“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.
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, NOD2 is involved in the immune response to lipopolysaccharide (LPS), also known as endotoxin, which is produced 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.
There are quite a few NOD2 variants that have been studied. Many have been found to increase the risk of Crohn’s disease and inflammatory bowel diseases.
rs2066844 -risk allele is T; also known as SNP8 and R702W in studies
rs2066845 – risk allele is T; also known as SNP 12 and G908R in studies
rs2066842 – risk allele is T; also known as SNP5 or P268S in studies
rs2066843 – risk allele is T
rs2067085 – risk allele is G
rs17224147 (risk allele is G)
rs5743289 (risk allele is T)
A 2004 study published in Gut found that a TLR4 (toll-like receptor 4) variant and three NOD2 variants were more frequently found in those with Crohn’s disease and ulcerative colitis. The introduction states that “During intestinal inflammation, intestinal epithelial cells (IECs), macrophages, and dendritic cells express TLR4 which represents the first frontline defense receptor against enteric Gram-negative bacteria”. The TLR4 SNP in this study is rs4986790 or Asp299Gly. G is the minor allele that is associated with a higher risk for CD and UC.
Many other studies have looked at the rs4986790 variant in conjunction with a higher risk for bacterial infections. Look through PubMed or Google Scholar using either rs4986790 or Asp299Gly as a search term.
rs6596075 (risk allele is C)
Diet and Lifestyle Actions:
NOD2 can be upregulated by butyrate in the intestines.[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 dairy. 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.
Here is an excellent video overview of how NOD2 plays a role in inflammatory bowel disease:
Dig deeper by reading this review of NOD2 mutations.