Gut – What causes gut problems

Gut – What causes gut problems

On this page, we’ll go over the various things that can cause gut issues.

Certain drugs


Overuse of antibiotics is a common cause of gut issues. British researchers showed that taking several courses of antibiotics increases diabetes risk. For example, people who took 5 or more courses of tetracyclines (a common anti-acne antibiotic) had 21% higher diabetes risk. The increased risk is most likely due to changes in gut microbiota. The lead researcher commented on MedScape:

Dr Yang said that the next step for the team will be to expand their focus, as the antibiotics data “provide indirect evidence suggesting the importance of gut microbiota on metabolic outcomes, including diabetes.”

Similarly, 2 studies have shown that people taking tetracyclines for acne have 65% to 70% higher risk of inflammatory bowel disease than the population average. Antibiotics prescribed for other conditions have also been linked to increased risk for IBD.

Painkillers (NSAID) and proton-pump inhibitors (PPI)

PPIs are drugs that suppress the stomach acid production and are used to treat heartburn, GERD, and other acid-related conditions. Brand names include Prilosec, Prevacid, Dexilent, Aciphex, and Protonix.

Nonsteroidal anti-inflammatory drugs (NSAID) are your everyday painkillers and fever-reducing drugs, like aspirin, ibuprofen, and naproxen. Brand names include Advil, Motrin, Celebrex, Aleve, and Naprosyn.

Note that paracetamol (Tylenol) is much safer. Studies show it causes little to no damage to the gut.

NSAIDs cause damage to the small intestine by altering the gut flora. Animal studies on antibiotic-treated mice and mice without gut flora (germ-free mice) don’t suffer small intestine damage as a result of NSAIDs.

It also seems that NSAIDs allow the bacteria to penetrate deeper into the gut wall than normally. This activates the immune system and causes inflammatory damage in the area.

However, what is clear is that NSAIDs do cause gut damage and increase intestinal permeability. The damage can take very long time to heal – especially if you don’t actively support the healthy bacteria in the gut.

Clinical and endoscopic observations indicate that even short-term administration of NSAIDs in low doses frequently induces several adverse effects in the small intestine as increased gut permeability, gut inflammation, mucosal erosions, and ulcerations.

Marlicz, W., Loniewski, I., Grimes, D. S. & Quigley, E. M. Nonsteroidal anti-inflammatory drugs, proton pump inhibitors, and gastrointestinal injury: contrasting interactions in the stomach and small intestine. Mayo Clin. Proc. 89, 1699–709 (2014).

PPIs, on the other hand, are linked to dysbiosis, or bacterial imbalance, in the gut. How exactly this happens is not yet known. My guess is that the reduction in stomach acids allows more harmful bacteria to pass to the small intestine; bacteria that stomach acid would have normally killed. Alternatively, reduction in stomach acid could mean incompletely digested proteins pass to the small intestine and feed the harmful bacteria.

The combination of PPIs and NSAIDs seems to be especially destructive. Dysbiosis from PPIs worsens the intestinal damage NSAIDs cause. Alas, the two are often prescribed together.

After taking NSAIDs and PPIs for two weeks, >50% of subjects had small intestine injuries.

Fujimori, S. What are the effects of proton pump inhibitors on the small intestine?World J. Gastroenterol. 21, 6817–9 (2015).

Fortunately, studies have also shown that supporting the gut flora either with pre- or probiotics can reverse the drug-induced damage.

The study group continuing standard therapy with probiotics showed almost complete mucosal healing in the small intestine and improvement in the full blood cell count parameters. No such observations were made in the group continuing NSAIDS and PPI standard therapy only.

Marlicz, W., Loniewski, I., Grimes, D. S. & Quigley, E. M. Nonsteroidal anti-inflammatory drugs, proton pump inhibitors, and gastrointestinal injury: contrasting interactions in the stomach and small intestine. Mayo Clin. Proc. 89, 1699–709 (2014).


Recent investigations indicate that an individual’s diet may strongly influence changes in the microbiota, which, in turn, affect intestinal permeability and result in a state of chronic low-grade inflammation.

