The bacteria population of our mouth is only about one-ten-thousandth of the number that live in the gut, yet we still taste the results of their work. Our digestive tract should be grateful for the fact that it has such a large population with such a wide range of skills. While simple glucose and fructose are easily digested, many people’s guts start to flag when it comes to lactose, the sugar contained in milk. Their owners then suffer from a lactose intolerance. Complex plant carbohydrates would flummox a gut if it were expected to have at the ready every enzyme needed to break them down. Our microbes are experts in dealing with these substances. We provide them with somewhere to live and the undigested remains of our food—and they keep busy dealing with the stuff that’s too complicated for us to do.
In the industrialized world, about 90 percent of our nutrition comes from what we eat, and we are fed about 10 percent by our bacteria. So, after nine lunches, meal number ten is on the house, so to speak. Feeding adults is the main occupation of some of our bacteria. That does not mean that it makes no difference what we eat—far from it. And the kind of bacteria that are feeding us also makes a big difference. In other words, if we are concerned about our weight, we need to think about more than just the big, fat calories we consume and remember that our bacteria are at the dinner table with us.
How Might Bacteria Make Us Fat?
Three Theories
1. “Chubby” Bacteria
THE GUT FLORA might include too many bacteria that program a person for chubbiness. These chubbiness-inducing bacteria are efficient at breaking down carbohydrates. If the number of chubby bacteria gets out of hand, we have a problem. Skinny mice excrete a certain quantity of indigestible calories while their overweight peers excrete significantly fewer. The chubby bacteria in the latter group extract every last smidgen of energy from the same amount of food and cheerfully feed it to Mr. or Ms. Mouse. For humans, that can mean some people pile on the pounds even though they eat no more than others. It could be that their gut flora is extracting more energy from the food they eat.
How can that be possible? Bacteria are able to make various fatty acids out of indigestible carbohydrates. Vegetable-loving bacteria tend to manufacture fatty acids for the gut and the liver, and others produce fatty acids that feed the rest of the body. A banana is less likely to make you fat than half a chocolate bar containing the same number of calories. That is because plant carbohydrates are more likely to attract the attention of bacteria that provide fatty acids to local customers like the liver. The chocolate bar, on the other hand, is more likely to attract the attention of the full-body feeders.
Studies carried out on obese subjects show that they have less overall diversity in their gut flora and that certain groups of bacteria prevail—primarily those that metabolize carbohydrates. To succeed in becoming obese, however, a few other conditions must be met. Experiments with laboratory mice showed that some weighed 60 percent more at the end of the trial than at the beginning. Full-body-feeding bacteria cannot cause so much weight gain alone. This prompted scientists to consider another marker for extreme weight gain: inflammation.
2. Inflammation
PATIENTS WHO HAVE metabolic problems, such as obesity, diabetes, and high blood-lipid levels, usually have slightly increased levels of infection markers in their blood, too. These infections are not so high that they require treatment, as they would, say, if they were caused by an infected wound or septicemia. That’s why doctors call these subclinical infections. If there is anyone who knows a thing or two about infection, it’s bacteria. They have a signaling substance on their surface that tells the body when to get infected.
When we get injured, this reaction is useful. Infection reactions flush out bacteria or attack them. As long as bacteria remain in their cozy mucus-membrane home in the gut, this signaling substance goes unnoticed. But when bacteria appear in disadvantageous combinations, or when their host eats an overly fatty diet, too many of them can find their way into the bloodstream. The body then slips into low-key infection mode. From the evolutionary point of view, it’s worth paying that price to build up fat reserves for leaner times.
Bacterial-signaling substances can also latch onto other organs and affect metabolism from there. In rodents and humans, they dock onto the liver or the fatty tissue itself and encourage the deposition of more fat. They also have an interesting effect on the thyroid gland. Bacterial infections hinder its function, causing it to produce fewer thyroid hormones, slowing the rate at which the body burns fat.
Unlike acute infections, which cause weight loss or even emaciation, subclinical infection causes weight gain. Bacteria are not the only possible cause of subclinical infections—hormone imbalances, too much estrogen, lack of vitamin D, or too much gluten-rich food have all been observed to have a similar effect.
