Gut Inflammation: 12 Causes (and 12 Effects)

I’ve previously discussed how your gut microbiome influences essentially every aspect of your health. However, gut inflammation is also a crucial determinant of intestinal and whole-body health. Read on to learn how various diet and lifestyle factors cause gut inflammation, the health consequences of a chronically inflamed gut, and practical strategies for alleviating inflammation and restoring gut health. 

Gut inflammation can contribute to the development of a wide range of serious conditions like type 2 diabetes, Parkinson’s disease, cardiovascular disease, and more. Find out what causes inflammation and what you can do to correct it. #optimalhealth #chriskresser

A Primer on the Gut

Gut health is influenced by two related variables: the intestinal barrier and the gut microbiota. Disturbances in either one of these factors can induce gut inflammation, inciting a chain reaction of damage that begins locally and may spread systemically throughout the body.

The Intestinal Barrier

The intestinal barrier is a multilayer system made up of intestinal epithelial cells, proteins, protective mucus, and immune cells. Enterocytes are absorptive cells that make up most of the epithelial cell layer of the intestine. Goblet cells are interspersed among enterocytes and secrete protective mucus that serves as a habitat for commensal bacteria (or the gut’s normal inhabitants) and inhibits infection by pathogens. Together, enterocytes and goblet cells function as “gatekeepers” of the gut, regulating gut bacterial interactions with the host immune system. (1)

M cells and Paneth cells have immune system functions, presenting gut luminal contents to the immune system, and releasing antimicrobial molecules such as lysozyme. (2, 3) Altogether, the intestinal barrier prevents the passage of non-nutritive substances and pathogens from the gut lumen into the systemic circulation, supports digestion, and regulates immunity.

Intestinal epithelial cells are bound together by tight junction proteins, including zonula-occludens-1, claudin-1, and occludin, forming a semipermeable seal between the gut lumen and the systemic circulation. This seal is delicate and easily disturbed by a variety of dietary and lifestyle factors. When intestinal barrier integrity is compromised, minuscule gaps open up between epithelial cells, allowing molecules to escape from the gut lumen into the systemic circulation. This condition is referred to as “leaky gut.” Leaky gut, in turn, causes the body to launch inflammatory responses both locally in the gut and systemically in distant tissues and organs.

Gut Microbiota

The human gut is home to 100 trillion microorganisms and their gene set, which is at least 150 times greater than our own. (4, 5, 6) Collectively referred to as the “gut microbiota,” these microbes and their genetic material co-evolved with the human species and influence nearly every aspect of our health. It is a crucial driver of immune system development and inflammatory balance both locally in the gut and systemically in distant tissues and organs. 

Dysbiosis is a disruption of the gut microbial community by various stressors, such as an unhealthy diet and antibiotics. Dysbiosis promotes gut inflammation, and, if left unchecked, contributes to the development of chronic diseases such as inflammatory bowel disease (IBD), colon cancer, obesity, and asthma.

12 Diet and Lifestyle Factors That Can Cause Gut Inflammation

1. Gluten, for Those with Celiac Disease or Non-Celiac Gluten Sensitivity

Gluten proteins are the primary energy storage proteins of wheat, barley, and rye. Localized in the endosperm of these grains, the gluten family encompasses a wide variety of proteins, including gliadins and glutenins.

Gluten causes inflammation in people with celiac disease and non-celiac gluten sensitivity (NCGS). Celiac disease is an autoimmune response to gluten marked by the disruption of healthy intestinal tissue structure, gastrointestinal (GI) distress, and extraintestinal symptoms such as rashes and anemia. (7) NCGS is characterized by intestinal and extraintestinal symptoms triggered by gluten in the absence of celiac disease and wheat allergy. (8) For many years, NCGS was diagnosable only through a gluten elimination diet; however, innovative labs such as Cyrex have now made it possible to test for NCGS in the clinical setting.

