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Gut Inflammation: Causes, Symptoms, and Supplementation

August 11, 2022 8 min read

Gut Inflammation: Causes, Symptoms, and Supplementation

Inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis, affects upwards of 0.5% of the total human population in the West, with cases rising each year. IBD is an immune-mediated disease characterized by inflammatory destruction of the intestinal tissue, decreased gut barrier integrity and increased gut permeability, and changes to the microbiome. Outside of overt inflammatory bowel disease, low-grade chronic inflammation of the gut can create sub-clinical symptoms that many consider “normal” including: 

  • gas and bloating after meals
  • irregular bowel movements
  • food sensitivities
  • abdominal distension 

However common these issues may be, over time the underlying inflammatory environment within the gut can lead to severe issues including dysbiosis, IBD or irritable bowel syndrome (IBS), and increased risk of diabetes, obesity, and bowel cancers [1, 2]. 

Thus, the dissemination of strategies that individuals can use to extinguish the fire of inflammation is prudent. To this end, we will outline here dietary and supplemental protocols anyone can use at home to shift their guts and their bodies into an anti-inflammatory state. 

Determining the inflammatory status of your gut 

Before implementing anti-inflammatory protocols, individuals may want to test whether or not they have an actively inflamed gut. Although the symptoms outlined above are indicative of inflammation, individuals can confirm this by titrating prebiotics known as human milk oligosaccharides (HMOs) into their daily routines. 

HMOs and Butyrate 

Prebiotics are molecules that we cannot digest, allowing them to pass intact to the colon where they serve as a food source for the microbiota. Specifically, HMOs are indigestible carbohydrate molecules originally discovered in human breast milk. Their function is to establish the microbiome in newborns by supporting Bifidobacteria colonization of the infant gut. In adults, the consumption of HMOs, like 2’-fucosyllactose, bolsters Bifidobacteriacommunities. In turn, these bacteria secrete metabolites that feed butyrate-producing species in the gut. Thus, supplementation with HMOs results in increased levels of butyrate. 

Gut Inflammation and Butyrate Metabolism 

In an inflamed gut, the transporters that mediate butyrate uptake into colonocytes (i.e. colon cells) and resident immune cells become downregulated. This results in: 

  1. Butyrate accumulation in the gut that is experienced as gas and bloating.
  2. Colonocytes being unable to burn butyrate—their preferred fuel source. 

The inability to oxidize butyrate for energy production subsequently drives up oxygen levels in the gut, facilitating the growth of pathogenic, aerobic (i.e. oxygen-loving) bacteria, and preventing the growth of the commensal anaerobic (i.e. oxygen-loathing) bacteria that secrete short chain fatty acids (SCFAs) like butyrate. 

Moreover, due to lack of transport into macrophages, butyrate is unable to inhibit the release of inflammatory factors and upregulate the release of anti-inflammatory factors from these immune cells. In this way, inflammation in the gut drives a vicious cycle that actively prevents itself from being extinguished. 

Testing Your Butyrate Tolerance 

To determine whether your colon is able to effectively take up and burn butyrate, you can consume a serving of PureHMO 2’-fucosyllactose mixed into water in the morning on an empty stomach. Alternatively, you can consume a meal that includes: 

  • Cold beans or chickpeas
  • Raw green beans
  • Raw asparagus 

as these foods contain indigestible carbohydrates that can similarly support Bifidobacteria and butyrate production. After consumption of the HMO or bifido-boosting meal, monitor your body for signs of gas, bloating, or other gastrointestinal distress. If you experience any of these symptoms, then your gut is likely inflamed and butyrate-intolerant to some extent, and you may benefit from implementing the anti-inflammatory protocols outlined here. 

Spinning Down Gut Inflammation Naturally 

The first step to healing the gut is to incorporate nutraceutical and nutritional interventions that can disrupt the feed-forward mechanism of butyrate intolerance and gut inflammation. During this period of 1-2 weeks, key bioactives are consumed at particular times of the day to both facilitate gut healing and suppress inflammation. After this time period, HMOs and/or high fiber foods can be titrated in to assess the body’s response. 