Frazier, T. H., DiBaise, J. K. & McClain, C. J. Gut microbiota, intestinal permeability, obesity-induced inflammation, and liver injury. JPEN J Parenter Enteral Nutr 35, 14S–20S (2011).

The paper mentioned above refers to a mouse study that showed 57% of the variation in gut microbiota are due to diet and only 12% due to genetics.

Let’s look at the kinds of diets that cause gut problems.

Crappy-food diet

Researchers from the Rockefeller University published a study showing the swift and dramatic effect diet has on metabolic endotoxemia (leakage of substances from the gut).

The researchers put eight people through 2 diet periods (both lasting one month): a Western-style diet and a ‘prudent’ diet. The Western style diet is the typical diet eaten in many Western countries; high in processed foods and low in fiber. The prudent diet was composed of whole foods and had much more complex carbohydrates and fiber.

After 4-weeks on the Western-style diet, endotoxin levels in the blood increased by a whopping 71%. In contract, they dropped by 38% after 4-weeks on the prudent-style diet.

The drastic increase in endotoxemia shows two things. First, the diets caused a significant change in the gut microbiota. Second, diet, in combination with the shift in gut microbiota, caused damage to the gut lining and increases intestinal permeability; i.e. allowed undesirable substances to leak from the gut into the bloodstream.

Fat, especially saturated and milk fats

The amount and type of dietary fat also seem to affect the gut microbiome. This is still an emerging area of research, and most of what follows is based on mice studies. So consider this as an interesting area to experiment on, rather than a proven fact.

That being said, studies suggest that eating too much and wrong type of fat does promote the growth of harmful bacteria in the gut.

For example, a bacteria called Akkermansia muciniphila resides in the gut lining and plays an integral role in supporting and protecting the gut lining. These bacteria typically make up for 3% to 5% of all the bacteria in the human gut. One study showed that the number of these bacteria was 100-fold lower in mice fed a high-fat diet (60% from lard). Of course, not many humans get 60% of their calories from lard, so it’s hard to say how applicable this is to humans.

The amounts of Bifidobacterium spp, a common probiotic bacteria, are also lower in high-fat fed mice than mice kept on low-fat, high-carbohydrate diets.

Other studies suggest that saturated fat not only reduces the number of beneficial bacteria in the gut but also supports the growth of harmful bacteria.

For example, saturated fat promotes the growth of bacteria that produce hydrogen sulfide, a gas that’s toxic to the cells in the gut and known to degrade the gut barrier.

Dairy fat seems to promote the growth of these hydrogen sulfide producing bacteria more than the other types of saturated fats. Dairy fat also includes butter.

There’s preliminary evidence to show omega-3 fats might protect the gut. For example, a 2010 study showed that higher ratio of omega-3 to omega-6 in the red blood cells reduced relapse of inflammatory bowel disease (IBD). However, other studies have shown little to no protection from omega-3 supplements.

Finally, there’s research to show fats increase intestinal permeability. Apparently, fat helps to transport bacterial toxins (LPS) through the gut wall.

Altogether, these results show that high fat diet can result in increased endotoxemia, which in turn could be triggered by repeated ingestions of single high fat meals. Indeed, lipid digestion and chylomicrons secretion can promote intestinal absorption of LPS from gut microbiota, which could contribute to post prandial inflammatory responses and thus to the onset and maintenance of chronic low-grade inflammation.

Laugerette, F., Vors, C., Peretti, N. & Michalski, M.-C. C. Complex links between dietary lipids, endogenous endotoxins and metabolic inflammation. Biochimie 93, 39–45 (2011).

Let’s take a moment to reflect here. I don’t want you to get the impression that you have to go on a low-fat diet to clear your skin. Not at all. Remember that there’s a lot of other research to show carbohydrates spike insulin and cause acne that way.

Aim for a balanced diet that contains a decent amount of fat and unprocessed carbohydrates that support the health of your gut bacteria.

