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Mapping the second brain: The latest science on the effect of your gut bacteria

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Most of us have heard the five-plus-a-day message for fruit and vegetables. But new research into gut health suggests that advice may soon need tweaking.

At Kiwi scientist Rob Knight’s laboratory at the University of California, San Diego, the shit isn’t so much hitting the fan as filling a knowledge vacuum. Poo sample swabs arrive here by post daily from all over the world: 42 countries, 15,000 samples, and 11,000 people so far. The information Knight and his team are gleaning from them is changing the world’s thinking on gut health.

Knight, a professor  of paediatrics and computer science and engineering, is co-founder of the American Gut Project, in which each participant pays US$99 to have their stool sample scrutinised. Launched in 2012, it’s the world’s largest citizen-science project to investigate and map the human microbiome – a system so complex and so important to our health it’s been called our second brain. In its first report last year, Knight’s team revealed one of its most exciting discoveries to date: that the greater the variety of plants in the diet, the greater the diversity of bacteria in the gut.

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“So far, the advice about what you should eat for your microbiome has been very generic,” Knight told the Listener. “It’s been mostly explaining stuff that your grandmother knew already – that you should eat your vegetables, avoid too many potatoes if you don’t want to get fat, that kind of thing. And there’s been some understanding that eating fibre is good because of your microbiome, but it’s stuff that’s been known for generations that people don’t really want to do.”

What is different now, says Knight, is that genetic results are enabling scientists to individualise advice – understanding, for example, that one person should eat tomatoes and another should avoid them, and what foods might help an individual to achieve better blood-sugar control. The differences are not only in our genome and microbiome, but in how each individual metabolises what they eat, and the chemical by-products that result. “You personally might be better off eating the cheapest white bread at the supermarket, or you might need fancy wholegrain bread, but for some people, the fancy wholegrain is bad for them.”

The study found that no matter what diet participants preferred – vegetarian, vegan or omnivore – those who ate more than 30 different types of plants a week (including herbs and spices) had more diverse gut microbiomes than those who ate 10 or fewer types. Numbers in each of those groups were small (about 40), but still statistically significant. There were also differences at less extreme levels, where participants numbered in the thousands.

Scientist Rob Knight. Photo/David Ahntholz/Supplied

Variety is the key

Knight says the information suggests that if you want to positively reshape your gut bacteria, “you shouldn’t just eat a big plate of broccoli, but rather eat a lot of different kinds of plants, including fruits and spices. In terms of what your microbiome looks like overall, you can be a vegan who eats vegetables or a vegan who mostly eats chips and biscuits. That’s going to have a much bigger effect on the microbiome than sometimes eating meat.”

Greater diversity of gut bacteria has been associated with better gut health, although the mechanisms are still not well understood. Less diversity has been linked to conditions including irritable bowel, diabetes and obesity.

For Knight, the biggest question is finding out, at a chemical level, what is in our food. “A chemical analysis of any new food will find thousands of molecules and no one will know what they are, what they do, or what effect they have on our bodies.” The second question is how food interacts with our microbiome, and our genetics, to positively or negatively affect our health – and how we can then predict which diet might work best. It’s unlikely research will discover a single new food “hero”. “If there was a hero that worked for everybody, we would know about it already.”

The project also found that antibiotics fed to animals, such as chickens and cows, could be detected in human stool samples and could potentially alter the gut microbiota.

Knight will discuss the latest findings in a keynote speech at the Foodomics 2019 conference in Auckland, hosted by the High-Value Nutrition National Science Challenge. The challenge is a Government-funded, $83 million, 10-year programme launched in 2014 with the aim of finding food-based solutions to some of our commonest maladies, including obesity and diabetes, gut problems, asthma and infant malnutrition.

The meeting has attracted leading local and international investigators in the field, including Australia’s most-cited researcher, Nicholas Talley, a professor of medicine and of epidemiology, known in scientific circles as the godfather of functional gastrointestinal disorders worldwide. Research both here and abroad into possible dietary causes of – and solutions to – gut ill-health are expected to dominate proceedings, but Talley will focus on the likely precursors: genetic predisposition and the triggering role of infection.

