Probably the most dangerous kind of food is one that is hidden, that doesn’t appear on a label. Currently my favourite is Chinese Gutter Oil. This is the polar opposite of extra virgin olive oil. It was investigative journalists who uncovered the sordid practice by which recycled oil is resold for cooking. It is consumed by as many as 10 per cent of the Chinese (generally the poorest families and in street cafés). And it’s produced by boiling and cleaned up by the addition of industrial chemicals.
It gets its name from being literally sucked out of drains and sewers, sieved to remove unpleasant solid sewer contents, then processed in home-made labs.1 It is a lucrative and still thriving business, even though as well as containing known carcinogenic chemicals the oil is likely to increase the risk of heart disease and other illnesses. Last year a gang was arrested for supplying over three million litres of it to a hundred cities. They had achieved its extra flavour by adding fat from decaying animal carcasses. This toxic substance is giving modern Chinese cuisine a bad image and can’t be good for the nation’s poor gut microbes either.
A law making this business illegal was introduced in 2009, after the US complained that imported Chinese milk tasted odd. It contained melamine (a furniture resin). Other recent Chinese food incidents include chemically produced fake eggs with wax shells, walnuts shells hollowed out and their contents replaced with concrete ‘nuts’, steamed dumplings containing cardboard instead of meat, and chemically treated rat and fox meat passed off as beef.2 McDonald’s was one of many corporations involved in yet another major Chinese food scandal in 2014: their main supplier had recycled and reprocessed condemned pork, chicken and beef, some of which was over a year past the expiry date.
Of course, the Chinese didn’t invent unhealthy chemical foods. Food industrialisation started on a large scale in the ever-innovative US after the Second World War. The cross-country transportation of natural butter and lard for cooking was becoming expensive and wasteful because the products went off after a few days. This led to a drive to replace them with chemically manufactured vegetable substitutes that would improve the structural qualities of the products, increase their shelf life, and increase profits. When they first emerged they were seen as miracles of US ingenuity, but the first margarines were originally banned from having yellow dyes to warn consumers.
The dye became legal and a ‘healthy’-looking cooking oil that was not only easily packaged and kept for months, but was also cheap, had to be good. Products like Crisco in the 1950s and 60s, made originally from leftover cotton-seed oil, were marketed heavily by Procter & Gamble. They had huge success, with recipe books and TV personalities encouraging housewives to use them for every meal.
The equivalent bestselling cooking oil in the UK, made by Unilever, was euphemistically called ‘vegetable shortening’ (Spry, Crisp ’n Dry) and promoted as a light and much healthier alternative to butter and lard. Unknown to the trusting public was the fact that to get these vegetable fat molecules to stick together required clever but drastic chemistry called hydrogenation, so as to artificially create new tough chemical bonds that were very hard for heat (or the enzymes of the body and its microbes) to break down.3 The industry loved these versatile chemicals, which were used in a huge variety of processed foods and dairy substitutes.
Helped by the US-led obsession to cut down on natural fats, the hydrogenated-fat market boomed in the 1970s and 80s and its products were seen as the ‘healthy’ alternative to dairy. By the early 1990s, the FDA estimated that 95 per cent of all biscuits and 100 per cent of all crackers and most other snacks contained these trans fats, as they came to be known. Many Americans were consuming 10 per cent of their calorie intakes as trans fats from cakes, biscuits, pastries, burgers, ice-cream, chips and other fried foods.4 A whole generation was brought up on the wonders of ‘healthy’ margarine and cooking oil. The first reports, in the 1980s, of adverse health effects of this chemical fiddling were largely ignored.5
It turned out that even small amounts – 1 to 2 per cent – of daily trans-fat intake were shown to massively increase lipid levels, and risk of heart disease and sudden death rose threefold, not counting the extra cancers. An estimated extra 250,000 Americans died each year just because they had consumed trans fats. But, hampered by the food lobby, no real action was taken for many more years.
In 2004 major global brands of snacks like Doritos and Cheetos still had considerable amounts of trans fats in them. In the US in 2003 a man in California successfully won a lawsuit against Nabisco, the biscuit company making Oreos, who subsequently withdrew trans fats. Only in 2010 did class actions start against Smucker Co., who promoted Crisco oil as healthy. The delays may have been coincidental, but for about fifteen years the world’s largest food company, General Foods, was owned by the world’s biggest tobacco company, R.J. Reynolds, who had considerable experience of dealing with health concerns and litigation.
Now, most Western countries have reduced or banned trans fats completely. While the US in 2015 only restricts trans fats to 4 per cent of fat intake (equivalent to around 1.5 per cent of total intake), by 2003 Denmark had already enforced a complete ban. For several years Scandinavian franchises of McDonald’s and KFC had stopped using trans fats in vegetable oils for cooking chicken nuggets and French fries, while the US was prevaricating and protecting its food industry from any sudden change.