Finally, this is one explanation for people who have noticed that going low-carb and eating a lot of fat causes acne for them.


Fructose, or fruit sugar, is another food to watch out for. A 2014 study on teenagers showed that even relatively moderate amounts of fructose can increase intestinal permeability (leakage through the gut wall) and result in endotoxemia.

In the study, they gave two groups of teenagers three 12-oz (350 ml) cans of either fructose or glucose-sweetened drinks to replace their usual consumption of sweetened beverages. After just two weeks, the levels of endotoxins in the blood increased by 19% in the group that got the fructose-sweetened drinks. They increased further 2% during the following two weeks. In contrast, the endotoxin levels did not change in the group consuming the glucose-sweetened beverages.

The researchers concluded:

Putting our data together with the previous studies, it appears possible that when subjects are chronically exposed to a high fructose environment, endotoxemia and subsequent activation of inflammatory cytokines occur and promote insulin resistance in the liver thus contributing to NAFLD [non-alcoholic fatty liver disease]

Jin, R. et al. Fructose induced endotoxemia in pediatric nonalcoholic Fatty liver disease. Int J Hepatol 2014, 560620 (2014).

I want to stress that just because consuming too much fructose causes health problems, it doesn’t mean you should avoid fruits. The amount of fructose you’ll get from fruits is usually far lower than the amounts you’ll get from foods and beverages sweetened with high-fructose corn syrup.

The takeaway here is to avoid foods and drinks with a lot of added sugar.


The term FODMAP is an acronym, deriving from “Fermentable Oligo-, Di-, Mono-saccharides And Polyols”. FODMAPs are short-chain carbohydrates that are poorly absorbed in the small intestine.

Because FODMAPs are not properly absorbed, they are available for bacterial fermentation. It’s important to keep in mind that everyone has trouble absorbing FODMAPs, but they don’t cause problems for most people.

While we don’t yet know for sure, it’s likely that SIBO (small intestine bacterial overgrowth) is what makes the difference. FODMAPs are rapidly fermented and quickly yield lots of gas. Other than some wind, that gas wouldn’t cause problems in the large intestine. However, if the fermentation happens in the small intestine, the gas gets trapped and causes bloating, cramping, and other GI symptoms.

Studies have shown that high FODMAP diets cause significantly more digestive problems than low FODMAP diets on people with IBS, whereas people without IBS just experience more flatulence. The gasses also affect motility (how quickly food passes through the gut) and may lead to constipation or loose stools – depending on the gasses are produced.

FODMAPs are found in many foods people consider healthy, including:

  • Onions, garlic, leek
  • Strawberries, blackberries
  • Dairy products
  • Wheat, barley, rye
  • Apples, nectarines, peaches, plums, pears
  • Beans, soy, soy milk

Stanford University has a PDF that lists high FODMAP foods along with suitable low FODMAP alternatives as well as tips and menu ideas. I highly recommend you download and print/save the PDF to keep it with you while shopping. Here’s the link:

The bad news is that a low FODMAP diet can be quite restrictive. The good news is that once your gut is in order, you can probably get away with eating more FODMAPs. There’s reason to believe that changing the bacterial population in the gut can make you more tolerant to FODMAPs and other quickly-fermenting carbohydrates. Many of the ‘core bacteria’ in the gut (Lactobacilli, Bifidobacterium) don’t produce gas; they produce short-chain fatty acids (like butyrate). Supporting such bacteria can reduce the number of gas-producing bacteria, which would mean better FODMAP tolerance.

You’ll likely find that you can tolerate some FODMAP groups better than others. The FODMAP groups are:

  • Fructose (fruits and sweeteners)
  • Lactose (dairy)
  • Fructans (vegetables, grains)
  • Galactans (legumes)
  • Polyols (fruits, vegetables, sweeteners)

Even after fixing your gut, I recommend keeping the biggest offenders; onions, garlic, and wheat, to the absolute minimum.


Gluten is a protein composite found in wheat and related grains. It’s a composite of proteins glutenin and gliadin.