It’s not in the mind

Talley and his team from the University of Newcastle were the first to discover a genetic contribution to some cases of irritable bowel syndrome (IBS) and indigestion, disproving the notion that functional gut problems with no obvious pathology were “all in the mind”. “Even now, there are a lot of gastroenterologists and doctors you will talk to who will say it’s just psychological. It doesn’t help at all, because there is no cure for that and you just suppress symptoms. So, we have gone from that paradigm to knowing there is probably real pathology set off by various processes that are potentially able to be interrupted and are therefore curable. There’s a long way to go to prove it, but it is certainly exciting.”

Talley believes a subtle inflammatory process is at play in people with IBS and other common gut disorders, set off when the gut bacteria break down food to release substances that produce an immune response. It’s a complex process, a combination of what the bacteria produce, how they interact with each other and the immune system, and whether the body is then able to suppress or change the immune reaction. “That ends up driving whether you end up ill when your neighbour eating the same thing is perfectly well.”

One of the obvious dietary candidates is wheat, and the role of proteins including gluten, and various fermentable carbohydrates (Fodmaps). But people must usually have a genetic predisposition for them to be a problem, Talley says. “If you are not set up to have an abnormal immune response to the food antigens, you’ll be fine.”

Researcher Nicholas Talley. Photo/Supplied

Gut problems and bacteria

Talley believes research will lead to the identification of certain gut bacteria that actively cause harm, such as Helicobacter pylori, which is a strong risk factor for stomach cancer, rather than problems being caused by the interaction of multiple bacteria. “Lots of other things change with Helicobacter, but the only thing that matters is Helicobacter. We are coming at it from that angle and it’s a little bit controversial.” Asked if the importance of gut diversity has been overemphasised, Talley says it isn’t clear. “Correlation and association doesn’t mean cause and effect.”

In New Zealand, some of the most detailed research teasing out the links between diet, gut bacteria and gut problems such as IBS is being done in a High-Value Nutrition National Science Challenge collaboration involving AgResearch, the University of Otago, Christchurch, the Riddet Institute, Massey University, the Malaghan Institute, Plant & Food Research and the University of Auckland, led by principal scientist Nicole Roy. Christchurch gastroenterologist Richard Gearry co-ordinates the clinical arm of the research. Says Roy: “People think about their gut as a long tube that food goes through and some nutrients are absorbed, but it’s an incredibly complex system and it is very difficult to define what a healthy gut actually is.” The work aims to identify foods capable of improving gut function, the metabolic pathways that can help scientists understand what is going on, and for biomarkers to be picked up in blood tests to diagnose the conditions. “If we can identify a molecule in their blood, faeces and even breath, we can better understand how the gut is working and which foods might improve their symptoms and quality of life.”

Christchurch gastroenterologist Richard Gearry. Photo/Supplied

Tracking the symptoms

More than 300 Christchurch patients who have had colonoscopies and have IBS or other functional gastrointestinal disorders have kept food and symptom diaries so their experiences can be integrated with analysis of gene testing and metabolomics (the study of metabolites produced during digestion) to understand what the bacteria do to help us digest food and modulate body functions. “You can think of a party where you have a bunch of people there – you know who they are, but you don’t know what they are all doing,” says Roy.

Gearry, a professor of medicine, says researchers have found clear changes in bacterial patterns in people with gut problems and those without. “With the metabolomics data, we have been able to show some quite clear, different metabolic pathways that are triggered in people with IBS compared with people without it. If we know that people who are symptomatic have these pathways upregulated, we can look at foods that work on the pathways, and alter the microbiome to change how that works.”

Individuals with different combinations of gut bacteria are likely to produce different by-products when digesting the same food. “What it is allowing us to do is say, ‘Gosh, most of these people with diarrhoea-predominant IBS have specific metabolites that we don’t see as much in others. Is the pathway that leads to that metabolite important?’ It helps us understand what the mechanism is.”

The data has also shown a strong association between poor gut function and symptoms of anxiety and depression. “The psychological outcomes of people with IBS are out of proportion compared with other health disorders that you might expect to have similar psychological reactions.”

