Probiotics – what are they and how do they work?

Probiotics are live microorganisms (in most cases, bacteria) that help to keep the digestive system healthy by reducing the growth of harmful gut microbes and boosting the number and variety of ‘friendly’ gut microbes. In this week’s blog nutrition practitioner Miguel Toribio-Mateas discusses probiotics, their safety, how they work and their health supporting properties.

As with all food supplements, some of the health benefits advertised by some remain to be validated by clinical research. However, there is consensus amongst scientists and clinicians that probiotic supplementation is generally safe and that its health potential justifies more research. This is a booming field and I expect within the next 5 years we’ll be able to make very targeted use of probiotic microbes, and not just bacteria, but potentially other microorganisms too.

The human gut is a huge complex ecosystem where our gut flora, nutrients, and our own cells interact 24 hours a day, from the moment we’re born until we die. I see this interaction as a symbiotic partnership where we provide food for the microbes that inhabit our gastrointestinal tract and, in return, they help us maintain the health of our gut, from the top to bottom, literally. Hence, any imbalance, known as “dysbiosis” could have negative consequences in terms of health. That’s why scientists continue to find associations between the impairment of our gut flora, and a number of health conditions. It is precisely because of these close links between our microbiota, health, and disease, that there’s a growing interest in supplementing with live micro-organisms, or “probiotics”, as well as the non-digestible substrates they feed on, known as “prebiotics” to positively affect a healthy balance in our gut microbiota and thereby support and maintain overall health.

Bad guys turn good

You might find it funny to think that up to about 30 years ago, a lot of the relationships between humans and bacteria were looked at through a pathogenic lens, i.e. bacteria (and other bugs that live in the gut, like yeasts and parasites) were seen as “bad”, as sources of dangerous toxins that could make you ill. We saw them as potential invaders of the gut’s outermost layer, which is covered in mucous (hence why we refer to it as the “mucosa”), where they’d reproduce and then move into the rest of the body, causing infections.

The current focus has experienced a U-turn, as an increasing number of scientists report the beneficial interactions between the microbes that live in our gut normally – which we call the commensal microbiota – and the rest of the human body. We’ve gone from seeing these bugs as enemies, to seeing them as partners that enable our growth and development beginning at birth.

So what are probiotics?

At the beginning of the 20th century, Elie Metchnikoff observed that Bulgarians seemed to live longer than other European populations, and he attributed their health to their high consumption of fermented milk, aka yoghurt. At the same time, Henry Tissier, a French pediatrician, continued to see how young children with diarrhoea had fewer Y shaped Gram-positive bacteria in their stools, whereas these “bifido” bacteria were dominant in the stools of healthy infants. In a ground-breaking report to the Biology Society he suggested that children presenting with loose stool should drink 1 to 2 glasses of fermented milk (a bit like kefir) so as to accelerate the building up of beneficial flora.

But using beneficial or probiotic (meaning pro-life) bacteria for medicinal purposes goes back several centuries. In fact, in the 12th century, during the Genghis Khan era, fermented milk was considered a source of strength and health, and Mongolian women sprayed both riders and horses with it to protect them during battles.

Metchnikoff’s observation led him to suggest that perhaps not all microbes were dangerous for health and that it could be beneficial to replace what he thought of as “putrid flora” by enriching our gut with bacteria able to ferment carbohydrates / sugars (like glucose, lactose and fibres). Since then a huge number of laboratory studies, where scientists look at the behaviour of bacteria in a test tube (referred to as “in vitro”), have taken place. In the last decade, animal models have verified the results of those in vitro experiments and now human studies, including clinical trials continue to confirm the potential of probiotic supplementation for many health conditions.

So which probiotics should your clients be taking?

I know this is the million dollar question. With so many different names and so many products out there, it is baffling. First of all, a probiotic really needs to meet some basic criteria, namely:

1. The microorganism, e.g. bacteria ingested must be able to reach its site of action, usually the gut, and thus survive the stress of the stomach acid, pancreatic juices and bile salts. You could buy a probiotic that has billions of bacteria advertised on the pot, but if 99% die in the stomach, the remaining 1% is highly unlikely to be doing much when it reaches the places you need them most.
2. These bugs must be backed by research showing a beneficial effect. So ideally you should be recommending a probiotic with names you could find in a science database. Running a quick search on PubMed, the US National Library of Medicine National Institutes of Health and the go to database for science researchers, will help. If the probiotic pot you’ve bought has some super fancy names on it but when you look for them there’s only one study done in mice, I’d say don’t waste your money. It could turn out that the product is totally amazing, but I’d rather stick to ones that come up with a good few studies on humans with similar issues to those your client is experiencing, e.g. bloating, loose stool, constipation, etc.
3. They need to be safe. I doubt that any probiotic product out there would be unsafe to take, as in actually make someone very ill. The most sinister thing that could happen is increased bloating (rather than the aim of less) by taking lots of the wrong type of probiotic, i.e. a type of bug that’s not the most indicated for that individual. The least sinister is that they may do nothing. But they’re highly unlikely to cause any harm.
4. Probiotics must also remain stable through the manufacturing process, but you needn’t worry about that when you buy your probiotic product from a reputable source as the manufacturer will have done their research when designing that product.

