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The 3 I’s of Building a Strong Gut-Immune Axis
By Vincent Pedre, MD

In practice, it can be a challenge to break down complex medical concepts and articulate them simply to our patients. This is especially true when we begin to talk about the connection between gut and immune function. In the world of functional medicine, we find our patients to be a lot more engaged and wanting to learn these complex concepts in a more digestible way. And so, to provide quality information in smaller bites, I often speak about the three I’s of building gut-immune health as a way to understand the importance of the types of nutrients we use together in order to enhance this synergistic relationship. After all, 70% of our immune system is found within the digestive tract. In this post, I will lay out the three I’s and include corresponding solutions to bring it all together.

The first of the three I’s is Inflammation–without taming complex inflammatory pathways, it will be difficult to build gut-immune strength. Balancing inflammation should be a starting point in any chronic illness treatment protocol. One of my favorite nutrients that work specifically to balance gut inflammation is turmeric. Turmeric has been used for thousands of years as a culinary and medicinal herb. Some believe it may account for the lower levels of dementia in India.It is one of my favorite kitchen spices, which I incorporate into many dishes, along with black pepper to augment the absorption of curcuminoids, turmeric’s anti-inflammatory component. But it turns out, enhancing absorption may not account for the whole story behind this special orange spice.

 As we worked to understand more about turmeric, research found that the most “bang for your buck” component of turmeric was curcumin. Until recently, we have been looking at bioavailability as the main issue with this nutrient. But new research now indicates that interaction with the gut is more important than ever. Instead of focusing on nutrients with enhanced bioavailability (made to bypass the gut), we should be focusing on how well they can interact with the gut and the microbiome.4,5 As food for thought, the pharmaceutical model should not be applied to botanicals. They were meant to be delivered in a more organic way so that the benefits of all their bioactives can be experienced.

A study that really caught my eye indicated that many non-curcuminoid components in turmeric have powerful anti-inflammatory effects.1 By focusing on a singular ingredient, we may have been missing out on all these beneficial bioactives that turmeric has to offer. These components, based on their chemistry, work with the gut microbiome to reduce inflammation and reset a hyper-vigilant immune system.3  Each of the components in turmeric (proteins, fibers and polysaccharides) have benefits of their own that cannot be ignored, and they all work very well to naturally tame inflammation.1,2,5 

Consequently, I started using a broader-spectrum turmeric supplement for my patients with gut and inflammatory issues. In fact, I recently tried a course of turmeric to help with non-resolving tendinitis, which much to my surprise made a big difference in their recovery process. When looking for a turmeric supplement, you want one that is a complete turmeric matrix with all the components that turmeric has to offer. This includes standardized amounts of curcuminoids (at least 45-55%), turmeric proteins, turmeric oils, polysaccharides and fiber.

Another great anti-inflammatory polyphenol is quercetin. This botanical has been shown to stabilize mast cells, thus helping to prevent degranulation and histamine release in the gut. This is a staple nutrient that I add to naturally soothe inflammation in the gut, as there is emerging data to suggest it may have a prebiotic effect on the gut microbiome.8 Along with a complete turmeric matrix and quercetin, I reach for an ingredient used in Traditional Chinese Medicine: skullcap root, which deserves an honorable mention for its role in gut-immune health. It is another botanical that helps reduce inflammation by inhibiting specific intracellular pathways like COX-2 and lowering NFkB expression, both of which are major drivers of inflammation.

The second “I” is gut Integrity–intestinal epithelial cell function is crucial for maintaining proper barrier function. The brush border is the main area where triggering foods, toxins, and microbes are kept out of the bloodstream. L-glutamine, the body’s most abundant amino acid, is also one of the best nutrients that helps repair the gut lining and restore the function of enterocytes. Along with L-glutamine, other amino acids that promote barrier integrity are glycine, proline and lysine, which are abundant in hydrolyzed collagen. These amino acids work well together and promote a healthy gut mucosa.6

Lastly, we want to tune the Immune system–when intestinal barrier function is optimized and the tight junctions are intact, the immune system is supported. Some of the top nutrients that I add to promote immune function are vitamin D3 and arabinogalactan. Vitamin D3 controls the expression of over 200 genes and is a major regulator of a balanced and appropriate immune response. Arabinogalactan are fermentable fibers that are used as fuel by certain gut flora to produce anti-inflammatory short-chain fatty acids (SCFAs), which then have wide-ranging effects, including supporting the health of colonocytes. In turn, they help tune a strong immune system.

