Probiotics and the Immune System: LGG, BB-12 and HN019 Explained
The gut and immune system are closely connected, which has led to growing interest in probiotics and immunity.
But not all probiotics are the same. Research is carried out on specific bacterial strains, and findings from one strain cannot automatically be applied to another.
So why does the gut matter for immunity, how might probiotics interact with the immune system, and what have human studies actually found?
How are the gut and immune system connected?
The gut does much more than digest food. It is closely connected with immune cells and the trillions of microorganisms that make up the gut microbiome. Gut microbes, intestinal cells and immune cells are constantly communicating.
Rather than simply “boosting” immunity, researchers are interested in how gut microbes may help regulate immune responses.
How might probiotics interact with the immune system?
There isn't one single mechanism. Research suggests several ways in which specific probiotic strains may interact with the gut and immune system.
1. Supporting the gut barrier
The cells lining the intestine are joined closely together to help control what passes from the gut into the body. Some probiotic strains have been shown to influence these connections, as well as mucus production and other parts of the intestinal barrier.
Why does this matter for immunity?
A well-functioning barrier helps keep microbes and other substances in the gut where they belong, reducing unnecessary exposure of the immune system to material from inside the intestine. Research across a range of probiotic strains has found effects on measures of intestinal barrier function, although results vary depending on the strain, population and study.
2. Communicating with immune cells
Bacteria in the gut can also communicate directly with immune cells. Researchers have studied effects on cells including T cells, dendritic cells, phagocytes and natural killer cells, as well as signalling molecules that help coordinate immune responses.
These cells perform different jobs. Some help identify potential threats, some coordinate the wider immune response, and others can attack infected or abnormal cells. Specific probiotic strains may influence how these cells behave. For example, human research on the strain HN019 has investigated its effects on natural killer cells and phagocytes.
3. Influencing compounds produced in the gut
Gut bacteria produce many different compounds as they process components of our diet.
One important group is short-chain fatty acids, which are produced mainly when certain gut bacteria ferment fibre. These compounds can help nourish cells lining the intestine, support the gut barrier and communicate with immune cells.
4. Interacting with the wider gut microbiome
A probiotic strain does not act in isolation. It enters an already complex ecosystem containing hundreds of different types of microorganisms. Specific strains may interact with these microbes, compete for nutrients or attachment sites and produce compounds that change the environment within the gut.
Why is this relevant?
The wider gut microbiome helps shape the intestinal environment, the compounds produced there and the signals received by immune cells. However, these interactions vary between bacterial strains. This is why evidence for one probiotic cannot automatically be applied to another.
Which probiotic strains have been studied for immune health?
Understanding the possible mechanisms is useful, but ultimately an important question is whether probiotics make a measurable difference in people.
A 2022 Cochrane review looked at 24 studies involving 6,950 people. Overall, the review found that probiotics may reduce the number of people experiencing an upper respiratory tract infection and may shorten the average duration of an episode.
However, the certainty of the evidence ranged from low to moderate, and the studies used many different probiotic strains and formulations.
So the review does not mean that every probiotic will have the same effect. To understand the evidence behind a particular supplement, we need to look at the exact bacterial strains that were studied.
LGG and BB-12: what did a human trial find?
One randomised, double-blind, placebo-controlled trial studied two specific strains: LGG and BB-12.
Researchers recruited 231 healthy college students and followed them for 12 weeks. Among those who developed an upper respiratory infection, the probiotic group experienced:
- around two days shorter median illness duration
- 34% lower median symptom severity
compared with placebo. The probiotic group also missed fewer days of college.
Because the study was carried out in healthy college students, the findings cannot automatically be applied to everyone. However, it adds to growing interest in how specific probiotic strains may interact with immune function, with researchers continuing to investigate the underlying mechanisms.
It is also a useful reminder that these findings relate to LGG and BB-12 specifically, rather than probiotics as a whole.
HN019 and immune-cell activity
Another strain, HN019, has been studied specifically for its effects on immune cells.
A systematic review and meta-analysis of four controlled studies in healthy older adults found that HN019 increased natural killer cell and phagocyte activity.
Natural killer cells help identify and respond to infected or abnormal cells, while phagocytes can engulf and process foreign material.
These findings provide human evidence that HN019 can influence cellular immune function and offer insight into how this specific strain may interact with the immune system. The studies measured immune-cell activity rather than infection rates, so further research is needed to understand how these changes translate into clinical outcomes.