The UK introduced a voluntary limit and better labelling only after action from pressure groups in 2005, but still resists an outright ban, despite experts agreeing there is no known safe minimum amount. The medical community and the National Institute for Clinical Excellence (NICE) unsuccessfully called for a trans-fat ban and for the legal reduction of salt and saturated fats in processed foods, which would prevent 40,000 deaths a year. The situation has improved slowly. In 2010 the UK population was estimated to take in on average less than 1 per cent of energy from trans fats, and in the US it is still around 2 per cent. However, there remain big social and regional differences, so that some people eating cheap fried and processed foods are still taking in three times these dangerous amounts. Unfortunately and perhaps inevitably, the problem has been exported around the world.
In many developing countries, such as Pakistan, trans fats are still sold as cheap cooking oil (mainly fake traditional ghee), and its use accounts for 7 per cent of calorie intake and is a major contributor to the country’s increasing rates of heart disease.6 Trans fats can also be produced outside the factory, just by frying food in very hot fat; and, oddly, in cows’ stomachs as part of the natural work of microbes. The small amounts of this otherwise toxic fat in cow’s milk don’t seem to be a major problem for us, though.
Different lactobacillus species, surprisingly, can produce tiny amounts of trans fats in our own intestines as well as potentially deal with tiny (but no larger) amounts of excess trans fats in our diet.7 So if you can’t resist the urge for an occasional blow-out on junk food potentially full of trans fats, choosing real cheese, yoghurt or probiotics for your dessert could possibly protect you.
One reason we think trans fats are so harmful is because of their effect on the small fatty acids produced from natural and artificial fats as signals for the healthy body. The fatty acids are key for effective communication between the immune system, the microbes and the metabolism of fat. The disruption caused by creating these artificial compounds leads to a major upheaval of our fatty acid signals and messes with our metabolism.
A bit off-colour
Jason, ten years old, enjoyed his crisps, so it was a little strange when one day at school during break he felt he didn’t want to eat the large bag he always brought with him. He felt particularly tired and lethargic, had a throbbing headache and was nauseous and sweaty. He had found it hard to concentrate on his maths lesson, though that wasn’t unusual recently. His teacher sent him to the school nurse who saw immediately that his legs had swollen to what seemed twice their normal size and his skin was a funny grey-yellow colour. He had never been slim, but his belly was protruding more than usual.
The nurse’s anxiety increased when she found his blood pressure was raised. She phoned his parents but couldn’t get hold of them, so took him straight away to the nearest big hospital: King’s College Hospital in south London. Luckily, he was seen quickly in the specialist centre and the alert doctors recognised the signs of liver disease. His blood tests were frightening: his cholesterol and triglycerides were high and the liver-function tests were off the scale. He had fluid in his belly and legs from a combination of the liver failure and the pressure this put on his heart. His blood showed he also had Type 2 diabetes, which used to be called ‘adult-onset’ diabetes before it became common in children too.
Eventually his mum was traced and arrived at the hospital, where the doctors quizzed her. ‘He has always been a bit overweight like me and has always been a good eater, though I’ve never managed to get him to eat much greens or vegetables – except chips. But I don’t suppose they count. I guess his weight has probably increased quite a lot recently and he don’t like playing football any more. He will get better won’t he?’
Jason was weighed at the hospital: at 63 kg he was about double the normal weight for his age, although some of that was the excess fluid. He was put on drugs to bring his sugar level down and statins to control the excess fats in his blood. After two weeks without recovery and the results of an MRI scan and liver biopsy, showing the organ and the tissue around it were massively infiltrated with fat, it was obvious – his only chance of survival was a liver transplant.
Jason’s story is becoming increasingly familiar to doctors, yet twenty years ago these cases were incredibly rare. Fatty liver used to occur only in lifelong alcoholics. Current estimates are that around 5 to 10 per cent of US kids now have blood tests showing fatty livers, the risk being higher in boys and in children with Asian or Hispanic genes. Most are overweight or obese, and all have low-nutritional-content high-fat diets. These are kids with a low threshold for storing excess fat. Their liver and their fat-storage cells get overwhelmed by the circulating fat and descend into a state of constant inflammation and stress. Liver transplant is relatively successful, but still one in three will die within five years.8
Junk food – the perfect obesity storm
That junk food is bad for you is not news – the combination of saturated fat, calories, sugar, chemicals and lack of fibre is an obvious signal. The lack of diversity in the diet, though, is an overlooked factor: as we have seen, 80 per cent of processed food is made up of just four ingredients – corn, wheat, soy and meat. Long-term studies consistently show that regular eating of junk food items like potato crisps, chips and processed meats leads to the greatest increases in weight compared to other foods.9
The most popular fast-food order in most countries is a Big Mac, fries and a large Coke, which in the US gives you instantly 1,360 calories and adds up to over half the average total intakes. Furthermore, much of it is fat, plus as a bonus the equivalent of nineteen extra teaspoons of sugar. Currently one in three Americans eat in a fast-food restaurant at least daily. Even in the UK, a third of children under ten now eat junk food every day. Fast-food culture has certainly changed our idea of the family meal, since the first TV dinner was invented in 1952. In the US nearly one in five meals eaten nationally is consumed in the car, and other countries are following the trend.
