Cold and Flu Season – The Gut-Immune Connection

The Science Behind Probiotics and RTIsCitations

Since the COVID-19 pandemic began, fears surrounding cold and flu season have intensified. First, there were predictions of a “twindemic” that included COVID-19 and a particularly virulent influenza virus.1 Then, experts pivoted to predicting a “tripledemic” that would see COVID-19, influenza, and RSV colliding.

So far, the idea that cold and flu season would be particularly worse this year compared to last year has somewhat materialized: From October 1st, 2022 to February 11th of this year, there have been an estimated 280,000 to 630,000 hospitalizations for flu illnesses in the U.S.3, compared to a total of 100,000 hospitalizations over the course of the entire 2021-2022 season.4 That’s a pretty staggering difference, which can at least, in part, be attributed to an increase in travel and socializing since the height of the COVID-19 pandemic. (For reference, during the entire 2018-2019 flu season, there were 380,000 flu-related hospitalizations.5 So, to some degree, this year’s increase may just be a return to baseline.)

And if you thought we were basically out of the woods by the end of February, you might be surprised to learn that flu season actually spans October to May, according to the Centers for Disease Control and Prevention.6 So how can you do your best to stay as healthy as possible as we ride out the next few months?

First, the standard recommendations for avoiding respiratory viruses all apply: Wash your hands often, follow guidelines for where and when to wear a face mask, and avoid close contact with people who are sick.7 But when we look at our immunity through the lens of the gut microbiome, we gain a more nuanced understanding of our health. Your gut is home to trillions of microbes that collectively comprise your gut microbiome. As the largest and most diverse microbiome in the body,8 the gut microbiome is most often associated with digestion and gastrointestinal health, though one of its most critical areas of influence is actually the immune system.

Here, we’ll briefly explain how the gut-immune connection works and the promising research behind certain probiotics to support your gut-immune function during a seemingly never-ending season of viruses. To dive deeper into these topics, you can

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Cold and Flu Season

The Gut-Immune Connection

The Science Behind Probiotics and RTIsCitations

The immune system is a vast network of cells, proteins, and organs that fight harmful substances which come into contact with the body (i.e., pathogenic bacteria) or disease-causing changes that occur within the body (i.e., damaged cells). It’s activated by substances the body doesn’t recognize as its own, which are called antigens. When the immune system is functioning properly, it recognizes, identifies, and neutralizes antigens, so they go unnoticed by you. But if it becomes weak or overwhelmed, it’s unable to fend off certain threats and you can get sick.

So how is the gut involved? The gut is centrally located and serves as a communication switchboard, connecting to the immune system through various pathways known as the gut-immune axis, or gut-immune system. Your resident gut microbes are a key component of this connection as they can directly impact the function of the immune system.

In fact, 70% of the immune system is located in your gut.9 That may be hard to conceptualize, but it’s actually just a matter of cell count: The gut contains the largest number of immune cells in your body, housed in tissue known as GALT (gut-associated lymphoid tissue). GALT represents 70% of immune cells in the entire immune system. It plays an essential role in protecting your body against threats your gut is exposed to, such as pathogenic microbes that have entered your system through food, liquid, air, and other external inputs. Studies have shown there is extensive “cross talk” between the gut microbiome and immune cells residing in GALT, which is important in the coordination of immune function within the gastrointestinal tract.10 

Peyer’s Patches

GALT includes oval masses of lymphatic tissue called Peyer’s Patches (shown above).

More generally, the gut microbiome helps to regulate and fine-tune the immune system, inducing protective reactions to pathogens and maintaining proper immune responses within the body. Gut microbes help protect you from external factors (including antigens) through various tactics.11 They:

  • Help control inflammation and mediate the inflammatory immune response. This helps your immune system respond to inputs appropriately, initiating a response when stimulated by a foreign antigen, while remaining passive to inputs that don’t pose a threat, like food or pollen.
  • Strengthen gut barrier integrity. Gut microbes support the presence of tight junctions, intercellular connectors that form the main scaffolding of the gut barrier. Tight junctions are important to reinforce the integrity of the gut wall and prevent foreign materials and contaminants from crossing. Disruptions in the intestinal barrier structure can result in flare ups of local immune reactions and allow for growth of unwanted microbes.12
  • Compete with potential pathogens for resources. If your gut microbiota utilize all of the available resources, such as space and nutrients, pathogens can’t survive or replicate.
  • Produce antimicrobial substances. Certain bacteria in the gut produce bacteriocins, proteins that inhibit or kill pathogenic bacteria such as Listeria, Clostridium, and Salmonella through targeted cell death.13  

