It’s the very nature of the type of clinical care that practitioners who use nutrition as a key mechanism of clinical care that the gastrointestinal tract becomes central to interventional strategy.
Whilst the gut is not always front and centre there is an inevitable engagement and understanding that all that is, or may be happening, in these remarkable tissues is an ongoing quest.
One area that those involved in the care of people with inflammatory bowel conditions have long recognised is that psychological stress is known to worsen their gut inflammation. Now scientists have found out why. New research outlines a sweeping narrative that begins with chemical cues produced in the brain and ends with immune cells in the gut, a sequence that spells trouble for people with these conditions[1]. Yet, despite the collective awareness across many disciplines of the connection, this understanding runs contrary to conventional medical treatment, which has completely neglected the psychological state of a patient as a major driver of the response to treatment.
For those practitioners with a long held understanding of psychoneuroimmunology the mechanisms involving the enteric nervous system and glucocorticoids may offer some additional details, but the concept, and consequently the importance of combining stress management with drug or non-drug therapy, is a well-recognised strategy.
A psychoneuroimmunology perspective looks to address possible neuro-visceral integration, immune modulation, and crucial intestinal microbiome changes in IBD. Furthermore, the bidirectionality of the brain-gut axis will be emphasised in the context of care by recognising that IBD pathophysiology increases the inflammatory response in the central nervous system and further contributes to anxiety- and depression-like behavioural comorbidities. That is, IBD increases anxiety just as anxiety increases IBD symptomology[2].
Interventions
Managing multiple points of intervention simultaneously is also known as ‘threshold therapy’ a key tenet of functional medicine. By combining small, meaningful and safe interventions, sequentially or synergistically it is possible to draw someone’s dysfunction, back into safe function.
Psychological stress and depression can promote consumption of highly palatable but problematic foods, adversely influencing which gut bacteria thrive. Additionally, stress and depression can reshape the gut bacteria’s composition through stress hormones, inflammation, and autonomic alterations. In turn, the gut bacteria release metabolites, toxins, and neurohormones that can alter eating behaviour and mood. Some bacterial species may actually encourage dysregulated eating. The gut bacteria may also upregulate stress responsiveness and heighten the risk for depression, which probiotic supplementation may attenuate[3].
In effect, the intersecting dynamic provides us a nexus of control, that is food selection and consumption.
LPS, stress, NCDs and weight gain
Fragments of bacteria leaking into the body from the gut are damaging fat cells and driving weight gain, research suggests[4]. Low-grade chronic systemic inflammation, characterised by increased circulating pro-inflammatory factors, is strongly associated with obesity and obesity-related diseases, such as type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Indeed, this chronic inflammation constitutes a major risk factor for cardio-metabolic morbidity and mortality.
Scientists at Nottingham Trent University have found that these microbe fragments, known as endotoxins, are able to enter the bloodstream and directly affect how well fat cell’s function.
Gut microbe fragments that enter the blood stream reduce normal fat cell function and their metabolic activity, which is exacerbated with weight gain, contributing to increased diabetes risk. It appears that, as we gain weight, our fat stores are less able to limit the damage that gut microbe fragments may cause to fat cells. Endotoxin from the gut reduces fat cell metabolic activity and its ability to become ‘brown-like fat cells’ that can be useful to help lose weight. This work suggests the need to limit endotoxin-induced fat cell damage is even more important when you have excess weight, as the endotoxin contributes to reduce healthy cellular metabolism.
Chronic low-grade inflammation is also characteristic for many non-communicable diseases (NCDs) including diabetes type II, cardiovascular disorders, autoimmune diseases, chronic fatigue syndrome, depression, and neurodegenerative pathologies, as well as weight management challenges. A fundamental driver of this is microbiome dysbiosis and increased permeability of the gastrointestinal wall.
Modern life-style factors, such as long-term psychosocial stress and components of our “Western” diet, constantly challenge the stress-axis and further compromise intestinal barrier function, resulting in endotoxaemia, low-grade inflammation, and its related diseases.
In summary, stress-induced disrupted barrier function in parallel with elevated circulating endotoxin levels may underlie disease onset and progression and should be considered much more than just a risk factor for chronic disease; it could be a cause.
