Stress, Digestion, and the Microbiome

By: Deanna Minich, MS, PhD, CNS, IFMCP, UWS human nutrition and functional medicine instructor

Reposted with permission from Dr. Minich’s professional blog page

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Photo: C-Motooka/
Photo: C-Motooka/

There is a strong bidirectional relationship between the brain and the gut, which has implications for immunity, mood, digestion, and more. Stress can negatively impact the gut-brain axis in a variety of ways. The activation of the hypothalamic-pituitary-adrenal (HPA) axis as part of the body’s stress response causes the release of corticotropin-releasing hormone (CRH), which affects immune function in the gut. CRH can impact intestinal barrier integrity, leading to hyper-permeability or “leaky gut” as well as increased inflammation. The gastrointestinal system also contains a rich network of nerves that  influences intestinal permeability, as well as factors such as gastric motility and pain perception.

The microbiome is involved in this interplay between the nervous system and the gut as well.  Germ-free mice have been shown to have impaired gut motility, as well as altered social behavior and anxiety. Offspring of monkeys that experienced prenatal stress exhibited significant perturbations to their microbiome within the first six months of life, including changes in levels of beneficial Bifidobacterium. In a study of Swedish men, lower stress resilience during adolescence was associated with an increased risk of irritable bowel disease later in life. Changes in gastric motility and enzyme secretion due to stress can alter the terrain and impact the composition of the microbiome.

The gut microbiota is also thought to influence serotonin production, which is significant since as much as 95% of serotonin is produced within the gut. The microbiome has been shown to influence psychiatric disorders and even the pathogenesis of neurodegenerative diseases, such Alzheimer’s disease and Parkinson’s disease. Finally, people with irritable bowel syndrome have an altered microbiome and often present with psychological comorbidities. A study assessing the interplay between the microbiome and mood disorders found that 65% of participants experienced increased psychological distress, and this distress correlated with increased abundance of Proteobacteria. Participants who reported anxiety had elevated Bacteroidaceae, a gram-negative bacteria. The cell walls of gram-negative bacteria contain lipopolysaccharides (LPS), which can trigger the immune system and cause increased inflammation in the central nervous system.

This web-like relationship between the brain, gut, and microbiota demonstrates the need to address the sources of stress in our lives so we can experience greater resiliency and improved health.

The Impacts of Stress

Living a sedentary lifestyle, overexercising without proper recovery, sleep deprivation, and eating a processed diet can all be physical stressors on the body. A study of soldiers undergoing an intense cross-country ski trip demonstrated that physical exertion increased intestinal permeability and inflammation. The change in intestinal permeability may have been caused in part by a disruption to the gut microbiome. Study participants experienced a decrease in certain bacteria associated with inflammation and immune regulation, such as Faecalibacterium and Roseburia, with a simultaneous increase in potentially pathogenic bacterial species. Faecalibacterium has also been shown to be lower in people with depression and anxiety. This bacterium produces butyrate, a short-chain fatty acid that exerts anti-inflammatory properties and maintains intestinal barrier integrity. Luckily, dietary changes can help to support the production of these short-chain fatty acids.

As explored in the field of nutritional psychiatry, the diet serves as a powerful modulator of mood, as well as the gut microbiome. Increased psychological stress impacts our eating habits by altering hunger hormones, which often causes us to overeat. It is tempting to reach for calorically dense foods that are high in sugar and/or fat when we are stressed. However, high-fat meals are thought to increase the production of endotoxins, which can cause inflammation and an increase of reactive oxygen species.

A study of the effects of culinary spices demonstrated that psychological stress causes elevated glucose and insulin levels after a high-fat meal. The inclusion of polyphenol-rich spices such as cinnamon, ginger, oregano, and turmeric led to the inhibition of pancreatic lipase and secreted phospholipase A2, and participants saw a 31% reduction in circulating plasma triglycerides. However, this effect was only seen if participants were in a restful state after eating. Antioxidant-rich foods can help to decrease oxidative stress, while dietary fiber and polyphenols nourish beneficial bacteria and can help boost the production of anti-inflammatory short-chain fatty acids.

Probiotic Supplementation

There has been a fair amount of research conducted on the use of probiotic supplementation to address stress and modulate the composition of the microbiome. Many of these studies involve students who are experiencing increased mental stress while preparing for academic exams. One such study found that milk fermented with Lactobacillus casei strain Shirota helped to attenuate increases in cortisol levels and reduced gastrointestinal symptoms, such as indigestion, in medical students. Gene sequencing showed that the probiotic led to significantly higher alpha diversity in the gut microbiome and a significant reduction in Bacteroidaceae. Probiotic supplementation also positively impacted genetic expression related to the metabolism of dietary fats. A separate study using this same probiotic strain showed that students experienced improvements in sleep quality leading up to the exam. This is thought to be due to a decrease in HPA activation by the probiotic.