Gluten triggers gut inflammation in susceptible individuals by binding to intestinal CXCR3 receptors, prompting the release of zonulin. Zonulin is a protein that facilitates the breakdown of tight junction proteins between intestinal epithelial cells, increasing intestinal permeability and gut inflammation. (9) Gluten also activates intestinal mast cells, which release proinflammatory molecules such as histamine and tryptase that perpetuate gut inflammation. (10, 11)

It’s important to note that gluten doesn’t cause inflammation in everyone. Those without celiac disease or NCGS may be able to tolerate gluten in their diet.

2. Industrial Seed Oils

Industrial seed oils, the highly processed oils extracted from soybeans, corn, rapeseed (the source of canola oil), cottonseed, and safflower seeds, occupy a majority stake in the Standard American Diet. Introduced to the human diet less than two centuries ago, these oils represent an evolutionary mismatch and promote gut inflammation.

The high omega-6 fatty acid content of industrial seed oils makes them susceptible to damage from heat and light. Processing and cooking with industrial seed oils create oxidized, inflammatory byproducts that, when consumed, induce gut inflammation. Indeed, a diet rich in industrial seed oils has been found to provoke gut inflammation, while also enhancing the growth of intestinal pathogens. (12, 13, 14)

3. Acellular Carbohydrates

Acellular carbohydrates are carbohydrate-containing foods that lack cell walls, such as flour and sugar, and thus have a high carbohydrate density. Acellular carbohydrates abound in the Standard American Diet and promote an inflammatory gut microbiota. (15) Cellular carbohydrates, on the other hand, are carbohydrate-containing foods with intact cells, such as sweet potatoes and whole fruit. Unlike acellular carbohydrates, cellular carbohydrates promote gut health by fueling the growth of anti-inflammatory gut bacteria.

4. Food Additives

Ultraprocessed foods comprise nearly 60 percent of energy intake in the United States and are loaded with food additives. (16) Most food additives have not undergone long-term safety studies, a troubling fact given the accumulating evidence of their harmful effects on gut inflammation.

Maltodextrin, a synthetic carbohydrate used as a thickener and preservative in processed foods, enhances the adhesion of harmful bacteria to intestinal cells, and promotes biofilm formation. (17) The artificial sweetener Splenda stimulates the growth of inflammatory gut bacteria. (18) Carrageenan, a seaweed-based polysaccharide used for its thickening and emulsifying properties, exacerbates IBD. Carboxymethylcellulose and polysorbate-80, two more ubiquitous food emulsifiers, increase intestinal permeability. (19, 20) Titanium dioxide, a whitening and brightening agent, provokes an inflammatory cytokine response in the gut. (21) To keep gut inflammation at bay, avoidance of these ubiquitous food additives should be a top priority.

5. C-Section Birth and Formula Feeding

C-section birth profoundly alters the developing infant gut, seeding the microbiome with microbial species derived from the surrounding environment, rather than beneficial microbes from the mother’s vaginal canal. Infants delivered via C-section are also exposed, via the placental circulation, to antibiotics administered to their mothers to prevent postoperative infection. This early-life antibiotic exposure further skews infant gut microbiota development, predisposing a child to gut inflammation and chronic inflammatory diseases, such as asthma and obesity, down the road. (22)

Formula feeding is also problematic for the fragile infant gut. Formula feeding promotes the growth of inflammatory gut bacteria and increases intestinal permeability and total bacterial load. (23) Conversely, breastfeeding increases colonization of the infant’s gut with anti-inflammatory Lactobacillus and Bifidobacteria, reducing the risk of gut inflammation and chronic inflammatory diseases. (24)

6. Gut Infections

Bacterial, viral, fungal, and parasitic gut infections alter the composition of the gut microbiota, creating a proinflammatory intestinal environment. (25, 26, 27, 28) For example, the influenza A virus transiently increases susceptibility to the Salmonella pathogen by reducing protective commensal bacteria, while Helicobacter pylori infection enhances the growth of Prevotella, a proinflammatory bacterium. (29, 30)

