gut health

mental health

CRHR1

The Hidden Link Between IBS and Anxiety (CRHR1)

Written by Aleksa Ristic, MS (Pharmacy) on May 9th, 2020

The CRHR1 gene encodes a receptor for CRH, a crucial hormone in the gut-brain connection and stress response. Read this post to learn about the variants in this gene associated with IBS and related anxiety.

CRHR1 and the HPA Axis

By Shelley Adams: HPA Axis Diagram (Brian M Sweis 2012).png, CC BY-SA 3.0

The CRHR1 gene encodes the first type of the CRH receptor (CRH-R1). The release of CRH sets off the hypothalamic-pituitary-adrenal (HPA) axis, resulting in the secretion of cortisol, the stress hormone [R].

In response to stress, the HPA axis stimulates the nervous system, cardiovascular system, and bowel movements. Excess CRH levels play a role in a range of physical and mental disorders [R, R, R].

The Role of CRH in IBS

Irritable bowel syndrome (IBS) is a gut condition that causes abdominal pain, bloating, and impaired bowel movements. The NIH estimates that as many as 20% of Americans may experience IBS symptoms, but doctors still don’t know the exact causes behind it [R].

Recent IBS research has focused on the gut-brain connection and the impact of psychosocial factors such as stress and anxiety [R, R, R].

As mentioned, CRH mediates stress response and impacts bowel movements, which makes it a key player in IBS. Administration of CRH can cause or worsen IBS symptoms in humans and lab animals [R, R, R].

Excess CRH may also increase pain sensitivity in the gut, potentially worsening the symptoms of IBS and other digestive disorders [R].

IBS is a bowel movement disorder with a strong mental component. By controlling stress response and gut sensitivity, CRH plays a crucial role in IBS development.

CRHR1 Variants and IBS Susceptibility

A study of 500 subjects found a link between CRHR1 variants and IBS: the condition was more common in people with the “G” alleles at rs110402 and rs242924. These SNPs were also associated with higher IBS-related anxiety [R].

The above trial excluded Asian subjects because they have drastically different allele frequencies for these variants. In a Japanese study, the opposite alleles correlated with higher IBS rates [R].

Previous research has associated the same SNPs with depression and anxiety, confirming the central role of CRH in the gut-brain connection [R, R, R].

The “G” alleles at rs110402 and rs242924 correlate with higher rates of IBS and related anxiety. These variants have the opposite effect in Asian populations.

How It Works

Unlike CRH-R2, the stimulation of CRH-R1 receptors stimulates bowel movements and increases gut sensitivity. CRH may also cause inflammation via CRH-R1. These receptors are a crucial link between stress response and IBS symptoms [R].

The studied SNPs are in the intron region of CRHR1; they may impact gene expression and the structure of the final product (receptor). In simple terms, the “G” alleles may enhance the activation of CRH-R1 receptors and thus contribute to IBS [R, R, R].

Your CRHR1 Results for IBS

SNP Table

variant	genotype	frequency	risk allele
rs110402
rs242924

SNP Summary

Primary SNPs:

CRHR1 rs110402

‘G’ = associated with higher rates of IBS and related anxiety
‘A’ = not associated with IBS

CRHR1 rs242924

‘G’ = associated with higher rates of IBS and related anxiety
‘T’ = not associated with IBS

Population Frequency

These two variants are almost always inherited together, which means they act as a single genetic factor. Around 50% of European descendants carry one copy, and 30% carry both copies of the “G” allele. This allele is much less common in East Asian populations (15%).

Recommendations

Lifestyle

Avoid Stress

Psychosocial stress is the primary HPA axis activator. Excessive CRH-R1 stimulation mediates various adverse effects of stress, both mental and physical [R, R].

Stress can trigger or worsen IBS symptoms. Some researchers refer to both “irritable bowel” and “irritable brain” as equal factors in the development of IBS. Many experts recommend stress management as part of a holistic strategy to treat this condition [R, R, R].

