Hyping the microbiome may have unpleasant side effects

Microbiome is one of relatively few technical/scientific terms to have entered public consciousness. It refers to the genes of the microorganisms, including bacteria, viruses, fungi and protozoa (the microbiota) that live on and inside the human body (on skin, inside the intestinal tract etc).

Science affirms the importance of the microbiome for human health, but the scale of this importance remains unclear. However, if one assessed the microbiome’s importance by the hype now pervading science journalism and public advertisements for probiotics, one might well conclude that there are few health problems that cannot be treated, or will not soon be treatable, by manipulating the microbiome.

A number of scientific papers recently warned against hyping the microbiome, including William Hanage in Nature (Volume 512, August 21st 2014) and Youghui Ma and others in Protein and Cell (Volume 9, Issue 5, 2018).

Invaders of the gut

The adult intestine hosts about 1.2kg of bacteria – about 39 trillion bacterial cells, outnumbering human body cells by a factor of up to 10 times – and many of these microbes are essential for good health. Collectively they crowd out harmful bacterial invaders of the gut. They also aid digestion by breaking down complex plant carbohydrates, allowing humans to extract nutrients from foods such as potatoes and oats. The microbes synthesise vitamins such as K and B12 for the human host and also help to train the immune system.

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We know the microbiome is important but we know little detail about how it works. Every person’s microbiome contains up to 1,000 species that interact with each other in unknown ways. Data on the microbiome is piling up but a theory with which to interpret it remains to be developed.

Much microbiome research correlates populations of gut bacteria with ill-health conditions and studies have linked microbial species to conditions as diverse as autism, depression, diabetes and cancer. But correlation does not entail causation. A microbe associated with a particular disease may just be an innocent bystander. Only time will tell how many useful medical treatments will flow from correlations discovered to date.

Probiotics

Nowadays many people regularly take probiotics – live microorganisms ingested with the intention of restoring or improving the microbiome. Fermented dairy products such as yoghurt are familiar examples and are intensively advertised as enhancers of gut health. But, Ferris Jabr points out in a review (“Probiotics are no panacea”) of probiotics in Scientific American, July 2017, “the majority of studies to date have failed to reveal any benefits of probiotics in individuals who are already healthy. The bacteria seem to help only those people suffering from a few specific intestinal disorders”, and “most of the health claims for probiotics are pure hype”.

A typical serving of yoghurt contains far too few to significantly alter the overall microbial composition of a healthy gut

Jabr explains why probiotics probably have little influence on a healthy gastrointestinal tract. A typical serving of yoghurt, for example, contains 100 million to 100 billion probiotic bacteria, far too few to significantly alter the overall microbial composition of a healthy gut containing 39 trillion bacteria.

‘Good’ bacteria

However, probiotics, properly prescribed, can help people with certain conditions; for example, by preventing side effects of antibiotic treatments to eliminate problem-causing microbes. Such treatments also kill “good” intestinal bacteria who may then be replaced by harmful bacteria that inflame the gut.

Probiotics, in conjunction with a course of antibiotics, decrease the chances of developing these complications. Probiotics can also ameliorate irritable bowel syndrome, possibly by impeding the growth of harmful microbes.

Faecal microbiota transplantation (FMT), the delivery of a healthy donor’s faeces containing large amounts of intestinal microbes into the intestinal tract of a patient, is now the most effective therapy for recurrent diarrhoea-causing Chlostridium dificile infections that can occur in patients recently treated with antibiotics. Such transplantations should only be done under expert medical supervision.

Overoptimistic expectation

Since 2000 science has awakened sharply to the fundamental importance of the microbiome. However, significant biological discoveries are usually accompanied by overoptimistic expectations about the practical applications that will flow from these discoveries.

There is good reason to hope that microbiome studies will, in time, pay significant human health dividends but we should not count these dividends in advance. Hyping the microbiome in the meantime distorts research funding priorities, encourages people to waste money on ineffective probiotics or, worse, to undertake risky microbiota transplantation procedures.

William Reville is an emeritus professor of biochemistry at UCC