3. Cravings
NOW, BRACE YOURSELF for a crazy idea! A hypothesis postulated in 2013 suggests that gut bacteria can affect their host’s appetite. Roughly speaking, the theory is that late-night cravings for chocolate-covered toffees followed by an entire bag of party pretzels do not originate in the organ that calculates our tax returns. Not our brains but our guts are the home of gangs of bacteria that crave hamburgers after three days on a diet. Somehow they manage to pass on that message in a very persuasive way, because we find it almost impossible to deny them any wish.
To understand this hypothesis, we have to try to get our head around the issue of food. Faced with the choice between two different dishes, we make the decision based on what we happen to fancy at that moment. The amount of our chosen dish that we actually eat is controlled by the feeling of satiety. In theory, bacteria have ways and means of influencing both those things. Again, we can currently only conjecture that they also have a say in our appetite. But in evolutionary terms, it is not such a silly idea. What and how much we eat can be a matter of life and death for them. In three million years of coevolution, even simple bacteria have had time to adapt optimally to life with their human hosts.
If you want to trigger a craving for specific foods, you have to gain access to the brain. That is no mean feat. The brain is wrapped in a sturdy membrane called the meninges. Even more impenetrable than the meninges are the coats that surround all the blood vessels passing through the brain. The only things that can make it through this tangled mess are pure sugar, minerals, and anything that is as small and fat-soluble as a neural transmitter. Nicotine, for example, makes it through to the brain, where it triggers reward signals or a feeling of relaxed alertness.
Bacteria can produce particles that are small enough to make it through the coating of the blood vessels into the brain. Examples include tyrosine and tryptophan. These two amino acids are converted into dopamine and serotonin in the cells of the brain. Dopamine? Wasn’t that famously associated with the brain’s reward system? And serotonin? That sounds familiar, too, doesn’t it? Lack of it causes depression. It can make us feel contented and sleepy. Just think about last year’s Christmas dinner. Did you end up dozing on the couch after enjoying it, feeling lethargic and sleepy but also contented?
So the theory is this: our bacteria reward us when we send them a decent delivery of food. It feels pleasant and whets our appetite for the next meal. They do this not only directly by means of the substances they produce, but also by cranking up the body’s production of certain transmitters. The same principle applies to the feeling of satiety.
Several studies have shown our satiety signal transmitters increase considerably when we eat the food our bacteria prefer. What our bacteria prefer is food that reaches the large intestine undigested, where they can then gobble it up. Surprisingly enough, those foods do not include pasta and white bread ;-). For more on this, turn to the section on prebiotics in the last chapter of this book.
The feeling of satiety generally comes from two sides: from the brain and from the rest of the body. A lot can go wrong here. In obese people, the gene that codes for satiety can be defective, and such people simply
do not get that full feeling after eating. According to the selfish brain theory, the brain does not receive enough of the energy eaten as food and so decides that it is still hungry. But it is not only our body tissue and our gray matter that depend on the food we eat—our microbes also need to be fed. They may seem small and insignificant by comparison with our body size—accounting for just 4½ pounds (2 kilos) of our body weight. So what right do they have to butt in?
When we consider the range of functions carried out by our gut flora, it is not surprising that these microbes are also able to express their wishes. They are, after all, the immune system’s most important trainers, digestion assistants, producers of vitamins, and experts in detoxifying moldy bread or medical drugs. The list is actually much longer, of course, but the message should be clear: they should be able to have a say in whether we feel full after eating.
We do not yet know whether different bacteria express different desires. When we give up sweets, we eventually stop missing them so badly at some point. Is that because the gummy bear and chocolate lobby has been starved out? We can only speculate.
The important thing is not to reduce the human body to a two-dimensional cause-and-effect machine. The brain, the rest of the body, bacteria, and the elements in our food all interact with each other in four dimensions. Striving to understand all these axes is surely the best way to improve our knowledge. However, we can more easily tinker with bacteria than with our brain or our genes—and that is what makes microbes so fascinating. The nutrition we receive from our bacteria is not only important for fighting the flab, it also affects the levels of fats such as cholesterol in our blood. This realization could be quite highly charged as obesity and high cholesterol levels are closely connected with the greatest health issues of our time: hypertension, arteriosclerosis, and diabetes.