In conclusion
Stressful stimuli activate the sympathetic nervous system (SNS) and hypothalamic–pituitary–adrenal (HPA)-axis. Activation of both systems increases the availability of water, minerals, and energy-rich substances to meet with the body’s transiently increased metabolic demand. The SNS responds instantly to physical and psychological stress by reallocating energy into different organs by neuronal regulation of heart rate, blood flow, release of catecholamines (adrenalin and noradrenalin) from the adrenal medulla, and stimulation of the renin–angiotensin–aldosterone system, involved in retention of water and sodium from the kidneys. In addition to the kidneys, water and sodium reabsorption can also be achieved at the level of the intestine. The intestinal wall is innervated by adrenergic sympathetic nerve fibres that upon stimulation increase water and sodium absorption, which is paralleled by increases in intestinal permeability.
Persistent stress is also a problem in that it leads to hypercortisolaemia as a compensatory defence, long-term permeability of barriers, endotoxaemia, and low-grade inflammation. Normally, the release of glucocorticoids puts a limit on the maximum activity of the immune system; however, chronic HPA-axis stimulation can result in glucocorticoid resistance at the level of the immune system, making it insensitive to its inhibitory and modulatory actions which as many clinicians recognise provide for a frustrating resolution challenge.
Improving food selection, utilising probiotics – as certain strains of the Gram-positive Lactobacilli decreased intestinal permeability in several animal and human disease models[5], and fibre sources to enhance the colonic food choice for bacteria, removing problematic bacteria, enhancing gut barrier function and supplying key nutrients as supplements, will all assist in the resolution of adverse inflammation.
Dietary fibres are largely metabolised by gut bacteria. This is because they can break down various types of carbohydrates since they encode over 260 glycoside hydrolases for the degradation of carbohydrates whereas a human has only 17 enzymes for digestion, meaning that humans themselves are poor at digesting a variety of dietary fibre[6].
In addition, more than 100 trillion bacteria can be engaged in consuming carbohydrates derived from dietary fibre that would help effective digestion of dietary fibre. Hence, dietary fibres resistant to digestion by the host, are termed as microbiota-accessible carbohydrates (MACs).
Dietary fibres are divided into soluble and insoluble fibres. Insoluble fibre includes cellulose, some hemicellulose, and lignin. Soluble fibre encompasses wheat dextrin, pectin, gums, β-glucan, psyllium, and fructans, as well as some hemicellulose. These fibres are derived from grains, fruits, vegetables, and legumes. Generally, insoluble fibres are poorly fermented by gut microbes, but they likely promote the gut transit rate and thus reduce the amount of time available for colonic bacterial fermentation of non-digested foodstuff. Soluble fibres can be further processed by bacteria into short chain fatty acids as metabolites although some of them are not fermentable.
Combined with lifestyle changes the outcomes will be overall control over the metabolic dysfunctionality that permeates modern lifestyle diseases.
References
[1] Schneider, Kai Markus et al. The enteric nervous system relays psychological stress to intestinal inflammation Cell, Volume 0, Issue 0
[2] Ge L, Liu S, Li S, Yang J, Hu G, Xu C, Song W. Psychological stress in inflammatory bowel disease: Psychoneuroimmunological insights into bidirectional gut-brain communications. Front Immunol. 2022 Oct 6;13:1016578.
[3] Madison A, Kiecolt-Glaser JK. Stress, depression, diet, and the gut microbiota: human-bacteria interactions at the core of psychoneuroimmunology and nutrition. Curr Opin Behav Sci. 2019 Aug;28:105-110.
[4] Omran, F., Murphy, A.M., Younis, A.Z. et al. The impact of metabolic endotoxaemia on the browning process in human adipocytes. BMC Med 21, 154 (2023
[5] Ahrne S, Hagslatt ML. Effect of lactobacilli on paracellular permeability in the gut. Nutrients (2011) 3(1):104–17.
[6] Usuda H, Okamoto T, Wada K. Leaky Gut: Effect of Dietary Fiber and Fats on Microbiome and Intestinal Barrier. Int J Mol Sci. 2021 Jul 16;22(14):7613.