Probiotics are live microbes that can provide a health benefit if taken in adequate amounts. But how do they work?
Probiotics don’t add ‘good’ bacteria to an empty space. Instead, the live microbes in a probiotic can have several effects once they reach the gut. These include competing with resident or potentially harmful microbes, producing metabolites for other microbes and interacting with the gut barrier and immune system.
Whether any of these effects happen and whether they lead to health benefits depends on the specific probiotic, and only evidence from clinical trials can confirm it.
In this article, we’ll break down how probiotics work in the gut, whether they need to colonise the gut to be effective, and what research can and can’t tell us about the health benefits of a particular probiotic. But first, let’s look at what happens before a probiotic can get to work.
What has to happen before a probiotic can work?
For a probiotic to work, it needs to reach the gut alive, having survived a hazardous journey.
On the way, probiotics travel through the stomach, where they meet acid and digestive enzymes in an environment designed to kill bacteria. In the small intestine, bile salts pose a further challenge.
Manufacturers design probiotics to maximise bacterial survival, but this varies significantly between products. Several factors influence this: whether it's a capsule, liquid or powder, whether you take it with food, and the specific bacterial strains involved.
Once probiotics reach the gut, they can get to work. Reaching the gut alive doesn't guarantee health benefits, though – survival is just one piece of the puzzle.
The only way to find out whether and how a probiotic works is through clinical studies, and different types of research answer different questions. We’ll cover this in more detail a little later on.
Do probiotics need to colonise your gut to work?
No, probiotics don’t need to take up permanent residence in the gut to provide health benefits – many are temporary visitors.
When probiotics arrive, they meet the residents of the gut microbiome, the trillions of microbes already living there.
For a probiotic to colonise the gut, it needs to compete with the existing community for nutrients and space. Because of this colonisation resistance, most probiotic bacteria are excreted. Once you stop taking them, they’ll no longer be detectable in your stool.
It isn't entirely clear why some probiotics take up permanent residence in the gut and others don't.
One study found that bacteria took up residence in the gut mucus lining in some human volunteers but not in others, though the volunteers had all taken the same probiotics. Which category a volunteer fell into had to do with the makeup of their gut microbiome at the outset, the researchers found.
So, taking a probiotic doesn't necessarily mean permanently adding new bacteria to your microbiome.
However, even if a probiotic doesn’t colonise the gut, it can still interact with the resident microbes while passing through. Excretion doesn't necessarily mean that the probiotic had no effect.
What can probiotics do once they reach the gut?
Probiotics can do a number of things once they reach the gut alive, but the exact effects depend on the bacterial strains. Different strains can have different properties and mechanisms.
Here's an overview of the possible mechanisms reported from many different studies. Not every probiotic will have each of these effects.
1. Interact with the bacteria already living in your gut
Taking a probiotic is more complicated than simply ‘adding good bacteria’. It means introducing bacteria into an existing microbial ecosystem, rather than an empty space.
The effects depend on how the probiotic bacteria interact with the resident microbes. Both groups compete for the same nutrients and spaces to attach along the gut lining.
Some probiotics can produce compounds like lactic acid. This leads to changes in the local environment, for example by lowering the pH, which can affect which microbes can thrive there.
Certain probiotics can also carry molecules that help them adhere to the gut lining, such as mucus-binding protein.
2. Compete with potentially harmful microorganisms
A recent meta-analysis, based on a small number of studies, found that probiotics were linked with reduced pathogen colonisation in the human gut.
Probiotics achieve this through competitive exclusion, which is when beneficial microbes compete with pathogenic microbes in several ways, including:
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Competing for nutrients: Some probiotic bacteria can use different carbohydrate sources (or a wider range) than pathogens, letting them colonise larger areas and inhibit pathogen growth.
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Taking up space on the gut lining: Attachment sites on the gut lining are limited. Probiotics with favourable adhesion properties can protect the gut from infection by preventing pathogens from attaching to it.
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Producing antimicrobial compounds: Probiotics can produce antimicrobial peptides called bacteriocins, which kill pathogens. Some can also produce acids, hydrogen peroxide and other molecules that can kill pathogens or make it harder for them to grow.
3. Produce substances that other gut bacteria can use
When bacteria break down nutrients, some of the metabolic by-products can act as fuel for other bacteria. This is called cross-feeding.
Some Lactobacillus and Bifidobacterium species produce lactate as they ferment carbohydrates. Other gut bacteria can utilise lactate and convert it into compounds, including short-chain fatty acids (SCFAs).
SCFAs, which include acetate, butyrate and propionate, are helpful metabolites that gut microbes produce. They support the health and integrity of the gut lining and the immune system.
Cross-feeding also provides other substances to microbes in the gut, including vitamins, amino acids, hydrogen and certain minerals.
4. Interact with the gut barrier
The gut lining is a barrier between the gut and the rest of your body, and it regulates what passes between the two.
It consists of a single layer of cells and a mucus layer on the side facing the gut. This mucus prevents bacteria and large particles from reaching the cell layer.
Specialised protein complexes, including tight junctions, occupy the space between the cells of the gut lining. Tight junctions control permeability by regulating the passage of water and other molecules.
Some probiotic strains may help protect the gut barrier by increasing tight-junction proteins or reducing inflammation that weakens them.
A meta-analysis of 26 randomised clinical trials reported that probiotics can improve gut barrier function. These effects appear to be strain-specific: not every probiotic affects the gut barrier in the same way.
