Walk into any pharmacy and you will find a wall of probiotics. Most of them contain the same familiar names, mainly Lactobacillus and Bifidobacterium, and most of them promise better gut health. Yet when researchers look closely at these classic products, the results are mixed. They help in some situations and do very little in others.

That gap is one reason scientists have started looking at something different. They call it next-generation probiotics, or NGPs. The idea is simple. Instead of using bacteria that happen to be easy to grow in a factory, why not study the microbes that actually live in a healthy human gut and find out which ones protect us from disease?

It is an exciting idea. It is also an early one, and a lot of online writing skips that part. This article explains what NGPs are, which ones are being studied, what the human evidence shows so far, and why you will not find most of them on a shelf yet.

What counts as a next-generation probiotic?

By the standard scientific definition, a probiotic is a live microorganism that gives a health benefit when taken in adequate amounts [1]. Traditional probiotics fit that definition and have a long history in fermented foods like yoghurt. Many were chosen because they were safe, familiar and easy to produce.

NGPs are different mainly in how they are found. Researchers usually begin with gut microbiome studies. They compare healthy people with people who have a condition such as obesity, type 2 diabetes or inflammatory bowel disease. If a certain bacterium is consistently lower in the sick group, it becomes a suspect. Scientists then test it in the lab, then in animals, and finally in people.

O'Toole, Marchesi and Hill described this shift in 2017. They explained that the field is moving along a spectrum, from food-style probiotics at one end to live biotherapeutics at the other, where the bacteria are treated more like medicines [2]. That point matters. Many NGPs are not meant to be a daily wellness capsule. Some are being developed to treat a specific condition, and they will be judged the way drugs are judged.

Why the older probiotics fell short

To understand why NGPs exist, it helps to see the problem with the first generation. Most common probiotic strains are not typical members of a healthy adult gut. They pass through, they may stay for a short time, and they can still do useful things along the way. But they were mostly picked for convenience, not because they were missing in people who were unwell.

There is also the issue of strain specificity. A benefit shown for one strain cannot simply be assumed for another strain of the same species, let alone for the whole group [1]. This is why a bottle with a big number of strains or billions of cells does not automatically mean a better product. What counts is whether the exact strain has been tested for the exact problem.

NGP research tries to fix this by going after bacteria with a clearer biological reason to matter. Whether that works in practice is the real question, and the answer so far is: promising, but unfinished.

The main candidates

Akkermansia muciniphila

This is the best known NGP candidate. It was first described in 2004 as a bacterium that lives on the mucus layer lining the human gut and feeds on mucin [3]. Later studies kept finding that people with obesity, type 2 diabetes and some inflammatory conditions tended to have lower levels of it. Cani and de Vos reviewed this work in 2017 and made the case that it could become a next-generation beneficial microbe [4].

The human evidence is still small, but it exists. In 2019, Depommier and colleagues ran an exploratory trial in overweight and obese adults with insulin resistance. Volunteers took either live Akkermansia, a heat-treated (pasteurised) version, or a placebo for three months. The pasteurised bacteria were safe and were linked to better insulin sensitivity and lower blood insulin and cholesterol compared with placebo [5]. This was a proof-of-concept study with a small group, so it shows the idea is worth testing further. It does not prove that Akkermansia fixes metabolic disease.

One detail from that trial is worth pausing on. The pasteurised form performed at least as well as the live one. That finding connects to an earlier mouse study, which showed that a single protein from the outer membrane of the bacterium could improve metabolism in obese and diabetic mice [6]. In other words, you may not always need the living organism. We will come back to that idea.

Faecalibacterium prausnitzii

F. prausnitzii is one of the most common bacteria in a healthy gut, and it is a major producer of butyrate, a short-chain fatty acid that feeds the cells lining the colon. In a well-known 2008 study, Sokol and colleagues found that people with Crohn's disease who had lower levels of this bacterium were more likely to relapse after surgery. In lab and mouse experiments, the bacterium and the substances it releases showed anti-inflammatory effects [7].

That made it a very attractive candidate. The catch is practical. F. prausnitzii is extremely sensitive to oxygen, which makes it hard to grow, store and put into a product that has to sit on a shelf. This is a good example of why many NGPs are still in research labs and not in your cupboard.