Since Ray Kroc took over from the McDonald brothers in 1948 and created the franchised fast-food empire, over 68 million people are now served daily in 118 countries. Like it or not, McDonald’s has become a global emblem of American culture, and with its iconic golden-arch M sign is seen as both a symbol of cleanliness and efficiency and a target for animal-rights and health campaigners. Back in 1974 President Richard Nixon endorsed the Big Mac as ‘the best burger in the US’, second only to his wife’s offerings. Maggie Thatcher in 1989 as the UK prime minister personally opened the new McDonald’s UK HQ in her constituency of Finchley, endorsing their business model thus: ‘You produce value-for-money food and added to that you also make a profit.’ Other US corporations are also massively successful: Burger King, KFC, Taco Bell, Pizza Hut and Subway, for instance, with their huge global markets, all conquer hearts, minds and bellies.
Americans spent $6 billion on fast food in 1970, and $195 billion by 2014. Real food has trouble competing with the billion-dollar marketing budgets of fast and processed foods. Also, their prices have fallen in relative terms, helped by government subsidies on the four key ingredients, while the cost of fresh produce has increased over the last two decades. As the relative cost of eating out compared to cooking at home has dropped, so has the range of food alternatives. There is now a ratio of five fast-food restaurants for every US supermarket, another trend being mirrored around the world.
When the food industry began developing processed foods they were preoccupied with microbes and with keeping products on the shelves longer without them going off, particularly given the distribution problems of a country the size of America. They knew that fermented products like yoghurt or sauerkraut or pickles that contained bacteria kept products fresh, but cakes, biscuits and snacks were more of a problem. They worked out that if you added enough sugar it would inhibit bacterial growth, and increasing the fat content reduced the water content, which in turn reduced bacterial and fungal growth. Finally, on top of fat and sugar the third of the holy trinity, salt, was added, which also preserved the food and extended its shelf life. Together they would produce the conditions for the perfect obesity storm.
Products with all three of these Holy Trinity ingredients could last a very long time. When a Utah man looked in his old coat pocket and discovered a Big Mac in its wrapper that he had forgotten for fourteen years, he found it had no mould or fungus on it. Only the gherkin showed its age, the rest having dried out like a fossil.10 Perhaps in future centuries such artefacts will be displayed in museums, like Tutankhamen’s remains.
The companies found that when fat, sugar and salt were used in appropriate combinations, not only did they have a product that didn’t go mouldy, they also had a winning combination for the public. Using high-tech labs and panels of tasters they could find the exact mix of the three that was irresistible for each item – what they called its ‘bliss point’.11 And once they had added the whole range of flavour enhancers and ingredients to change the texture, the poor consumer didn’t stand a chance. It is no surprise that burgers, pizza, cakes and crisps (potato chips) all contain the big companies’ holy trinity. Moreover, there is increasing evidence that we are adapting to seek this novel mixture of salt, sugar and fat, so different from real food.
Junk food can alter rat-brain activity in a manner some believe is similar to addictive drugs like cocaine. In one recent American study, after a diet of unlimited junk food (a good mix of highly processed bacon, sausage, cheesecake, pound cake, frosting and chocolate), the pleasure centre of some rats’ brains became desensitised to the neurochemical dopamine after only five days.12 This meant they required yet more of the same to keep the pleasure going.13 When the junk food was stopped, the now obese rats preferred to slowly starve for two weeks rather than return to eating their healthy but less tasty replacement fare.14 Evidently the effects of junk food on the pleasure-seeking centres in the brain persist way longer than the time it takes to eat a burger and fries.
Another study showed that a love of junk food in pregnant rats could be passed on to their offspring.15 It could be transmitted to the babies by subtle (epigenetic) changes switching their genes up or down, or alternatively by maternal gut microbes that got passed on at birth, or via suckling. Some people claim to be addicted to junk food, but although they meet many of the criteria for addiction, whether addiction is really at issue here is controversial, as it clearly differs from addiction to artificial chemicals like glue or heroin. A similar debate addresses the question of whether a few rare people (usually celebrities) can really be addicted to sex, a pleasurable activity that we are programmed to seek out.
The American documentary maker Morgan Spurlock famously went on a total McDonald’s diet for thirty days for his documentary Supersize Me. His cholesterol went up 30 per cent, his uric acid levels (associated with gout) doubled, and the results of tests for liver damage more than trebled. He had gut ache, sweats and occasional nausea, and after a few days experienced strange cravings, depression and headaches, which were relieved temporarily on resuming eating. By the end of day 30 he had eaten 12 lb of fat, 30 lb of sugar and gained 7 per cent of body fat, most of it visceral. I was inspired to recreate the Supersize Me experiment, but with the aim of seeing how it would affect gut microbes.
Supersize Tom
I bravely considered doing the experiment myself, but after talking it through with my twenty-two-year-old son Tom it became obvious that he had far superior qualifications as a fast-food expert than I had. Tom, in common with other university students in the UK, has an appalling diet. Most students put on considerable weight that is often never lost; this is known in the US as the Freshman 15, after the average 15 lb (7 kg) gained. In term time Tom and his friends would regularly visit fast-food outlets like McDonald’s once or twice a week (though, unusually for a student, Tom is a good cook). Anyway, the study appealed to him more than to me, and as a bonus he could write it up as his student project. The reason students eat so badly in the UK and the US is not solely financial or from laziness, but may relate to the stresses of living away from home plus the fact that cooking in many countries lacking strong food cultures is not seen as ‘cool’.