5. Interact with the immune system
A large proportion of the body’s immune cells are located in the gut, and there’s a steady exchange of immune signalling between gut microbes, the cells of the barrier and gut immune cells.
Probiotic bacteria can have beneficial effects on the immune system, including:
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Antibody production: Several probiotic strains can support an increase in B cells which produce immunoglobulin A antibodies. These bind to potentially harmful microbes and prevent them from attaching to the cells of the gut barrier.
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T regulatory cell activation: Some strains can stimulate the activation of T regulatory cells which maintain the balance between pro-inflammatory responses and anti-inflammatory responses.
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Inflammatory signalling: Certain probiotics can stimulate the release of inflammatory signalling molecules called cytokines. There are many cytokines: some pro-inflammatory, some anti-inflammatory. The direction of the effect depends on the strain of probiotic.
Research in this area aims to understand how probiotic microbes interact with the immune system. Still, this doesn't guarantee immune-supporting health benefits for every probiotic.
As with the other mechanisms covered here, how probiotics interact with the immune system differs from strain to strain. The results of a study of one probiotic don’t mean that a different product will have the same effects.
Do all probiotics work in the same way?
No, probiotics don’t all work in the same way. There are many probiotic products, and different strains, doses and formulations can behave very differently in the gut. So there's no guarantee that a benefit shown for one probiotic applies to another.
For example, good evidence shows that the probiotic strain Lactobacillus rhamnosus GG can prevent antibiotic-associated diarrhoea in children. However, in studies testing the same strain for several other conditions, including traveller’s diarrhoea and antibiotic-associated diarrhoea in adults, researchers didn’t find sufficient evidence of benefits.
A meta-analysis of 42 clinical trials investigating probiotics and treatment for irritable bowel syndrome showed that several products improved at least one symptom, like abdominal pain, but not others. This indicates that a probiotic might help with a specific symptom or aspect of a health condition, but not all symptoms or all people with the condition.
Not every mechanism covered in this article so far applies to every probiotic. How a specific product works depends on:
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the specific probiotic strain or combination of strains
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how many microbes are in the product (the dose)
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the formulation and delivery method
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how many microbes reach the gut alive
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the person taking the probiotic
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the health outcome being measured
It’s important not to assume that evidence for one probiotic strain applies to a different product, even if the microbes are similar.
How do scientists know what a probiotic is doing?
To investigate what a probiotic is doing, scientists use laboratory models that simulate the gastrointestinal environment or intestinal barrier. They also conduct microbiome and metabolite analyses and run human clinical trials.
Different types of research answer different questions about how probiotics survive the journey to the gut, how they interact with other microbes and what metabolites they produce.
Laboratory studies, like experiments using simulated gastric fluid, can show whether a probiotic survives the stomach, while gut barrier models show how it behaves in gut-like conditions.
Researchers can use microbiome analysis to see how a probiotic changes the gut's microbial community. Metabolite analysis can identify the substances a probiotic produces, such as SCFAs.
The types of studies can help scientists understand how a probiotic could work. But only human clinical trials can show whether there are measurable benefits. In a clinical trial, researchers test a specific probiotic and dose against a placebo.
A single clinical trial can provide one piece of evidence. But the strongest level of evidence is a meta-analysis of several clinical trials, according to the World Gastroenterology Organisation Global Guidelines on probiotics. Pooling and analysing studies together makes results more reliable and less dependent on any one study.
Remember that any evidence applies to a specific probiotic strain, dose, formulation and aspect of health. You can read more about what we mean by ‘evidence’ when it comes to probiotics here.
What can probiotic mechanisms tell us, and what can't they?
Research into the mechanism of action of probiotics can help explain how a particular strain or product might work. This matters because it helps us understand if a biological effect is possible.
However, demonstrating a mechanism in a study isn’t the same as showing that taking the probiotic can lead to a measurable health benefit.
The results of a study can show that a probiotic might interact with resident gut microbes, produce metabolites, or influence the gut barrier or immune system. The research could also show that there isn’t a measurable improvement in health.
When research identifies the mechanism for one probiotic strain, it doesn’t apply to a different strain, even if it’s closely related. And don't assume results hold for the same strain in a different formulation or dose.
That’s why evidence from human clinical trials and meta-analyses of these trials is so important. Clinical evidence can show whether a specific probiotic product, at a specific dose and formulation, can produce a specific health outcome.
Probiotics don’t just add ‘good’ bacteria to your gut. Live microbes can interact with your gut microbial community, gut barrier and immune system in different ways. Which mechanisms occur, and whether they produce the benefit you're after, depends on the specific probiotic and the evidence behind it.
FAQs
Here are answers to some common questions about how probiotics work.
Do probiotics colonise the gut permanently?
No, most probiotics don't colonise the gut permanently – they're temporary visitors, excreted in your poo. Some can take up permanent residence, and whether they do may depend on your existing gut microbiome. Still, colonising the gut isn't necessary for a probiotic to work.
Does surviving stomach acid mean a probiotic works?
No, surviving the stomach doesn’t ensure that a probiotic works. But it does need to reach the gut alive to interact with the resident microbes, the gut barrier and the immune system. Only evidence from clinical trials in humans can show whether a probiotic has the desired effect.
Are all probiotic effects the same?
No, not all probiotics work the same way. The effect of a probiotic depends on the strain, the dose and whether it’s a liquid, powder or capsule. Health benefits shown for one probiotic strain don't guarantee the same effect for a different strain, or even a different dose or formulation of the same strain.
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