Supplemental Approaches 

There are six key supplements that can help restore an anti-inflammatory environment in the colon and support butyrate metabolism: 

  • Hesperidin
  • N-acetyl cysteine
  • Omega-3 fatty acids
  • Polyphenols
  • Zeolite and charcoal
  • Amino acids (glycine, arginine, glutamine) 

Hesperidin is a phenolic compound that is abundant in citrus like oranges. Hesperidin has been shown to ameliorate colitis (i.e. colon inflammation) by upregulating antioxidant pathways within colon cells [3]. This results in the increased production of enzymes involved in neutralizing free radicals. Furthermore, hesperidin has been shown to upregulate proteins involved in maintaining the integrity of the tight junctions between cells in the gut. The failure of these tight junctions is what leads to the condition known as leaky gut, which exacerbates inflammation in both the gut and body at large. 

The effective dose for hesperidin is between 6-8 mg/kg, or roughly 500 mg for a 150 lb individual. Although pulp-free organic orange juice is a good source hesperidin, supplementation is preferred as the volume of orange juice one would need to consume to reach this dose is quite high (~3,500 mL). Hesperidin should be consumed with water on an empty stomach to ensure that the concentration in the gut remains at the level needed for efficacy. 

N-acetyl cysteine(NAC) is the precursor to glutathione: the most abundant antioxidant molecule produced the body. Glutathione is synthesized by cells and neutralizes free radicals. Individuals can consume 1000-2000 mg per day before bed for optimal results. 

Omega-3 Fatty acidsare essential fatty acids, meaning that they cannot be synthesized by the body. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are the two most important omega-3s. EPA and DHA can both alleviate inflammation acutely while also preventing excessive inflammation from occurring in the future [4]. Sources of these critical fats include:

  • Fatty fish (salmon, mackerel, sardines)
  • Fish roe
  • Fish, krill, or algal oil supplements 

Note that these polyunsaturated fatty acids are easily oxidized. Thus, if supplementing, choose an EPA/DHA product formulated with antioxidant, as the consumption of rancid oils can be harmful. Additionally, choosing a formulation that contains EPA and DHA in their triglyceride or phospholipid forms has greater bioavailability than formulations containing the ethyl ester forms. Optimal dosing for anti-inflammatory effects is at least 2 g per day of combined EPA and DHA taken before bed. 

Polyphenols are colorful pigment molecules present in a range of fruits and vegetables. Polyphenol rich foods like berries not only support a healthy microbiome, but the polyphenols can also directly neutralize free radicals and exert anti-inflammatory effects in the gut. Because the inflamed gut does not fare well in response to large amounts of fiber, a red fruit powder can be consumed in lieu of polyphenols from whole foods during the inflammation spin down period. Individuals can consume 1-2 scoops daily, preferably on a light or empty stomach (can be combined with hesperidin). 

Zeolite and activated charcoalare important allies in not only helping to acutely relieve gastrointestinal distress, but also by helping to restore gut barrier integrity. Research shows that zeolite can decrease gut permeability and inflammation [5], whereas activated charcoal has the ability to adsorb volatile molecules in the gut. Therefore, gas and bloating can be relieved acutely through supplementation with charcoal, while zeolite can promote the restoration of gut barrier integrity and support an anti-inflammatory environment that helps to prevent future GI disturbances. The effective dose for zeolite is around 1.6-2g per day (half with the first meal of the day and half with the last meal of the day), and the research suggests supplementation may be maintained for 3 months [5]. The effective dose for charcoal is around 250mg. Charcoal can be taken on an as-needed basis for acute relief of gastric discomfort. Note that, because charcoal adsorbs molecules from the surrounding environment, taking other supplements or drugs around the same time as charcoal may render them ineffective. 

Amino acids are present in high amounts in protein rich foods. However, there are specific amino acids that have been shown to be of particular benefit to the gut. These are:   

  • Glutamine
  • Glycine
  • Arginine 

Research suggests that glutamine has the ability to help maintain the tight junctions within the gut barrier while also suppressing the production of inflammatory factors [6]. Glycine has been shown to protect organs, including the gut, against inflammation and injury [6], and arginine supplementation was able to ameliorate colitis in experimental models [6]. Doses of 1g glutamine, 2g glycine, and 1g arginine can be taken together at bedtime to support gut health and anti-inflammation. In lieu of a glycine supplement, individuals can also consume ~10g collagen peptides as a source of glycine. 