Gearry says there are many other reasons to suspect the gut may have a role in mental illness, including the fact that 90% of the body’s serotonin – a neurotransmitter that is a major target of antidepressant drug treatment – is in the gut. “The nervous system in the gut is probably as big as the nervous system in the brain.”

AgResearch scientist Nicole Roy. Photo/Supplied

The science behind diet

One of the most important takeouts from the research, he says, is that “science and medicine are now listening to patients. We have accepted for a while that diet plays a major role, but we are starting to understand the science that underlies that. My hope is that as we understand the science, we can give much better patient-specific information and education about diet.”

For example, the research is giving scientific support to the Fodmap diet embraced by many people with irritable bowel symptoms. AgResearch microbiologist Wayne Young, who’s involved in sequencing the DNA of the gut bacteria in the Christchurch patients, says when IBS patients are examined, the bacteria involved in the fermentation of carbohydrates seem to be working faster than they should. In patients who don’t have IBS, those same types of gut bacteria are depleted. Other bacteria that are “enriched” in people with IBS are primarily involved in metabolising sulphur – another important lead that the researchers will be following up this year. The metabolism of sulphur produces hydrogen sulphide, an irritant to the gut lining that may also cause other gut symptoms.

In January, a study published by University of Otago scientist Tim Kortlever, in association with colleagues in Australia and the Netherlands, which followed 50 IBS patients on a low-Fodmap diet for six months, reported significant improvements in their gut symptoms, anxiety, depression and fatigue.

Researchers say it’s too soon to recommend genetic testing for gut disorders, or to suggest we start downing anti-inflammatories for indigestion. But it’s relatively easy to add more variety to the fruit and vegetables we eat. Five-plus a day is still sound advice, but it might help to try a different five each time.

Changing your microbiome takes time, Rob Knight says. “Basically, nothing you can do in a week – even starving yourself for three days – will make your microbiome look like someone else’s. But if you pick a radically different diet and stick with it for a year, the transformation can be profound.”

Researcher Peng Du prepares an electrode array that will be used to record electrical activity in the gut. Photo/Supplied

In rhythm with the body

An award-winning new device detects differences in electrical activity in healthy and abnormally functioning guts.

We’ve all heard of electrocardiograms to check electrical activity in the heart, but now New Zealand scientists are developing a similar device to diagnose problems in the gut.

Researcher Peng Du, a senior research fellow at the Auckland Bioengineering Institute at the University of Auckland, was in March awarded the $200,000 Prime Minister’s MacDiarmid Emerging Scientist Prize for his work on the device, which can detect differences in electrical activity in healthy and abnormally functioning guts. The muscular contractions, which move food through the gut, are triggered by waves of electrical activity, although the signals are much more subtle and difficult to measure than those in the heart.

He says three types of gut disease are definitely associated with electrical abnormalities: stomach paralysis (which can be the end stage of very severe indigestion), chronic nausea and vomiting, and in certain cases, gastric cancer. “Indigestion, nausea and vomiting are symptoms, but they don’t tell us what is causing the disease. Understanding the electrical rhythm and relating it to the disease help the clinician with the mechanism for why it is happening.” In the US, the Auckland device was used in studies on patients who were having an implanted gastric pacemaker to normalise the electrical activity in their gut.

Because irritable bowel syndrome is a catch-all descriptor of a number of gut conditions, Peng says it’s possible a subgroup of people with the condition could also have electrical dysrhythmias in their small intestine.

The first device was tested in people having gut surgery at Auckland City Hospital, and Auckland will now lead international multi-centre trials, expected to begin this year, to validate results from the device.

New Nutrition Business’ Julian Mellentin. Photo/Supplied

Science playing catch-up

Consumers have long understood the need to experiment to find foods that suit them. Now science is reducing the guesswork.

“Digestive wellness” tops the 10 main nutrition and health trends for 2019, says Julian Mellentin, founder of international food trend-watching consultancy New Nutrition Business. It’s a position gut health has held for about three decades.

