Genetics is an area of medicine that fascinates me. As a biochemistry student we are taught that our bodies operate at 100% efficiency. This is simply not the case, but for educational purposes you are not exposed to the truth when learning the many hundreds of cool enzymatic reactions that are occurring in our bodies at any given time. Genetics in undergraduate studies is similar. Sure there are a few genetic complications that are taught in pre-medicine but nothing remotely like what occurs in really life! Although this area fascinates me and I have spent hundreds of hours learning about it, genetics bore most people, so we need to stick to what is known to be relevant in this section.
As a caveat, although some genetic polymorphisms are connected to greater susceptibility to SIBO, a whole lot more potential genetic issues arise as a result of SIBO. That is to say that it is well known now that the microbiome effects our genes, which can lead to almost all types of diseases in the body, from autoimmune diseases (rheumatoid arthritis, ulcerative colitis, multiple sclerosis, Parkinson’s and ALS) to atopic conditions like asthma, eczema, allergic rhinitis, and Crohn’s disease to metabolic disorders like cancer, diabetes, fatty liver, heart disease, obesity, and Alzheimer’s dementia and finally mental health conditions like anxiety, depression, schizophrenia and bipolar. Therefor the most relevant discussion about genetics and SIBO should actually be in reverse, but the topic is so large that it would take many websites to fit!
The most significant genetic problems that I will touch on associated with SIBO are around several different single nucleotide polymorphisms (SNPs) that affect gut integrity, gut motility or gut immunity. SNPs are essentially variations in what are recognized to be “normal” genetic code that can have several different effects on health. They can be good; making us stronger, faster or better in some way; they can be neutral, or they can be bad; making us weaker and more susceptible to disease. The interesting thing about working for years with genetic variations is that many times people have SNPs but do not have the characteristic condition that has been clinically or research associated with the SNP. Essentially, genetics are not everything … they are a piece of the puzzle.
Celiac disease is now thought to be a genetically inherited illness with several SNPs that dramatically increase susceptibility. The SNPs are thought to connect to the autoimmune component of William Davis’ wheat belly, but can also have a very negative effect on many organs in our body, including the thyroid gland, brain and nerves. Essentially gluten damages the gut which can lead to malabsorption and motility issues. Malabsorption and decreased motility create the environment for SIBO!
Toll-like Receptors (TLR’s) are a type of pattern recognition receptor that help our immune systems identify “stuff” in the dark depths of the intestines. Several SNPs have been identified in different TLR subclasses that have been correlated to increased susceptibility to infection, invasion of pathogens and normal bacteria, autoimmunity and gastrointestinal motility related issues. There is also connections with TLRs to cancer and other metabolic diseases. TLR SNP’s can create a perfect storm for SIBO in some people.
Leaky gut has strong associations with SIBO and a host of other health conditions. The most frequently seen clinical condition that correlates to leaky gut is the group of diseases known as atopic disease, which include asthma, allergies, eczema and possibly Crohn’s disease. Polymorphisms have been identified in the genes that encode for the actual proteins that stick our cells together in the gut and skin. This group of proteins are affectionately known as the tight junctions, which include proteins like cadherins, zonulins, TAMPs and JAMs. Leaky gut can result in major damage, not only to absorption, but also motility and immunity, which leads to greater problems with SIBO.
IgA deficiencies also create risks for SIBO as suboptimal levels are linked to the potential for greater reactions to foods and poor identification of microorganisms which can damage the gut lining and motility. IgA deficiencies can also lead to great susceptibility to autoimmune disease.
Gilbert’s Syndrome is another genetic condition that may result in SIBO. Gilbert’s is quite common, affecting 3 to 12% of the population, and characterized by elevated unconjugated bilirubin in the serum. The genetic defect is complex and the extent of poor bilirubin conjugation varies from person to person. Non-the-less, lack of bilirubin production and excretion can lead to common digestive complaints and poor fat digestion. Poor biliary secretion can also affect intestinal bacterial overgrowth do to the fact that bile also works to sterilize the small intestine.
Finally I would not be able to discuss genetics without mentioning my beloved methylation SNPs. Methylation is pretty much amazing, in that it makes everything from our neurotransmitters to proteins, phospholipids and antioxidants! The importance of methylation genetics in SIBO is to do with motility, as our entire intestinal tract actually relies on neurotransmitters like dopamine, histamine, and serotonin to move. Since methylation genetics is what impacts neurotransmitter production, there can be a big problem with motility when the level of neurotransmitters are affected. More importantly, in trying to recover from SIBO, knowing how to enhance neurotransmitter functions can help restore motility to the digestive tract.