Chronic inflammation is responsible for the leading causes of death worldwide. The prevalence of diseases associated with chronic inflammation is anticipated to continue to rise. Inflammation can occur anywhere in the body and is implicated in many health conditions like Alzheimer’s disease, heart disease, cancer, autoimmune diseases, and type 2 diabetes. In the gastrointestinal tract, inflammation is involved in conditions like inflammatory bowel disease (IBD), gastritis, diverticulitis, celiac disease, and irritable bowel syndrome (IBS). While these diseases are typically the results of local inflammation, they can contribute to systemic (whole-body) inflammation as well. 

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What Is Gut Inflammation?

Inflammation is a mechanism our body’s immune system uses to protect against harmful stimuli and heal injuries. Our gastrointestinal tract is constantly exposed to a variety of stimuli, including food proteins, bacteria, viruses, fungi, and toxins. Due to this constant exposure, the gastrointestinal tract can experience both acute and chronic inflammation. Acute inflammation occurs when the body fights off an infection or heals an injury. It typically resolves within a few hours to days. An example of acute gastrointestinal inflammation would be viral gastroenteritis. Chronic inflammation occurs when the process does not resolve normally and lasts for prolonged periods, like months to years. Examples of chronic inflammation in the gastrointestinal tract include reflux esophagitis, celiac disease, ulcerative colitis, and Crohn’s disease. Causes of gastrointestinal inflammation include: (26, 54, 62)

• Diet
• Medications
• Toxins
• Stress
• Infections
• Ischemia
• Dysbiosis
• Excess alcohol consumption
• Smoking, including e-cigarettes

The Gut Microbiome

The microbiome is the collection of bacteria, viruses, fungi, and other microorganisms that live in and on our bodies. The intestinal microbiome is home to over 100 trillion organisms. About 70% of immune cells are located in the gut, where they interact with the microbial organisms that reside there. The composition of our microbiome and its interaction with our immune system play a role in how our immune system develops and functions. Some organisms can stimulate the development of immune cells called regulatory T cells, which help to control immune responses and can prevent excess inflammation, while others stimulate the activity of immune cells involved in promoting inflammation. Beneficial commensal bacteria ferment dietary fibers to create short chain fatty acids (SCFA), which have anti-inflammatory effects. Certain gram-negative bacteria contain lipopolysaccharides (LPS), or endotoxin, in their cell walls. Exposure to excess LPS can lead to inflammation both locally in the gut as well as systemically. Dysbiosis is a term used to refer to an imbalance in the commensal microorganisms that live in the gastrointestinal tract. As research on the microbiome has expanded, dysbiosis has been linked to inflammatory gastrointestinal diseases such as IBS, Crohn’s disease, ulcerative colitis (UC), and colorectal cancer (CRC), as well as systemic inflammatory diseases like type 2 diabetes, obesity, and autoimmune diseases.

Factors Contributing to Gut Inflammation

Certain medical conditions, like autoimmune diseases, infections, and ischemia, can cause gut inflammation. In addition to these conditions, certain lifestyle and environmental factors can also contribute to inflammation.

Diet

Our dietary choices influence the composition of the microbiome. Western-style diets that are high in fat, particularly saturated fat, and processed foods cause dysbiosis and gut inflammation. Lower amounts of bacteroides and higher amounts of firmicutes and proteobacteria are seen in the microbiomes of individuals who eat high fat diets. Dietary fiber increases microbial diversity and supports the growth of beneficial commensal bacteria, like lactobacillus and bifidobacterium, which have been shown to inhibit inflammatory responses. Diets high in simple sugars decrease microbial diversity, increase small intestinal permeability, and have been associated with an increased risk of IBD. In animal studies, sugar has been shown to damage Paneth cells (immune cells in the gut that modulate inflammation), decrease SCFA production, increase intestinal permeability, and increase the levels of inflammatory cytokines. These studies suggest possible mechanisms by which high sugar diets might contribute to increased gastrointestinal inflammation in humans. (26, 40, 43)

Lifestyle Factors

The “gut-brain” axis is a term that refers to the bidirectional relationship that exists between the brain and the gastrointestinal system. This axis involves interactions between the nervous system, the endocrine system, and the immune system. Stress negatively impacts gut health through this axis. Research shows that stress can affect intestinal permeability, motility, intestinal secretions, microbiome composition, and intestinal inflammation. Some studies have also found associations between stress and IBD relapse or exacerbation. (26)

Sleep deprivation has been shown to increase inflammatory cytokines, like interleukin-6 (IL-6), that are associated with gastrointestinal diseases, including IBD, gastroesophageal reflux (GERD), liver disorders, and colorectal cancer. (1)

Exercise habits can also influence gut health and inflammation. Over-exercising can disrupt the composition of the microbiome and increase intestinal permeability. Lower intensity exercise, on the other hand, has protective effects, lowering the risk of inflammatory GI conditions like diverticulosis, colon cancer, and IBD. It can reduce transit time, which lowers the interaction between pathogens and the mucosal layer, and it also improves the microbiome composition and production of SCFAs.