Bacteroides species

Bacteria such as Bacteroides thetaiotaomicron are very good at breaking down complex plant fibres, and they are part of normal gut ecology. Researchers are interested in them for gut barrier health and inflammation. Most of the evidence here is still from lab and animal work, so it is too early to say much about benefits for people.

Clostridium butyricum

This one is a bit of an outlier on the "next-generation" list. It forms spores, which makes it far tougher than the oxygen-sensitive candidates, and it has been used as a probiotic in parts of Asia for a long time. It makes butyrate too. It is called an NGP mainly because it sits outside the traditional Lactobacillus and Bifidobacterium group, not because it is brand new.

The manufacturing problem nobody mentions

It is easy to get excited about the biology and forget the engineering. Many NGP candidates are strict anaerobes, which means they die when exposed to oxygen. Growing them in large amounts needs special equipment. Keeping them alive through freeze-drying, packaging, shipping and months of storage is harder still. Then they have to survive stomach acid and bile and reach the right part of the gut.

Compare that with a classic Lactobacillus, which can handle a lot more rough treatment. This is a big reason the first NGP products that reached the market were not the most fragile organisms, and why some companies chose heat-treated cells instead of live ones.

Rules and regulation

Because NGPs are new and some are aimed at treating disease, regulators treat them with more care than a normal supplement. In the United States, a product made of live organisms that is meant to prevent or treat a disease is generally handled as a live biotherapeutic product, which means it goes through a drug-style approval process rather than a supplement route [2].

In Europe, new bacteria with no significant history of use in food need approval as novel foods. In 2022, pasteurised Akkermansia muciniphila was authorised in the European Union under that system [8]. This is a useful example of how the field is moving. The first approved form is the heat-treated one, which sidesteps some of the survival problems and, based on the early human data, seems to hold up well.

The lesson for readers is simple. When a product claims to be a revolutionary NGP, ask what regulatory status it actually has, and what the claim is based on.

Where postbiotics fit in

The Akkermansia story leads naturally to postbiotics. In 2021, an expert panel from the International Scientific Association for Probiotics and Prebiotics (ISAPP) defined a postbiotic as a preparation of inanimate microorganisms and/or their components that gives a health benefit to the host [9]. Notice what is inside that definition and what is not. Heat-killed bacteria and parts of bacteria count. Pure chemical byproducts on their own, such as butyrate, do not strictly count under that definition, even though people often use the word loosely.

Postbiotics have real practical appeal. They do not need to stay alive, so shelf life is easier and the problem of surviving stomach acid mostly goes away. They may also be an option for people whose immune systems make live bacteria a worry. But it is worth being careful with the claim that they offer the same benefits as live probiotics. The evidence is still being built, and the effects are specific to each preparation, just like with live strains.

What the evidence honestly says

It helps to be clear about what we know and what we do not.

What we know: some gut bacteria are consistently lower in people with certain conditions. Some of these bacteria, when given to animals, change metabolism or inflammation in helpful ways. A small number have been tested in humans, with encouraging safety results and some positive signals.

What we do not know: whether these effects hold up in large, long trials. Whether the benefits last after people stop taking the product. Which people respond and which do not. And whether being low in a bacterium is a cause of disease or just a result of it. That last question is easy to overlook, yet it is central. If a bacterium is low because someone is already ill, replacing it may not change much.

You may also see claims about personalised probiotics matched to your own microbiome. That is mostly a hope for the future. The science of predicting who will respond to which strain is still young, and no one should sell it to you as settled.

Safety and who should be careful

Most probiotics are well tolerated by healthy people, but that is not a reason to relax about every product. People with weakened immune systems, those with serious illness, and very premature infants are groups where live bacteria need medical supervision. NGPs are less studied than traditional strains, so there is less long-term safety data. If you have a medical condition or take medication that affects your immune system, talk to your doctor before trying any live-bacteria product.

How to think about NGPs as a consumer

If you are curious about this area, a few habits will help you avoid being misled.

First, look for the strain, not just the species. A label that names the exact strain and points to a study on that strain is more credible than one that lists a long mix of names.

Second, be wary of big numbers. A high cell count and a long list of strains look impressive, but they say little about whether the product works for your problem.

Third, check the source of the claim. Social media videos and ranked lists on commercial sites are not the same as clinical trials. A claim is only as strong as the study behind it.