We decided that ten days should be enough to see an effect without interfering with his work – or, more importantly, his social life. His only proviso was that he could alternate Chicken McNuggets with Big Macs. Although he had to keep his sugar levels high by having a regular Coke and a McFlurry ice-cream dessert (600 calories of sugar and saturated fat) with his main course, in the evening he could supplement the diet with vital extra nutrients supplied by crisps and beer.
His student friends were envious of Tom’s sponsored junk-food fest. Students may get plenty of calories but not many nutrients, and I remember from my own time a fellow medical student who used the pub as his second home. He lived for two terms on nothing but cheese sandwiches and bitter ale, and developed bleeding gums and bruising. After several months, he was finally diagnosed with scurvy and given some oranges and lemons. So taking no chances, before he started I made sure Tom had a full week of fresh and varied fruits and vegetables.
His local restaurant was a fifteen-minute walk away, but for convenience there was a drive-through section for cars, which saved him valuable time and energy. He said there was no way he could eat breakfast there as well, but I suspected that was because he would have to get out of bed too early. So we agreed he could skip breakfast.
The first few days went well and he got to know his local staff on first-name terms and often brought along other student supporters. By day 3, though, the novelty had worn off and by day 4 he was starting to dread the second evening trip. By day 5 he was having fruit and salad cravings. On day 6 he noticed feeling bloated and sluggish after eating. On day 8 he had sweats after the meals which now left him tired for three hours afterwards; and he wasn’t sleeping well. The last three days were the hardest with his tiredness increasing, and on day 9, unlike the addicted rats, he couldn’t face returning for his evening nuggets and skipped the meal entirely. His productivity dropped and he found his assignments took him even longer than usual. Friends remarked that his skin seemed to have a yellow tinge and he looked unwell.
He was very relieved when the trial stopped. He had gained two kilos (4 lb) in weight and uncharacteristically went straight to the supermarket to buy salads and a fruit salad. It was six weeks before he could eat a Big Mac again, which he says is a record, and that was as part of a hangover cure. Clearly, although attracted to junk food, Tom wasn’t addicted. Unlike Spurlock he didn’t experience any cramps, cravings, headaches or vomiting – maybe because of his genes or because he’d already had plenty of training.
The results of Tom’s microbiome tests after the ten days of burgers and nuggets were impressive. His levels of Bacteroidetes doubled from 25 per cent to 58, and his Firmicutes went down from 70 per cent to 38. His friendly bifido bacteria rates also halved. Importantly his microbial richness had been decimated and after only three days he had lost 40 per cent of his detectable species. Generally his microbes had taken on an aggressive and inflammatory fat-digesting function, particularly resistant to the extra bile acids his gall bladder was producing. His overall diversity profile moved in just a few days from being close to a healthy rural Venezuelan’s that we mentioned earlier to looking like an average American’s. Several rare species flourished on the diet, including one called Lautropia which is usually only noticed in immune-deficient patients. His profile was still abnormal with reduced diversity a week later, but then very slowly normalised.
A group in Harvard did a shorter but more detailed study on six of their lab volunteers who for three days ate a diet high in fat and protein made up of salami, meats, eggs and cheese with no carbs or fibre. What was special was that one volunteer was a lifelong vegetarian ‘encouraged’ to eat salami and burgers. His results showed even more dramatic changes that were seen within two days. Like Tom, he had big increases in Bacteroidetes and reductions in Firmicutes; and his Prevotella, which flourish in vegetarians, and normally reflect fibre in the diet, plummeted.16
These short-term but pretty extreme trials of junk food that sadly many people practise daily demonstrate the dramatic effects of losing nearly half your gut species. Such studies show that we can change our gut-microbe composition more easily than we had thought, just within a few days. The altered microbiome community produces a whole new set of metabolites and chemicals, which can alter our bodies in ways beyond just the effects of the fat and sugar. The good news is that our microbes are flexible and can reverse some of the unhealthy effects of these diets.
Toxic food and fast food mice
A group in Boston has been feeding mice the equivalent of Big Macs in liquidised form to see how they and their microbes fare compared to mice on normal diets. Both sets were allowed to eat as much as they wanted. Unsurprisingly the fast-food mice gained considerably more weight, particularly the dangerous visceral internal fat. As well as showing major differences in their microbiomes, the fattened-up mice were in a marked pro-inflammatory state, meaning that their cells were in alert mode as if being attacked, sending out signals to heighten chemical defences and make cell walls leaky.17 Inflammatory states are normal in short bursts, but if sustained are unhealthy. Several other rodent studies have confirmed that high-fat and high-sugar diets produce these inflammatory changes as well as a leaky gut wall, which allows gut microbes and chemicals to pass through into the blood.18
The idea that the deadly mix of fat, sugar and salt plus a myriad of preservatives and chemicals that make up most processed food is itself pro-inflammatory has been around for a while, but without much hard evidence. However, a large number of rodent studies like the ones described above have now shown that when you feed them high-fat/high-sugar diets their bodies react as if under attack. Could it be that it is the food itself that makes the fat cells expand and produce the inflammatory signals?
