How your genes shape your gut microbiome and weight

Key takeaways:
~ Your genes impact which microbes live in your gut
~ Your gut microbiome impacts your weight
~ Together, understanding your genetics, your diet, and your gut microbiome can help with weight management.

Members will see their genotype report below and the solutions in the Lifehacks section. Consider joining today.

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Gut Microbiome and 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.[ref] 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).

Genetics and microbes:

Here are a few of your genes that play a role in which gut microbes are likely to be hosted in your gut microbiome. See the Genotype Report section for your genetic variants for these genes.

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]

MYD88 gene:

The MYD88 gene is a signal receptor involved in the innate immune system. It’s a part of the TLR (Toll-like receptor) and interleukin-1 receptor (IL-1R) signaling pathways, which regulate the immune response to foreign invaders like bacteria – including gut bacteria.

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 it is worthwhile to read through if you have T1D.[ref]

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.[ref]

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.[ref]

Other mouse studies have found that MyD88 knockout mice are more susceptible to tuberculosis.[ref] This has been confirmed in humans with MyD88 polymorphisms as well.

NOD1 gene:

The NOD1 gene encodes nucleotide-binding oligomerization domain containing 1, which is a receptor that helps the immune system recognize certain types of bacteria and then stimulates the immune response.

Mice deficient in Nod1 have increased susceptibility to H. pylori.[ref] 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]

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.[ref][ref]

SLC39A8 gene:

SLC39A8, also called ZIP8, is a metal ion transporter in the intestines as well as on cell membranes. Zinc and manganese are the primary metals transported by SLC39A8, and they are also key to a balanced immune response. SLC39A8 is upregulated in response to a pathogen infection. The gut microbiome is also affected by how much zinc is available in the gut vs. taken up into the body. The gut microbiome actually uses about 20% of your dietary zinc, so the amount left for the gut microbiome can affect which types of bacteria are more likely to be abundant.

High levels of zinc supplementation increase in relative abundance of Bacteroidetes and decrease Firmicutes sp. Similarly, the SLC39A8 A391T variant has been shown to cause a reduced abundance of Anaerostipes, Coprococcus, Roseburia, Lachnospira, SMB53, Ruminococcaceae, Eubacterium, Dorea, and Bacteroides.[ref]

Now let’s take a look at how your genetic variants impact the function of these genes.

Gut and Weight Genotype Report:

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

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

Members: Your genotype for rs651821 is —.

MYD88 gene:
Encodes myeloid differentiation factor 88, which is involved in receiving the signal from inflammatory cytokines. Keep in mind that these are just the variants covered in 23andMe or AncestryDNA. Other variants also reduce MYD88 levels.

Check your genetic data for rs4988453 (23andMe v4, AncestryDNA):

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 genetic data for for i5000725 (rs137853065) (23andMe v4, AncestryDNA):

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

Members: Your genotype for i5000725 is — or for rs137853065 is —.

Check your genetic data for i5000726 (rs137853064) (23andMe v4, AncestryDNA):

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

Members: Your genotype for i5000726 is — or for rs137853064 is —.

NOD1 gene:
Encodes Nucleotide-binding oligomerization domain containing 1 (or NOD1)

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

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

Members: Your genotype for rs2075822 is —.

TLR4 gene:
Encodes Toll-like receptor 4 (TLR4), which plays an important role in our innate immunity and is especially active against gram-negative bacterial infections.

Check your genetic data for rs4986790 (23andMe v4, v5; AncestryDNA):

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 v4; AncestryDNA):

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

Members: Your genotype for rs10759932 is —.

SLC39A8 gene:
Encodes a metal ion transporter that is involved in the absorption of uptake of zinc, manganese, iron, cadmium, and selenium in the intestines and their transport into cells.

Check your genetic data for rs13107325 A391T (23andMe v4):

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

Members: Your genotype for rs13107325 is —.

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Lifehacks:

Eating prebiotic fiber, such as inulin or FOS, may increase your bifidobacteria.[ref]

There are probiotics available containing multiple strains of bifidobacteria.

Recap of your genes:

Gene	RS ID	Effect Allele	Your Genotype	Notes About Effect Allele
APOA5	rs651821	C	--	Reduced Bifidobacterium levels, higher triglycerides, and MetS risk
MYD88	rs4988453	A	--	Reduced MYD88
MYD88	i5000725	C	--	Rare mutation, listed as pathogenic for MYD88 deficiency
MYD88	rs137853065	C	--	Rare mutation, listed as pathogenic for MYD88 deficiency
MYD88	i5000726	T	--	Rare mutation, listed as pathogenic for MYD88 deficiency
MYD88	rs137853064	T	--	Rare mutation, listed as pathogenic for MYD88 deficiency
NOD1	rs2075822	G	--	Increased risk of IBD
TLR4	rs10759932	C	--	Decreased risk of H. pylori
SLC39A8	rs13107325	T	--	Changes in the gut microbiome, obesity, and Crohn’s disease risk
TLR4	rs4986790	G	--	Increased risk of gram-negative bacterial infection, septic shock, and metabolic syndrome