An acute bout of food poisoning can also trigger gut inflammation and irritable bowel syndrome (IBS) by stimulating intestinal production of inflammatory autoantibodies. (31)

7. Stress

The human gut is acutely sensitive to chronic stress. Chronic psychological stress increases intestinal permeability and allows lipopolysaccharide (LPS), an inflammatory bacterial byproduct, to enter the blood circulation; this causes both localized and systemic inflammatory responses. (32) Stress also depletes the protective GI mucous layer and increases bacterial adhesion and penetration into intestinal epithelial cells, provoking gut inflammation. (33, 34)

8. Sedentary Lifestyle and Overtraining

Moderate exercise boosts beneficial gut bacteria, including anti-inflammatory short-chain fatty acid (SCFA)-producing bacteria, thus inhibiting gut inflammation. (35, 36) Conversely, a sedentary lifestyle is associated with increased infiltration of inflammatory molecules into the gut. (37)

Importantly, while moderate exercise is good, more is not necessarily better. Excessive physical activity increases intestinal permeability and negatively alters the gut microbiota. If you have a chronic inflammatory illness or are under significant psychological stress, you’ll want to limit strenuous exercise and focus on gentler activities such as walking, yoga, or swimming. (38, 39, 40)

9. Circadian Rhythm Disruption and Sleep Loss

Your circadian rhythm is a set of internal biochemical processes that occur in approximately 24-hour cycles and regulate many aspects of your physiology, including gut health and inflammation. When the circadian rhythm is disrupted by factors such as evening blue light exposure and irregular sleep schedules, gut health suffers. Circadian disruption has been found to promote the growth of inflammatory gut bacteria, decrease beneficial microbes, and upregulate intestinal permeability and LPS transport into the systemic circulation. (41, 42)

Sleep loss is closely linked to circadian disruption and is equally harmful to gut health. Just two nights of partial sleep deprivation induces changes in the gut microbiota, increasing proinflammatory bacterial species. (43) Insufficient sleep also exacerbates gut inflammation in IBD. (44, 45) To minimize gut inflammation, supporting your circadian rhythm and optimizing your sleep is crucial. (46)

10. Antibiotics

The frequency with which clinicians prescribe antibiotics has instilled a false sense of security in many patients; after all, your doctor wouldn’t prescribe you a drug unless you really needed it, right? Unfortunately, flippant prescribing of antibiotics is the norm in our society, and the effects on gut health tend to be minimized. However, abundant research indicates that antibiotics can have long-term deleterious effects on the gut microbiota and induce gut inflammation. (47)

Antibiotics reduce the diversity and abundance of commensal gut bacteria, allowing the overgrowth of inflammatory pathogens such as Clostridium difficile and pathobionts such as Escherichia and Candida. (48) These microbial changes can last for months or years after cessation of the antibiotic. Their adverse effects are most pronounced in infants and young children, who are going through a critical time window in their gut microbiota development. (49)

Alarmingly, antibiotic-resistant bacteria have been found to morph into more inflammatory versions of themselves upon exposure to antibiotics. (50) Antibiotic use also increases intestinal permeability, thus reducing the gut’s natural immune defenses. (51) Antibiotic treatment thus directly promotes gut inflammation.

11. Non-Antibiotic Drugs

I’d wager that very few clinicians consider the impact of non-antibiotic drugs on their patients’ gut health before pulling out their prescription pad. However, a growing body of evidence indicates that this is a significant oversight, as multiple classes of non-antibiotic drugs alter the gut microbiota and induce gut inflammation. (52)

Proton-pump inhibitors (PPIs), used in the treatment of gastroesophageal reflux disease (GERD) and acid reflux, decrease stomach acid. When the stomach produces sufficient acid, bacterial entry from the environment into the gut is limited. By inhibiting stomach acid production, PPIs allow more bacteria to enter the digestive tract and proliferate in the small intestine, inducing bacterial overgrowth and gut inflammation. PPIs also reduce the growth of anti-inflammatory SCFA-producing bacteria. (53) PPIs really do a number on the gut.