Until recently it was thought that fat cells were boring storage depots with little contact with the rest of the body. We now know they are covered in helpful immune cells (Tregs) that help them communicate with the rest of the body’s immune system.19 Once someone becomes obese and the fat cells change, these response-dampening Treg cells on the fat cells’ surface disappear, and the door is opened for all the inflammatory signals to be released. As we know, microbes and Tregs talk to each other, so could our microbes be playing a key role in making us fat?
If you feed germ-free mice these high-fat diets very little happens, and it needs the addition of microbes to make them put on weight, confirming that microbes are indeed crucial. In the Boston experiment and others, adding a probiotic like our friend lactobacillus or bifidos protected the mice from the effects of the junk food.20 When the fat content of the diet increases rapidly there’s a sudden increase in a certain type of bacteria that have a thick protective cell wall. Fragments of these cell walls (made up of lipids and sugars called LPS, or lipopolysaccharide) quickly build up and form an endotoxin, an internal poison that humans are very sensitive to.
We know LPS is the key player, because if you inject this LPS endotoxin into mice you get the same series of reactions as if they were eating the junk food, but without the brief fun. This includes triggering a reaction in the lining of the gut that starts the inflammatory process.21 The gut lining then becomes leakier, allowing these toxic fragments into the bloodstream where they can reach the fat tissue and other organs like the liver. A chain reaction is started and the body goes into a state of high alert which we call sub-clinical inflammation, a biological version of a code orange alert.22 A recent study of forty-five overweight and obese French subjects confirmed that regardless of body fat, junk-food diets with few vegetables lead to less microbial diversity and richness and more inflammation markers in the blood.23
What effect does all this low-level inflammation have on us? As well as sending increased stress signals to the body via the bloodstream which make our cells replicate faster and potentially shorten our lives, it affects the fat cells. These produce yet more inflammatory chemicals and signals which increase blood insulin, which in turn after a while prevents glucose being metabolised efficiently. This then signals for more (unneeded) fat to be stored, especially visceral fat around the belly. As we now know, this is not good.
Junk-food infections
In order to understand whether it is the microbes themselves that can actually make you fat or they are just a consequence of bad diets and the extra fat, some cleverer experiments were needed. Luckily, twins and germ-free mice again came to the rescue. From the local twin register Jeff Gordon’s lab in St Louis found four American female twin pairs in their twenties (one identical and three fraternal pairs) ‘discordant for obesity’ (meaning one was obese and the other wasn’t).
As expected, there were differences between their gut microbes, the leaner twin in each pair having a richer and healthier set with the usual higher rates of bifidos and lactobacilli and the fatter twin having a less diverse, inflammatory-looking profile. They then transferred the twins’ eight stool samples and transplanted them into the germ-free mice, randomly dividing the lean and fat twins’ output to see what would happen.
The results were surprisingly clear-cut, the mice receiving the fat twins’ stool samples quickly became 16 per cent fatter, in particular putting on inflammatory internal (visceral) fat. This was clear proof that fat-associated microbes are really toxic and can be transmitted like an infection.24 These toxic microbes are more likely to grow rapidly in our guts and be a problem if there is a community imbalance, if other microbes are suppressed, or if there is a general lack of diversity.
Up to this point the germ-free mice had been raised after their sterile C-section birth in isolated cages – in solitary confinement. To test whether the mice could make each other fat or thin by swapping microbes, the researchers now gave them a cell mate. Mice, like many other rodents, naturally eat their own droppings, but for a bit of variety they also like to sample their cell mates’ too, and in this way exchange useful microbes. What the team found was a surprise.
The lean mouse, the one with the healthy microbes to start with, didn’t get fat from the microbes of her obesity-prone neighbour. In fact, the reverse was true. The mouse with the toxic microbes was completely protected against obesity and inflammation by the transmission of the lean-mouse microbes (particularly the Bacteroidetes variety) into her guts. The other important finding was that this healthy transfer could be blocked by feeding them a high-fat/low-fibre diet and the mice still got fat. Conversely, a healthy low-fat/high-plant diet seemed to aid the healthy transfer, presumably making it hard for the original obese microbes to thrive. We performed a similar experiment with our twin study mentioned earlier. We transplanted a microbe associated with being lean into germ-free mice. This little-known microbe called Christensenella prevented mice from getting fat on high-fat diets.25 The humans that have this microbe appear to be protected against obesity, but unfortunately many do not.
This phenomenon of toxic-microbe infection could explain many observations in humans such as why fat mothers, even if not overeating, produce even fatter babies – who, remember, are much like germ-free mice. Changing the diets of pregnant women could potentially alter this vicious cycle. The data we have so far suggests people who are naturally lean or those on high-fibre diets seem relatively protected from the bad effects of the high-fat or junk-food diets. We don’t know exactly why this is, but it is probably because they have microbes that are producing more of the healthy short-chain fatty acids (SCFAs), like butyrate, that keep the Treg cells happy and suppress the state of inflammation. Eventually, even these protective systems can be overcome, as after days of intensive high-fat, high-sugar junk food and no fibre.