Fourth, remember the basics. Fibre-rich foods, fermented foods and a varied diet support the gut microbiome in ways that no capsule fully replaces. NGPs are an area to watch, not a shortcut around everyday habits.

The road ahead

The next few years will be interesting. Larger human trials of Akkermansia and similar candidates will show whether the early results were real. Better manufacturing methods may make fragile anaerobes practical. Regulators will keep deciding how to classify these products, and that will shape which ones reach the public and in what form.

It is also possible that the biggest winners will not be live bacteria at all, but heat-treated cells or specific bacterial molecules. The Akkermansia research already hints at that direction.

Final thoughts

Next-generation probiotics are a real and serious area of research, not just a marketing phrase. They represent a more thoughtful way of asking which microbes matter for health and why. But they are not yet a proven answer for everyday wellness, and most of the strongest candidates are still working their way from the lab to the clinic.

The healthiest attitude is curious but careful. Follow the science, check the claims, and treat any product that promises too much with a little suspicion.
No NGP has firmly established efficacy yet. Not one has been confirmed by multiple large, independent human trials the way some classic probiotics have. The ranking below is by how much human evidence exists, from strongest to weakest, and that is not the same as proven benefit.

NGP candidate

Best evidence so far

Status

Akkermansia muciniphila (pasteurised)

A small 2019 human trial in overweight adults with insulin resistance showed safety and modest metabolic improvements

Approved in the EU as a novel food (a safety approval, not an efficacy one). Larger trials are needed

Clostridium butyricum (for example the MIYAIRI 588 strain)

Decades of use in Japan and parts of Asia, with small clinical trials mainly on antibiotic-associated diarrhoea and some gut conditions

Sold as a probiotic in some countries. Evidence is moderate and trials are small

Faecalibacterium prausnitzii

Strong lab data and observational links to Crohn's disease and colitis

No approved product. Early-phase trials of candidate strains only, as far as I know

Bacteroides species (such as B. thetaiotaomicron and B. fragilis)

Mostly animal and lab studies

Preclinical, with a few early human studies

Eubacterium hallii, Christensenella minuta, Roseburia species

Animal and observational data

Preclinical

The closest thing to proof that the concept works. The FDA has approved microbiome-based treatments for recurrent C. difficile infection, such as Rebyota (2022) and Vowst (2023), as far as I know. These are not single-strain NGPs. They are mixtures of gut bacteria taken from donors. They show that giving back missing gut microbes can work as a treatment, but they don't validate any single NGP.

If you want proven efficacy today, look at classic strains rather than NGPs. Saccharomyces boulardii and Lactobacillus rhamnosus GG have the strongest evidence for preventing antibiotic-associated diarrhoea. They are not next-generation, but their evidence is much stronger.

References

1. Hill C, Guarner F, Reid G, et al. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nature Reviews Gastroenterology & Hepatology. 2014;11(8):506-514.

2. O'Toole PW, Marchesi JR, Hill C. Next-generation probiotics: the spectrum from probiotics to live biotherapeutics. Nature Microbiology. 2017;2:17057.

3. Derrien M, Vaughan EE, Plugge CM, de Vos WM. Akkermansia muciniphila gen. nov., sp. nov., a human intestinal mucin-degrading bacterium. International Journal of Systematic and Evolutionary Microbiology. 2004;54(5):1469-1476.

4. Cani PD, de Vos WM. Next-generation beneficial microbes: the case of Akkermansia muciniphila. Frontiers in Microbiology. 2017;8:1765.

5. Depommier C, Everard A, Druart C, et al. Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study. Nature Medicine. 2019;25(7):1096-1103.

6. Plovier H, Everard A, Druart C, et al. A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice. Nature Medicine. 2017;23(1):107-113.

7. Sokol H, Pigneur B, Watterlot L, et al. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proceedings of the National Academy of Sciences. 2008;105(43):16731-16736.

8. European Commission. Commission Implementing Regulation (EU) 2022/168 of 8 February 2022 authorising the placing on the market of pasteurised Akkermansia muciniphila as a novel food. Official Journal of the European Union.

9. Salminen S, Collado MC, Endo A, et al. The International Scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics. Nature Reviews Gastroenterology & Hepatology. 2021;18(9):649-667.