Harnessing the Microbiota-Gut-Brain Axis to Improve the Stress Response

New understandings of the intricate connections between gut and brain are revolutionizing medicine’s approach to mood, brain function and digestion, giving our “gut-wrenching experiences” or our “gut-feelings” a lot more meaning than they already have. The emerging evidence in this area is providing new tools to influence both gut and brain health.

The gut-brain axis

The gut as we know includes all organs involved in digestion such as the esophagus, stomach, small and large intestine, gall bladder, liver, and pancreas. It is often referred to as the ‘second brain’ and it communicates with our central brain in two ways: physically via the vagus nerve, which is the main nervous system connection from the brain to the gut, and chemically through hormones (like the stress hormone cortisol) and neurotransmitters that circulate through blood. This ‘second brain’ sitting in the gut is also referred to as the enteric nervous system or the ENS which consists of millions of nerve cells extending from the esophagus to the rectum.

When we talk of the gut-brain axis, it refers to the bidirectional communication between the brain, our central nervous system, and the enteric nervous system in the gut. *

The microbiota-gut-brain axis

We also now know that our microbiota interacts with our gut-brain axis, creating an extended microbiota-gut-brain axis. This interaction appears to be via the nervous, hormone, and immune systems.* The net result is a complex communication system that influences health and balance in the digestive tract as well as in mood and brain function * (1)

One of the interesting research developments in this area is the section of the microbiota-gut-brain axis that involves the stress response. A stress response originating in the brain can influence the health and function of the digestive tract. And what is especially exciting to know is that the health of the digestive tract and the microbiota can influence the health of that stress response. It’s bidirectional.

Let’s look a little closer.

Stress and the microbiota-gut-brain axis

Environmental factors such as emotions or stress activate the central nervous system. One of the ways this occurs is via the hypothalamic pituitary adrenal (HPA) axis (see the dashed line in the image below). When the HPA axis is activated, the hypothalamus (HYP) area of your brain secretes corticotropin-releasing factor (CRF) that further stimulates the brain’s pituitary gland to secrete adrenocorticotropic hormone (ACTH). ACTH travels through your blood to your adrenal glands and causes them to release the hormone cortisol. (1)

Microbiome gut-brain axis structure. (1)

 

In parallel to the HPA axis, the central nervous system communicates with different intestinal targets such as enteric nervous system (ENS), the gut muscle layers and the gut mucosa.

These hormonal and nervous system interactions directly alter and/or impair digestive motility, gut immunity, intestinal permeability, and the secretion of mucus (an important digestive and immune component). Through these actions, and their effect on immune function, they also have a knock-on effect on the microbiota. *(1)

Our emerging understanding of using microbiota interventions to influence stress response

One of the most compelling developments today is our understanding that, while exposure to stress can impact the gut microbial profile, microbial populations can also influence the stress response. * (2)  Although our understanding of applying therapeutic interventions that target the microbiota to influence stress response is still limited, evidence is building that the manipulation of the gut microbiota through probiotic intervention may be a novel approach to influence stress, mood and well-being. * (3)

Human studies have been limited in this space, however one clinical study on a particular strain of proflora known as Lacticaseibacillus paracasei Lpc-37®, formerly known as Lactobacillus paracasei Lpc-37, has shown some promising results. Previously, this strain had been studied in combination with other viable probiotic strains for functional gastrointestinal symptoms (4), cardiometabolic parameters and autonomic modulation (5), and constipation. (6)

This most recent human clinical trial of Lpc-37, published in 2020, was an evaluation of stress response. (3) This study assessed the impact of Lpc-37 supplementation on stress response among health adults (ages 18-45 years) over a 5-week duration. The dosage studied was a daily capsule containing 17.5 billion colony forming units (CFU) of Lpc-37. The intake of Lpc-37 for five weeks reduced perceived stress levels in both male and female adults (p=0.048). * In addition, in the low chronic stress subgroup, Lpc-37 reduced exhaustion following the Trier Social Stress Test (p=0.037). In the high chronic stress subgroup, participants experienced an increased perceived health (p=0.012) and sleep-related recovery (0.006). Productivity scores trended towards an increase across the whole study population and especially in males (nearly reaching significance at p=0.054). These results suggest that Lpc-37 supports the stress response and is an important gut-brain axis intervention. * (3)

Even as the understanding of gut-brain therapeutics is far from complete, practitioners have existing tools to engage both systems to support either the gastrointestinal system, brain function, or both. *

Learn more about Integrative Therapeutics and their work in therapeutic prebiotics, probiotics, and enzymes here.

References

1. Carabotti M, Scirocco A, Maselli MA, Severi C. Ann Gastroenterol. 2015;28(2):203-209.
2. Foster J.A., Rinaman L., Cryan J.F. Stress & the gut-brain axis: regulation by the microbiome. Neurobiol Stress. 2017;7:124–136.
3. Patterson E, Griffin SM, Ibarra A, Ellsiepen E, Hellhammer J. Neurobiol Stress. 2020;13:100277. Published 2020 Nov 24. doi:10.1016/j.ynstr.2020.100277
4. Harris LA, Cash BD, Moftah K, Franklin H. [published online ahead of print, 2021 May 24]. J Clin Gastroenterol. 2021;10.1097/MCG.0000000000001567. doi:10.1097/MCG.0000000000001567
5. Romão da Silva LF, de Oliveira Y, de Souza EL, et al. Food Funct. 2020;11(8):7152-7163. doi:10.1039/d0fo01661f
6. Airaksinen K, Yeung N, Lyra A, et al. Benef Microbes. 2019;10(6):617-627. doi:10.3920/BM2018.0163

* This statement has not been evaluated by the Food & Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.