gut health

KLB

What is the Connection Between β-Klotho and Gut Inflammation? (KLB)

Written by Jasmine Foster, BSc, BEd on April 28th, 2020

β-klotho regulates the production of bile and how long it takes for digested food to pass through the gut. Does it affect the development of IBS-D? Read on to learn more.

What is β-Klotho?

Beta-klotho (β-klotho) is one of the three subtypes of klotho protein, the other being alpha-klotho (α-klotho). α-klotho is the better-known of the two, especially as it relates to longevity [R].

β-klotho activates a growth factor called FGF21, regulates the production of some sex hormones (gonadotropins), and appears to protect against heart disease. It also plays a role in the regulation of fat, though researchers currently do not know whether it is protective or potentially harmful in fatty tissues [R, R, R, R].

β-Klotho, Bile Acids & Digestion

Much of β-klotho’s effect on the gut appears to be tied to the production and release of bile. Mice without a functioning β-klotho gene produce more bile than normal, and the composition of their bile acids changes. In humans, increased stability of the β-klotho protein is associated with reduced bile production [R, R].

The main function of bile is to help digest dietary fats. It is produced by the liver, stored in the gallbladder, and released into the small intestine [R].

Normally, bile is reabsorbed by the intestinal wall as digested food moves through the gut. However, some digestive disorders—including bile acid malabsorption (BAM) and diarrhea-predominant IBS (IBS-D)—may prevent the reabsorption of bile acids. In these disorders, the excess bile acid seems to make digested food pass through the gut more quickly, leading to diarrhea [R].

β-klotho regulates the release of bile and therefore has an effect on the digestion of fats. Lower β-klotho has been associated with food passing through the gut more quickly.

KLB Variants and Gut Transit

One study found a link between the KLB gene and the amount of time it takes for digested food to travel through the intestines [R].

At rs17618244, the more common ‘G’ allele codes for a less stable protein than the uncommon ‘A’ allele. The ‘A’ version’s increased stability appears to result in less bile acid being delivered into the gut, leading to food spending more time in the intestine [R].

People with IBS-D and the ‘GG’ genotype had the shortest transit time (time taken to pass food through the digestive tract) when compared to healthy people, people with other types of IBS, and people with different genotypes [R].

The ‘GG’ genotype is very common—about 72% of the world’s population has it—so don’t assume you have IBS based on this gene alone! Genetic predispositions to disease tend to come from many genes and SNPs interacting, not just one.

The common ‘G’ allele at rs17618244 produces a less stable β-klotho protein than the less common ‘A’ allele. The ‘G’ allele has been linked to IBS-D.

Your KLB Results for Gut Inflammation

SNP Table

variant	genotype	frequency	risk allele
rs17618244

SNP Summary and Table

KLB rs17618244

‘G’ = Associated with IBS-D; less stable β-klotho protein, more bile acid released, shorter gut transit
‘A’ = Not associated with IBS-D; more stable β-klotho protein, less bile acid released, longer gut transit
About 72% of all people worldwide have the ‘GG’ genotype.
The ‘GG’ genotype is most common among people of African descent (90%).

Recommendations

Diet

Adjust Dietary Fat Levels

Bile is released when we eat fatty foods. We do not currently know whether dietary fats affect β-klotho expression, but a low-fat diet may reduce bile production and increase the amount of time that it takes for digested food to pass through the gut [R, R].

Many doctors and dietitians recommend a low-fat diet for patients with IBS-D. In observational studies and small clinical trials, increased dietary fat induced symptoms in IBS-D patients [R].

If you have IBS-D, you can try adjusting your dietary fat levels to see it helps symptoms.

Choosing Healthy Fats

Even people on a low-fat diet need to eat some dietary fats. Polyunsaturated fatty acids (PUFAs, which include omega-3s) may be the best choice; they have been found to increase β-klotho in mice [R].

In cells, omega-3 PUFAs also stimulate the breakdown of bile acids and reduce the expression of other genes that promote bile production [R].

Your doctor or dietitian can help you develop an ideal diet for your situation, but omega-3 PUFAs are among the safest and healthiest dietary fats for IBS-D.

Avoid Simple or Refined Sugars

According to a mouse study, glucose (one of the basic subunits of sugar) represses the expression of β-klotho, possibly increasing bile production [R].

Glucose is not usually implicated in IBS; a different simple sugar, fructose, is more often considered a potential villain. However, if you have IBS-D and potentially reduced β-klotho production, you may want to reduce your intake of sugar – both fructose and glucose [R].

Fortunately, reducing glucose intake is generally considered a healthy diet choice for other reasons, as well [R].

Dietary interventions seem to have the most potential to help correct problems related to β-klotho. Reducing total dietary fat, choosing healthy fats, and avoiding simple or refined sugars may reduce the symptoms of IBS-D.

Drugs

While there are no known drugs that increase or stabilize β-klotho directly, there are drugs that bind to bile, such as cholestyramine. These are typically prescribed to reduce cholesterol, but they may be used off-label to treat bile acid malabsorption [R].

If you are suffering from IBS-D and you have the ‘GG’ genotype of rs17618244, you may want to ask your doctor if you might have bile acid malabsorption or a similar digestive disorder. Do not take cholestyramine or any other prescription medication without your doctor’s instruction.

Jasmine Foster

BSc, BEd

Jasmine received her BS from McGill University and her BEd from Vancouver Island University.

Jasmine loves helping people understand their brains and bodies, a passion that grew out of her dual background in biology and education. From the chem lab to the classroom, everyone has the right to learn and make informed decisions about their health.

Disclaimer

The information on this website has not been evaluated by the Food & Drug Administration or any other official medical body. This information is presented for educational purposes only, and may not be used to diagnose or treat any illness or disease.

Also keep in mind that the “Risk Score” presented in this post is based only on a select number of SNPs, and therefore only represents a small portion of your total risk as an individual. Furthermore, these analyses are based primarily on associational studies, which do not necessarily imply causation. Finally, many other (non-genetic) factors can also play a significant role in the development of a disease or health condition — therefore, carrying any of the risk-associated genotypes discussed in this post does not necessarily mean you are at increased risk of developing a major health condition.

Always consult your doctor before acting on any information or recommendations discussed in this post — especially if you are pregnant, nursing, taking medication, or have been officially diagnosed with a medical condition.

More gut health blogs

Could This Gene Be Linked To Gut Inflammation? (ATG16L1) Could This Gene Play A Role In Inflammatory Bowel Disease? (STAT3) How Do Your Genes Respond to Dietary Fat? (TCF7L2) Do Your Genes Favor the Mediterranean Diet? (TCF7L2) How Does this Serotonin Receptor Affect Gut Inflammation? (HTR3E) The Impact of a Serotonin Receptor on IBS-D (HTR3A) How Can Neurotrophins Affect Gut Inflammation? (BDNF) Could Your IBS Symptoms Be Caused by an Enzyme Deficiency? (SI) What is the Connection Between β-Klotho and Gut Inflammation? (KLB) Can This Gene Worsen Gut Inflammation? (NOS2)

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What is β-Klotho? β-Klotho, Bile Acids & Digestion Your KLB Results for Gut Inflammation

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