Cholesterol and Gut Bacteria
THE CONNECTION BETWEEN bacteria and cholesterol was first discovered in the 1970s. American scientists studying Maasai warriors in Africa had been surprised to find the levels of cholesterol in their blood were low, despite a diet consisting almost entirely of meat and milk. This excessive amount of animal fat did not cause high blood-lipid levels. The scientists suspected a mysterious substance in the milk they drank might be causing their cholesterol levels to remain low.
The scientists then set about doing all they could to find that mysterious ingredient. They tested cow’s milk and camel’s milk and even rat’s milk. Sometimes they managed to reduce cholesterol levels, sometimes not. These results told the scientists nothing. In another experiment, they gave the Maasai warriors a vegetable-based milk replacement product (Coffee-mate®) with high levels of cholesterol added to it. Still, the subjects’ blood cholesterol levels did not rise. The scientists saw that their theory about a mysterious milk component was disproven.
They had meticulously noted that the Maasai often drank curdled milk, but no one considered the fact that certain bacteria are required to curdle milk. That would have explained the results of their Coffee-mate® experiment. Bacteria that have already settled in the gut can continue to live there even when milk is replaced with plant-based creamer enriched with cholesterol. Even when the Maasai’s cholesterol levels were seen to sink by 18 percent whenever they drank curdled milk rather than fresh milk, scientists continued to search for the mysterious milk substance—blind dedication that brought no results.
These studies of the Maasai would not live up to modern scientific expectations. The test groups were too small, and the Maasai spend about thirteen hours a day walking and one month a year fasting. They simply cannot be compared to meat-eating Westerners. However, the results of these studies were rediscovered decades later by researchers who were now aware of the importance of bacteria. Cholesterol-lowering bacteria? Why not test that in the lab? Take a flask of nutrient broth warmed to a balmy 98.6 degrees Fahrenheit (37 degrees Celsius), add cholesterol and some bacteria—et voilà! The bacterium they used was Lactobacillus fermentus, and the cholesterol they had added was . . . gone! At least a considerable proportion of it was.
Experiments can have very different results, depending whether they are carried out in glass flasks or inside opisthokonts. It’s like an emotional rollercoaster ride for me when I read in scientific papers sentences like “The bacterium L. plantarum Lp91 can significantly lower high cholesterol and other blood lipid levels, increase good HDL cholesterol, and lead to significantly lower rates of arteriosclerosis, as could be shown in 112 Syrian golden hamsters.” I have never been so disappointed by Syrian golden hamsters. Experiments on animals are a good way to begin tests on living systems, but if the sentence had ended “as could be shown in 112 obese Americans,” the whole thing would be a lot more impressive.
But a result like that can still be worth a lot. Studies on mice, rats, and pigs yielded such promising results for some bacteria that scientists considered it reasonable to begin human testing. The subjects were regularly administered certain bacteria and after a period of time their cholesterol levels were measured. The bacteria species, the quantities, the duration, and the way they were administered were all varied. Some results were positive and others were not. Also, no one really knew whether sufficient numbers of the administered bacteria even survived their bath in the acid juices of the stomach long enough to have an effect on blood cholesterol levels.
Really valuable studies began about twenty years ago. For one experiment in 2011, 114 Canadians ate specially produced yogurt twice a day. The bacterium added to the yogurt was Lactobacillus reuteri—in a form particularly resistant to digestion. Within six weeks, their levels of bad LDL cholesterol sank by 8.91 percent. That’s about half the improvement attained by taking a mild anti-cholesterol drug—but without the side effects. Studies using other types of bacteria lowered cholesterol levels by as much as 11 to 30 percent. Follow-up research still needs to be carried out to verify these promising indications.
