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Introduction

Surface facts

Most people would view the human skin as our most important point of contact to the outside world. After all, the skin protects us from heat, cold, harmful chemicals and dangerous microbes, and yet it is so sensitive that we can even feel a weak breeze picking up. But if we look at the total surface area, the human intestines are actually larger on the inside than our skin is on the outside.[1, 2] While our digestive tract is only about five meters long, the large and small intestine have countless folds and creases that are layered with tiny tentacles, not unlike an origami octopus. In that way, the intestines are in a more active and direct contact with the things we eat than our skin is in contact with the outside air. This allows us to effectively absorb most of the nutrients and fluids from our food. But there is one other advantage to a large surface area: the ability to house microbes.

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Fig. 1: Your inner octopus

Secret kidney

The total number of microbes populating our digestive tract at any given time is very close to the number of human cells in our body.[3] That means we’re half microbe by number – even if not by weight. All those bacteria together weigh around 200 g, which is “only” as much as one or two average kidneys.[4] Because of this, and because the gut flora produces many metabolically active substances, the microbiome is often called a forgotten organ.[5] Science is slowly but steadily remembering this organ, and by now we know that more than 1,000 different species of bacteria can be found in the human intestines, while the average person houses at least 150 of these.[6] Individual people share many of the bacterial species, but there is still enough variety to create a “bacterial fingerprint” of each person’s microbiome.[7] The exact composition of the gut flora depends less on your genes, and more on the early years of your personal history.[8, 9] Shortly after birth, the intestine of a baby is populated by friendly bacteria from the mother’s vaginal flora and breastmilk, and has an immature and very unstable bacterial profile.[10] After the introduction of a nutritious solid food diet, the microbiome rapidly matures into an adult profile that is stable and resistant against invading microbes.[11, 12] In cases of malnutrition the gut flora cannot develop and stays at an immature stage, but can mature temporarily whenever enough nutrients are present.[13]

 

The healthy microbiome

Floral functionality

There used to be this popular idea that every gut flora needs to contain a certain selection of bacterial species to be considered healthy, a so-called “core microbiome.” But analyses from all over the world clearly show that what is really important is not the classification of the bacteria, but their function within the current life situation. For example, infants fed with breast milk tend to have high levels of bacteria that can digest lactose. From the point where solid plant foods enter the diet, bacteria that can break down fiber become more common.[12] The type (genus and/or species) of these bacteria can be very different from person to person, but they generally have the same functionality or “job” within the total microbiome.[14] Which of these functional types of bacteria are dominant then depends on both the past and the current diet. In rural areas of Africa, where the diet is traditionally made up by large amounts of fiber-rich foods, the typical microbiome was found to contain large amounts of fiber-digesting bacteria. This was not the case with samples from the EU and the US, which were dominated by amino-acid digesting bacteria, probably shaped by high animal protein intake.[15, 16]

The gut flora as a whole is a kind of alchemical powerhouse.[17] One of its main jobs is the digestion (“fermentation”) of fiber to produce short-chain fatty acids, which can be used as an energy source by the intestine itself, and can provide up to 10% of your total daily caloric intake.[18-20] Many of these fatty acids are signal molecules that can reduce inflammation, strengthen the gut wall, regulate the immune system and influence satiety and insulin sensitivity.[19, 21-23] On top of that, the gut flora seems to take on several different “useful” roles depending on the diet. In carnivores and humans consuming high amounts of meat, the gut bacteria adapt to digest amino acids, synthesize vitamins that may lack in the diet and break down carcinogenic substances found in charred meat. In herbivores and humans with high fiber intake, the gut flora primarily digests fiber and may contribute to the production of amino acids. Adaptations of the microbiome to a herbivore or carnivore diet can happen within the short time frame of only one day. It’s possible that this is a mechanism optimized for the short-term changes in the diet of hunter-gatherer humans, with high meat availability after a successful hunt, and a diet otherwise based on fiber-rich plant-matter.[24-26]

V0025560 An alchemist at a furnace with a large 'receiver', with diag
Credit: Wellcome Library, London. Wellcome Images
images@wellcome.ac.uk
http://wellcomeimages.org
An alchemist at a furnace with a large 'receiver', with diagrams of alchemical apparatus. Woodcut, 1658.
1658 after: Johannes Rudolph GlauberPublished: 1658  Copyrighted work available under Creative Commons Attribution only licence CC BY 4.0 http://creativecommons.org/licenses/by/4.0/
Fig. 2: The gut flora fermenting some fiber... probably
 

The not-so-healthy microbiome

Balance is key

While a balanced and stable gut flora is necessary for health, an imbalanced microbiome is a culprit in disease from as early as directly after birth. Infants with disturbed or reduced microbiomes in the first 100 days of life have been shown to develop more allergies either immediately or years later.[27-32] Influences that can cause disturbances in the gut flora are early (preterm) birth, delivery via caesarean section and/or antibiotic therapy.[33-36] Exposing the mother during pregnancy, or the child after birth, to environments rich in diverse bacterial species, such as farms or day-care facilities, seems to reduce allergy development.[37-42]

Adult microbiomes are generally very stable, but can be disturbed by antibiotic therapy, infection with invasive microbes, an unhealthy diet or even “just” psychological stress.[16, 24, 43-45] As the result of such a disturbance, the gut flora loses many species of bacteria and enters an unstable, low-diversity state. After the negative factors have been removed, an incomplete recovery to a degraded, but stable state takes place.[14] A reduced or imbalanced gut flora, also called “dysbiosis,” can then worsen or even cause a number of diseases of the digestive tract, like malabsorption of nutrients, indigestion, irritable bowel syndrome and many others.[46-48] More than that, dysbiosis can also have a profoundly negative influence on the immune system and the central nervous system, and can contribute to obesity, inflammation, ageing and cancer incidence.[49-53]

 

Probiotics

Regaining what was lost

Once a gut flora is imbalanced or has low diversity, the most logical thing to do is re-colonize it. This can be achieved using so-called “fecal microbiota transplantations,” which involve taking stool samples from a donor, extracting the bacteria and giving them to a patient. This technique has been used with success for disturbed microbiomes, but has led to unexpected weight gain in some people.[54-56] It is never exactly clear which bacteria are contained in the transplant, so choosing a healthy donor is very important.

