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Inflammatory Bowel Disease, Genes, and Gut Microbes

Key takeaways:
~ Inflammatory bowel diseases include Crohn’s and ulcerative colitis, which are serious, life-altering diagnoses.
~Genetics plays a big role in susceptibility to IBD.
~Knowing which genetic variants you have may help you figure out which lifestyle changes would be most helpful.

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What is Inflammatory Bowel Disease?

IBD (inflammatory bowel disease) is a general term that encompasses two chronic inflammatory conditions of the gastrointestinal tract: Crohn’s disease and ulcerative colitis.  Crohn’s disease can affect any part of the GI tract, but usually affects the small intestine. Ulcerative colitis usually affects the colon and rectum. [ref] These are characterized by chronic, relapsing-remitting inflammation of the gastrointestinal tract.

The immune system seems to go haywire in IBD and causes inflammation in the GI tract. This eventually leads to the destruction of part of the intestines, causing pain, diarrhea, fever, malnutrition, and other symptoms.[ref]

Pathogenesis and Disease Mechanisms

Both genetic and environmental factors are thought to cause IBD.  The pathophysiology of IBD involves complex interactions between multiple factors:

Immune Dysregulation:
In IBD, there is a disruption of the mucous lining in the intestines, which changes the gut microbiome and causes an inflammatory response and immune dysregulation.[ref]

Related article: Emulsifiers, gut mucosa, and inflammation

Intestinal macrophages play critical roles in mucosal immunity, microbial surveillance, and tissue repair. When the gut microbiome shifts so that there are more Bacteroides fragilis, a toxin is released that modifies macrophages and promotes an inflammatory shift in the macrophages.[ref]

B Cell and T Cell Involvement:
B cells and T cells are types of white blood cells that are part of the innate immune response. IBD used to be viewed as primarily T cell-driven,  but accumulating evidence demonstrates critical roles for B cells.[ref]

NOD2 gene: Risk factor for IBD

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.[ref]

NOD2 interacts with components found on both Gram-positive and Gram-negative bacteria found in your colon. It can also detect single-stranded RNA from viruses. Your gut microbiome interacts with your immune system in many ways. NOD2 plays an essential role in the way that the immune system keeps gut microbes in the right place and at the right levels in the colon. When encountering bacterial components, NOD2 activates the NF-κB or MAPK signaling pathways, which causes an inflammatory response that balances and keeps the microbial composition in the gut under control.[ref][ref]

When NOD2 is impaired, the gut microbiome is often not in homeostasis. The loss of this regulatory factor in the intestines increases the risk of IBD.[ref]

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


IBD Genotype Report:

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Lifehacks:

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 dairy. Resistant starch (found in cooked and cooled potatoes and rice) feeds the kind of bacteria that produce butyrate.

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Related Articles and Topics:

TNF-alpha: Inflammation, Chronic Diseases, and Genetic Susceptibility

Leaky Gut Genes: Emulsifiers in Processed Foods

Is IBS genetic? Targeted Solutions, Based on Your Genes

 


About the Author:
Debbie Moon is a biologist, engineer, author, and the founder of Genetic Lifehacks where she has helped thousands of members understand how to apply genetics to their diet, lifestyle, and health decisions. With more than 10 years of experience translating complex genetic research into practical health strategies, Debbie holds a BS in engineering from Colorado School of Mines and an MSc in biological sciences from Clemson University. She combines an engineering mindset with a biological systems approach to explain how genetic differences impact your optimal health.