In two studies of 232 participants, different relaxation strategies significantly reduced IBS symptoms, in some cases even better than conventional treatment [R, R].

Stress can stimulate CRH-R1 receptors, activate the HPA axis, and trigger IBS symptoms. Different relaxation techniques may provide relief from this condition.

Diet

Fermented Foods

Probiotic-rich foods may reduce HPA axis activity and keep the stress hormones under control. Imbalances in the gut microbiota can trigger gut inflammation and activate the HPA axis, while probiotics may lessen this effect [R, R].

Most IBS patients have impaired gut microbiota, featured by low diversity and numbers of beneficial probiotic strains [R].

Fermented foods are a great way to increase your intake of probiotics and control IBS symptoms. The following foods have shown promising results in clinical trials [R, R, R, R]:

Buttermilk
Yogurt
Kefir
Sauerkraut (fermented cabbage)

Probiotics may prevent over-stimulation of the HPA axis. Fermented foods help restore your gut microbiota, which is essential for IBS prevention and control.

Zinc-Rich Foods

Zinc deficiency activates the HPA axis and increases cortisol secretion. In a trial of 27 volunteers, i.v. zinc administration suppressed cortisol levels [R, R, R].

IBS patients often have a zinc deficiency. Zinc supplementation can be effective against diarrhea, especially in malnourished children [R, R, R, R].

That said, over-supplementation with zinc may also cause digestive issues. Most people can get enough of this mineral from dietary sources, such as [R, R, R]:

Meat
Seafood (especially oysters)
Dairy products
Nuts and seeds
Legumes

However, people with gut inflammation might have impaired zinc absorption and require higher levels of zinc, in which case supplements can help.

Zinc deficiency can activate the HPA axis and worsen IBS symptoms, especially diarrhea.

Limit Caffeine Intake

Caffeine is a psychostimulant that spikes cortisol and increases alertness. This effect is more pronounced in people who don’t regularly consume caffeinated beverages [R, R].

In a trial of 330 IBS patients, coffee was one of the top ten food items associated with symptoms such as indigestion, pain, and loose stools. Most dietary guidelines for IBS patients recommend limiting caffeine intake [R, R, R].

In sensitive people, higher doses of caffeine may provoke anxiety, which is closely related to IBS [R].

Caffeine may spike cortisol and contribute to unpleasant digestive symptoms in some IBS patients.

Supplements

Peppermint Oil

Peppermint is an age-old traditional remedy for stress and digestive issues. Its relaxing properties partly stem from the ability to suppress CRH, leading to lower cortisol levels [R].

Peppermint oil is a well-known natural remedy for IBS with a significant chunk of evidence to back up its use. In a meta-analysis of 12 studies and 835 patients, it reduced abdominal pain and other symptoms of IBS without adverse effects [R].

Up to 80% of IBS patients may have small intestinal bacterial overgrowth or SIBO. Peppermint oil reduced intestinal gas production and IBS symptoms in patients with bacterial overgrowth [R].

Peppermint oil may suppress CRH, improve the gut flora, and reduce IBS symptoms.

Probiotics

As mentioned, probiotics can prevent over-stimulation of the HPA axis. The following strains showed promising clinical results in IBS patients:

Bifidobacterium infantis [R]
Bifidobacterium lactis [R]
Saccharomyces cerevisiae (Brewer’s yeast) [R]

According to a review of 10 studies, probiotics may reduce anxiety and improve mood and cognition in depressed patients. Given the robust gut-brain connection, this effect is crucial for people struggling with IBS [R].

Probiotics may balance the gut-brain connection and improve IBS symptoms.

Aleksa Ristic

MS (Pharmacy)

Aleksa received his MS in Pharmacy from the University of Belgrade, his master thesis focusing on protein sources in plant-based diets.

Aleksa is passionate about herbal pharmacy, nutrition, and functional medicine. He found a way to merge his two biggest passions—writing and health—and use them for noble purposes. His mission is to bridge the gap between science and everyday life, helping readers improve their health and feel better.

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.

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