More about Intestinal Flora
This section is for those of you who want to dig down even more into the gut flora. We also give a series of references at the bottom for those who are especially interested.
Intermittent Fasting
For many years discussions about food exuded a fear of hunger, and dietary advice was often based on eating little but often. As if the assumption was that hunger is dangerous. Famine is dangerous, but hunger seems instead to do the body good.
If we constantly stuff ourselves with food insulin will always be high. The muscles and liver react as we do when someone nags all the time: they shut off, becoming less sensitive for insulin.
But if we can put up with hunger, then what starts is called the survival response, which has helped us to live with limited food. The body slows down growth and starts instead to decompose damaged proteins and send them to the body’s waste sorting, which takes care of damaged proteins. The brain is sharpened, probably because over the millennia we needed to be most attentive when we were hungry and looking for food.
During fasting, after at least six hours without food, the cells become more sensitive to insulin so that they respond better and take care of the energy once we eat. Inflammation is reduced and the yellow-white layers of fat start to break down. From the fatty acids the liver forms ketones, including butyric acid, which gives energy during fasting and a stronger defense against toxins and, at least in animals, better memory. In addition, studies show that cancer cells are more easily broken down.
Fasting for a longer period every 24 hours by limiting food intake to eight or at most 12 hours in a 24-hour period can give both better blood lipids and lower weight. The best seems to be to eat breakfast and lunch but reduce the evening meal in order to follow the circadian rhythm of the muscles and liver, which means that the release of and sensitivity to insulin is reduced in the evening. In order not to be harmful, the calorie limitation and fasting must be combined with food with a lot of nutrition, such as green leafy vegetables, e.g. spinach, kale and arugula, especially in the elderly and people with many diseases.
Another variation is to reduce food on certain days every week during a 24-hour period, what is called intermittent or periodic fasting, for example the 5:2 diet. In animals the risk of high blood pressure and cardiovascular disease and cancer is reduced. And the intestinal flora become richer to the point that the quantity of bacteria species increases, which helps us to take care of the food we eat.
Note that individuals who take insulin injections should be more careful with fasting because it can require adjustment of the insulin dose in order not to get too low blood glucose between meals.
Better Low than High Temperature
When food is heated up, chemical compounds are formed between sugar and proteins and between sugar and fats. These compounds are called AGE (advanced glycation end products) and ALE (advanced lipoxidation end products). Especially from 80 degrees Celsius (176 degrees Fahrenheit) and upward AGE and ALE increase rapidly. They are also formed with microwave heating.
AGE and ALE bind to vascular walls and nerve cells, causing chronic inflammation. Increased levels of AGE and ALE are seen in connection with Alzheimer’s disease, with type 2 diabetes and cardiovascular disease, and with breast and prostate cancer, although the causal connections are not fully mapped.
Burnt bread crusts, rusks, flatbread and cookies contain a lot of AGE and ALE. They also occur in large quantities in fried meat and fish, soy sauce, roasted peanuts, ice cream (due to milk powder) and in fast food like pizza, French fries and tacos.
Vegans have been reported to have lower levels of AGE and ALE than meat-eaters. On the other hand, lactovegetarians have surprisingly high levels, possibly due to a greater consumption of cheese and other dairy products.
A simple way to reduce the damaging AGE and ALE is to lower the cooking temperature. Many chefs maintain that poultry, meat and fish actually get more tender if prepared at low temperature for a longer time. Poultry needs to be heated to at least 70 degrees C (158 F), but meat and fish are often best at temperatures between 55 and 60 degrees (140 F). Boiling generally produces less AGE and ALE than oven roasting and considerably less than frying. Most vegetables merit eating raw, because the antioxidants are inactivated already between 30 and 70 degrees C (86 and 158 F).
Hormesis
Hormesis is a concept that was introduced in the 1800s and means that small doses of harmful substances can be health-giving. The concept has had a renaissance through the research on intestinal flora. Many substances that are in green leaves are toxins that protect the plant against attacks. For us humans however they are beneficial in small quantities because they arouse the body’s own antioxidant response, that is, our capacity to take care of harmful acid radicals.
Many studies indicate that it is actually more beneficial to consume these plant toxins in small quantities than to eat large quantities of antioxidants. That may seem paradoxical but the following explanation has been put forth.
When we supply high doses of antioxidants, for example through vitamin pills, the body’s own protective system goes on low. There is no reason to produce your own antioxidants when they are constantly being supplied from outside. Problems arise however if at some point we consume a large quantity of hazardous substances, for example through a heavily grilled piece of beef without taking antioxidants in at the same time in the form of vegetables. The body then has difficulty gearing up its own defense systems. This could explain that high doses of vitamins and antioxidants do not provide any protection whatsoever against cardiovascular disease and cancer according to major review studies. On the contrary, beta-Carotene and vitamin E have been shown to increase the risk of disease.
