Can Probiotics Really ‘Boost’ Immunity?
Understanding the fascinating connection between your gut and immune system can help you support them both in the months ahead.
We’re entering the time of year when immunity is top of mind. So, we’d be remiss not to remind you that if you’re trying to keep your immune system healthy, the gut plays a critical role. That’s because your gut, the community of microbes that reside there, and the immune system are intricately intertwined, a relationship known as the gut-immune axis.
Given the close connection between these systems, we frequently receive questions about immunity and gut health. Here, our SciCare* team answers three of these questions and shares five science-derived strategies to foster a healthy gut-immune connection.
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What is the connection between the immune system and the gut?
The immune system is highly complex and cooperative, and there are many factors involved in how it functions—including your gut. The link between gut function and immunity is so integral to our overall health that the interplay between these systems has been coined the “gut-immune axis.” Your gut and immune system influence one another through a variety of pathways. Here we’ll focus on three of the most impactful, beginning with the gut barrier.
The gut barrier serves as a first line of defense, separating the inside of your GI tract from the rest of your body. It regulates what can pass through, allowing harmless substances (like nutrients and water) to cross, while inhibiting harmful ones (like bacteria and toxins).1 In this way, you can think of it like a gatekeeper between your bloodstream and the external world. When the permeability of your gut barrier increases, known as “leaky gut,” it may allow for the invasion of pathogens (disease-causing microbes) or other foreign materials into your body, where they can trigger an immune response.2 Sometimes, an immune response is warranted, like in the case of harmful foreign antigens (like viruses). Other times, a response is not appropriate, like in the case of an antigen that doesn’t pose a threat (like food or pollen).
Second, your gut also houses the largest “immune organ” in the body—a collection of immune cells stored in tissue known as gut-associated lymphoid tissue (GALT). GALT represents about 70% of all the cells in the immune system, which is where the popular stat “70% of your immune system is in your gut” comes from.3 GALT acts as an immune barrier, protecting against external threats the gut is constantly exposed to. It also carries out a host of other immune functions, including the production of antibodies.4
Third, your gut microbiome is critical to the overall functioning and maintenance of your immune system. For example, the microbes within it compete with pathogens for resources (think: space and energy).1 It is also in constant communication with your immune system to regulate immune responses, control inflammation, and facilitate “cross-talk” between your intestinal and immune cells.4 In fact, it is now widely accepted that alterations of your gut microbial communities (known as “dysbiosis”) can result in uncontrolled or heightened immune responses, leading to certain diseases and conditions like autoimmune disorders, food allergies, asthma, inflammatory bowel disease, and more.4 This is why nurturing your gut microbiome is important to supporting a resilient immune system.
Which brings us to our next question…
Can probiotics really boost immunity?
The connection between the gut and immune system means that a healthy gut and microbiome can encourage healthy immune responses. That’s where probiotics can come in to support. However, given the variability in probiotic strains and their function, it’s essential to choose a probiotic with clinically studied strains, in effective doses, to support the immune benefits you’re looking for.
When it comes to “boosting” immunity, this may sound favorable, but an overstimulated immune system is actually not always beneficial. That’s because increasing immune function in a nonspecific manner can lead to increased inflammation, which is not always a positive outcome. Chronic inflammation is a hallmark of diseases such as arthritis, allergies, and diabetes,5 and an excessively active or overstimulated immune system can potentially lead to certain autoimmune diseases or even immune-mediated neurodegenerative disorders.6
Instead, you want to foster a resilient immune system that reacts appropriately to external factors. Specific probiotics can support this by selectively targeting immune pathways and immune cells, as well as supporting the gut barrier. For example, certain probiotic strains have demonstrated the ability to promote the integrity and “tightness” of your gut barrier by enhancing gene expressions involved in tight junction signaling.7 (Tight junctions are intercellular connectors that are important for reinforcing the integrity of the gut wall.)
Beyond enhancing tight junctions, probiotics may produce various metabolic compounds like short-chain fatty acids (SCFAs) that deliver immune benefits. One SCFA, in particular, butyrate, helps modulate inflammatory responses by either increasing anti-inflammatory immune cells or inhibiting pro-inflammatory cells.8 Butyrate can also strengthen the gut barrier by enhancing the expression of mucus-related genes that bolster the mucus layer of the gut barrier and increase the production of certain antimicrobial proteins that target microbes trying to cross.9,10
So, back to the question. Specific probiotic strains can support your immune system, not by “boosting” it, but by helping support beneficial immune responses.