Selective serotonin reuptake inhibitors (SSRIs) are known to cause constipation and appetite changes; preclinical studies indicate that fluoxetine (Prozac) alters gut microbial community structure, increasing dysbiotic gut bacteria. (54)

Oral contraceptives also trigger gut inflammation. In fact, their use is associated with an increased risk of Crohn’s disease, a subtype of IBD. (55, 56)

12. Environmental Toxins

Thousands of new chemicals are developed by industries each year. In the United States, most of these chemicals do not undergo comprehensive safety testing before release. (57) This fact is alarming, considering the host of adverse health effects linked to existing chemicals in our environment.

Gut inflammation is one of the most frequently cited consequences of exposure to environmental toxins. Bisphenol A (BPA), found in plastic water bottles and food containers, children’s toys, and cash register receipts, promotes gut inflammation by increasing harmful gut bacteria and intestinal permeability. (58, 59) Alternative plasticizers, found in BPA-free products, are equally, if not more, damaging.

Triclosan, a synthetic antibacterial agent used in hand sanitizers and personal care products, also increases intestinal inflammation. (60) Glyphosate, the main component of Roundup herbicide, decreases Lactobacillus and facilitates the growth of antibiotic-resistant Escherichia coli, suggesting that glyphosate acts as an antibiotic in the gut microbiome. (61)

12 Consequences of Intestinal Inflammation

An inflamed gut predisposes you to an array of chronic diseases, ranging from IBD and colon cancer to autism and Alzheimer’s disease. Stopping gut inflammation in its tracks is essential for both the prevention and management of chronic disease. 

1. Allergies

Gut inflammation may be at the root of seasonal allergies. An imbalance between beneficial and harmful gut microbes increases the release of proinflammatory cytokines in the gut. These cytokines stimulate mast cell, basophil, and eosinophil activity, which induce allergic inflammation. Dysbiosis-associated gut inflammation is linked to atopic dermatitis and food allergies. (62)

A healthy gut, on the other hand, inhibits allergic sensitization through the release of anti-inflammatory SCFAs and immune-balancing T regulatory cells.

2. Autoimmune Diseases

Gut inflammation is a preceding factor in the development of autoimmune diseases. (63, 64, 65) Individuals with type 1 diabetes demonstrate higher circulating levels of LPS compared to individuals without diabetes. (66) Zonulin, a protein released in the gut when the intestinal barrier is compromised, is higher in people with autoimmune diseases compared to healthy controls, denoting the role of leaky gut in autoimmune diseases. (67) Gluten sensitivity and chronic stress are two triggers of gut inflammation that often precede autoimmunity. (68, 69)

3. Arthritis

Inflammatory alterations in the oral and gut microbiota, including overgrowth of the cariogenic bacterium Porphyromonas gingivalis and decreased commensal bacteria, are associated with the progression of arthritis. Dysbiosis and leaky gut induce a systemic inflammatory response, triggering the release of cytokines that cause musculoskeletal degeneration. (70, 71) Conversely, anti-inflammatory commensal bacteria and SCFA have been found to alleviate arthritis and protect against bone loss. (72)

4. Cardiovascular Disease

Cardiovascular disease (CVD) is the leading cause of death worldwide, and medication and surgery are the cornerstones of conventional medical treatment. (73) However, growing evidence of the link between the gut and heart health suggests that gut-targeted therapies may be the treatment of the future for CVD.

Multiple inflammatory processes within the gut impact the course of CVD. (74) Dysbiosis contributes to CVD through the release of LPS and peptidoglycan (PG), inflammatory cell wall components of Gram-negative and Gram-positive bacteria that promote atherosclerotic plaque formation and hypertension. Dysbiosis also affects bile acid metabolism, impairing the excretion of blood lipids such as cholesterol and triglycerides. (75)

5. GI Disorders

IBD

Gut inflammation is a key feature of IBD, including ulcerative colitis and Crohn’s disease. A series of detrimental gut changes, including dysbiosis and increased intestinal permeability, contribute to the progression of IBD. (76)

IBS

Until recently, the role of gut inflammation in IBS was unclear. However, research has since elucidated the role of mast cells, immune cells that release irritating compounds such as histamine, and persistent low-grade inflammation in the pathogenesis of IBS. (77)

In people with diarrhea-predominant IBS or mixed IBS, autoimmunity may also play a role in gut inflammation. In these forms of IBS, a past episode of food poisoning can lead to the production of autoantibodies that damage the GI tract.

