Inflammatory Bowel Disease, Genes, and Gut Microbes

“Fix your gut!” seems to be the standard advice from most healthy living blogs, but concrete advice on how to actually accomplish this seems to be lacking. While general suggestions abound, specific actions that actually work for an individual are hard to find.

I find the microbiome intriguing: the complexity of the interaction between our human genome, the gut microbiome, and environmental factors is mind-boggling.

While what we eat is important to our microbiome, our genes also play a role in which gut bugs will flourish and which ones will never take up permanent residence.

All of the general advice — fix your gut, eat more fiber, eat fermented foods, avoid sugar, grains, dairy, etc. — may work for some but not for everyone. We need to get personal here and take a good look at some of the genes that affect our microbiome.

Genetic variants:

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NOD2, also referred to as CARD15, is a gene that encodes a protein (nucleotide-binding oligomerization domain-containing protein 2) that recognizes bacteria in order to initiate an immune response.  Specifically, the immune response to lipopolysaccharide (LPS) involves NOD2.  The LPS is an endotoxin and can be found in the outer membrane of Gram-negative bacteria.[ref] The background section of this study will give you more specific information on NOD 1 and 2 if you are wanting to dive deeper.

Check your genetic data for rs2066844 R702W(23andMe v4, v5):

  • T/T: 17-35x increased risk for Crohn’s disease [ref][ref][ref][ref]
  • C/T: 2-3x increased risk for Crohn’s disease
  • C/C: typical

Members: Your genotype for rs2066844 is .

Check your genetic data for rs2066845 G908R(23andMe v4):

  • C/C: 17-35x increased risk for Crohn’s disease [ref][ref]
  • C/G: 2-3x increased risk for Crohn’s disease
  • G/G: typical

Members: Your genotype for rs2066845 is .

Check your genetic data for rs2066842 (23andMe v4, v5):

  • T/T: Increased risk of IBD (especially ulcerative colitis) [ref][ref] decrease the risk of allergic rhinoconjunctivitis by about 20%[ref]
  • C/T: Increased risk of IBD
  • C/C: typical

Members: Your genotype for rs2066842 is .

Check your genetic data for rs2066843 (23andMe v4):

  • T/T: Increased risk of Crohn’s disease[ref][ref]
  • C/T: Increased risk of Crohn’s disease
  • C/C: typical

Members: Your genotype for rs2066843 is .


The TLR4 gene encodes the toll-like receptor 4, which is an important player in the immune response. Toll-like receptors recognize and initiate an immune response against bacteria and viruses.

Check your genetic data for rs4986790 (23andMe v4, v5; AncestryDNA):

  • G/G: Increased risk of Crohn’s disease and ulcerative colitis[ref]
  • A/G: Increased risk of Crohn’s disease
  • A/A: typical

Members: Your genotype for rs4986790 is .



Check your genetic data for rs6596075 (23andMe v4; AncestryDNA)

  • C/C: increased risk of Chron’s disease
  • C/G: lower risk of Crohn’s disease
  • C/C: lower risk of Crohn’s disease [ref][ref]

Members: Your genotype for rs6596075 is .


Diet and Lifestyle Actions:

NOD2 can be upregulated in the intestines by butyrate.[ref] Butyrate is a short-chain fatty acid produced by certain gut bacteria and also found in small amounts in foods such as butter and other full-fat dairies. Resistant starch (found in cooked and cooled potatoes and rice) feeds the kind of bacteria that produce butyrate.

Vitamin D plays a role in stimulating NOD2.[ref] Get your vitamin D levels checked to see if you have sufficient levels. Sunshine is the natural way to boost your vitamin D levels, but you can supplement vitamin D if you can’t get enough sun to boost your levels. I like the ones that are coconut oil-based. Learn more about vitamin D.

Learn More:

The Health Benefits of Butyrate: Meet the Anti-Inflammatory Fat

Here is an excellent video overview of how NOD2 plays a role in inflammatory bowel disease:

Recap of your genes:

Related Articles and Genes:

TNF-alpha: Inflammation and Your Genes
Do you feel like you are always dealing with inflammation? Joint pain, food sensitivity, skin issues, gum disease, etc… It could be that your body genetically gears towards a higher inflammatory response due to high TNF-alpha levels.

Emulsifiers in Processed Foods: Your genes and your microbiome
Our genes and our environment both contribute to our gut microbiome, allowing some species to flourish and keeping others away. How does this all come together to cause the diseases that plague our modern society?

Problems with IBS? Personalized solutions based on your genes
There are multiple causes of IBS, and genetics can play a role in IBS symptoms. Pinpointing your cause can help you to figure out your solution.

About the Author:
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering and also an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.