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The immune system in your gut

Your gut does more than just digest food!

You might think that your skin is your body’s largest surface to the outside world. However, in terms of surface area, it’s actually the lining of your gut. The gut lining, or ‘mucosa’, is constantly exposed to substances called ‘antigens’ from your food and the bacteria living in your gut. These antigens could  potentially trigger an immune response.1 To cope with all these antigens, 70% of the body’s entire immune system is actually located in the gut.2 

The gut mucosal immune system needs to be able to tell the difference between something that is a threat to your health and something that is not. For example, it wouldn’t be helpful for your immune system to react to the food you eat or to the healthy bacteria that live in the gut. However, you do want the immune system to protect you against harmful bacteria or viruses.3 Therefore, the intestinal mucosa is constantly being monitored by your immune system. 

Three specific parts of the gut lining are involved in your immune system

There are three important structures in the gut lining that make up the intestinal immune system: 4

  • Peyer’s patches, which are relatively large lymphoid structures scattered along the intestines. They contain lots of different types of immune cells3
  • The lamina propria, which is a thin layer of connective tissue just under the epithelium that also contains numerous immune cells
  • The epithelium, which is the name for the cells forming the outer layer of the gut lining. These cells are at the frontline and connect to the immune system

Within these structures, immune cells send messages, to help defend your body

Firstly, special immune cells called ‘dendritic cells’ are able to look out for antigens. There are lots of dendritic cells in Peyer’s patches. Dendritic cells are also able to squeeze through tight gaps between the cells making up the epithelium to reach inside the intestine and check for antigens.5 When a dendritic cell finds an antigen, it becomes activated and tells another type of immune cell, ‘T-helper cells’, about the antigen.

Depending on the message the dendritic cell gives, the T-helper cells either help the body to build up tolerance to a non-threatening antigen or to start defensive tactics to protect the body against a harmful antigen. Defensive tactics can lead to inflammation, which you may feel as symptoms like fever, aches and pains when your body is fighting an infection.6,7 

When T-helper cells are given a message from the dendritic cells, they start sending out chemicals called ‘cytokines’ that give instructions to either ‘turn down’ (anti-inflammatory) or ‘turn up’ (pro-inflammatory) the level of inflammation.

An example of an important anti-inflammatory cytokine is interleukin-10 (IL-10). IL-10 is important for ‘turning down’ the immune system and reducing the inflammatory response.1,8 Other cytokines such as IL-1β, IL-6, and TNF-α are important for activating the immune system.9

When a harmful antigen is detected, dendritic cells send out cytokines that boost the number of particular pro-inflammatory T-helper cells called Th1, Th2, or Th17.10,11 These in turn attract other types of immune cells to join in to fight the infection.12,13 The fact that many different cells are involved means that the immune system is well equipped to protect us from many pathogenic microorganisms which may be present in the gut.14 

Inflammation can be ‘acute’ or ‘chronic’

As noted earlier, inflammation is a result of the immune system fighting an infection. Sometimes, inflammation starts quickly and goes away quickly. This is called ‘acute’ inflammation.15,16 Inflammation that lasts longer or doesn’t completely go away, often because the intestinal barrier is not functioning well, is called ‘chronic’ inflammation.17 Low-level chronic inflammation is an underlying factor in a range of diseases, such as inflammatory bowel disease (IBD),18 atherosclerosis,19 arthritis,20 and neurodegenerative diseases such as Alzheimer’s disease.21

The effects of probiotics on the immune system and how they work varies between different probiotic strains.11 Studies suggest that Lactobacillus rhamnosus, LGG®, Lactobacillus paracasei, L. CASEI 431® and Bifidobacterium, BB-12® probiotic strains may support the immune system, and have been shown to reduce the occurrence, duration and severity of respiratory issues in children and adults.22-26 Data suggest that these strains support the immune system by helping Th1 cells to mature and stimulating them to send out the important cytokines that make your body produce antibodies to fight invading pathogens.27-32

LGG®, L. CASEI 431®, and BB-12® are registered trademarks of Chr. Hansen A/S.

The article is provided for informational purposes regarding probiotics and is not meant to suggest that any substance referenced in the article is intended to diagnose, cure, mitigate, treat, or prevent any disease.
 