In a collaboration between Gothenburg University and Johns Hopkins University we recently investigated the substance sulforaphane, whose effects are a typical example of hormesis. Sulforaphane releases small quantities of harmful acid radicals when it is absorbed in the cells, which for one thing produces a strong activation of the body’s own antioxidant system in the liver. Sulforaphane is found in high concentration in broccoli. For that reason we did a clinical study, where individuals with type 2 diabetes got a concentrate of broccoli or inactive substance daily for 12 weeks. The results showed that overweight individuals with poorly controlled type 2 diabetes had lower glucose production from the liver and improved blood sugar control after intake of the broccoli concentrate.
Sulforaphane is uncommon in that the effect mechanism is explained, but the same principles probably apply for many substances that are found in vegetables and which through hormesis keep the body’s own antioxidant response in tiptop shape.
How Are Intestinal Flora Affected by Proteins, Carbohydrates and Fat?
High consumption of meat has been shown to produce growth of bacteria that produce the substance TMAO. These bacteria transform L-carnitine, which is in red meat, to TMAO, which hastens atherosclerosis and is linked to cardiovascular disease. Studies have shown that meat-eaters get higher TMAO concentration in the blood than vegetarians after intake of the same quantity of L-carnitine. The intestinal bacteria can thus contribute to the connection between red meat and cardiovascular disease.
Food with high protein content can produce increased weight loss, but has also been shown to be harmful for intestinal flora through production of ammoniac, phenols and amines which can produce DNA injuries in the cells of the intestinal mucosa. The harmful effect can however be prevented to some degree with dietary fiber. Large consumption of meat can produce high doses of sulfides, which are toxic for the colon epithelium and inhibit butyric acid production. If you eat meat, for that reason you should be sure to consume a lot of dietary fiber too, for example through large quantities of vegetables.
Very few human studies have examined the effect of a high fat diet on bacterial flora. One Australian study showed that a low-carbohydrate/high-fat diet reduced the quantity of butyric acid-producing bacteria, which can increase bowel inflammation, but more studies about this are needed.
Food rich in carbohydrates with little dietary fiber and high glycemic index, such as white rice, pasta and white bread, seldom reaches all the way down in the large intestine but is instead absorbed quickly. This has several negative consequences. For one thing the intestinal flora becomes poorer, because little fiber reaches the intestinal bacteria. Second, this leads to a rapid rise in blood sugar and a powerful insulin response. Paradoxically this may subsequently produce low blood sugar which increases hunger sensations. Third, the powerful insulin response results in an increased strain on the insulin-producing beta cells. This can lead to their function deteriorating and that they die, with increased risk of type 2 diabetes as a result.
”No man is an island”
These old words from the poet John Donne come to mind when new studies show that we carry 100 times more bacteria genes than human genes. The research on intestinal flora therefore turns the individualistic ideas that permeate modern society on end. If my body’s own genes only constitute one percent of all the genes I carry around, how could I then assert that I am an independent, isolated individual?
Studies have shown that if sterile mice are transplanted with intestinal flora from fat mice, the sterile mice will also become fat. But if at the same time they are allowed to mingle with slender mice, the obesity is prevented! Corresponding investigations are still lacking on humans, but it is not improbable that the individuals we associate and live with, in addition to all the other inter-human aspects, also affect our intestinal flora and thus our health. It is no understatement to say that we are all woven together in a greater whole.
Prebiotics
Antibiotics are familiar to most people. Probiotics, prebiotics and synbiotics, on the other hand, are perhaps new concepts for some.
Prebiotics are the substances that are not broken down by the body’s own enzymes, but instead by bacteria and promote their growth Examples are inulin, fructooligosaccharides and resistant starch. These are substances that are found in large quantities in green bananas, onions, garlic, asparagus, Jerusalem artichoke and in a number of other fruits and vegetables as well as in flakes and legumes. Prebiotics act by 1) stimulating the formation of butyric acid, which in turn improves glucose control through release of GLP1; 2) preventing leakage of harmful substances like LPS through the intestinal mucosa; 3) regulating the immune cells in the intestines; 4) increasing mineral absorption in the intestines; and 5) improving blood lipids.
Probiotics are bacteria that are supplied for the purpose of improving intestinal flora. Lactic acid bacteria (lactobacteria) are a typical example. Synbiotics in turn are a combination of pre- and probiotics.
At the present time studies have not been able to unambiguously show a positive effect of prebiotics and probiotics in humans. Treatment with lactobacteria has in some studies shown improvement of blood sugar control but in other studies no effect at all. It is also unclear whether the possible benefit of prebiotics truly is by way of effect on intestinal flora or through a purely mechanical effect where the fiber leads to slower nutrient absorption and thereby more stable blood sugar.
Measured optimism
As fascinating as the new research on intestinal flora is, it is equally difficult to exaggerate the significance of these small microorganisms.
It seems clear that dietary changes with fiber and vegetables improve the intestinal flora and at the same time reduce weight, insulin resistance and inflammation. At the present time however it is not clear that it truly is the improved intestinal flora that causes the positive effects in the body. These may very well be two completely separate phenomena. Above all it has been hard to show effects from particular foodstuffs, while the effect of overall life patterns such as the Mediterranean diet is more convincing.
