Gut Genes

Did you know that you have more bacteria in your gut than you have total cells in your body?  You are their host, their environment…And your genes influence which bacteria can use you as a host!

Your gut microbiome and your genes:

Your gut microbiome is unique to you. But why? Have you ever wondered why our gut microbes are different?

The bacteria that take up residence in your intestines depend on:

  • the foods you eat (or rather, what you feed your bacteria)
  • exposure to different bacteria
  • exposure to toxins or antibiotics
  • and your genes!

This article is going to dig into how all of this comes together — why the genetic variants you inherited from mom and dad influence the bacteria that can reside within you and how dietary changes can make a difference.

How your genes impact your gut microbiome:

It is weird to think that the bacteria in our colon are doing more than just breaking down the extra food waste — the fiber that we didn’t digest. But research shows that the influence of our gut microbes on our health is huge.

Your gut microbiome influences:

  • susceptibility to infections, such as h. pylori[ref]
  • your body weight (big time)[ref]
  • your mood — including regulating anxiety and depression[ref]
  • whether you have asthma and allergies[ref]
  • your risk for cardiovascular disease[ref]
  • and even some types of cancer[ref]

While it may seem odd to think of yourself as a host, as an environment… that is just what you are to the microbes living within or on you. And just like your genetic variants make you look and act differently than everyone else, your unique makeup also influences the types of microbes that can flourish within you.

Studies on identical twins and fraternal twins show that part of what drives the composition of your gut microbiome is your genes.[ref]

Why is your gut microbiome important?

Whether bloating, rumbling, or running to the bathroom, we have all experienced the misery at some point of not having happy intestinal function…

But when all it’s working just fine, most people tend to ignore the tiny microbes hard at work in their intestines.

Your gut microbes can play an important role in your health, though.  Some microbes produce vitamins such as vitamin K and some B-vitamins. Others produce short-chain fatty acids used by the intestinal cells as well as signaling to the liver to decrease cholesterol synthesis.[ref]

In people who are overweight or obese, the gut microbiome increases how much energy is obtained from food.[ref] You are what you eat — and also what your microbes eat and produce fatty acids from.


Genetic Variants that Impact Gut Microbes:

Your genetic variants play a role in which species are likely to make up your gut microbiome. Research on this is in its infancy, though, so there is still a lot more to learn on this topic.

Select your data file to see your data below.

FUT2 gene:

The FUT2 gene encodes an enzyme, fucosyltransferase 2, which controls whether the oligosaccharides that make up your blood type will be expressed in your bodily fluids (other than your blood). While it may seem a bit odd to think about, those oligosaccharides in your gut mucosa feed some of the commensal bacteria there. They also act as adhesion receptors for microbes. Thus, not secreting your blood type into your intestinal mucosa causes a shift in the types of bacteria.[ref]

Check your genetic data for rs601338 (23andMe v4, v5; AncestryDNA (some)):

  •  G/G: blood type secretor
  •  A/G:  blood type secretor
  •  A/A:  non-secretor of blood type, low / no of Bifidobacteria,[ref] lower RuminococcusClostridium and Akkermansia[ref]; resistant to norovirus

Members: Your genotype for rs601338 is .

 

VDR gene:

The VDR gene encodes a vitamin D receptor. This receptor also binds with microbial metabolites, and microbial metabolites may then feedback to regulate the expression of VDR.

Animal studies show that eliminating the vitamin D receptor substantially changes the diversity in the gut microbiome. In people who have inflammatory bowel disease, VDR is upregulated and accompanied by lower amounts of Parabacteroides.[ref]

Check your genetic data for rs7974353 (AncestryDNA):

  • T/T: possibly altered gut microbiome, influences Parabacteroides[ref]
  • C/T: possibly altered gut microbiome, influences Parabacteroides
  • C/C: Typical

Members: Your genotype for rs7974353 is .

 

LCT gene:

The majority of people with a Caucasian background still produce lactase as an adult. This allows for the digestion of dairy products containing lactose.  Worldwide, though, most people of other backgrounds no longer produce lactase as an adult and are therefore limited in their dairy digestion. The LCT gene codes for the persistence of the lactase enzyme into adulthood. People who do not have lactase persistence are reliant on their gut microbiome for breaking down any dairy that they consume. While Lactobacillus are well known for consuming lactose, some Bifidobacterium strains also metabolize lactose.

Check your genetic data for rs182549 (23andMe v4, v5; AncestryDNA):

  • C/C: no lactase as an adult; likely to have more bifidobaceria[ref] (possibly due to drinking less milk)
  • C/T: lactase persistence; likely to have a normal amount of bifidobacteria
  • T/T: lactase persistence;  likely to have a normal amount of bifidobacteria

Members: Your genotype for rs182549 is .