What kind of bacteria are used as probiotics?

The Lactobacillus and Bifidobacterium “families” (technically correct “genera”) are the most frequently used bacteria when it comes to making probiotics for human use. They are known as lactic bacteria, because they convert sugars in food to lactic acid. This acidifies the pH in the gut, which is a good thing as an alkaline gut provides a better environment for pathogenic bacteria, and a more acidic gut a more hostile one for those bugs that are likely to cause illness. Most probiotic bacteria are produced from fermented dairy products such as yoghurt or kefir. For example, traditionally grown kefir, i.e. from kefir grains, can contain up to 60 different types of lactic acid bacteria types. Some probiotic strains (very specific types of bacteria) can be isolated from non-fermented food such as meat, and vegetables and fruits. Vegan and dairy-free probiotic bacteria can be isolated from coconut milk yogurt, non-dairy kefir, tempeh (fermented soya beans), kimchi (fermented cabbage), sauerkraut, kombucha and miso paste, which can be made with fermented soy, barley or rice. Apart from bacteria, some yeasts such as Saccharomyces boulardii have also been used because of their probiotic properties.

Scientists have been looking at new types of probiotic bacteria that will do things like help with weight loss and blood sugar management. To that extent, a specific type of Verrucomicrobia called Akkenmansia muciniphila, known as the “skinny” or “weight loss bacteria” is currently being tested in clinical trials to see if it really will do the same thing when taken in a capsule as what it already does in the gut, where it represents around 3% of the total of the microbiota. Akkenmansia muciniphila communicates with the control centre of metabolism in the brain via the vagus nerve (a chunky “cable” that connects the gut and the brain, but also the adrenal and the thyroid glands), helping to manage blood sugar, regulate calorie “burning” and keeping us nice and trim. This is one I’ll be watching out for in coming months when the results of the studies are likely to hit the papers.

So are probiotics safe for everyone to take?

The answer to this question depends on the specific type (or strain) we’re talking about. As part of the requirements I described above for a bacterium to be considered as probiotic, it must lack the potential to cause harm of any kind. Probiotics, especially Bifidobacteria and even more Lactobacilli, have a long history of safety with their use in fermented milk and other foods. Both Lactobacilli and Bifidobacteria occur in plants, animals, and in humans where they form part of their commensal microbiota. That’s why these bacteria along with Lactococci, and yeasts (e.g. Saccharomyces boulardii) are classified in the category of organisms Generally Regarded As Safe (GRAS) by organisations such as EFSA and the FDA. Nevertheless, if you are severely immunocompromised, e.g. end-stage HIV-infection/AIDS, you might want to be careful with any type of microbial supplementation. Best be ultra safe in this kind of circumstances. But for most people probiotic supplements should be seen as safe.

How do probiotics work?

The way probiotics work is not always 100% understood. This is one of the reasons why the European Food Safety Authority (EFSA) has refused the health claims of marketed probiotics. EFSA wants more clear-cut proof of the mechanism of action, coupled with absolute clarity about the effects to be expected. For example, when you take a paracetamol for a headache, you know exactly what to expect and that your pain is likely to decrease over the following hour or so. That is clear cut and replicable for 99% of people. That’s the kind of reassurance EFSA wants. However, what scientists have been finding about probiotic supplementation is that various benefits are observed, but they were not always those that their studies had set out to measure. In research this is what’s called “a surrogate marker”, i.e. something changes that you were not expecting and that allows you to assume that the intended effect has taken place, but not by means of what you had hoped to measure in the first place. For that reason, the mechanisms of action of probiotics are most often documented through studies in test tubes or animal models. And whilst mice are allegedly quite close to humans when it comes to research, they are not humans. So a mouse experiencing benefit from probiotic supplements does not necessarily mean human beings would see the same result.

So what do we know for real? Well, we do know that probiotics may work their magic by regulating our own gut flora. One of the first suggested modes of action is the “barrier” effect, also called “resistance to colonisation”. This happens when probiotic bacteria like Lactobacilli and Bifidobacteria produce molecules called “broad-spectrum inhibition bacteriocins” aka “natural antibiotics”, as well as short-chain fatty acids like butyrate, acetate and propionate, three waxy molecules that help lower the local pH in the gut, making it a less hospitable environment for disease carrying bacteria, e.g. Clostridium difficile, to adhere to the intestinal wall and reproduce there.

