No evidence probiotics promote 'gut diversity' in he...

"Probiotic goods a 'waste of money' for healthy adults, research suggests," The Guardian reports. A new review of previously gathered data found no evidence that probiotics improved the balance of gut bacteria in healthy adults.

Probiotics are live bacteria and yeasts, often added to yoghurt or taken as a supplement, that are promoted as helping stimulate the growth of "friendly bacteria" in the gut.

Supporters claim they can help treat a wide range of conditions, from eczema to irritable bowel syndrome (IBS), but there's little evidence to support many of these claims.

It has also been claimed that healthy people should take probiotics to improve their digestive health, a claim assessed in this latest review.

The review found seven trials, all with vastly different designs, methods and assessment of outcomes. As such, trial results could not be pooled in any meaningful statistical way.

Four of the trials found the probiotic had no different effect on gut bacteria from inactive placebo. Three of the trials reported some effect, but the overall quality of reporting for all trials was poor.

Given the limitations of the studies – including the variety of probiotics examined – it is not possible to conclude with certainty that all probiotics are ineffective.

Absence of good-quality evidence is not evidence of there being no effect. Better-designed studies may yet find some benefit from taking probiotics.

Where did the story come from?

The study was carried out by researchers from the University of Copenhagen and was funded by the Novo Nordisk Foundation.

It was published in the peer-reviewed journal, Genome Medicine.

The UK media's reporting takes a very black and white attitude towards the review, concluding that probiotics "don't work" and are "a waste of time".

But they would benefit from considering the limitations of the small number of diverse trials included in this study. It would have been more accurate to say that based on the current evidence, we don't know whether they work or not.

It should also be noted that photos of yoghurt drinks – including Tesco own-brand – are misleading. Only one of the seven trials assessed a milk-based drink and we don't know what brand it was. Considering these were all non-UK studies, though, it is very unlikely to have been a UK supermarket brand.

What kind of research was this?

This systematic review aimed to gather the evidence from randomised controlled trials (RCTs) that have looked at the effect of probiotic supplements on gut bacteria.

As the researchers say, in recent years the composition of bacteria in the human gut has received considerable attention as a possible modifiable risk factor for various digestive and metabolic diseases.

This has led to a surge in the use of probiotic supplements to try to boost the health of the gut, through ways such as improving the intestinal lining and introducing more "friendly" bacteria to compete against the "bad" bacteria.

However, the effect of probiotic supplements – particularly in healthy individuals – is poorly understood.

This review therefore aimed to compile the evidence, looking at RCTs that have compared supplements with inactive placebo and used molecular approaches to measure gut bacteria.

A systematic review is the best way of seeing if the evidence to date shows whether they are effective. But reviews are only as good as the studies they include.

Because of the vastly different designs of the various studies, the researchers were unable to perform a meta-analysis of the results.

What did the research involve?

The researchers searched three literature databases up to August 2015 to identify RCTs of any duration that:

included healthy adults only
compared probiotics with placebo
assessed gut bacteria composition using specific molecular techniques and reported this as the main outcome

They excluded studies where other interventions were combined with supplement use, such as antibiotics or other medications.

Two reviewers separately assessed trials for eligibility, and carried out quality assessment and data extraction from the trials included.

Seven trials met eligibility criteria: two from Italy, two from Denmark, and one trial each from the US, Germany and Finland.

All were conducted in healthy adults aged 19 to 88 years, and the sample size of the individual studies ranged from 21 to 81.

Most supplements included Lactobacillus, in one trial combined with Bifidobacterium, and one trial used Bacillus. These were provided as capsules in four trials or in biscuits, drinks or sachets in one trial each. The length of the trials was typically one to two months.

The main source of potential bias in the studies was the lack of blinding of researchers assessing outcomes.

What were the basic results?

The results of the seven studies are not pooled and are only reported study by study.

Essentially, none of the studies provided evidence that probiotics had a beneficial effect on gut bacteria.

The results were as follows:

Four studies reported no difference in the diversity of, composition of, or stability of bacteria between probiotic and placebo groups.
One study reported that the probiotic reversed the age-related increase in certain disease-causing bacteria (such as C. difficile and Campylobacter), but did not compare between groups.
One study reported some difference in the diversity of bacteria, with increased abundance of certain bacteria (such as Proteobacteria) in the probiotic group.
One study also reported some differences in the abundance of certain bacteria, but did not directly compare between groups.

How did the researchers interpret the results?

The researchers concluded that, "Overall, this systematic review demonstrates that there is no convincing evidence for consistent effects of probiotics on faecal microbiota composition in healthy adults."

Conclusion

This review finds no evidence that probiotic supplements have beneficial effects on the composition of gut bacteria in healthy adults.

The review has strengths in that it pre-specified exactly which trials would be eligible – that is, only RCTs in healthy adults, comparing probiotics with placebo, that assessed changes in gut bacteria levels as the main outcome.

This should aim to reduce diversity between the trials and try to find a definitive answer on the effect in a specific population.

However, despite this, the seven trials were still highly variable in their methods and design, such as the type of probiotic given and how gut bacteria were assessed.

This variability is demonstrated by the fact they are only reported narratively and the results could not be pooled to give an overall quantitative effect, as would be the case in a meta-analysis.

The trials also contained several quality limitations. In most, the researchers were not blinded to the assigned group, which may have biased their assessment of outcomes.

Only one of the seven trials had calculated beforehand how many participants they would need to recruit to detect whether the treatment had a significant effect. This is a notable limitation, given that all had sample sizes of less than 100.

Also, several of the trials had not statistically assessed, or not clearly reported, whether there was a difference between the probiotic and placebo groups.

As the researchers say, future studies would benefit from clearly specifying the main outcome they're looking at, giving transparent results with statistical analyses, and clearly distinguishing within-group treatment effects – such as changes from study start to end – and between-group effects.

Further points to bear in mind:

These trials only included healthy adults with no known diagnoses or conditions. This means the study can't tell us whether probiotics are effective in IBS or for "rebuilding" the gut bacteria in people who have had an illness. However, even though they were healthy adults, the trials included quite variable populations – for example, one was in elderly people, another specifically in postmenopausal women. We also do not know the effectiveness in children.
There were only seven trials, and these used different probiotics containing different "friendly" bacteria, in different forms, from capsules to yoghurt drinks and biscuits. As such, there is not enough evidence to definitely conclude that all probiotics are ineffective, particularly given the limitations of the trials. It could be that certain bacteria in particular formulations could have different effects.
None of the trials were from the UK, so the formulations used may differ from those on the UK market.
The trials were only of a couple of months' duration, so we don't know what longer-term use might have.
The trials only looked at direct effects on gut bacteria level. We don't know whether taking the probiotic increased the person's sense of health and wellbeing, for example. If probiotics help some people in this way, that can only be a good thing – even if it is just a placebo effect.

Overall, the current state of the evidence does not demonstrate that probiotics have any effect on gut bacteria in healthy people.

Given the limitations of these studies, that is not to say that all probiotics definitely have no effect. Further high-quality research in their use is needed.