I eat well, exercise, and take care of my body, yet I still feel under the weather from time to time. Why is that? How else can I support my immune system?
Diet, nutrition, and exercise are all critical tools for supporting your body and building foundational health. Still, they work in conjunction with many other factors that also influence your general health and wellness, which can impact why you do or don’t get sick.
Take genetics, for example. While you can do your best to take care of yourself and control certain factors that may influence your immune system (think: washing your hands or eating a balanced diet), genetics are a strong determinant of immunity, so some individuals may simply be more susceptible to getting sick.11
Age is another crucial factor. Both the immune system and the gut microbiome undergo significant changes in composition and function with increased age, and these changes are correlated with altered immunity.12
This is not to say that genes or your age will entirely determine how you fare this cold and flu season. Epigenetics (the field of study which explores how our biology interacts with your environment) shows that just about everything you do on a daily basis can contribute to your digestive, metabolic, and immune health.13 So, in addition to diet and exercise, factors such as how stressed you are, how well you’re sleeping, and even your hormone levels can determine whether or not you get sick or stay well.
If you’re looking for simple ways to support your immune system this season, here are five science-derived strategies to foster a healthy gut-immune connection:
- Increase your daily fiber intake. In the digestive tract, certain fibers are fermented by gut microbes and biotransformed into short-chain fatty acids (SCFAs).14 SCFAs exert a range of powerful effects in your body, including the maintenance of immune health. They interact with immune cells and regulate anti-inflammatory responses to help protect you from pathogens and even against autoimmune conditions.15,16
- Prioritize sleep. Your body operates on a 24-hour cycle, known as your circadian rhythm or “clock.” Emerging data also show that the gut microbiome has its own circadian clock, exhibiting daily shifts in its composition (i.e., some bacterial species are more abundant in the morning, others at night).17 Because your microbiome’s clock is intertwined with your own, changes to your normal rhythms (think: the season’s shifting light-dark cycles) can disrupt your microbes and the important immune functions they perform, such as preventing pathogens from entering your body.
- Manage stress. When you’re physically and emotionally stressed, your body secretes catecholamines and other hormones that impact your gut. For instance, they can directly influence microbial growth and alter the proportions of bacteria in your microbiome.18 The inflammation that often accompanies high levels of stress can also trigger blooms of pathogenic microbes that promote dysbiosis (an imbalance in the microbiome) and increase intestinal permeability (a.k.a. leaky gut). Both of these outcomes can disrupt your gut-immune function.
- Stay physically active. Regular exercise can directly impact immune regulation by influencing cells involved in immune function, including red blood cells, white blood cells, and cytokines. Because exercise has an anti-inflammatory effect on the body, it can also influence metabolic and cardiorespiratory processes, and, in turn, microbial diversity and gut permeability.19
- Consider taking a probiotic. Specific strains of probiotics have been studied to support a range of gut-immune benefits, including the reinforcement of gut-barrier function and the support of cross-talk between gut and immune cells.20,21
We receive and answer questions like these every day. Stay tuned for more SciCare roundups on Cultured. If you have any questions of your own, email us at firstname.lastname@example.org.
- Pickard, J. M., Zeng, M. Y., Caruso, R., & Núñez, G. (2017). Gut microbiota: Role in pathogen colonization, immune responses, and inflammatory disease. Immunological reviews, 279(1), 70–89. https://doi.org/10.1111/imr.12567
- Bischoff, S. C., Barbara, G., Buurman, W., Ockhuizen, T., Schulzke, J. D., Serino, M., Tilg, H., Watson, A., & Wells, J. M. (2014). Intestinal permeability–a new target for disease prevention and therapy. BMC gastroenterology, 14, 189. https://doi.org/10.1186/s12876-014-0189-7
- Wiertsema, S. P., van Bergenhenegouwen, J., Garssen, J., & Knippels, L. (2021). The Interplay between the Gut Microbiome and the Immune System in the Context of Infectious Diseases throughout Life and the Role of Nutrition in Optimizing Treatment Strategies. Nutrients, 13(3), 886. https://doi.org/10.3390/nu13030886
- Jiao, Y., Wu, L., Huntington, N. D., & Zhang, X. (2020). Crosstalk between gut microbiota and innate immunity and its implication in autoimmune diseases. Frontiers in Immunology, 11. https://doi.org/10.3389/fimmu.2020.00282
- Pahwa, R. (2023, August 7). Chronic inflammation. StatPearls – NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK493173/
- Blach-Olszewska, Z., & Leszek, J. (2007). Mechanisms of over-activated innate immune system regulation in autoimmune and neurodegenerative disorders. Neuropsychiatric disease and treatment, 3(3), 365–372.