Even if much research remains to be done before we can explain the exact mechanisms, one thing is clear: the research around intestinal flora has been a fatal blow to those who maintain that illnesses are only genetic destiny, something we cannot influence. On the contrary, the research clearly shows that you can do surprisingly much to influence your health with lifestyle starting today, regardless of your background or your age.
References
Arora et al., Microbial regulation of the L cell transcriptome. Sci Rep. 2018 Jan 19;8(1):1207. doi: 10.1038/s41598-017-18079-2.
Bäckhed F et al., The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A. 2004 Nov 2;101(44):15718-23.
Bambury A Finding the needle in the haystack: systematic identification of psychobiosis. Br J Pharm 2018
Bengmark S. Vår tids kost bakom inflammation och sjukdomsutveckling. Läkartidningen 2007 nummer 51
Brahe LK et al., Dietary modulation of the gut microbiota--a randomised controlled trial in obese postmenopausal women. Br J Nutr. 2015 Aug 14;114(3):406-17. doi: 10.1017/S0007114515001786.
Claesson MJ et al., Gut microbiota composition correlates with diet and health in the elderly. Nature. 2012 Aug 9;488(7410):178-84. doi: 10.1038/nature11319.
Clase M, Nertby Aurell L, Food pharmacy, Bonnier Fakta
Cotillard A et al., Dietary intervention impact on gut microbial gene richness. Nature. 2013 Aug 29;500(7464):585-8. doi: 10.1038/nature12480.
David LA et al., Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014 Jan 23;505(7484):559-63. doi: 10.1038/nature12820.
Davison KM et al., Cereal fiber, fruit fiber, and type 2 diabetes: Explaining the paradox. J Diabetes Complications. 2018 Feb;32(2):240-245. doi: 10.1016/j.jdiacomp.2017.11.002.
Duell F, Mat, myt, vetenskap, Norstedts förlag
Duncan SH et al., Reduced dietary intake of carbohydrates by obese subjects results in decreased concentrations of butyrate and butyrate-producing bacteria in feces. Appl Environ Microbiol. 2007 Feb;73(4):1073-8.
Ekstedt N, Ennart H. Happy food. Bookmark Förlag
Foster JA et al., Stress & the gut-brain axis: Regulation by the microbiome Neurobiology of Stress 2017:7 124e136
Karlsson FH et al., Gut metagenome in European women with normal, impaired and diabetic glucose control. Nature. 2013 Jun 6;498(7452):99-103. doi: 10.1038/nature12198.
Koeth RA et al., Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 2013 May;19(5):576-85. doi: 10.1038/nm.3145.
Kovatcheva-Datchary P et al., Dietary Fiber-Induced Improvement in Glucose Metabolism Is Associated with Increased Abundance of Prevotella. Cell Metab. 2015 Dec 1;22(6):971-82. doi: 10.1016/j.cmet.2015.10.001.
Levy M et al., Microbiota-Modulated Metabolites Shape the Intestinal Microenvironment by Regulating NLRP6 Inflammasome Signaling. Cell. 2015 Dec 3;163(6):1428-43. doi: 10.1016/j.cell.2015.10.048.
Martucci M et al., Mediterranean diet and inflammaging within the hormesis paradigm. Nutr Rev. 2017 Jun 1;75(6):442-455. doi: 10.1093/nutrit/nux013.
Ridaura VK et al., Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science. 2013 Sep 6;341(6150):1241214. doi: 10.1126/science.1241214.
Rothschild D et al., Environment dominates over host genetics in shaping human gut microbiota. Nature. 2018 Mar 8;555(7695):210-215. doi: 10.1038/nature25973.
Schroeder BO et al., Bifidobacteria or Fiber Protects against Diet-Induced Microbiota-Mediated Colonic Mucus Deterioration. Cell Host Microbe. 2018 Jan 10;23(1):27-40.e7. doi: 10.1016/j.chom.2017.11.004.
Seganfredo FB et al., Weight-loss interventions and gut microbiota changes in overweight and obese patients: a systematic review. Obes Rev. 2017 Aug;18(8):832-851. doi: 10.1111/obr.12541.
Telle-Hansen VH et al., Does dietary fat affect inflammatory markers in overweight and obese individuals? - a review of randomized controlled trials from 2010 to 2016. Genes Nutr. 2017 Oct 4;12:26. doi: 10.1186/s12263-017-0580-4.
Turnbaugh PJ et al., An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006 Dec 21;444(7122):1027-31.
Turnbaugh PJ et al., A core gut microbiome in obese and lean twins. Nature. 2009 Jan 22;457(7228):480-4. doi: 10.1038/nature07540.
Wu GD et al., Linking long-term dietary patterns with gut microbial enterotypes. Science. 2011 Oct 7;334(6052):105-8. doi: 10.1126/science.1208344.