A separate group of medical students ingested the probiotic Lactobacillus gasseri CP2305 for 24 weeks and experienced a significant reduction in anxiety and sleep disturbance leading up to a national exam. Depression scores, abdominal discomfort, and salivary CgA levels (used to assess catecholamines) were also all significantly reduced. Gene sequencing showed that stress caused a decrease in beneficial Bifidobacterium and an increase in Streptococcus in the placebo group, but this perturbation was attenuated by the probiotic. Yet another group of medical students who supplemented with the Lactobacillus gasseri CP2305 probiotic while enrolled in a human cadaver course experienced significant improvements in sleep and decreased depression and anxiety. Salivary cortisol levels, CgA levels, abdominal pain, and indigestion were all reduced in the probiotic group. The probiotic also inhibited the proliferation of gram-negative Enterobacteriaceae and Veillonella, which significantly increased in the placebo group during this period of heightened stress. Finally, students who received supplementation of Lactobacillus rhamnosus CNCM I-3690 for 4 weeks had a lower excretion of mannitol (mannitol is used to assess intestinal permeability) and reduced scores of perceived stress.

Healthy adults experienced a reduction in symptoms of anxiety and depression, as well as an increase in sleep quality, after ingesting a probiotic blend of Lactobacillus reuteri NK33 and Bifidobacterium adolescentis NK98. Participants also had decreased levels of Enterobacteriaceae and the pro-inflammatory cytokine interleukin-6 while experiencing increases in Bifidobacterium and Lactobacillus. Certain probiotic strains have also been shown to alter brain activity and impact the activation of the stress response. Healthy women who drank a fermented milk with five probiotic strains experienced changes in the midbrain cortices associated with emotional response. A separate group of healthy volunteers receiving Bifidobacterium longum 1714 had an increase in activation of the frontal and cingulate cortices of the brain as well as a change in resting neural activity after the completion of a stressful task. Researchers suggest this resting neural activity can reduce mental fatigue and helps to buffer against negative emotions. A final study showed that probiotic supplementation containing multiple strains of LactobacilliLactococcus, and Bifidobacterium led to improvements in working memory amidst acute stress in healthy women. The abundance of eight microbiome genera were altered in the probiotic group, including those that produce short-chain fatty acids.

Stress Management Techniques

Stress management techniques can exert a positive effect on gastrointestinal symptoms, particularly for those with irritable bowel syndrome and inflammatory bowel disease. A prospective study of patients with irritable bowel syndrome demonstrated that traditional cognitive behavioral therapy (CBT) and  a modified CBT home-study program led to moderate to substantial improvements in gut symptoms. Patients who only received education on how to manage irritable bowel syndrome also experienced improvements in gastrointestinal (GI) symptoms (44.8% improvement), but not to the same degree as those who were taught stress management techniques (58.4% improvement).

Gut-derived hypnotherapy is another modality that shows promise in supporting both psychological and physiological symptoms of irritable bowel syndrome and inflammatory bowel disease with one study demonstrating symptom improvements ranging from 24% to 73%. Gut-derived hypnotherapy can also help to improve resiliency, or the ability to cope with stress, as well as self-efficacy. This technique has been shown to positively affect gut motility, as well as nervous system activity.

Closing Thoughts

  • A diet rich in fiber, antioxidants, and polyphenols can support a healthy microbiome. This means plenty of fruits and vegetables with a focus on including a variety of different colors in each meal.
  • Stress can negatively impact digestion so be sure to set yourself up for success by eating your meals in a calm and undistracted state. Take 5 deep belly breaths before each meal to ground yourself and calm the nervous system. Chewing our food is a necessary first step of the digestive process. However, a systematic review also found that chewing can have a positive effect on attention and stress relief, perhaps by increasing blood flow to the brain and influencing serotonin pathways. Therefore, chewing each bite of food thoroughly is an excellent way of supporting the stress response and smooth digestion.
  • Probiotics exert positive effects on the gastrointestinal system and may also be helpful for supporting the stress response and sleep quality. It is important to find the right probiotic strain when choosing a supplement. If you plan to incorporate probiotic supplementation into your routine, talk to your doctor, nutritionist, dietician, or another member of your healthcare team for personal options based on your individual circumstances.
  • Stress management techniques, such as cognitive behavioral therapy and gut-derived hypnotherapy, can help to improve gastrointestinal symptoms due to the connection between the brain and gut.

If you plan to incorporate more colorful, plant-based, whole foods and/or supplements into your daily eating, or have food allergies or questions about which foods or supplements can best support your physical and mental health, talk to your doctor, nutritionist, dietician, or another member of your healthcare team for personal options based on your individual circumstances. There are certain medications that may interact with plant-based foods and supplements.