- La Fata, G., Weber, P., & Mohajeri, M. H. (2018). Probiotics and the Gut Immune System: Indirect Regulation. Probiotics and antimicrobial proteins, 10(1), 11–21. https://doi.org/10.1007/s12602-017-9322-6
- Singh, N., Gurav, A., Sivaprakasam, S., Brady, E., Padia, R., Shi, H., Thangaraju, M., Prasad, P. D., Manicassamy, S., Munn, D. H., Lee, J. R., Offermanns, S., & Ganapathy, V. (2014). Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. Immunity, 40(1), 128–139. https://doi.org/10.1016/j.immuni.2013.12.007
- Liang, L., Liu, L., Zhou, W., Yang, C., Mai, G., Li, H., & Chen, Y. (2022). Gut microbiota-derived butyrate regulates gut mucus barrier repair by activating the macrophage/WNT/ERK signaling pathway. Clinical science (London, England : 1979), 136(4), 291–307. https://doi.org/10.1042/CS20210778
- Raqib, R., Sarker, P., Bergman, P., Ara, G., Lindh, M., Sack, D. A., Nasirul Islam, K. M., Gudmundsson, G. H., Andersson, J., & Agerberth, B. (2006). Improved outcome in shigellosis associated with butyrate induction of an endogenous peptide antibiotic. Proceedings of the National Academy of Sciences of the United States of America, 103(24), 9178–9183. https://doi.org/10.1073/pnas.0602888103
- Lazzaro, B. P., & Schneider, D. S. (2014). The genetics of immunity. Genetics, 197(2), 467–470. https://doi.org/10.1534/genetics.114.165449
- Bosco, N., & Noti, M. (2021). The aging gut microbiome and its impact on host immunity. Genes and Immunity, 22(5–6), 289–303. https://doi.org/10.1038/s41435-021-00126-8
- Ho, S. M., Johnson, A., Tarapore, P., Janakiram, V., Zhang, X., & Leung, Y. K. (2012). Environmental epigenetics and its implication on disease risk and health outcomes. ILAR journal, 53(3-4), 289–305. https://doi.org/10.1093/ilar.53.3-4.289
- Kim, C. H. (2021). Control of lymphocyte functions by gut microbiota-derived short-chain fatty acids. Cellular & Molecular Immunology, 18(5), 1161–1171. https://doi.org/10.1038/s41423-020-00625-0
- Mariño, E., Richards, J. L., McLeod, K. H., Stanley, D., Yap, Y. A., Knight, J., McKenzie, C., Kranich, J., Oliveira, A. C., Rossello, F., Krishnamurthy, B., Nefzger, C. M., Macia, L., Thorburn, A. N., Baxter, A. G., Morahan, G., Wong, L. H., Polo, J. M., Moore, R. J., . . . Mackay, C. R. (2017). Gut microbial metabolites limit the frequency of autoimmune T cells and protect against type 1 diabetes. Nature Immunology, 18(5), 552–562. https://doi.org/10.1038/ni.3713
- Park, J., Wang, Q., Wu, Q., Mao-Draayer, Y., & Kim, C. H. (2019). Bidirectional regulatory potentials of short-chain fatty acids and their G-protein-coupled receptors in autoimmune neuroinflammation. Scientific Reports, 9(1). https://doi.org/10.1038/s41598-019-45311-y
- Zarrinpar, A., Chaix, A., Yooseph, S., & Panda, S. (2014). Diet and feeding pattern affect the diurnal dynamics of the gut microbiome. Cell metabolism, 20(6), 1006–1017. https://doi.org/10.1016/j.cmet.2014.11.008
- Lyte, M., & Ernst, S. (1992). Catecholamine induced growth of gram negative bacteria. Life sciences, 50(3), 203–212. https://doi.org/10.1016/0024-3205(92)90273-r
- Wang, J., Liu, S., Li, G., & Xiao, J. (2020). Exercise Regulates the Immune System. Advances in experimental medicine and biology, 1228, 395–408. https://doi.org/10.1007/978-981-15-1792-1_27
- Zheng, Y., Zhang, Z., Tang, P., Wu, Y., Zhang, A., Li, D., Wang, C. Z., Wan, J. Y., Yao, H., & Yuan, C. S. (2023). Probiotics fortify intestinal barrier function: a systematic review and meta-analysis of randomized trials. Frontiers in Immunology, 14, 1143548. https://doi.org/10.3389/fimmu.2023.1143548
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