Nutritional Approaches 

In addition to the aforementioned supplements, individuals may opt to also adhere to a liquid diet (or a low-residue/low-fiber diet) during the 1-2 week inflammation spin down period if they suspect they are suffering from more severe gut inflammation. The liquid diet limits the amount of substrate reaching to the colon, thereby limiting gas production and reducing gastric discomfort. Foods to prioritize during this time are broths, blended soups, low sugar juices, and smoothies with ripe fruit. If meat is consumed, opt for ground meat as it is more easily digested and assimilated than whole cuts of meat. Additionally, digestive enzymes can be consumed with meals to facilitate nutrient absorption and prevent excess nutrient spillover to the gut microbiome. 

Protocol Summary 

1-2 weeks consuming the following: 

AM (empty stomach): 1 scoop red fruit powder, 500 mg hesperidin 

With first meal: 800 mg zeolite 

PM: 1 scoop red fruit powder in water 

With last meal: 800 mg zeolite 

Before bed: 2 g omega-3 fatty acids, 1000 mg N-acetyl cysteine, 2 g glycine, 2 g glutamine, 1 g arginine 

Activated charcoal can be taken as needed to manage any gastrointestinal discomfort (both within and outside of this 1-2 week period) and individuals who suspect more extensive gut inflammation can follow a liquid diet during the protocol timeframe.  Digestive enzymes may also be taken with each meal to expedite results. 

Following the successful completion of this protocol and restoration of butyrate tolerance, steps can be taken to boost butyrate production via microbiome optimization. Specifically, the consumption of fermented foods and prebiotics (e.g., HMOs, polyphenols, resistant starches) can be prioritized to bolster levels of Bifidobacteria and Akkermansia and improve the function and resiliency of the gut. 

 

Author: Dr. Alexis Cowan, a Princeton-trained PhD specializing in the metabolic physiology of nutritional and exercise interventions.

Follow Dr. Cowan on Instagram: @dralexisjazmyn 

Disclaimer: These statements or protocols have not been evaluated by the Food and Drug Administration. The protocols are not intended to diagnose, treat, cure, or prevent any disease. You should consult with your doctor before taking any supplements.   

References

[1] Axelrad JE, Lichtiger S, Yajnik V. Inflammatory bowel disease and cancer: The role of inflammation, immunosuppression, and cancer treatment. World J Gastroenterol. 2016 May 28;22(20):4794-801. doi: 10.3748/wjg.v22.i20.4794. PMID: 27239106; PMCID: PMC4873872. 

[2] Scheithauer TPM, Rampanelli E, Nieuwdorp M, Vallance BA, Verchere CB, van Raalte DH, Herrema H. Gut Microbiota as a Trigger for Metabolic Inflammation in Obesity and Type 2 Diabetes. Front Immunol. 2020 Oct 16;11:571731. doi: 10.3389/fimmu.2020.571731. PMID: 33178196; PMCID: PMC7596417. 

[3] Guo K, Ren J, Gu G, Wang G, Gong W, Wu X, Ren H, Hong Z, Li J. Hesperidin Protects Against Intestinal Inflammation by Restoring Intestinal Barrier Function and Up-Regulating Treg Cells. Mol Nutr Food Res. 2019 Jun;63(11):e1800975. doi: 10.1002/mnfr.201800975. Epub 2019 Mar 20. Erratum in: Mol Nutr Food Res. 2020 May;64(10):e1970058. PMID: 30817082. 

[4] Calder PC. Omega-3 fatty acids and inflammatory processes. Nutrients. 2010 Mar;2(3):355-74. doi: 10.3390/nu2030355. Epub 2010 Mar 18. PMID: 22254027; PMCID: PMC3257651.

[5] Lamprecht M, Bogner S, Steinbauer K, Schuetz B, Greilberger JF, Leber B, Wagner B, Zinser E, Petek T, Wallner-Liebmann S, Oberwinkler T, Bachl N, Schippinger G. Effects of zeolite supplementation on parameters of intestinal barrier integrity, inflammation, redoxbiology and performance in aerobically trained subjects. J Int Soc Sports Nutr. 2015 Oct 20;12:40. doi: 10.1186/s12970-015-0101-z. PMID: 26500463; PMCID: PMC4617723.

[6] Sugihara K, Morhardt TL, Kamada N. The Role of Dietary Nutrients in Inflammatory Bowel Disease. Front Immunol. 2019 Jan 15;9:3183. doi: 10.3389/fimmu.2018.03183. PMID: 30697218; PMCID: PMC6340967.


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