Gut microbiota and the immune system partnership

A diverse mix of microbes lives throughout the human body, in the skin, lungs, urinary tract, and especially the gut, forming a complex ecosystem that profoundly influences our health. Among these, the gut microbiota stands out for its close connection to the immune system.

Around 70–80% of our immune cells are found in the gut-associated lymphoid tissue, where they interact with food, microbes, and microbial byproducts. This relationship begins at birth, when the gut microbiome and immune system start developing side by side.

This ongoing partnership influences how our bodies tolerate harmless substances and respond to infections, including how we react to vaccines. Throughout life, this balance continues to shift, shaped by genetics, diet, and environment.

Children often have immature immune systems, while older adults may experience weaker immune responses and increased inflammation, a natural part of ageing known as immunosenescence and inflammaging.

 

Why do vaccine responses differ from person to person?

Some individuals develop strong and long-lasting protection after vaccination, while others exhibit weaker immune responses. Researchers continue to investigate this variability, exploring the factors that influence immune status in vaccinated individuals.

Some are beyond our control, like genetics, age, sex, and even the time of day the vaccine is given. But others can be shaped by our lifestyle, including stress levels, physical activity, body fat, diet, and the composition of our gut microbiota.

  • Age: Older adults often respond less effectively to vaccines due to natural changes in the immune system (known as immunosenescence) and the presence of chronic conditions.
  • Nutrition: Macro and micronutrients like protein, iron, zinc, and vitamins A and D help fuel immune cells and support the production of antibodies and other defence molecules while also nourishing the gut microbiota, which in turn influences immunity.
  • Gut microbiota: Microbes can enhance innate and adaptive immune responses by boosting antibodies or training immune cells like regulatory T cells. Thus, nutrients that foster beneficial microbes strengthen immunity without exceeding safe intake levels.
  • Geography and lifestyle: These factors also influence the gut microbiota and immunity. Diverse studies have shown that vaccine responses vary widely across the globe. However, most studies point to diet and lifestyle as the most influential. For instance, traditional lifestyles support a greater gut microbial diversity than urbanized habits.

 

What science says: gut microbiota and vaccine effectiveness

Many studies in both adults and children have looked at how gut microbes might influence how well vaccines work. A balanced gut microbiota is essential for a healthy immune system and boosting immune responses to vaccines.

Researchers have explored this connection across a range of vaccines, from polio and rotavirus to influenza and, more recently, COVID-19. Here’s what they’ve found so far:

  • Oral vaccines: A higher amount of certain gut bacteria, like those from the Bacillota, Pseudomonadota, and Bacteroidota groups, has been linked to better responses to oral rotavirus vaccines (ORV) in both infants and adults.
  • COVID-19 vaccines: In adults, having more bacteria from the Actynomycetota and Bacteroidota groups was associated with stronger immune responses to SARS-CoV-2 However, results for Bacillota were mixed.
  • Age differences: Interestingly, infants and adults don’t always respond the same way to similar bacteria. For example, infants who responded well to vaccines often had lower levels of Bacillota and Pseudomonadota, while adults showed the opposite trend. Still, this trend cannot be generalized to all vaccines (e.g.; the mentioned ORV).
  • Antibiotics: Using antibiotics was shown to reduce the production of specific antibodies after several infant vaccines and also weakened the response to one flu strain in adults with a history of low vaccine responsiveness.

Overall, there is growing evidence that changes in gut microbiota can affect how well vaccines work. Still, more large-scale studies are needed to better understand these links and the biological mechanisms behind them.

 

How can nutrition improve vaccine responses?

Recent research shows that we can support our gut microbiota, and potentially improve vaccine responses, through diet. For instance, getting enough immune-supporting nutrients, like vitamins A (including β-carotene), B6, B9 (folate), B12, C , D and E, and the minerals I, Zn, Se, Fe and Cu, can help reverse deficiencies and strengthen immune function, particularly in those with low intakes. In addition, prebiotics and probiotics have also shown promise in supporting immunity through direct and indirect effects.

Studies in adults vaccinated against flu strains like H1N1, H3N2, and influenza B found enhanced immune responses after supplementation with Lactobacillus and Bifidobacterium. Complementary findings in children suggest that adding Propionibacterium to probiotic formulations may further improve responses to influenza B vaccination.  

These findings further support previous evidence showing that two probiotic strains, from the Bifidobacterium and Lactobacillus genera, may enhance both systemic and mucosal immune responses to influenza vaccination. However, other researchers have reported mixed outcomes in a trial assessing the effectiveness of a Lactobacillus strain in enhancing the antibody response to Hepatitis A vaccination.

Prebiotics like inulin, galactooligosaccharides (GOS), and fructooligosaccharides (FOS) help grow beneficial bacteria such as Bifidobacteria and boost the production of short-chain fatty acids like butyrate, which help reduce inflammation by interacting with immune cells. For instance, a study in healthy middle-aged adults found that a combination of inulin and oligofructose enhanced antibody responses to the seasonal flu vaccine, suggesting a modest but measurable boost in immune function.

Some of these prebiotics, GOS, FOS, and 2′-fucosyllactose, have been linked to fewer infections and higher antibodies in infants,  while yeast β-glucan reduced respiratory infection symptoms in healthy adults. Similarly, an eight-week prebiotic blend of oligofructose and inulin increased antibody levels against the H3N2 flu strain in middle-aged adults, though not for other strains.