The intestines are essentially an immune organ consisting of a complex cellular network that not only works as our border patrol, but also manages inflammation.  Looking at the big picture of health, what our patients eat and the lifestyle choices they make affect their gut-immune axis. Factors that impact the health of the gut and the balance of gut microbiota in turn affect immune function. Therefore, the immuno-resilience we seek to enhance in our patients can be built by taking a full-spectrum approach that addresses inflammatory challenges, gut barrier integrity, and immune strength. It is possible for our patients to feel a certain extent of overwhelm with making changes at first. But if we explain that these criteria are the foundation of robust gut-immune health, we not only empower our patients, we also increase their rate of compliance with these therapies. 


1.Aggarwal, Bharat B., et al. “Curcumin-Free Turmeric Exhibits Anti-Inflammatory and Anticancer Activities: Identification of Novel Components of Turmeric.” Molecular Nutrition & Food Research, vol. 57, no. 9, 12 July 2013, pp. 1529–1542, 10.1002/mnfr.201200838. Accessed 2 June 2020.

2.Ghiamati Yazdi, Fariba, et al. “Turmeric Extract: Potential Use as a Prebiotic and Anti-Inflammatory Compound?” Plant Foods for Human Nutrition, vol. 74, no. 3, 16 May 2019, pp. 293–299, 10.1007/s11130-019-00733-x. Accessed 19 Jan. 2020.

3.Gopi, Sreeraj, et al. “Comparative Oral Absorption of Curcumin in a Natural Turmeric Matrix with Two Other Curcumin Formulations: An Open-Label Parallel-Arm Study.” Phytotherapy Research, vol. 31, no. 12, 13 Oct. 2017, pp. 1883–1891, 10.1002/ptr.5931. Accessed 20 June 2019.

4.Ghosh, Siddhartha S., et al. “Curcumin-Mediated Regulation of Intestinal Barrier Function: The Mechanism Underlying Its Beneficial Effects.” Tissue Barriers, vol. 6, no. 1, 2 Jan. 2018, p. e1425085, 10.1080/21688370.2018.1425085. Accessed 12 Dec. 2019.

5.Zam, Wissam. “Gut Microbiota as a Prospective Therapeutic Target for Curcumin: A Review of Mutual Influence.” Journal of Nutrition and Metabolism, vol. 2018, 16 Dec. 2018, pp. 1–11, 10.1155/2018/1367984.

6.Dai ZL, Wu G, Zhu WY. Amino acid metabolism in intestinal bacteria: links between gut ecology and host health. Front Biosci. 2011 Jan 1;16:1768-86

7.Mishra, Shrikant, and Kalpana Palanivelu. “The Effect of Curcumin (Turmeric) On Alzheimer′s Disease: An Overview.” Annals of Indian Academy of Neurology, vol. 11, no. 1, 2008, p. 13, www.ncbi.nlm.nih.gov/pmc/articles/PMC2781139/, 10.4103/0972-2327.40220.

8.Kawabata, Kyuichi, et al. “Flavonols Enhanced Production of Anti-Inflammatory Substance(s) By Bifidobacterium Adolescentis: Prebiotic Actions of Galangin, Quercetin, and Fisetin.” BioFactors, vol. 39, no. 4, 29 Mar. 2013, pp. 422–429, 10.1002/biof.1081. Accessed 12 June 2020.

Vincent Pedre, MD

Dr. Vincent M. Pedre is the medical director of Pedre Integrative Health and founder of Dr. Pedre Wellness, medical advisor to two health-tech start-ups (MBODY360 and Fullscript), and a functional medicine-certified practitioner in private practice in New York City since 2004.

He is a clinical instructor at the Mount Sinai School of Medicine, and is certified in yoga and medical acupuncture. On faculty at The Institute for Functional Medicine, Dr. Pedre taught the first AFMCP in Lima, Peru in November 2017. Most recently, he joined the Lifestyle Matrix Resource Center as a Clinical Expert serving the Pillars of GI Health Program. He believes the gut is the gateway to excellent health. For this reason, he wrote the book, Happy Gut—The Cleansing Program To Help You Lose Weight, Gain Energy and Eliminate Pain, which helps people resolve digestive and gut-related health issues.

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