In order for your gut microbiome to carry out these functions, its composition needs to maintain a stable profile—meaning, it has to be populated primarily by beneficial microbes, with a low presence of microbial species typically characterized as “harmful.” When the balance is disrupted— from infection, inflammation, immune deficiency, sleep pattern, stress, changes in diet, or exposure to antibiotics or toxins—the gut microbiome can shift in composition, leading to uncontrolled or heightened immune responses.14

Cold and Flu SeasonThe Gut-Immune Connection

The Science Behind Probiotics and RTIs

Citations

People often use the terms “cold” and “flu” interchangeably, and that’s because they have similar symptoms. Most of the everyday infections that make headlines, increase hospitalizations, and more generally lead people to take “sick days” are under the umbrella of respiratory tract infections, or RTIs, a term that refers to respiratory illnesses that result in infections of the sinuses, throat, airways, and lungs. These include the common cold, laryngitis, bronchitis, pneumonia, RSV, and COVID-19. Influenza, or the flu, isn’t technically an RTI, but that’s because it’s not confined to your respiratory tract—it’s considered a systemic infection, since it also affects other systems in the body.

The good news is that there are a number of high-quality studies demonstrating how probiotics reduce the incidence and duration of RTIs in otherwise healthy children and adults.15,16,17 In studies where people with RTIs were given certain probiotic strains or placebo, the researchers found that those who were given probiotics were sicker for fewer days and had fewer “illness episodes.”18 One 2019 health economics study even found that the use of probiotics was associated with reducing the annual number of sick days by over 54 million in the U.S.19

While we don’t (yet) have a clear protocol for preventing and/or treating RTIs with probiotics, research has begun to uncover some clues as to why probiotics may be protective against RTIs:

  • Probiotics may deliver gut microbes that activate the body’s own immune response. Unlike over-the-counter cold and flu medications, which are designed to reduce only the symptoms of these infections, the gut microbiome activates an immune response that helps fend off pathogens. High-quality probiotics can acutely alter the composition of your gut microbiome, which may help explain their protective effects when it comes to RTIs.
  • Probiotics may support overall respiratory health.20 Several clinical studies have demonstrated the beneficial effect of Lactobacillus and Bifidobacterium probiotic strains on the incidence, symptoms, and duration of flu-like sickness.21 In one 2013 study, for example, healthy college students who received a combination of two probiotic strains for 12 weeks had 33% fewer days with RTI symptoms. Their symptoms were also less severe than those who received a placebo.22
  • Probiotics may increase the efficacy of the flu shot. A 2017 systematic review and meta-analysis looked at the effect of supplementary probiotic and prebiotic use on the flu vaccine efficacy in adults. After reviewing several randomized controlled trials, it was found that supplementing with probiotics or prebiotics before vaccination increased the immunogenicity (i.e., how well a vaccine works) to specific flu virus strains.23
  • Probiotics may help limit the use of antibiotics. Studies suggest that taking probiotics may reduce the number of people who are prescribed antibiotics for acute upper respiratory tract infections (URTIs). One study that looked at children ages 3 to 5 found that, for those taking either single-strain or multi-strain combination probiotics, antibiotic use was reduced by 68.4% (single strain) and 84.2% (multi-strain).24 In fact, results from a 2019 study suggest that the use of probiotics could help avoid approximately 2.2 million courses of antibiotics per year in the U.S.19 Taking fewer antibiotics, in turn, can help support the native gut microbiome and therefore the gut-immune response.