The second mode of action we know about involves the improvement of the barrier function of the gut mucosa. Between each of the cells in the intestinal wall there are tight junctions. Think of a line of bricks with mortar between them. The mortar is the junction, which is supposed to be tight but flexible in order to let nutrients and other molecules through the intestinal wall and into the bloodstream.  Probiotic bacteria help keep this flexibility, known as “tight junction integrity”. Some molecules like zonulin are involved in this process and can be measured by means of a stool test. High zonulin is seen as a sign of intestinal permeability or “leaky gut”, which is normally a symptom of overall disruption as opposed to “a diagnosis” and that should be addressed as part of an all-encompassing plan to restore gut balance. I wrote a paper about this earlier this year entitled “Harnessing the Power of Microbiome Assessment Tools as Part of Neuroprotective Nutrition and Lifestyle Medicine Interventions” and you can read the full text for free clicking on this link.  Apart from working on tight junctions, probiotics also increase the quality of the mucus layer that protects the intestinal wall and enhance the production of molecules called defensins, another type of anti-microbial regulator that keeps nasty bugs under control.

Probiotics also work by modulating the immune system, i.e. if the immune system is working too hard, they’ll “talk to it” and ask it to slow down. If it’s not working hard enough, they’ll support it so it works more efficiently. More than 70% of immune cells are located in the gut, especially in the small intestine, making up what’s called “gut associated lymphoid tissue” or GALT. Probiotic bacteria, especially lactic-acid bacteria like Lactobacilli and Bifidobacteria, trigger different effects on the immune system, from stimulation of gut immunity at local level, e.g. producing local, first line immune molecules like secretory IgA, for example, to systemic responses, lowering the levels of inflammatory molecules such as C-reactive protein (CRP), a protein that is normally raised in the blood of people at higher risk of cardiovascular disease. One could argue, therefore, (and scientists would agree) that probiotic supplementation, if it helps reduce CRP, could be seen as protective of cardiovascular events. It’s unlikely to be a miracle cure, but if it helps only a little, there’s no harm in adding to your nutrition and lifestyle arsenal of protective measures.

So can probiotics be used just as if they were drugs?

Probably not, because we’re still a little unsure as to which specific types and at what doses they will have an effect that can be measured accurately and replicated over and over again in controlled trials. Such data would give us comparable evidence to that coming from drug development. However, the effectiveness of probiotics has been demonstrated for a number of conditions, including irritable bowel syndrome (IBS), diarrhoea, constipation, inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn’s, allergies, particularly to airborne particles and in children, and the list keeps growing.

Looking at the totality of the evidence available today, the rule of thumb when choosing a probiotic product would be to go for variety as opposed to for dose strength, i.e. a probiotic that gives you a few different strains, even if the levels aren’t huge, is more likely to work than if you buy a super dose of one single strain. If a label on a pot of probiotics told me that the product is going to give me a decent dose of 4 to 10 different strains of lactic-acid producing bacteria, I’d be happy.

The future

As research in this field keeps advancing, we’re likely to see newcomers making interesting claims. With my neuroscience background, I’m particularly attracted to bugs that can interact with us in ways that help our brain feel more at ease, e.g. less anxious or depressed. This is likely to happen because some bacteria are known to really work on the integrity of the gut lining and on that “tight junction flexibility” I mentioned before. When tight junctions work more efficiently, the whole gut ecosystem achieves better balance, and the communication between the gut and the brain via the vagus nerve improves dramatically. I’ll be watching out for formulations that can help protect the integrity of the gut and for probiotic strains that, combined with protective, repairing nutrients, can help you take your gut-brain connection to the next level.

Miguel is a doctoral researcher in clinical nutrition practice with wide-angle, first-hand experience of the research process. From the laboratory bench, having completed a lab-based Masters in Clinical Neuroscience focusing on brain ageing, to the design and implementation of human clinical trials on the effect of fermented foods on mood and cognition as leading investigator at the “Bowels and Brains™️” project at the London Agri-Food Innovation Clinic. Miguel has been delivering quality individualised nutrition care to his clients from 2009, translating complex science findings into meaningful recommendations that can be used by people like you to improve health and wellbeing. Miguel’s background includes 15+ years in senior consulting and training roles in life sciences and medical publishing, having trained clinicians and scientists around the world.

With many thanks to Miguel for this blog; if you have any questions regarding the health topics that have been raised, please don’t hesitate to get in touch with Clare via phone; 01684 310099 or e-mail clare@cytoplan.co.uk

Last updated on 16th April 2021 by cytoffice