The Best Australian Science Writing 2013 (32 page)

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What are these neurotransmitters doing in the gut? In the brain, dopamine is a signalling molecule associated with pleasure and the reward system. It acts as a signalling molecule in the gut too, transmitting messages between neurons that coordinate the contraction of muscles in the colon, for example. Also transmitting signals in the ENS is serotonin – best known as the ‘feel-good' molecule involved in preventing depression and
regulating sleep, appetite and body temperature. But its influence stretches far beyond that. Serotonin produced in the gut gets into the blood, where it is involved in repairing damaged cells in the liver and lungs. It is also important for normal development of the heart, as well as regulating bone density by inhibiting bone formation.

But what about mood? Obviously the gut brain doesn't have emotions, but can it influence those that arise in your head? The general consensus is that neurotransmitters produced in the gut cannot get into the brain – although, theoretically, they could enter small regions that lack a blood–brain barrier, including the hypothalamus. Nevertheless, nerve signals sent from the gut to the brain do appear to affect mood. Indeed, research published in 2006 indicates that stimulation of the vagus nerve can be an effective treatment for chronic depression that has failed to respond to other treatments.

Such gut-to-brain signals may also explain why fatty foods make us feel good. When ingested, fatty acids are detected by cell receptors in the lining of the gut, which send nerve signals to the brain. This may not be simply to keep it informed of what you have eaten. Brain scans of volunteers given a dose of fatty acids directly into the gut show they had a lower response to pictures and music designed to make them feel sad than those given saline. They also reported feeling only about half as sad as the other group.

There is further evidence of links between the two brains in our response to stress. The feeling of ‘butterflies' in your stomach is the result of blood being diverted away from it to your muscles as part of the fight-or-flight response instigated by the brain. However, stress also leads the gut to increase its production of ghrelin, a hormone that, as well as making you feel hungry, reduces anxiety and depression. Ghrelin stimulates the release of dopamine in the brain both directly, by triggering
neurons involved in pleasure and reward pathways, and indirectly, by signals transmitted via the vagus nerve.

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In our evolutionary past, the stress-busting effect of ghrelin may have been useful, as we would have needed to be calm when we ventured out in search of food, says Jeffrey Zigman at UT Southwestern Medical Center in Dallas, Texas. In 2011, his team reported that mice exposed to chronic stress sought out fatty food, but those that were genetically engineered to be unable to respond to ghrelin did not. Zigman notes that in our modern world, with freely available high-fat food, the result of chronic stress or depression can be chronically elevated ghrelin – and obesity.

Gershon suggests that strong links between our gut and our mental state evolved because a lot of information about our environment comes from our gut. ‘Remember the inside of your gut is really the outside of your body,' he says. So we can see danger with our eyes, hear it with our ears and detect it in our gut. Pankaj Pasricha, director of the Johns Hopkins Center for Neurogastroenterology in Baltimore, Maryland, points out that without the gut there would be no energy to sustain life. ‘Its vitality and healthy functioning is so critical that the brain needs to have a direct and intimate connection with the gut,' he says.

But how far can comparisons between the two brains be taken? Most researchers draw the line at memory – Gershon is not one of them. He tells the story of a US army hospital nurse who administered enemas to the paraplegic patients on his ward at 10 o'clock every morning. When he left, his replacement dropped the practice. Nevertheless, at ten the next morning, everyone on the ward had a bowel movement. This anecdote dates from the 1960s and while Gershon admits that there have been
no other reports of gut memory since, he says he remains open to the idea.

Then there's decision-making. The concept of a ‘gut instinct' or ‘gut reaction' is well established, but in fact those fluttery sensations start with signals coming from the brain – the fight-or-flight response again. The resulting feeling of anxiety or excitement may affect your decision about whether to do that bungee jump or arrange a second date, but the idea that your second brain has directed the choice is not warranted. The subconscious ‘gut instinct' does involve the ENS, but it is the brain in your head that actually perceives the threat. And as for conscious, logical reasoning, even Gershon accepts that the second brain doesn't do that. ‘Religion, poetry, philosophy, politics – that's all the business of the brain in the head,' he says.

Still, it is becoming apparent that without a healthy, well-developed ENS we face problems far wider than mere indigestion. Pasricha has found that newborn rats whose stomachs are exposed to a mild chemical irritant are more depressed and anxious than other rats, with the symptoms continuing long after the physical damage has healed. This doesn't happen after other sorts of damage, like skin irritation, he says.

It has also emerged that various constituents of breast milk, including oxytocin, support the development of neurons in the gut. This might explain why premature babies who are not breastfed are at higher risk of developing diarrhoea and necrotising enterocolitis, in which portions of the bowel become inflamed and die.

Serotonin is also crucial for the proper development of the ENS where, among its many roles, it acts as a growth factor. Serotonin-producing cells develop early on in the ENS, and if this development is affected, the second brain cannot form properly, as Gershon has shown in mutated mice. He believes that a gut infection or extreme stress in a child's earliest years may have
the same effect, and that later in life this could lead to irritable bowel syndrome, a condition characterised by chronic abdominal pain with frequent diarrhoea or constipation that is often accompanied by depression. The idea that irritable bowel syndrome can be caused by the degeneration of neurons in the ENS is lent weight by recent research revealing that 87 out of 100 people with the condition had antibodies in their circulation that were attacking and killing neurons in the gut.

A growing realisation that the nervous system in our gut is not just responsible for digestion is partly fuelled by discoveries that this ‘second brain' is implicated in a wide variety of brain disorders.