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Microbiome dysbiosis

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Surviving the stomach

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Mucus Layer

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Reference list

  1. Hasegawa H, Matsumoto T. Mechanisms of tolerance induction by dendritic cells in vivo. Front Immunol. 2018;9:350. (PubMed)
  2. Vighi G, et al. Allergy and the gastrointestinal system. Clin Exp Immunol. 2008;153(SUPPL. 1):3–6. (PubMed)
  3. Mörbe UM, et al. Human gut-associated lymphoid tissues (GALT); diversity, structure, and function. Mucosal Immunol. 2021;14(4):793-802. (PubMed)
  4. Shi N, et al. Interaction between the gut microbiome and mucosal immune system. Mil Med Res. 2017;4:14. (PubMed)
  5. Rescigno M, et al. Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat Immunol. 2001;2(4):361–7. (PubMed)
  6. Iberg CA, et al. Dendritic Cells As Inducers of Peripheral Tolerance. Trends Immunol. 2017;38(11):793–804. (PubMed)
  7. Sun T, et al. Dendritic Cell Subsets in Intestinal Immunity and Inflammation. J Immunol. 2020;204(5):1075–83. (PubMed)
  8. Wei HX, et al. IL-10 and IL-22 in Mucosal Immunity: Driving Protection and Pathology. Front Immunol. 2020;11:1315. (PubMed)
  9. Holdsworth SR, Can PY. Cytokines: Names and numbers you should care about. Clin J Am Soc Nephrol. 2015;10(12):2243–2254. (PubMed)
  10. Smith IM, et al. Kluyveromyces marxianus and Saccharomyces boulardii induce distinct levels of dendritic cell cytokine secretion and significantly different T cell responses in vitro. PLoS One. 2016; 11(11):e0167410. (PubMed)
  11. Smits HH, et al. Selective probiotic bacteria induce IL-10-producing regulatory T cells in vitro by modulating dendritic cell function through dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin. J Allergy Clin Immunol. 2005;115(6):1260–1267. (PubMed)
  12. Condotta SA, Richer MJ. The immune battlefield: The impact of inflammatory cytokines on CD8+T-cell immunity. PLoS Pathog. 2017;13(10):e1006618. (PubMed)
  13. Hwang JR, et al. Recent insights of T cell receptor-mediated signaling pathways for T cell activation and development. Exp Mol Med. 2020;52(5):750–61. (PubMed)
  14. Annunziato F, et al. The 3 major types of innate and adaptive cell-mediated effector immunity. J Allergy Clin Immunol. 2015;135(3):626–35. (PubMed)
  15. Rogovskii V. Immune Tolerance as the Physiologic Counterpart of Chronic Inflammation. Front Immunol. 2020; 11:2061. (PubMed)
  16. Maskrey BH, et al. Mechanisms of resolution of inflammation: A focus on cardiovascular disease. Arterioscler Thromb Vasc Biol. 2011;31(5):1001–1006. (PubMed)
  17. Serhan CN, et al. Resolution of inflammation: state of the art, definitions and terms. FASEB J. 2006; 21(2):325-32. (PubMed)
  18. Mann ER, et al. Intestinal dendritic cells: Their role in intestinal inflammation, manipulation by the gut microbiota and differences between mice and men. Immunol Lett. 2013;150(1–2):30–40. (PubMed)
  19. Lorenzatti AJ. Anti-inflammatory Treatment and Cardiovascular Outcomes: Results of Clinical Trials. Eur Cardiol. 2021;16:e15. (PubMed)
  20. Coates LC, et al. Psoriasis, psoriatic arthritis, and rheumatoid arthritis: Is all inflammation the same? Semin Arthritis Rheum. 2016;46(3):291–304. (PubMed)
  21. Ng A, et al. IL-1β, IL-6, TNF-α and CRP in Elderly Patients with Depression or Alzheimer’s disease: Systematic Review and Meta-Analysis. Sci Rep. 2018;8(1):12050. (PubMed)
  22. Hojsak I, et al. Lactobacillus GG in the prevention of gastrointestinal and respiratory tract infections in children who attend day care centers: A randomized, double-blind, placebo-controlled trial. Clin Nutr. 2010;29(3):312–316. (PubMed)
  23. Rizzardini G, 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;107(6):876–84. (PubMed)
  24. Trachootham D, et al. Drinking fermented milk containing Lactobacillus paracasei 431 (IMULUSTM) improves immune response against H1N1 and cross-reactive H3N2 viruses after influenza vaccination: A pilot randomized triple-blinded placebo controlled trial. J Funct Foods. 2017;33:1–10. Source: (Source)
  25. De Vrese M, et al. Probiotic bacteria stimulate virus-specific neutralizing antibodies following a booster polio vaccination. Eur J Nutr. 2005;44(7):406–413. (PubMed)
  26. Smith TJ, et al. Effect of Lactobacillus rhamnosus LGG® and Bifidobacterium animalis ssp. lactis BB-12® on health-related quality of life in college students affected by upper respiratory infections. Br J Nutr. 2013;109(11):1999–2007. (PubMed)
  27. López P, et al. Distinct Bifidobacterium strains drive different immune responses in vitro. Int J Food Microbiol. 2010;138(1–2):157–165. (PubMed)
  28. Miettinen M, et al. The survival of and cytokine induction by lactic acid bacteria after passage through a gastrointestinal model. Microb Ecol Health Dis. 1998;10:141–147. Source: (Source)
  29. Miettinen M, et al. Nonpathogenic Lactobacillus rhamnosus activates the inflammasome and antiviral responses in human macrophages. Gut Microbes. 2012;3(6):510–522. (PubMed)
  30. Dong H, et al. Comparative effects of six probiotic strains on immune function in vitro. Br J Nutr. 2012;108(3):459–470. (PubMed)
  31. Rocha-Ramírez LM, et al. Probiotic Lactobacillus Strains Stimulate the Inflammatory Response and Activate Human Macrophages. J Immunol Res. 2017;2017:4607491. (PubMed)
  32. Latvala S, et al. Potentially probiotic bacteria induce efficient maturation but differential cytokine production in human monocyte-derived dendritic cells. World J Gastroenterol. 2008;14(36):5570–5583. (PubMed)