boulardii stimulates intestinal immunoglobulin a immune response to Clostridium difficile toxin A in mice. Infect Immun [Internet]. 2001 [cited 2020 Dec 21];69(4):2762–5.
  45. Hałasa M, Maciejewska D, Ba´skiewiczba´skiewicz-Hałasa M, Machalí Nski B, Safranow K, Stachowska E. Oral Supplementation with Bovine Colostrum Decreases Intestinal Permeability and Stool Concentrations of Zonulin in Athletes. [cited 2020 Jan 29];
  46. Hojyo S, Uchida M, Tanaka K, Hasebe R, Tanaka Y, Murakami M, et al. How COVID-19 induces cytokine storm with high mortality [Internet]. Vol. 40, Inflammation and Regeneration. BioMed Central Ltd; 2020 [cited 2020 Dec 21].
  47. Sirisinha S. The pleiotropic role of vitamin A in regulating mucosal immunity. Asian Pac J Allergy Immunol. 2015;33(2):71–8.
  48. Hossain MS, Urbi Z, Sule A, Rahman KMH. Andrographis paniculata (Burm. f.) Wall. ex Nees: A review of ethnobotany, phytochemistry, and pharmacology. Sci World J. 2014;2014.
  49. chapowal A, Klein P, Johnston SL. Echinacea Reduces the Risk of Recurrent Respiratory Tract Infections and Complications: A Meta-Analysis of Randomized Controlled Trials. Adv Ther. 2015;32(3):187–200.
  50. Svagelj M, Berovic M, Gregori A, Wraber B, Simcic S, Boh B. Immunomodulating Activities of Cultivated Maitake Medicinal Mushroom Grifola frondosa (Dicks.: Fr.) S.F. Gray (Higher Basidiomycetes) on Peripheral Blood Mononuclear Cells. Int J Med Mushrooms [Internet]. 2012;14(4):377–83.
  51. Hu XY, Wu RH, Logue M, Blondel C, Lai LYW, Stuart B, et al. Correction: Andrographis paniculata (Chuān Xīn Lián) for symptomatic relief of acute respiratory tract infections in adults and children: A systematic review and metaanalysis(PLoS ONE (2018) 12:8 (e0181780)
  52. Segerstrom SC, Miller GE. Psychological stress and the human immune system: A meta-analytic study of 30 years of inquiry. Psychol Bull [Internet]. 2004 Jul [cited 2020 Dec 21];130(4):601–30.
  53. Cohen S, Doyle WJ, Alper CM, Janicki-Deverts D, Turner RB. Sleep habits and susceptibility to the common cold. Arch Intern Med [Internet]. 2009 Jan 12 [cited 2020 Dec 21];169(1):62–7.

Related Articles

GI Microbiome, Neurological
Mood & The Microbiome

For many years, mental health was thought to be only a problem of the mind, and not linked to the processes and functioning of the body that houses the mind. ...

GI Microbiome, Immunology & Inflammation
IBD & The Microbiome

The range of disorders cumulatively known as IBD affects many people across the UK, and the human microbiome is involved in more ways than one. The question is, what can ...

GI Microbiome
IBS: A Spectrum

IBS is a catch-all diagnosis for someone suffering from bowel discomfort such as cramping, abdominal pains, bloating, diarrhoea, or constipation, or sometimes an alteration between the two. The trouble with ...