There are several hundred bacteria candidates that might be tested in future. To sift out the less likely ones, we have to ask the following kinds of questions. What abilities does such a bacterium need to have? Or rather, “What genes does it need to have?” The most likely candidates we know of today are BSH genes. BSH stands for bile salt hydrolase. Bacteria with these genes can convert bile salts. But what do bile salts have to do with cholesterol? The answer is in the name. Cholesterol comes from the Greek words chole (bile) and stereos (solid). Cholesterol was first discovered in gall stones. Bile, which is stored in the gall bladder, is the body’s transport medium for fats and cholesterol. BSH allows bacteria to alter bile to make it work less efficiently. The cholesterol and fat dissolved in bile can then no longer be absorbed by the body and they end up, to put it bluntly, down the toilet. This mechanism is useful for bacteria because it weakens the effect of bile, which can attack their cell membranes. This protects the bacteria on their long journey to their final destination—the large intestine. Bacteria also have a few other mechanisms for dealing with cholesterol: they can absorb it directly and incorporate it in their cell walls, they can convert it into a new substance, or they can manipulate organs that produce cholesterol. Most cholesterol is produced in the liver and the gut, where tiny messenger substances manufactured by the bacteria can partly control those processes.
But we need to take a step back and ask cautiously: does the body always want to get rid of its cholesterol? It produces between 75 and 90 percent of our cholesterol itself. And that takes a lot of work! One-sided media reporting has given cholesterol a bad name, making people believe it is only evil. That is quite wrong. Too much cholesterol is not such a good thing, but neither is too little. If it weren’t for cholesterol, we would have unstable cells and no sex hormones or vitamin D. Fat and cholesterol are not only an issue for Granny and her weakness for cream cakes or sausages. They are an issue for every one of us. Studies have shown a connection between too little cholesterol and memory problems, depression, and aggressive behavior.
Cholesterol is also the miraculous base material for building all sorts of structures. Too much of it is indeed harmful—it’s all about finding the right balance. Our bacteria would not be our bacteria if they didn’t have the ability to help us achieve that. Some bacteria produce more of a substance called propionate, which inhibits the production of cholesterol. Others produce more acetate, which promotes the production of cholesterol.
Who would have thought it? A chapter that began with bright, little spots of bacteria ending with concepts like appetite and satiety or substances like cholesterol? To summarize: Bacteria help to feed us, make some foods more digestible, and produce their own substances. Some scientists now support the theory that our gut microbiota can be considered an organ. Just like the other organs in our body, this organ has an origin, develops along with us, is made up of a load of cells, and is in constant contact with its fellow organs.
The Bad Guys—Harmful Bacteria and Parasites
THERE ARE GOOD guys and there are bad guys in the world—and the same goes for the world of our microbes. One thing unites most of the bad guys: they only want what’s best . . . for themselves.
Salmonellae in Hats
EVEN THE MOST courageous of cooks sometimes feel a pang of primal fear while beating eggs—fear of the raw threat posed by Salmonella! Everyone knows someone who has endured devastating diarrhea and venomous vomiting after eating chicken that was not quite done or nibbling on a bit of raw cake mix.
Salmonella bacteria can get into our food in unexpected ways. Sometimes, globalization helps them find a home in our chicken, meat, or eggs. This is how it can happen in Germany, where I live. The cheapest source of feed grain for chickens is Africa. So, we fly it in to feed the fowl in our poultry farms. However, there are more wild tortoises and lizards wandering around in Africa than Germany. Salmonella bacteria travel to our climes along with the chicken feed. How so? Well, they are part of the normal gut flora of reptiles. While the African farmer is working in the fields, a tortoise might merrily be doing its business in a sack of grain destined for Germany. After an exciting flight with a wonderful view over the clouds, the grain, along with its stowaway tortoise-poop bacteria, ends up in a German poultry farm, where it is eaten by a hungry chicken. Salmonella bacteria are not part of a chicken’s natural gut flora, but they are a common pathogen. Similar contamination can occur in other countries when animal feed contains materials where Salmonellae may lurk.
Gut: The Inside Story of Our Body's Most Underrated Organ (Revised Edition) Page 15