In Parkinson's disease, for example, the problems with movement and muscle control are caused by a loss of dopamine-producing cells in the brain. However, Heiko Braak at the University of Frankfurt, Germany, has found that the protein clumps that do the damage, called Lewy bodies, also show up in dopamine-producing neurons in the gut. In fact, judging by the distribution of Lewy bodies in people who died of Parkinson's, Braak thinks it actually starts in the gut, as the result of an environmental trigger such as a virus, and then spreads to the brain via the vagus nerve.

Likewise, the characteristic plaques or tangles found in the brains of people with Alzheimer's are present in neurons in their guts too. And people with autism are prone to gastrointestinal problems, which are thought to be caused by the same genetic mutation that affects neurons in the brain.

Although we are only just beginning to understand the interactions between the two brains, already the gut offers a window into the pathology of the brain, says Pankaj Pasricha at Johns Hopkins University in Baltimore, Maryland. ‘We can theoretically use gut biopsies to make early diagnoses, as well as to monitor response to treatments.'

Cells in the second brain could even be used as a treatment
themselves. One experimental intervention for neurodegenerative diseases involves transplanting neural stem cells into the brain to replenish lost neurons. Harvesting these cells from the brain or spinal cord is not easy, but now neural stem cells have been found in the gut of human adults. These could, in theory, be harvested using a simple endoscopic gut biopsy, providing a ready source of neural stem cells. Indeed, Pasricha's team is now planning to use them to treat diseases including Parkinson's.

If nothing else, the discovery that problems with the ENS are implicated in all sorts of conditions means the second brain deserves a lot more recognition than it has had in the past. ‘Its aberrations are responsible for a lot of suffering,' says Pasricha. He believes that a better understanding of the second brain could pay huge dividends in our efforts to control all sorts of conditions, from obesity and diabetes to problems normally associated with the brain such as Alzheimer's and Parkinson's. Yet the number of researchers investigating the second brain remains small. ‘Given its potential, it's astonishing how little attention has been paid to it,' says Pasricha.

Brain power

Organs

The carnivore's (ongoing) dilemma

Åsa Wahlquist

When News Limited began its 1 Degree program, which aimed to make the company carbon neutral, it invited employees to submit the steps they would take to reduce their own personal greenhouse gas emissions. In response, a number of News employees offered to reduce the amount of red meat in their diets, or even cut out eating meat altogether.

In that choice, they joined such eminences as Britain's Lord Stern, the Nobel-winning Rajendra Pachauri of the Intergovernmental Panel on Climate Change, and the vegetarian Sir Paul McCartney who popularised the phrase: less meat = less heat.

Popular wisdom has it that industrial livestock production is killing the environment. But while there are some sound reasons to eat less meat or even become a vegetarian, doing it to save the planet is not necessarily one of them.

We can look at it this way: red meat comes from cattle and sheep, which play a vital role in utilising grasslands, the 60 per cent of the world's farmland unfit for any other agriculture. When the world's population of hungry people is rapidly growing, you have to ask whether we can ethically refuse to produce food from so much land.

We could also consider the fact that, on mixed farms – those
that run livestock and grow crops – the animals play a critical role in eating farm waste and providing natural fertiliser. If human diets shift towards more legumes, such as soybeans, that will mean more cropping and the accompanying need for more irrigation and higher inputs of nitrogenous fertilisers, which pose their own serious greenhouse gas emission problem (more on this later).

As the implications of people swapping meat for vegetables are totted up, there are signs that the greenhouse gas debate is changing.

In his book,
Meat: A benign extravagance
, Simon Fairlie, a British journalist and farmer, makes a strong case for sustainable, small-scale farming that incorporates livestock. So persuasive is his argument that Fairlie's book famously convinced well-known environment writer George Monbiot that his pro-vegan stance was wrong.

The case for meat is not helped by the fact that two of the earliest, most influential and most frequently quoted contributions to the debate are wrong. First was the Food and Agriculture Organisation's report
Livestock's Long Shadow
, which claimed 18 per cent of global greenhouse gas emissions come from livestock. More recently, the International Panel for Climate Change put livestock greenhouse gas emissions at 5.4 per cent of global emissions.

The other highly quotable early entrant was US researcher David Pimentel's claim that it takes 100 000 litres of water to produce 1 kilogram of beef.

However the Water Footprint Network estimates a global average water footprint of 15 400 litres of water per kilogram of beef. Beef grown on Australian farms seems to require less again, with research by a team including Brad Ridoutt from the CSIRO estimating water use at 6.6 to 440 litres per kilogram.

Ridoutt explains: ‘When people use these figures of 100 000
or even 15 000 [litres of water] these numbers go out into the public domain. The information is not given about what these numbers mean. It just becomes a source of misinformation that can be used in quite a scandalous way'.

Ridoutt is working with the International Organisation for Standardisation to set up a rigorous system, similar to carbon footprinting, that would give comparable figures for water usage by all kinds of agriculture and other human pursuits. ‘The underlying question is to what extent is producing this product contributing to a reduction in fresh water that is available for the environment or for others to use.'

Fairlie ridiculed Pimentel's figure, citing the case of Bramley, an Angus/Jersey-cross steer he raised. He estimated that if the figure of 100 000 litres per kilogram was correct, young Bramley would have had to consume about 25 000 litres of water a day.

What makes all this so difficult to precisely calculate is that we're talking about animals, not machines. Farmed animals are biological individuals with different constitutions and diets, living in different geographies, bred and used for different purposes, playing different roles in different farm systems. The result is huge variability in the productivity and resource consumption of livestock around the world: for example, beef produced in Africa in a Sahelian pastoral system – where cattle are used for transport, and ownership is an indicator of wealth – has the lowest carbon footprint at 8.4 kilos of greenhouse gases per kilogram of meat; whereas beef produced in Japan, from the world's most pampered cattle, has the highest value at 26 kilos of greenhouse gases per kilogram of meat.