Commercial probiotics, in comparison, contain only a few well-known species of bacteria that are traditionally found in fermented milk products.[57] It would seem like having so few species of bacteria in a probiotic preparation will at least make it easier to analyse their positive effects. Unfortunately, even the effects of supplementing a single species will depend on the current microbiome, diet, medications, psychological stress and many other factors. This would explain why even recent, large-scale meta-reviews come to the conclusion that there is no definite health effect for taking probiotics.[58-66] It’s also unlikely that the meager 1-20 different bacterial species that are contained in probiotics can improve the diversity of the more than 1,000 different species and subspecies found in the human microbiome.[67] That said, taking a probiotic preparation can temporarily increase the number of the supplemented bacteria in the gut, which could lead to them out-competing harmful microbes and possibly providing food and metabolites for other friendly bacteria that can then populate the flora.[68-73] On the other hand, they could also drive out good bacteria and cause gastrointestinal side-effects in healthy people, or infections in immunodeficient people.[74-77] All in all, probiotics seem like a relatively safe and promising, if somewhat unpredictable option to improve the micobiome.[78]

 

Prebiotics

Feeding what was found

There is yet another way in which one can try to balance an out-of-whack gut flora. Instead of introducing live bacteria to your system, the idea of prebiotics is to feed select parts of what you already have. It’s easy to confuse pre- and pro-biotics, not only because the words are similar but also because their naming is very much counter-intuitive. It may help you to remember which is which if you take the “pre” to mean “present”, as in, a present from you to your gut flora in gratitude for all its years of service. And similar to chocolate bunnies given to children at Easter, this is the kind of present that will be eaten right away – or “fermented”, to use the bacteria-appropriate word. Ideally, prebiotics are intended to feed only some select kinds of bacteria which are believed to be overall beneficial for health.[79]

The most popular prebiotic is probably inulin, a type of fiber called “non-digestible oligosaccharide.” These kinds of fiber can be found in chicory and other vegetables and are especially popular with lactic acid bacteria from the genus Lactobacillus and Bifidobacterium.[80] As these are also the bacteria used in probiotics, both kinds of supplements have the same goal: increase the amount of beneficial lactic acid bacteria in the gut, once by seeding (probiotics) and once by feeding (prebiotics). On top of that, prebiotic fibers are used by our friendly microbes to produce short-chain fatty acids, which can have all kinds of positive effects on the metabolism, as mentioned in the section about floral functionality.[81] This is probably one of the main arguments in favor of prebiotics. After all, even if you have a healthy gut flora, it can’t produce any beneficial substances if it doesn’t have the base material. On the other hand, the potential risks are similar to those we see with probiotics. Compared to the natural balance of different fibers found in a typical vegetable, prebiotics are more like chemical substances. They are heavily processed and are taken in high concentrations and without their usual “food matrix” (that is, the entire rest of the vegetable). As such, their impact on the gut flora is unpredictable, even though side effects are rare and usually only consist of mild digestive troubles.[82]

easter-nest-2157015_1280 - Copy
Fig. 3: May feed your soul, but not your gut flora
 

Dietary fiber

Sir, I’m gonna need that kidney bean

Neolithic humans certainly didn’t go out to gather probiotic pills or hunt for chicory fiber. So how is it that we believe we need those specialized health products to be well? One aspect of it is certainly just effective marketing. The other one is that Neolithic humans also didn’t have fast food joints and desk jobs. The modern lifestyle puts unusual stresses on practically all aspects of our health, and that certainly includes our gut flora. Highly refined ingredients like sugar and alcohol feed bacteria we don’t want and suppress those we would need. Diets dominated by comfort foods lack the nutrients the flora needs to flourish in diversity. The result is mild to moderate dysbiosis and negative effects on areas of our life that we never even remotely thought were connected to the gut flora, including our brain health, mood and the way we interact socially.[53, 83] With that said, there’s no reason not to use the natural pre- and probiotics of our ancestors to improve our modern lives. It was Hippocrates who suggested to “let food be thy medicine”, and the only reason he didn’t vanish under mysterious circumstances is that there were no supplement companies in ancient Greece. And indeed, choosing the proper foods may be all that is needed to optimize the gut flora better than any product could, no matter how well it may be marketed.

The answer is almost disappointingly simple: it’s the fiber. Short-chain fatty acids are probably the single most important metabolite produced by the gut flora, and they’re essentially made from soluble fiber.[84-88] Which foods contain soluble fiber? Whole grains, legumes and vegetables. On top of that, raw vegetables contain a large selection of beneficial bacteria on their surface, and so they double as natural probiotics.[89] Some of these bacteria have even been suggested for use in future probiotic supplements.[90] But why wait? You can make use of the probiotic power of all different kinds of fruits, berries and vegetables right now by simply integrating them into your diet.[89] In addition, you can protect your gut flora by limiting the consumption of processed foods, sugar and alcohol. Day-to-day stress levels can be reduced by structuring your work schedule ahead of time and leaving some time slots open for rest & relaxation in your time off. Your friendly flora is sure to appreciate it.

Kidney-comparison - Copy
Fig. 4: Spooky similarities
 

Frequently asked questions (FAQ)

 

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