Medications

Antibiotics are prescribed to eradicate infections, but in doing so, they also disrupt the host’s microbiome and reduce diversity. (56) This leaves the gastrointestinal tract vulnerable to opportunistic infections, like Candida and Clostridium dificile, as well as small intestinal bacterial overgrowth (SIBO). Antibiotic use has also been identified as a possible risk factor in the development of IBD. (43, 37, 20)

Other medications have also been shown to impact gut health and inflammation. Nonsteroidal anti-inflammatory (NSAID) medications can cause mucosal injury along the entire gastrointestinal tract. The estrogen in oral contraceptive pills can disrupt the microbiome composition and intestinal barrier function. An increased risk of developing IBD is seen in combined oral contraceptive pill use. (26)

Functional Medicine Labs to Assess Inflammation and Gut Health

The following functional labs can help to assess inflammation and gut health:

Comprehensive Stool Test

The Gut Zoomer measures over 300 microorganisms in the stool to identify any dysbiosis or pathogens that can cause inflammation. Furthermore, it measures markers of gastrointestinal inflammation, such as calprotectin and lactoferrin, and zonulin, which can indicate possible intestinal permeability.

Cyrex Intestinal Permeability

The Array 2 measures antibodies that can be useful in identifying patients with intestinal permeability. It provides information on immune reactivity to LPS, the route of intestinal permeability (transcellular or paracellular), and epithelial dysfunction. 

Food Sensitivity Panel & Wheat Zoomer

The Complete Food Sensitivity Panel measures immune responses to 210 foods. The Wheat Zoomer measures antibodies to different proteins in wheat, both gluten-containing and non-gluten-containing. Food sensitivities and intolerances can be contributing factors in both mucosal inflammation in the GI tract and intestinal permeability. 

Adrenal Testing

Genova's Adrenal Stress Profile with Cortisol Awakening Response measures the diurnal rhythm of cortisol via four salivary measurements throughout the day and the Cortisol Awakening Response (CAR), which provides information on how the body is responding to stress.

Systemic Inflammatory Markers

Poor gastrointestinal health and inflammation can lead to an increased risk of systemic inflammation. Markers such as c-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are commonly used to monitor inflammation. The liver produces CRP in higher amounts in the presence of inflammation. ESR measures how quickly red blood cells separate from a blood sample. Inflammation increases the tendency of red blood cells to clump together, making them fall to the bottom faster, causing a higher ESR.

Micronutrient Panel

When there are higher levels of gastrointestinal inflammation, poor digestion and absorption can occur. The Spectracell Micronutrient Test measures 31 vitamins, minerals, and other nutrients to identify any nutritional deficiencies.

Managing Gut Inflammation

There are a multitude of possible triggers for gut inflammation. Therefore, a holistic treatment approach can include dietary and lifestyle modifications, supplement recommendations, and, in more severe cases, medications.

Dietary Changes and Anti-Inflammatory Foods 

A whole-food, anti-inflammatory diet, like the Mediterranean diet, can reduce gastrointestinal inflammation. Foods like refined carbohydrates, fried foods, sugar-sweetened beverages, and processed meats that can negatively affect the microbiome and promote inflammation should be avoided. Foods like whole grains, fruits, vegetables, nuts, and seeds that are good sources of fiber, nutrients, and flavonoids should be emphasized. (21, 64)

Lifestyle Modifications 

Stress can negatively influence the microbiome and intestinal barrier function. Stress management tools, like meditation, can benefit the microbiome and reduce inflammatory markers in inflammatory bowel conditions.

Sleep disruption increases inflammation and can exacerbate inflammatory gastrointestinal conditions. The National Sleep Foundation recommends 7-9 hours of sleep for adults. Implementing a good sleep hygiene routine can be an important first step in improving sleep quality. Good sleep hygiene practices include things like daily physical activity, maintaining similar sleep and wake times each day, keeping the bedroom cool and dark, and avoiding distractions before bed like TV and cell phones. Cognitive behavioral therapy (CBT) can also be considered in patients suffering from both insomnia and gastrointestinal inflammation.

Physical activity influences our microbiomes. Active individuals tend to have higher levels of health-promoting bacterial species and increased bacterial diversity. Research in patients with IBD has shown that sedentary individuals have a higher risk of developing IBD, and moderate physical activity can decrease the risk of relapse. Regular, moderate-intensity exercise is beneficial for promoting overall gut health and reducing inflammation.