Colorectal Cancer

Colorectal cancer is the fourth most common cancer in the United States in both men and women, and the third leading cause of cancer-related deaths in the United States. (78) Research suggests that pre-existing GI inflammation precedes the development of colorectal cancer. (79) Several inflammatory triggers of colorectal cancer have been identified, including gut pathogens, low levels of butyrate-producing bacteria, and the processed, refined Western diet. (80)

Diverticulitis

Diverticulitis, an irritation of the walls of the intestines, is triggered by gut inflammation. It is characterized by dysbiosis in the colon and elevated fecal calprotectin, a protein released by white blood cells when there is active inflammation in the GI tract. (81)

6. Depression and Anxiety

Emerging research indicates that immune system activation plays a central role in the development of depression and anxiety. (82) The human gut harbors approximately 70 percent of the immune system, so it’s no surprise that gut inflammation significantly impacts mental health. (83)

The gut–brain axis, a bidirectional signaling network between the enteric nervous system of the gut and the central nervous system, mediates the relationship between gut inflammation and mental health. Inflammatory stimuli in the gut send signals along this axis to the brain, inducing neuroinflammation and altering neurotransmitter production. The consequence of these biochemical changes is altered brain activity, including depression and anxiety.

Inflammatory gut–brain axis signaling is triggered by gut dysbiosis and intestinal barrier dysfunction, both of which are common in people with depression and anxiety. People with depression and anxiety also demonstrate a reduced ability to counteract gut inflammation due to decreased intestinal levels of anti-inflammatory SCFA. (84, 85, 86, 87)

7. Neurodegenerative Disease

The gut–brain axis also plays a pivotal role in neurodegenerative diseases. Gut inflammation is recognized as a “silent driver” of Parkinson’s disease, with inflammation preceding the onset of symptoms by as much as two decades. (88) A gut-derived inflammatory response has also been found to precipitate the deposition of amyloid-beta plaques, which contribute to neuronal degeneration and cognitive dysfunction in Alzheimer’s disease. (89)

8. Neurodevelopmental Disorders

Neurodevelopmental disorders are exploding in prevalence around the world; the prevalence of autism has increased to one in 59 children while, as of 2016, 11 percent of children and adolescents have been diagnosed with attention-deficit/hyperactivity disorder (ADHD) or attention deficit disorder. (90, 91) Pediatric acute-onset neuropsychiatric syndrome (PANS) and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are emerging neurodevelopmental disorders characterized by a sudden onset of tics and obsessive-compulsive disorder.

Research indicates that dysbiosis and gut inflammation are contributing factors in each of these disorders. Children with ADHD demonstrate decreased gut microbial alpha-diversity, a measure of the number of bacterial species in the gut; higher diversity is generally associated with better health outcomes. (92) Children on the autism spectrum and those with PANS/PANDAS also demonstrate dysbiosis. (93, 94) These inflammatory changes alter crosstalk between the gut and brain, ultimately inducing neurobehavioral deficits.

9. Osteoporosis

Several lines of evidence indicate that gut inflammation promotes osteoporosis by disrupting the balance between bone-building and bone-resorbing cells, leading to a net loss of bone mass. Gut inflammation also decreases the absorption of critical bone-building nutrients, including vitamin D, calcium, and magnesium. (95)

10. Skin Conditions

I’ve written at length about the connection between gut and skin health mediated by the gut-skin axis. Much like the gut-brain axis, the gut-skin axis is a network of signaling molecules that connects the gut and its microbes with the skin. Inflammatory changes in the gut, including dysbiosis and increased intestinal permeability, are linked to a spectrum of skin conditions including acne, psoriasis, rosacea, and eczema. (96, 97, 98)

11. Metabolic Syndrome, Type 2 Diabetes, and Obesity

Metabolic syndrome, type 2 diabetes (T2D), obesity, and gut inflammation form a vicious cycle: blood sugar dysregulation and excess body fat promote gut inflammation, while gut inflammation exacerbates metabolic dysfunction.

