HOW DOES STRESS IMPACT THE GUT MICROBIOTA?
BIOHUB

HOW DOES STRESS IMPACT THE GUT MICROBIOTA?

by Jelena Vulevic on Oct 28, 2021

Today’s environment and our lifestyles put additional stresses on our body, often involuntarily, that challenge our overall health, cognition and physical function. Health implications associated with exposure to these stressors are interrelated, have multi-factorial aetiologies and have recently been associated with the gut microbiota/microbiome. This should not be surprising, given the widespread roles of this microbial community in:

 The Gut Microbiota

Our bodies are hosts to trillions of microorganisms, collectively known as the human microbiota. Depending on the different anatomical site, and as a result of their unique physio-chemical conditions (eg pH, moisture level, oxygen and substrate availability), the diversity, composition and function of the local microbiotas varies. Nevertheless, research from the past decade has highlighted the importance of those microbiomes not only to local sites but also to our overall wellness and health. As a consequence, relevant scientific communities have started to recognise humans as ‘superorganisms’ or ‘holobionts’ comprising of an integrated network of human cells and microorganisms whose dynamic bi-directional interactions react and respond to intrinsic and extrinsic stressors to influence health. In fact, only about a third of the cells in your body are of human origin, the rest are microorganisms. 

The most densely populated area with microorganisms of our body is our gut, with trillions of bacteria only in just 1g of its content. The gut microbiota has therefore attracted the most attention so far. Based on a mutualistic relationship that has been shaped after years of co-evolution, we humans provide a hospitable environment and nutrients, while our gut microbiota contributes to energy homeostasisprevents infections and mitigates immune system hypersensitivity. Most importantly, it contributes to the maintenance of an intact gut barrier which is crucial in ensuring nutrient absorption and not allowing transfer of undesirable or toxic content from the gut into the body. Improper function of this barrier is related to infectious, inflammatory and allergic diseases, as well as the ageing process. 

The gut microbiota generally demonstrates resilience to distress and long-term stability. However, disturbances in the gut microbiota can initiate a vicious cycle whereby consequent dysbiotic shifts in the gut microbiota exacerbate declines in gut physiology that further maintain dysbiosis. Any impairment of the gut microbiota, for example, by administration of oral antibiotics or lifestyle choices, affects the functionality of our human local defence systems. Concurrently, any malfunction in gut physiology, immune or intestinal nervous systems, affects the microbiota composition, diversity and function. Especially, the gut barrier, and consequently the gut microbiota, are directly altered not only by local disturbances but also by any systemic stressor. A normal, balanced gut microbiota of rich diversity, and more importantly an intact gut barrier that counteracts and cooperates with the existing microbiota, are therefore essential to maintain gut health and support overall health and wellness. 

Mild dysbiosis is associated with temporal health impacts, including the gut permeability and inflammationincreased susceptibility to illness and infection, as well as psychological impairments. However, untreated long-term dysbiosis is associated with multiple chronic diseases such as obesity and associated cardiometabolic diseasesinflammatory bowel diseasecolon cancerautoimmune diseases and psychological disorders among others

Recent animal studies have shown that the gut microbiota impairments can also affect our mood, anxiety levels, stress resilience and depression through a bidirectional communication along the gut-brain axis, which involves many organ systems, including the endocrine, immune, autonomic, central (CNS), and enteric (intestinal) nervous systems. This is further validated by the fact that in humans:

Stress and the Gut Microbiota

Stress, defined as the result of physical and mental responses that our body produces when experiencing any intrinsic or extrinsic stressors, is a ubiquitous part of daily human life. It has varied biological effects, including impairments of the gut microbiota. When the body experiences stressors, it causes a cascade of events that are designed to help it escape imminent danger. It shuts down non-essential activities like sexual desire, reproduction and digestion, and it uses chemical messengers to direct its resources and energy to the brain and organs in need. 

Although stressors can be varied in nature (e.g. physiological, psychological, environmental etc), the biological stress response is coordinated primarily by the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS). Stressor-induced activation of the HPA axis and SNS stimulates the release of glucocorticoids, catecholamines, and other hormones which have varied effects throughout the body including modulation of the immune system and of gut function. The stress response is largely adaptive and acts to quickly restore homeostasis, but varies as a function of the source, magnitude and duration of exposure to stressors. The impact is often transient, aims to build resilience to combat stress, but it can compromise performance, increase attrition, and contribute to the development of chronic health conditions in some individuals. Severe or chronic exposure to stressors can exceed the adaptive capacity of an organism causing reduced physical and cognitive performance, illness, and maladaptive responses leading to chronic disease. This has implications for the gut microbiota too, as a growing body of evidence suggests that our human responses to intrinsic and/or extrinsic stressors are in part mediated by the impact on the gut microbiota. 

Several pathways by which stress mediates gut microbiota community structure and activity, as a result of lifestyle-relevant, psychological, environmental and physical stressors have been elucidated. The studies demonstrate that the gut microbiota’s response to stress over both the short- and long-term, can: 

  • promote health (eg with cold exposure)

  • degrade health (eg with psychological stress, circadian disruption, and high altitude) 

  • or both (eg with physical activity and diet)

The vagus nerve: This is the longest nerve in your body that connects the brain with other organs (eg heart, lungs and gut). Its essential in regulating function of these organs in terms of heart rate, respiratory rate, digestion, swallowing, sneezing, etc. Stress-induced changes in signalling via the vagus nerve and intestinal nervous system alter gut motility and reduce digestive activity. This impacts the gut microbiota by modulating physical forces within the gut and by altering nutrients available for their growth. Blood is also redirected away from the gut during the stress response, especially in response to vigorous exercise and heat stress, which can initiate a cycle of hypoperfusion, ischemia and reperfusion that alters the amount of oxygen delivered to the gut and leads to oxidative stress and inflammation. These effects ultimately degrade the physical gut barrier thereby increasing gut permeability and allowing transfer of various toxins and inflammatory molecules into our body and impact the gut microbiota.

The immune function: It is well established that stress alters immune function. The largest collection of lymphoid tissue (immune system) in your body is in your gut (as much as 70% of it). Its called the gut-associated lymphoid tissue, and it provides a dynamic immunological barrier throughout the gut. Changes in the activity of immune cells, and cells that comprise the gut barrier, lead to the secretion of various chemicals by the immune system in response to stress, and directly alter gut microbiota composition and function. 

The gut environment: Finally, your lifestyle and environmental factors such as diet, some medication (e.g., antibiotics), pathogens, environmental toxicants and pollutants, stress the gut microbiota both directly and indirectly via altering inflammation, oxidative stress, immune function, and the gut environment. Diet in particular is a major factor influencing the gut microbiota, due to nutrient intake directly affecting the types and nutrients available to gut microbes, and to the myriad effects of different nutrients on our human physiology.

In conclusion, the gut microbiota is an underappreciated mediator of stress responses contributing to adverse stress-associated health outcomes, but it can also provide a tool for favourably modulating our human response to stress. Both are heavily influenced by your lifestyle choices and can therefore be altered.