Pioneering work by Dr. Alessio Fasano has shown how gliadin causes intestinal permeability.

The intestinal wall faces a serious challenge. On one hand, it has to allow the passage of nutrients. On the other hand, it has to keep out bacterial toxins and other harmful substances. To do this, the intestinal wall must be able to regulate permeability. One way it achieves this is by opening and closing of the gaps between the cells that make up the intestinal wall. In medical speak, these gaps are called tight junctions.

Zonulin is a protein that regulates these tight junctions between intestinal cells.

Research by Dr. Fasano and colleagues showed that exposing intestinal cells to gliadin causes them to release zonulin and open up the tight junctions – causing intestinal permeability.

These combined data demonstrate that Zot [zonulin] regulates TJ [tight junctions] in a rapid, reversible, and reproducible fashion.

Fasano, A. Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer. Physiol. Rev. 91, 151–75 (2011).

The link between zonulin and intestinal permeability is so robust that the levels of zonulin in the blood are used to detect intestinal permeability.

Zonulin has been linked to other health problems, among others:

  • An Indian study from 2014 showed that zonulin and LPS levels are linked to diabetes. The study showed that those with higher levels of LPS in the blood were 13 times more likely to develop type-2 diabetes.
  • A 2015 study on PCOS patients showed that women with PCOS have significantly higher levels of zonulin in the blood and that the higher the zonulin levels were, the more menstrual problems the women experienced.
  • A 2005 study linked zonulin to skin problems. The study showed that 87.5% of the dermatitis herpetiformis patients in the study had higher than average blood zonulin levels, which were linked to increased intestinal permeability and inflammatory damage in the skin.
  • A 2012 study linked high blood zonulin levels to elevated blood sugar, insulin, and inflammation levels.

While these results seem alarming, this doesn’t mean everybody has to avoid gluten, or that avoiding gluten would even be beneficial to everybody. I go more into detail about this in the gluten page LINK in the diet chapter.


Lectins are a family of proteins found in nearly all foods, but they are especially high in legumes and grains. Most plants don’t ‘want’ to be eaten and develop defense mechanisms. Lectins are thought to be one such mechanism.

When consumed in large quantities, lectins are toxic, even deathly. While most of the research is highly preliminary, they have been shown to cause intestinal permeability in animal studies (nobody has looked at whether the same happens in living humans). Once in the blood, lectins stimulate the immune system and have been linked to various autoimmune diseases.

Recent research has suggested that these lectins may effectively serve as a vehicle allowing foreign proteins to invade our natural gut defenses and cause damage well beyond the gut, commonly in joints, brain, skin and various body glands…

When consumed in excess by sensitive individuals, they can cause 3 primary physiological reactions: they can cause severe intestinal damage disrupting digestion and causing nutrient deficiencies; they can provoke IgG and IgM antibodies causing food allergies and other immune responses and they can bind to erythrocytes, simultaneously with immune factors, causing hemagglutination and anemia.

Hamid, R & Masood, A. Dietary lectins as disease causing toxicants. Pakistan Journal of Nutrition (2009).

That being said, most people have no problems with eating foods that contain lectins. One, because most lectins are destroyed during cooking. And two, the gut can easily deal with the small amounts of lectins that are left after cooking.

So why am I mentioning lectins if most people can eat them without any problems? Because they can be an issue for people who, for whatever reason, are more sensitive to them. For individuals who struggle with allergies, autoimmune issues, or just seem sensitive to almost everything. In such cases, eliminating lectins can be a big help. It might be the key to stopping the rampant inflammation and put them back on the road to health and clear skin.

Lectins are mainly found in these food families:

  • Legumes; all beans, including soybeans and peanuts
  • Grains; especially wheat, white rice is unlikely to be a problem
  • Nightshades (potatoes, tomatoes, eggplants, bell peppers, hot peppers); unlikely to be an issue for most people
  • Dairy products
  • Eggs

For more on lectins and how to do a lectin elimination and re-challenge, please see the lectins page in the diet section.