Probiotics and Prebiotics 

Dysbiosis can promote gastrointestinal inflammation. Probiotic supplements contain live microorganisms to improve microbiome composition. Taking probiotic supplements can prevent gastrointestinal inflammation by decreasing LPS, increasing mucus production, and preventing the breakdown of tight junction proteins that maintain the intestinal barrier. Prebiotics are fibers that fuel bacterial organisms in the gut. Common prebiotics include fructo-oligosaccharides (FOS) and galacto-oligosaccharides (GOS). Consuming prebiotics increases microbial diversity and improves SCFA production, which can reduce intestinal inflammation.

Medications and Supplements

Medications, like loperamide or bile acid sequestrants, can be prescribed as needed for diarrhea that commonly occurs in gastrointestinal inflammation. In the case of inflammatory bowel diseases, medications are often prescribed to get inflammation under control. Anti-inflammatory drugs, like aminosalicylates and corticosteroids, are often prescribed as first-line treatments. Immunomodulators, such as azathioprine, 6-mercaptopurine, or methotrexate, and biologics, like infliximab or adalimumab, can be used in more moderate-severe cases.

Omega 3s

Omega-3 fatty acids are essential nutrients involved in proper cell structure and function and regulating inflammatory signaling. The most important and bioavailable omega-3 fatty acids are Docosahexaenoic Acid (DHA) and Eicosapentaenoic Acid (EPA), found in fatty fish. The standard American diet tends to be low in omega-3 fatty acids. Omega-3 fatty acids can influence microbiome diversity, decrease inflammatory cytokines and endotoxin (LPS), and regulate the production of SCFAs to reduce gastrointestinal inflammation. Supplementation with EPA & DHA has been used to reduce intestinal inflammation and induce remission in IBD.

Curcumin

Curcumin is a compound found in turmeric. In the gastrointestinal tract, it can regulate the microbiome, modulate inflammatory cytokines, and provide antioxidant protection. Curcumin has been used as a treatment for inflammatory conditions such as IBD and ulcers. Piperine, from black pepper, can be added to curcumin supplements to increase bioavailability.

Colostrum

Colostrum is the first milk produced after birth and is rich in immunoglobulins, peptides, and growth factors. Bovine colostrum aids in mucosal healing in a variety of gastrointestinal conditions where the mucosal barrier has been affected, like NSAID enteropathy, IBD, infectious diarrhea, and injury due to cancer therapies or surgery. (4, 35) 

Glutamine

Glutamine is an amino acid used throughout the body. The intestines utilize about 30% of the body’s glutamine, which demonstrates how important it is in the gastrointestinal tract. It supports intestinal cell growth, regulates intestinal barrier function, balances inflammatory signaling pathways, and protects intestinal cells against apoptosis (cell death). Glutamine has been used as a treatment for multiple forms of gastrointestinal inflammation, including radiation-induced esophagitis, NSAID-induced intestinal permeability, and exercise-induced intestinal permeability.

Zinc Carnosine

Zinc is an essential mineral that is involved in more than 300 biochemical reactions in the body, including DNA and RNA synthesis, which is crucial for tissue repair. It plays a role in maintaining intestinal barrier function. Zinc deficiency has been associated with increased infection risk, delayed wound healing, and intestinal inflammation. Zinc-carnosine is a chelated compound formed by combining a zinc ion with carnosine in a 1:1 ratio. Research has demonstrated its benefit in conditions like H. Pylori infection, peptic ulcers, and chemotherapy-induced enteritis and esophagitis.

Long-Term Consequences of Untreated Gut Inflammation

When inflammation in the gastrointestinal tract is not properly treated, it increases the risk of developing nutritional insufficiencies, strictures and bowel obstruction, cancer, and intestinal ulcers, abscesses, or perforations. Untreated gut inflammation can also cause harm outside of the gastrointestinal tract. Under normal circumstances, the intestinal lining is a semi-permeable barrier. It should allow for the absorption of water and properly digested nutrients and prevent the absorption of partially digested food particles, toxins, and microbes. When there is inflammation in the gastrointestinal tract, it can cause this barrier to break down and increase intestinal permeability. This condition is also known as leaky gut syndrome. Toxins and microbes can enter the bloodstream, activating the immune system and promoting inflammation. Intestinal permeability has been associated with many health conditions, including metabolic disorders, asthma, autoimmune diseases, fibromyalgia, chronic fatigue syndrome, liver disease, and depression (23) The symptoms of inflammatory bowel diseases have a negative impact on quality of life and well-being, affecting daily activities, work and school performance, and social life. Patients with IBD have a higher risk of experiencing anxiety and depression.

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Summary

Chronic inflammation is associated with the most prevalent chronic health conditions, such as heart disease, diabetes, and cancer. Gastrointestinal inflammation can disrupt normal functioning, reduce quality of life and well-being, and increase the risk of developing other chronic health conditions. Functional medicine labs allow practitioners to identify the root causes of this inflammation, such as dysbiosis, stress, or diet, to personalize treatment protocols for patients. Nutritional and lifestyle counseling, stress management practices, and supplements can all be useful tools in reducing gastrointestinal inflammation.