Chinese gruel and rogue bacteria
Wu, living in Shanxi Province in China, had always been larger than his schoolmates. By the time he was eighteen he weighed 120 kg and by twenty-nine that had risen to 175 kg, and he had an impressive body mass index of 59. At only 172 centimetres (5 feet 7 inches) tall, he resembled a large barrel. Wu was not on any medication but he had a wealth of medical problems such as diabetes, high blood pressure, high cholesterol, abnormal liver-test results and very raised inflammatory markers. Basically, he was a mess. He didn’t smoke, and only had the occasional alcoholic drink. He liked his noodles and his fatty meat and ate more than most Chinese of his age group, but not so much as to explain his extraordinary dimensions.
He was referred to Professor Liping Zhao in Shanghai, an expert in obesity and microbes. He suspected that Wu’s case was rather special, and after routine tests to rule out other diseases he decided to look at the constituents of his gut microbiome.
A DNA sample of his stool revealed it was totally dominated by one type of bacteria called Enterobacter. This bacteria is usually harmless in small amounts in healthy people, but in this case was behaving like a ruthless rogue killer and producing a specific endotoxin (B29) in huge quantities that attacked the cell walls of other competing gut bacteria. The invasive takeover had killed off most of his friendly species and also sent major aggressive inflammatory messages around the body.
Zhao put Wu on a specially designed diet. He was asked to eat around two-thirds of his normal calorific requirements, 1,500 calories a day made up of 70 per cent carbs, 17 per cent protein and 13 per cent fat. What was different was that it was composed of a combination of whole grains, traditional Chinese medicinal foods and foods that encourage the growth of the healthy microbes known as prebiotics. Amazingly this gruel-like diet worked fast.
Wu had lost 30 kg after nine weeks and 51 more after four months. These weight changes were mirrored in his blood, which returned to normal, as did his blood pressure. After nine weeks on the gruel diet, this dominating Enterobacter population and its toxins shrank from 30 per cent to less than 2 per cent and became undetectable after six months. This was mirrored by substantial improvement in the inflammation. As the toxic microbe was eliminated Wu noticed his feeling of constant hunger also subsided.26
Now, once again, it was hard to separate cause and effect. Had the state of obesity itself produced a weakening in the immune system that had allowed the dominance and strange behaviour of the microbe and its toxin? Or could the microbe itself have caused the obesity? Professor Zhao came up with a cunning plan to transplant the Enterobacter from Wu into the guts of germ-free mice. Now, as we have seen, these mice devoid of gut microbes don’t get fat, even if overfed on high-fat diets.27 28 However, when put on a high-fat/low-fibre (junk food) diet and implanted with just this one bacterial species they got very fat, and did so very quickly.
For the first few days all the mice lost weight, as a side effect of the inflammatory B29 toxin coming from the rogue bacteria. Then, within a week they were all putting on weight, and soon after started showing signs of diabetes, high lipid levels and signs of inflammation. Again, the combination of the high-fat diet and the toxic microbe was crucial, whereas the effects were minimal for mice fed on normal mouse diets.
Although this is only one isolated case it shows that a single microbe can directly cause obesity, just like an infection. It is probably (and hopefully) an unusual situation akin to a rare genetic mutation in humans. Other experiments using just a handful of implicated microbes have failed to produce the same dramatic effects. Usually to fatten up rodents the whole interacting microbial community is needed, and the same is likely true in humans.
After the end of the trial, a trimmer and more energetic Wu was so happy with the results that he stayed on his gruel diet for another year so as to lose even more weight. Prof Zhao was also happy with the outcome and he is now a big star in China, with TV appearances and a blog site that attracts over six million followers. Many more extremely obese Chinese of all ages are coming to him for his special diets.
Pang Ya was a three-year-old girl from north-west China who weighed 46 kg but whose parents were of normal size. The child had an uncontrollable appetite and would scream hysterically and employ many other tactics to get food. The desperate parents agreed to move to Shanghai close to the clinic and adhere to the strict Zhao diet for three years. The astonishing story of her weight loss and her regaining control of her normal microbes and appetite was the subject of a Chinese TV documentary.29
Over one thousand Chinese have so far been treated with his methods, many undergoing intensive investigation of their microbiomes. He has been reluctant to give away all his professional details but has published some early results of his special vegetarian diet.
In one study Zhao recruited ninety-three obese and early diabetic Shanghai volunteers who were placed on what he calls the WTP diet, based on a mixture of twelve whole grains, traditional Chinese medicinal foods and a selection of prebiotics. If you fancy whipping these up for breakfast instead of your Quaker Oats, the gruel contains a mixture of oats, adlay seeds, buckwheat, white bean, yellow corn, red bean, soybean, yam, big jujube, peanut and lotus seeds. Some patients get bitter melon too. The regime provides around 1,350 calories per day plus masses of fibre for nine weeks, followed by a maintenance diet for a total of five months. Most of the volunteers showed lowered levels of blood inflammation and insulin resistance, and the average person lost 5 kg while only 9 per cent failed to lose weight.30 He has extended his studies and found that many referred children had undiagnosed genetic conditions that made them overeat (such as Prader-Willi syndrome). Nevertheless, these children also responded to the diet, which reduced – but didn’t prevent – their excessive food cravings.