 

SLC39A8 gene:

This gene encodes a metal influx transporter that regulates the intake of manganese into cells.[ref]

Check your genetic data for rs13107325 (23andMe v4, AncestryDNA):

  • C/C: typical
  • C/T: increased risk of Crohn’s disease; altered gut microbiota with lower Anaerostipes, Coprococcus, Roseburia, Lachnospira, and SMB53
  • T/T: increased risk of Crohn’s disease; altered gut microbiota with lower Anaerostipes, Coprococcus, Roseburia, Lachnospira, and SMB53[ref] altered gut barrier function[ref]

Members: Your genotype for rs13107325 is .

APOA5 gene:

This gene affects plasma lipoprotein levels including triglyceride levels as well as levels of certain gut bacteria. Several SNPs in this gene have associations with triglyceride levels and obesity risk.

Check your genetic data for rs651821 (23andMe v4, v5; AncestryDNA):

  • T/T: typical
  • C/T: reduced Bifidobacterium levels, higher triglycerides, and MetS risk[ref]
  • C/C: reduced Bifidobacterium levels, higher triglycerides, and MetS risk

Members: Your genotype for rs651821 is .

ALDH1L1 gene:

The ALDH1L1 gene codes for a protein called Aldehyde dehydrogenase 1 family member L1 that plays a role in folate metabolism and the regulation of cell proliferation. Additionally, it impacts formate oxidation (linked to blood pressure).[ref]

Check your genetic data for rs2276731 (23andMe v4, v5)

  • C/C: linked to higher SHA-98 in a GWAS[ref]
  • C/T: linked to higher SHA-98
  • T/T: typical

Members: Your genotype for rs2276731 is .

 

IL4 gene:

Interleukin-4 is an anti-inflammatory cytokine that is involved in the regulation of the immune system.

Check your genetic data for rs2243250 (23andMe v4, v5; AncestryDNA):

  • T/T: increased susceptibility to Clostridium difficile infection in IBD[ref]
  • C/T: increased susceptibility to Clostridium difficile infection in IBD
  • C/C: typical susceptibility to C. diff

Members: Your genotype for rs2243250 is .


Lifehacks:

Work with your gut microbes instead of against them:

If you do not produce lactase (LCT variant), you are going to have a hard time breaking down larger amounts of dairy. Instead, go with lactose-free milk, stop drinking milk, or supplement with a lactobacillus probiotic.

If you carry the SLC39A8 variant associated with lower manganese and altered gut microbiota, take a look at how much manganese you get in your diet. It is estimated that manganese intake has decreased by 42% over the last couple of decades due to changes in the modern diet.[ref]

The link between the VDR gene variant and different gut bacteria is interesting. Vitamin D deficiency increases the risk of inflammatory bowel disease. Additionally, some research points to intestinal barrier dysfunction in vitamin D deficiency. Supplemental vitamin D (1,25(OH)2D3) treatment shifts the microbiome composition.  In mice that lack the VDR receptor, there is a lack of lactobacillus bacteria. This seems to be a two-way street between vitamin D impacting the microbiome and the microbiome impacting vitamin D. Studies show that probiotics, such as lactobacillus reuteri and Lactobacillus plantarum, increase circulating levels of vitamin D.[ref]

 


Related Genes and Topics:

TNF-alpha: Inflammation and Your Genes
Do you feel like you are always dealing with inflammation? Joint pain, food sensitivity, etc? Perhaps you are genetically geared towards a higher inflammatory response. Tumor necrosis factor (TNF) is an inflammatory cytokine that acts as a signaling molecule in our immune system. In an acute inflammatory situation, TNF-alpha plays an essential role in protecting us.

Fatty Liver: Genetic variants that increase the risk of NAFLD
Non-alcoholic fatty liver disease (NAFLD) is now the leading cause of liver problems worldwide, bypassing alcoholic liver disease. It is estimated that almost half of the population in the US has NAFLD caused by a combination of genetic susceptibility, diet, and lifestyle factors.

CTLA-4: Autoimmune Genetic Risk
The CTLA4 gene codes for a protein that is important in the immune system. It acts as a checkpoint that can downregulate your immune system response. Genetic variants in the CTLA4 gene can increase your risk for several different autoimmune diseases.



Author Information:   Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University and an undergraduate degree in engineering from Colorado School of Mines. Debbie is a science communicator who is passionate about explaining evidence-based health information. Her goal with Genetic Lifehacks is to bridge the gap between the research hidden in scientific journals and everyone's ability to use that information. To contact Debbie, visit the contact page.