Try lectin and gluten elimination diet for 2 to 3 weeks

If you suspect gluten or lectins cause problems for you, I recommend 2 to 3-week elimination diet followed by a rechallenge. Please see the lectins page for details on how to do this.

Other possible trigger foods

Compiling a definitive list of trigger foods for gut problems is problematic, to say the least. Mainly because what triggers gut problems for one person may not cause any problems for another. However, a 2007 review complied common trigger and safe foods based on patient feedback. Common trigger foods include:

  • Milk and milk containing products: such as ice cream, cream cheese, cheese, cottage cheese, yogurt, ice milk, cream soups, butter, pudding, whipped cream, cream, cheesecake, chocolate, pastries, crackers, pretzels, cookies, etc.
  • Caffeine-containing products: such as coffee, tea, colas, sodas, chocolate, etc.
  • Alcohol products; beer, wine, coolers, foods containing or cooked in alcohol.
  • Fruits and fruit juices; particularly apples, apple juice or cider, citrus fruits, orange juice, tomatoes, tomato juice, etc.
  • Spices and seasonings; hot sauce, barbecue sauce, chili sauce, salsa.
  • Diet beverages, diet foods, diet candies, diet gum, sugar free products, “lite or light” products that look good and taste good, but to not put on weight, go right through you, causing diarrhea, or stay in the GI tract and cause symptoms.
  • Fast foods and Chinese food; contain spices, sauces, and hidden ingredients.
  • Condiments; ketchup; mustard; mayonnaise; relish.
  • Fried foods and fatty foods.
  • Whole grain or multigrain breads; sourdough breads and bagels.
  • Salads; usually not the lettuce, but rather added ingredients such as bacon bits, croutons, onions, peppers, etc.
  • Salad dressings; particularly those containing mayonnaise, cheese and spices.
  • Vegetables; particularly cabbage, broccoli, cauliflower and corn.
  • Legumes; beans, lentils, chili, etc. Popcorn. Foods with high fiber content.
  • Red meats; steak, hamburger, sausage, bacon, prime rib. Spicy marinades or gravies tend to cause even greater problems.
  • Gravies, spaghetti sauce, cream sauces, cheese sauces, soups, stews, and stuffing.
  • Artificial flavorings, preservatives, and sweeteners.
  • Foods containing large amounts of fructose or high fructose corn syrup (honey, grapes, raisins, nuts, etc).
  • Cookies, crackers, pretzels, cakes and pies.

I realize that this list is very extensive and might make you feel like there’s nothing left to eat. But keep in mind that it’s highly unlikely all of the above cause problems for you. Please consider the above list as a starting point for your own investigation.

Also, many of the foods above fall into the problem food categories we discussed above. Many of the beans, grains, and vegetables contain FODMAPs, and low FODMAP alternatives are likely to be safe.


Stress is one of the biggest factors in most, if not all, of the gut-related problems. A 2015 paper titled “Stress induces endotoxemia and low-grade inflammation by increasing barrier permeability” reviews the many effects stress has on the gut, including:

  • Increases intestinal permeability. In a 2014 study, the researchers measured intestinal permeability before and after public speaking stress; the participants were asked to give an impromptu speech. Their results showed that stress caused about 50% increase in intestinal permeability.
  • Alters the bacterial balance in the intestines. Animal studies show stress reduces the numbers of probiotic bacteria and supports the growth of harmful bacteria in the gut.
  • Causes inflammation in the gut wall. Stress has long been known to cause inflammation in the gut and aggravate inflammatory bowel conditions.
  • Stress reduces ‘motility’ (the time it takes for food to move through the gut), which in turn encourages SIBO and growth of pathogenic bacteria.
  • Stress reduces stomach acid secretion, which in turn again encourages the bacteria to migrate up to the small intestine.

About Me

Hi, I am Acne Einstein(a.k.a. Seppo Puusa). I'm a bit of a science nerd who is also passionate about health. I enjoy digging through medical journals for acne treatment gems I can share here. You can read more about my journey through acne and how I eventually ended up creating this.