Interestingly, a study from Pediatric Allergy and Immunology have revealed that human milk oligosaccharides may also support immunity in the respiratory and urinary tracts by interacting with immune cells in the bloodstream.

Despite some studies showing modest improvements in vaccine responses among younger adults, consistent benefits in older people are harder to prove. More research will help to understand how nutrition affects immunity across different age groups and health conditions.

 

Conclusions

While scientists continue to uncover the full picture, everyday habits offer a practical way to support your gut and your immunity. Eating more fiber-rich foods, enjoying fermented foods, and avoiding unnecessary antibiotics are simple steps that can help.

The first advice to support immune function is to eat a diverse and well-balanced diet rich in coloured fruit and vegetables. Prebiotic and probiotic supplements, along with adequate intake of macro and micronutrients, can help restore immune function, especially in older adults or those with low nutrient intake.

Small changes can make a meaningful difference, not just for fighting off infections, but potentially for helping your body respond better to vaccines too. While specific people, such as the elderly, can benefit from particular food supplements of nutrients that support the immune system, the best dose should be personalized balancing the benefits and risks.

 

References

  1. Calder PC, Ortega EF, Meydani SN, et al. Nutrition, immunosenescence, and infectious disease: an overview of the scientific evidence on micronutrients and on modulation of the gut microbiota. Advances in Nutrition. 2022;13(5): S1-S26.
  2. Wu D, Lewis ED, Pae M, et al. Nutritional modulation of immune function: analysis of evidence, mechanisms, and clinical relevance. Frontiers in Immunology. 2019;9.
  3. Macia L, Thorburn AN, Binge LC, et al. Microbial influences on epithelial integrity and immune function as a basis for inflammatory diseases. Immunol Rev. 2012;245(1):164-76.
  4. Cervantes-Barragan L, Chai JN, Tianero MD, et al. Lactobacillus reuteri induces gut intraepithelial CD4+CD8αα+T cells. Science. 2017;357(6353):806-810.
  5. Dutta, S., Chatterjee, N., Gallina, N. L. F. et al. Diet, microbiome, and probiotics establish a crucial link in vaccine efficacy. Critical Reviews in Microbiology. 2025: 1–26.
  6. Parizadeh M, Arrieta MC. The global human gut microbiome: genes, lifestyles, and diet. Trends in Molecular Medicine. 2023;29(10):S1471-4914(23)001521.
  7. Choe YJ, Blatt DB, Lee HJ, et al. Associations between geographic region and immune response variations to pneumococcal conjugate vaccines in clinical trials: A systematic review and meta-analysis. Int J Infect Dis. 2020; 92:261-268.
  8. Ardura-Garcia C, Curtis N, Zimmermann P. Systematic review of the impact of intestinal microbiota on vaccine responses. npj Vaccines. 2024;9(1).
  9. Tunc HA, Calder PC, Cait A, et al. Impact of non-digestible carbohydrates and prebiotics on immunity, infections, inflammation and vaccine responses: a systematic review of evidence in healthy humans and a discussion of mechanistic proposals. Critical Reviews in Food Science and Nutrition. Published online June 14, 2025:1-74.
  10. Kukkonen K, Nieminen T, Poussa T, et al. Effect of probiotics on vaccine antibody responses in infancy–a randomized placebo-controlled double-blind trial. Pediatr Allergy Immunol. 2006 Sep;17(6):416-21.
  11. Lei WT, Shih PC, Liu SJ, et al. Effect of Probiotics and Prebiotics on Immune Response to Influenza Vaccination in Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients. 2017 Oct 27;9(11):1175.
  12. Rizzardini G, Eskesen D, Calder PC, et al. Evaluation of the immune benefits of two probiotic strains Bifidobacterium animalis ssp. lactis, BB-12® and Lactobacillus paracasei ssp. paracasei, L. casei 431® in an influenza vaccination model: a randomised, double-blind, placebo-controlled study. Br J Nutr. 2012 Mar;107(6):876-84.
  13. Redondo N, Nova E, Gheorghe A, et al. Evaluation of Lactobacillus coryniformis CECT5711 strain as a coadjuvant in a vaccination process: a randomised clinical trial in healthy adults. Nutr Metab (Lond). 2017 Jan 5;14:2. doi: 10.1186/s12986-016-0154-2. Erratum in: Nutr Metab (Lond). 2017 Jun 14;14:40.
  14. Rayman MP, Calder PC. Optimising COVID-19 vaccine efficacy by ensuring nutritional adequacy. British Journal Of Nutrition. 2021;126(12):1919-1920.
  15. Hediye Arioz Tunc, Calder PC, Cait A, et al. Impact of non-digestible carbohydrates and prebiotics on immunity, infections, inflammation and vaccine responses: a systematic review of evidence in healthy humans and a discussion of mechanistic proposals. Critical Reviews in Food Science and Nutrition. 2025:1-74.
  16. Lomax AR, Cheung LVY, Noakes PS, et al. Inulin-Type β2-1 Fructans have Some Effect on the Antibody Response to Seasonal Influenza Vaccination in Healthy Middle-Aged Humans. Frontiers in Immunology. 2015;6.
  17. Eiwegger T, Stahl B, Haidl P, et al. Prebiotic oligosaccharides: In vitro evidence for gastrointestinal epithelial transfer and immunomodulatory properties. Pediatric Allergy and Immunology. 2010. 21(8):1179–88.