What’s particularly exciting about the mounting evidence is that studies have shown beneficial effects of probiotics across the age spectrum when it comes to RTIs. For children ages 3 to 5, a 2009 study found that taking two specific probiotic strains reduced the incidence and duration of fever, coughing, and runny nose (not to mention, days absent from group child care) compared to placebo.24 A 2016 review of randomized controlled trials found that taking probiotics resulted in an 11% reduction in the number of children getting RTIs.25

When it comes to the elderly, viral respiratory and gastrointestinal infections are a major cause of morbidity and mortality, as aging is associated with a decline in immunity. A 2015 study, which looked at healthy adults aged 60 to 74 years old, found a significant decrease in respiratory infections within a subset of 44 patients who were taking a single-strain probiotic. The researchers also found an increase in concentrations of IgA (one of the most common antibodies that fights pathogenic bacteria, viruses, and toxins) in the subjects’ saliva, suggesting that this probiotic strain was able to enhance their immune responses. That being said, while they had fewer infections, there was no difference in their symptoms compared to people who didn’t take probiotics when they did get sick.26

Аntibody

An illustration of an antibody. Antibodies, also called immunoglobulins, are proteins produced by the immune system in response to the presence of foreign substances like bacteria and viruses.

While research is still emerging about the supportive effects of probiotics in reinforcing immunity during cold and flu season, a large body of evidence points to the intimate and intricate connections between the gut and the immune system. That’s why nurturing your gut microbiome is important to support healthy immune function in December, March, or any other time of year.

Cold and Flu SeasonThe Gut-Immune ConnectionThe Science Behind Probiotics and RTIs

Citations

  1. Rubin, R. (2022). The Dreaded “Twindemic” of Influenza and COVID-19 Has Not Yet Materialized—Might This Be the Year? JAMA, 328(15), 1488. https://doi.org/10.1001/jama.2022.15062
  2. Mandavilli, A. (2022, October 27). A ‘Tripledemic’? Flu, R.S.V. and Covid May Collide This Winter, Experts Say. The New York Times. https://www.nytimes.com/2022/10/23/health/flu-covid-risk.html
  3. Preliminary In-Season 2021-2022 Flu Burden Estimates. (2023, February 24). Centers for Disease Control and Prevention. https://www.cdc.gov/flu/about/burden/preliminary-in-season-estimates.htm
  4. Preliminary Flu Burden Estimates, 2021-22 Season. (2022, October 4). Centers for Disease Control and Prevention. https://www.cdc.gov/flu/about/burden/2021-2022.htm
  5. Estimated Flu-Related Illnesses, Medical visits, Hospitalizations, and Deaths in the United States — 2018–2019 Flu  Season | CDC. (n.d.). https://www.cdc.gov/flu/about/burden/2018-2019.html
  6. Learn more about the flu season. (2022, September 20). Centers for Disease Control and Prevention. https://www.cdc.gov/flu/about/season/flu-season.htm
  7. Preventing Flu, COVID-19 and Monkeypox: Infographic. (n.d.). Johns Hopkins Medicine. https://www.hopkinsmedicine.org/health/conditions-and-diseases/coronavirus/flu-prevention-and-coronavirus-infographic
  8. Gupta, V. K., Paul, S., & Dutta, C. (2017). Geography, Ethnicity or Subsistence-Specific Variations in Human Microbiome Composition and Diversity. Frontiers in Microbiology, 8https://doi.org/10.3389/fmicb.2017.01162
  9. Wiertsema, S. P., Van Bergenhenegouwen, J., Garssen, J., & Knippels, L. M. (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
  10. 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
  11. O’Hara, A., & Shanahan, F. (2007). Gut Microbiota: Mining for Therapeutic Potential. Clinical Gastroenterology and Hepatology, 5(3), 274–284. https://doi.org/10.1016/j.cgh.2006.12.009
  12. Pickard, J. G., 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
  13. Anjana, N., & Tiwari, S. K. (2022). Bacteriocin-Producing Probiotic Lactic Acid Bacteria in Controlling Dysbiosis of the Gut Microbiota. Frontiers in Cellular and Infection Microbiology12https://doi.org/10.3389/fcimb.2022.851140
  14. Wu, H. K., & Wu, E. Q. (2012). The role of gut microbiota in immune homeostasis and autoimmunity. Gut Microbes3(1), 4–14. https://doi.org/10.4161/gmic.19320
  15. Zhao, Y., Dong, B. R., & Hao, Q. (2022). Probiotics for preventing acute upper respiratory tract infections. The Cochrane database of systematic reviews8(8), CD006895.

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