Gut dysbiosis and circulating LPS induce insulin and leptin resistance, key features of metabolic syndrome, T2D, and obesity. (99) Acellular carbohydrates and exposure to obesogenic environmental toxins, including BPA and phthalates, alter the gut microbiota. These microbial changes incite gut inflammation and influence the progression of metabolic dysfunction. (100, 101, 102)

12. Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD), an accumulation of excess fat in the liver in people who consume little or no alcohol, is closely related to metabolic syndrome, T2D, and obesity. A compromised gut microbiota appears to drive inflammation in NAFLD, whereas beneficial gut-targeted therapies, such as probiotics, alleviate liver inflammation and dysfunction. (103, 104)

How to Correct Gut Inflammation

It’s nearly impossible to find a health disorder in which gut inflammation doesn’t play a role! Diet and lifestyle strategies that relieve gut inflammation and restore gut health should thus be a central part of any protocol designed to prevent or reverse chronic disease.

Eat a Nutrient-Dense, Unprocessed Diet

A nutrient-dense, unprocessed diet provides the substrates (i.e., fermentable fibers, polyphenols, and other nutrients) that your gut bacteria need to thrive, creating an anti-inflammatory gut ecosystem. A particular focus on prebiotic foods can bolster your levels of anti-inflammatory SCFA-producing bacteria. Avoid acellular carbohydrates, including refined flour-based products, and industrial seed oils.

For people with severe gut inflammation, such as IBD, an autoimmune protocol diet can offer significant relief.

Address Dysbiosis and Food Sensitivities

Food sensitivities and dysbiosis keep the gut in a perpetual state of inflammation, so identifying these issues is critical for restoring gut health. Cyrex is my preferred lab for gluten and food sensitivity testing, while Genova Diagnostics and Doctor’s Data offer good commercial stool testing options for microbiome assessment. Probiotics and prebiotics can be used to alleviate gut inflammation, with specific probiotic strains indicated for particular conditions; for example, “psychobiotics” such as Lactobacillus rhamnosus counteract gut inflammation to improve mental health. (105)

Manage Stress

Chronic stress can really wreck your gut health, so managing your stress is crucial for reducing gut inflammation. Meditation regulates the stress response, helping to maintain healthy gut barrier function and inflammatory balance. (106) A consistent exercise routine and healthy sleep habits are also crucial for managing stress and supporting gut health.

Be a Conscientious Consumer of Pharmaceutical Drugs

To limit gut inflammation, be judicious about your use of antibiotics and non-antibiotic drugs. While our understanding of the effects of non-antibiotic drugs on gut health is in its infancy, the available information is worrisome. Conversely, the evidence of the harmful effects of antibiotics on the gut is robust. If you are currently on PPIs, read my article “How to Cure GERD without Medication” to learn how diet and lifestyle changes can reduce or eliminate your need for acid-suppressing drugs.

Limit Your Exposure to Toxins

Environmental toxins are everywhere, but there are some simple steps you can take to reduce your exposure and protect against gut inflammation:

• Forgo receipts when you shop to limit your exposure to BPA.
• Use stainless-steel or glass water bottles and food storage containers rather than plastic at home.
• Filter your drinking and bathing water with a high-quality water filter.
• Use organic and natural personal care products. Check out the EWG’s Skin Deep Cosmetics Database for information on how to shop for healthy personal care products.
• Don’t use pesticides in your yard or inside your home.

Taking these simple steps will reduce your cumulative exposure to environmental toxins, removing an important obstacle to long-term gut health and whole-body well-being.