How our genes shape our gut microbiome and our weight

Several studies have come out recently showing that those who are overweight have a different gut microbiome composition than those who are lean. There have also been interesting mouse studies showing that transplanting feces from obese mice into lean mice causes lean mice to become obese.  A 2010 study found that supplementation with the probiotic Lactobacillus gasseri SBT2055 decreased abdominal fat and body weight.  The case for our microbes helping to shape our weight is fairly strong.

But why do some people have higher gut microbe populations of certain beneficial species than others?  Genetics!  Along with diet and environment, of course!

I find it fascinating that genetics plays a big role in the types of microbes that can live in our bodies.  Specific genetic variants can promote or discourage microbes in our guts.  For example, a FUT2 polymorphism causes some people to be immune to the Norovirus and the rotavirus (sometimes called the stomach flu).


Genetic variants related to weight gain and your gut microbiome:

Here are a few of the genes that play a role in determining which microbes inhabit the gut microbiome:
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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.

An April 2016 twin study looked at metabolic syndrome (including weight) and found that rs651821 was associated with metabolic syndrome (MetS).  The study results found that metabolic syndrome was more common in those with the C allele and, for each C allele, there was an average increase in triglycerides of 24.65 mg/dL.  In looking at the gut microbiome, the study found that those with the minor allele (C) had fewer Bifidobacterium regardless of their MetS status.   Bifidobacterium species have links (in this study and in others) to lower BMI and better overall health.[ref]

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

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

Members: Your genotype for rs651821 is .


MYD88 gene

  • A mouse study using mice bred to be deficient in (MyD88 knockout) found that the mice had significantly reduced levels of Lactobacillaceae (Firmicutes), Rikenellaceae (Bacteroidetes),  and Porphoromadaceae (Bacteroidetes) bacteria compared to mice with normal MyD88.  The study was looking at the influence of the microbiome and genetics in type 1 diabetes and is worthwhile to read through if you have T1D.
  • Another study found that MyD88 is important in clearing Listeria monocytogenes infection.  Listeria infections usually come from eating contaminated foods, giving some people a nasty case of food poisoning.  Normally the intestinal mucosa can protect against systemic infection, but MyD88 deficiency increases susceptibility to systemic infection by the pathogen.
  • A recent mouse study found that MyD88 knockout mice had an increased number of bacteria in contact with the epithelial wall of the intestine.  Normally, the intestinal mucosal layers protect the cell wall of the intestines from direct contact with bacteria.
  • Other mouse studies have found that MyD88 knockout mice are more susceptible to tuberculosis. This has been confirmed in humans with MyD88 polymorphisms as well.

Several MYD88 variants reduce levels of MYD88 (most not covered by 23andMe data). These are just reduced levels, though, not a complete ‘knockout’, so the results of the mouse studies may not be completely applicable.

Check your genetic data for rs4988453 (23andMe):

  • C/C: typical
  • A/C: reduced MYD88 (5x risk of tuberculosis)
  • A/A: reduced MYD88 (5x risk of tuberculosis)[ref]

Members: Your genotype for rs4988453 is .

 

Check your 23andMe results for i5000725 (rs137853065):

  • T/T: typical
  • C/C: Rare mutation, listed as pathogenic for MYD88 deficiency

Members: Your genotype for i50007253 is .

 

Check your 23andMe results for i5000726 (rs137853064  ):

  • C/C: typical
  • T/T: Rare mutation, listed as pathogenic for MYD88 deficiency

Members: Your genotype for i5000726 is .


NOD1 gene

Nucleotide-binding oligomerization domain containing 1 (or NOD1)

Mice deficient in Nod1 have increased susceptibility to H. pylori.  Other studies have shown that NOD1 variants lead to an increased risk of inflammatory bowel diseases in some populations.  One study concluded, “Taken together, these data may suggest that NOD1 plays a variable role in different populations that could depend upon environmental and dietary factors.”[ref]

Check your genetic data for rs2075822 (23andMe v4):

  • A/A: typical
  • A/G: increased risk of IBD
  • G/G: increased risk of IBD[ref]

Members: Your genotype for rs2075822 is .


TLR4 gene

Toll-like receptor 4 (TLR4) plays an important role in our innate immunity and is especially active against gram-negative bacterial infections. TLR4 variants have been investigated in conjunction with cancer risk, vaccine response, and transplant rejection among other things.

Check your genetic data for rs4986790 (23andMe):

  • A/A: typical
  • G/G: increased risk of gram-negative bacterial infection, septic shock[ref][ref], and metabolic syndrome[ref]

Members: Your genotype for rs4986790 is .

 

Check your genetic variant for rs10759932 (23andMe ):

  • T/T: typical
  • C/C: decreased risk of H. pylori[ref]

Members: Your genotype for rs10759932 is .


SLC39A8 gene

From Genetics Home Reference: “This gene encodes a member of the SLC39 family of solute-carrier genes, which show structural characteristics of zinc transporters. The encoded protein is glycosylated and found in the plasma membrane and mitochondria, and functions in the cellular import of zinc at the onset of inflammation. It is also thought to be the primary transporter of the toxic cation cadmium, which is found in cigarette smoke.”

Check your genetic data for rs13107325 (23andMe):

  • C/C: typical
  • C/T: changes in the gut microbiome, obesity, and Crohn’s disease risk
  • T/T: changes in the gut microbiome, obesity, and Crohn’s disease risk[ref]

Members: Your genotype for rs13107325 is .


Lifehacks

Eating prebiotic fiber, such as inulin / FOS may increase your bifidobacteria.[study]

There are probiotics available containing multiple strains of bifidobacteria.

More to read:

A recent study did an extensive analysis of the microbes associated with visceral fat, BMI, and other obesity markers.  The study also found several genes correlated with specific bacteria that are associated with obesity.  The SNPs (none of which are included in 23andMe results) were in the FHIT, TDRGI, and ELAVL4 genes.  The full study is open to read and worth checking out.



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.