Why does the probiotic strain matter?
Even bacteria belonging to the same species can have different properties. For example, Lactobacillus rhamnosus describes a bacterial species, while Lactobacillus rhamnosus GG (LGG) identifies the particular strain.
Clinical trials are carried out using exact strains, so if a supplement simply lists Lactobacillus rhamnosus, you cannot assume it contains LGG or that research conducted using LGG applies to it.
This is also why more strains or a higher total CFU count does not automatically mean a better probiotic.
When looking at the research behind a probiotic, consider:
- the exact strain
- whether it has been studied in humans
- what outcome was studied
- the dose used in that research compared to the product
What about vitamin D and the immune system?
Probiotics are only one part of the immune-health picture. Vitamin D has an established role in immunity and contributes to the normal function of the immune system.
Interestingly, vitamin D receptors are highly expressed in cells lining the gut, where vitamin D signalling is involved in maintaining the intestinal barrier and regulating immune responses.
In the UK, the NHS advises that everyone should consider taking a daily vitamin D supplement during autumn and winter, when sunlight is not strong enough for most people to make sufficient vitamin D through their skin.
And of course, the foundations still matter: a balanced diet, enough sleep, regular physical activity and overall health all play an important role in supporting normal immune function.
EVIDOSE® Live Biotic Daily+
EVIDOSE® Live Biotic Daily+ combines four extensively studied live bacteria strains: LGG, DSM 15954 (BB-12), NCFM and HN019, alongside vitamin D, which contributes to the normal function of the immune system.
Our approach is to look beyond long strain lists and high total CFU numbers and instead consider the specific strain, the human research and the dose used in that research.
The takeaway
The gut microbiome and immune system are closely connected, and research suggests that specific probiotic strains may influence the gut barrier, immune signalling and immune-cell activity.
Human studies have investigated LGG and BB-12 for respiratory infection outcomes and HN019 for effects on immune-cell activity.
But probiotics are not interchangeable. Look at the exact strain, what it has been studied for and the dose used in that research.
References
- Zhao Y, Dong BR, Hao Q. Probiotics for preventing acute upper respiratory tract infections. Cochrane Database of Systematic Reviews 2022, Issue 8. Art. No.: CD006895. DOI: 10.1002/14651858.CD006895.pub4. Accessed 05 October 2026.
- Smith TJ, Rigassio-Radler D, Denmark R, Haley T, Touger-Decker R. 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 Jun;109(11):1999-2007. doi: 10.1017/S0007114512004138. Epub 2012 Oct 1. PMID: 23020819.
- Miller LE, Lehtoranta L, Lehtinen MJ. The Effect of Bifidobacterium animalis ssp. lactis HN019 on Cellular Immune Function in Healthy Elderly Subjects: Systematic Review and Meta-Analysis. Nutrients. 2017 Feb 24;9(3):191. doi: 10.3390/nu9030191. PMID: 28245559; PMCID: PMC5372854.
- Zheng Y, Zhang Z, Tang P, Wu Y, Zhang A, Li D, Wang CZ, Wan JY, Yao H, Yuan CS. Probiotics fortify intestinal barrier function: a systematic review and meta-analysis of randomized trials. Front Immunol. 2023 Apr 24;14:1143548. doi: 10.3389/fimmu.2023.1143548. PMID: 37168869; PMCID: PMC10165082.
- Plaza-Diaz J, Ruiz-Ojeda FJ, Gil-Campos M, Gil A. Mechanisms of Action of Probiotics. Adv Nutr. 2019 Jan 1;10(suppl_1):S49-S66. doi: 10.1093/advances/nmy063. Erratum in: Adv Nutr. 2020 Jul 1;11(4):1054. doi: 10.1093/advances/nmaa042. PMID: 30721959; PMCID: PMC6363529.
- Fakhoury HMA, Kvietys PR, AlKattan W, Anouti FA, Elahi MA, Karras SN, Grant WB. Vitamin D and intestinal homeostasis: Barrier, microbiota, and immune modulation. J Steroid Biochem Mol Biol. 2020 Jun;200:105663. doi: 10.1016/j.jsbmb.2020.105663. Epub 2020 Mar 16. PMID: 32194242.
This article is for educational purposes only and is not a substitute for individual medical advice.