Keeping people on any diet for nearly six months is a major challenge, but when I spoke to Liping Zhao in London, he told me he thought he might have the answer. ‘Compliance is a challenge in China like in other countries, but if you tell them the aim of the diet is to change their microbial community to reduce symptoms of hunger and other problems, this makes a big difference. It motivates them to continue treatment as if they had an infection. They are seen by a dietitian weekly and every two weeks by medical staff, who at the same time analyse how the microbes are changing. As well as the special diets, patients are urged to complement their diet with vegetables, tofu and the less sweet fruits. Potatoes are forbidden.’ His plan is to work out the top fifty microbe species found in obese patients and replace them with the top fifty found in lean people, effectively changing the keystone species to produce a healthy environment. Many of the Chinese herbs that Zhao uses have been around for centuries and have undergone plenty of trial-and-error testing.
Beware the golden juice
During the Dong Jin dynasty in the fourth century, a well-known traditional Chinese medicine doctor, Ge Hong, became famous for describing the first use of a special herbal mix as a cure for patients who had food poisoning or severe diarrhoea. This apparently produced great results, and several miraculous cures were reported in the first Chinese handbook of emergency medicine, Zhou Hou Bei Ji Fang (or ‘Handy Therapy for Emergencies’).31 The exclusive top product was called Golden Juice, made from a selection of powerful herbs mixed with healthy human dung and clay, and left in a sealed urn buried underground to mature for twenty years before being served to the sick patient, usually in the form of tea.
It’s a pity that Golden Juice was not on Zhao’s list of twelve herbs, one of which, berberine, has been studied in great detail. Berberine is derived from the herb Coptis chinensis, which has been shown to prevent the inflammatory adverse effects of high-fat diets in rats and may act like a prebiotic, encouraging healthy microbes to grow.32 A meta-analysis of a number of small-scale Chinese clinical studies suggests berberine could be used as an alternative treatment for diabetes, and it is widely touted as a miracle cure on the internet. Buyers, however, beware. Herbs like this often have strong effects and the quality and strength of the product is difficult to ascertain.
We come to the major problem of assessing the quality of Chinese clinical studies. Although at the top end Chinese scientists are now producing some of the best academic papers, at the lower end anyone can put out an academic publication if they pay for it. There is a whole industry – which even includes toll-free phone numbers – devoted to writing and publishing bogus papers for struggling scientists who have a few thousand dollars and want to succeed but lack the time, the ideas or, most importantly, any real data.33 Sadly, the scandal of fake journals is not limited to China: it is a global problem for science.
Liping Zhao has an interesting life story to tell. He grew up in a small farming town in Shanxi Province, and like most Chinese born on the eve of the Cultural Revolution, he and his two younger brothers had a simple upbringing. His father was a high school teacher and his mother worked in a textile factory. Both parents were firm believers in traditional remedies. Zhao remembers watching his father drinking a pungent, murky herbal concoction twice a day to try to fight a hepatitis B infection.
Zhao earned his PhD in molecular plant pathology and spent several years in the US at Cornell in the early 1990s learning about diet and health. He also learned first-hand that the American diet made his waist expand considerably. When he returned to Shanxi to start his laboratory, he focused on using beneficial bacteria to control plant infections. Throughout the 1990s he dabbled in research exploring the notion that bacterial strains might control infections in pigs, and might even work in humans. Meanwhile, his family’s health was falling apart. His now overweight father’s lipid levels had risen dramatically, and he had suffered two strokes. Zhao’s two brothers had become obese as well. He decided to change his focus from plants and animals to human health.
After reading a 2004 paper by Jeff Gordon, the US microbiome pioneer who suggested that gut microbes could influence obesity, his interest was reignited. Lacking big funding, he used himself as a guinea-pig to try to pin down which microbes might be involved in weight gain. To Zhao, Western methods of weight loss that combined a low-calorie diet and strenuous exercise made no sense. ‘Nutritionally, your body is under stress,’ he says. ‘Then you add to that physical stress. Maybe you can lose weight, but you might also damage your health.’
Having thought again about his father’s herbal concoctions, he turned instead to traditional methods. He went on a diet of fermented prebiotic foods – Chinese yams and bitter melon – and whole grains to see if he could alter the bacterial ecology of his digestive system. During this personal experiment, he lost in just two years the extra 20 kg around his belly that he had gained in the US ten years before. His microbes became more diverse and one in particular, F. prausnitzii, which has anti-inflammatory powers, increased dramatically. His results convinced him that harmful microbes could be replaced by healthy ones using special prebiotic diets. This motivated him to find the funds to start treating and investigating his now obese countrymen.
The great leap backwards
Many Chinese alive today remember the famines of the 1950s and 1960s caused by the zealous government movement for collectivisation, ironically called ‘The Great Leap Forward’, in which millions of Chinese died of starvation. We discussed earlier the 1980s studies’ discovery that China had incredibly low levels of heart disease and cancer and their promotion of the Chinese diet as a potential saviour for the West.