Mellentin, a keynote speaker at April’s Foodomics conference in Auckland, says it’s long been the biggest driver of growth in food and drink. “The World Health Organisation says about a third of us have a digestive disorder at any one time, and the biggest, most successful and well-established products in the business of food and health all tackle digestive wellness.” Examples include the probiotic Yakult, launched in Japan in 1955 and internationally in 1964, which now has global sales of US$5.5 billion.

“In digestive wellness, wacky works,” he says. “Today, people are more willing to try new products to support digestive wellness than they’ve ever been before.” Kombucha, the Asian fermented tea, has been the breakout product of recent years, reinvented for the Western market, with a better look and taste. “It no longer has a pad of bacteria floating on it, for example.” The US market grew 30% last year and is now worth US$1 billion and rising.

Consumers’ access to information via mobile phones is driving buying decisions, and it often doesn’t matter if what they read is unreliable. “Who’s decided it’s reliable? This is a tricky question. If you were around in the 1990s, people with heart disease were being told not to eat eggs because they contained cholesterol and it was meant to be bad for you, but now that advice has changed. People now have access to more information on their phones than humans have ever had and do their own searching online, arrive at their own decisions, and experiment with their own foods to find what works for them. The role of the expert is kind of limited.”

But scientists such as those taking part in New Zealand’s High-Value Nutrition National Science Challenge – aimed at producing reliable evidence to support nutritional claims and therefore added value around food products – aren’t wasting their time, says Mellentin. “It’s the right thing to do, because it enables you to communicate the benefits of the product within the context of the regulations and to understand how things really work. But, what’s also true is that you have to win consumer confidence. The science by itself is not enough; you have to understand how the consumer thinks, what motivates them and where they get their information from and make sure you are getting your message to them.” Social-media influence can and often does trump the science.

Fermented black tea. Photo/Getty Images

A recent survey by New Nutrition Business, of 3000 people in the UK, Australia, Spain, Brazil and the US, found widespread confusion about which foods are good or bad for gut health. Nearly 40% singled out bread as a key culprit, but 24% said it was good for digestion. Likewise, nearly half of those surveyed thought dairy milk was good, while nearly a third thought it was bad. Of course, both takes could be correct – for them. “People have more and more fragmented views about what constitutes healthy for them, so health is becoming very personalised,” says Mellentin. “They try different foods and see what makes them feel better.”

Recent advances in understanding DNA and variations in the microbiome came long after consumers had recognised the differences and tried to adapt their diets. “The consumer has been running ahead of science, and now science is running to catch up.”

The international focus on microbiome research looks set to keep gut health at the top of the trend list for years to come. “We’re on day one of a many-year improvement in our understanding of how it works – not just how it makes you feel, but how it affects many other things, including weight control, mood, cognition and inflammation.”

The key food trends for the year, as identified by Mellentin, are:

  • Digestive wellness: the importance of the microbiome and its effect on overall health and well-being.
  • Plant based: people want to eat more plants, and are looking for novel ingredients and tastes, with 20% of consumers saying they are trying to reduce meat intake.
  • Protein: the connection with weight management and sports performance. Not everyone knows why or how protein is good for them, but they’re aware of its importance.
  • Sugar: the move to consuming less sugar and more protein. But trends are complex – in the UK, yogurt sales are down 10% because of concerns about sugar, but luxury ice cream sales are up 10%.
  • Good carbs, bad carbs: people are experimenting with grains that are new, interesting and different from traditional wheat.
  • Fragmentation and personalisation: for most people, the key motivation in regard to diet is weight management and looking good, rather than treating disease and maintaining health. Diet personalisation will likely involve niches such as weight management and sports performance.
  • Snackification: the power of convenience. Giving people permission to enjoy an “indulgent snack” is one of the most effective strategies marketers use.
  • Redefining beverages: fears about sugar are driving innovation and forcing producers to become more creative in how they make drinks.
  • Fat reborn: some people will continue to avoid fat, while others will pick and choose according to their personal definition of “good fats”.
  • Authenticity and provenance: artisan products are moving from lifestyle into mainstream.

This article was first published in the March 30, 2019 issue of the New Zealand Listener.