A Chinese medical text written two thousand years ago entitled Huangdi Neijing identified obesity as a rare disease found among the elite class that was caused by eating too much ‘fatty meats and polished grains’. You might well think that most modern Chinese have been elevated to this ‘elite’ status themselves, as the country now boasts more obese people than any other on earth. Looking at the changing shape of China is like watching a speeded-up film of the UK and the USA over the last three decades. More than a quarter of the adult Chinese population is overweight or obese and 7 per cent of children are clinically obese, indicating that the country’s problem will worsen as they age. Many chubby children, lacking restraint when it comes to food and unwilling to exercise, are sent by desperate parents to US-style fat camps. This fat epidemic has already produced 100 million diabetics and 500 million pre-diabetics. The Chinese are even more prone, genetically, to diabetes than Europeans, laying down more visceral belly fat, and they are seeing a massive increase in heart disease. Although average calorie intakes haven’t increased in the last decade, rising incomes have impacted on food consumption to the extent that meals now contain more than twice as much oil and meats as in the 1980s, when vegetables predominated.
Despite this increase in body fat, many kids in rural areas paradoxically suffer from vitamin deficiencies and reduced growth, so in common with other rapidly developing countries like India and many parts of Africa we are witnessing the weird phenomenon of both under- and over-nutrition going on at the same time. This is probably because when an individual has some persistent nutritional deficiency their body and fat cells experience an increased drive to lay down protective fat. These signals are likely to involve our microbes.
So the more poor-quality junk or processed food people eat, lacking in fibre and nutrients, the more signals the body sends to eat more in order to recover those ‘missing factors’, causing a vicious cycle of obesity and under-nutrition. And each country has its own version of junk foods, which are not just found in fast-food restaurants or cheap supermarkets.
Zhao believes the two main causes of the current Chinese epidemic are high levels of protein and fat (via meat) and a lack of whole grains, fibre and nutrients to build up the microbes and mop up the inflammation. A shift to dairy products is not the reason. When he was a child in the north, he remembers, the wheat noodles and rice were always greyish because they had been coarsely ground with plenty of fibre and nutrients. Now both the noodles and the rice are gleaming white, with no fibre or nutrients to attract microbes, and they keep for ever.
Many Chinese work long hours and don’t have time to eat breakfast; they have a big lunch, usually provided free by their employer, then may go to dinner with clients or customers. Every dish contains meat, allowing little or no space for whole grains or vegetables. Now that women are working they have no time to cook, and most modern Chinese women no longer know how to prepare food or cook it themselves, leading to ever more reliance on restaurants or fast foods. There are over two thousand McDonald’s outlets in China. Liping thinks the Chinese are now nutritionally more American than the Americans – and that’s no compliment.
Microbe mind control and zombie burger eaters
If we know that these high-fat/high-sugar processed foods are bad for us, what drives us to keep eating them? What controls that inner desire?
It could be your microbes.34 We already discussed how microbes via the brain chemicals they produce can influence moods, anxiety and stress. Each species of microbe has a preference for certain food sources, which allows them to feed and reproduce. They therefore have their own evolutionary drive to maintain their ecological niche and will do anything to ensure their survival. This includes sending signals to the hosting human that they want more of the same junk food that they thrive on.
This idea is now more than just a wild theory. It has actually been shown in mice that have been bred to artificially lack an immune receptor (TLR5). This disrupts normal gut–immune-system communications and leads to a change in gut microbes that trigger hunger. The hunger effects can be replicated by transplanting these microbes into normal mice and reversed by antibiotics – showing that the microbes are crucial.35
This mechanism has yet to be proven in humans, but it is likely to be particularly true of the toxic species that take over some individuals – the example of Enterobacter in Wu is a case in point. Small microbes controlling the larger host are well known in nature: for instance, the fungi that infiltrate the brains of ants and make them into ‘zombies’ to do their evil bidding. These ants are driven to climb up plants and then, feeding off the underside of leaves, they drop fungal spores onto uninfected ants underneath. Other bacteria can trick fruit flies into producing more insulin, thus laying down fat which helps the bacteria to multiply but doesn’t help the poor fly.36
The notion that microbes could affect our food behaviour by providing us with brain-chemical rewards triggering us to eat more burgers is not so crazy – indeed, for our highly evolved and specialised bacteria it should be a piece of cake.37
We now see that our relationship with the fat in our diet is extremely complex, and that the simple dogma that we should all reduce total fat intakes has no scientific basis. Fats in processed foods with lots of salt and sugar are, we know, bad for us, and the artificially created trans fats are even worse. On the other hand, many fats such as the saturated varieties, previously condemned as unhealthy, turn out to be good for us as well as containing many key chemicals and nutrients that also feed and improve the diversity of our microbes. Fats in their multifarious forms are an essential part of many foods, so fixating on a few subtypes is futile. Furthermore, it diverts our attention from the importance of high-fat but healthy diets like the Mediterranean, in which diversity, colour and freshness are the key. So treat the ‘zero fat’ sticker as a sign of processing, not of health. Except in the artificial world of food labels, fat and protein are inseparable.
Let’s now look at the effects of different forms of protein on our health.