Stress, the Microbiota and Visceral Pain

A high proportion of individuals with IBS have comorbid anxiety and depression affecting the HPA axis and microbiota.

During the past several decades, recognition of the impact of gut microbiota on health is gathering increasing support.The gut microbiota comprises upwards of 1014 microorganisms, with an estimated 15,000 to 36,000 species.1,2

Gut microbiota profiles are distinct between individuals, and evolve over one’s lifetime, particularly during periods of high stress.Stress activates the hypothalamic-pituitary-adrenal (HPA) axis, ensuing in the subsequent release of corticotropin-releasing hormone, adrenocorticotopic hormone and cortisol.1

HPA axis activation allows for an adaptive response alerting the organism of noxious stimuli. Its chronic activation however, results in maladaptive changes at the cellular, structural functional and microbial levels, the latter resulting in microbial dysbacteriosis-the imbalance and/or impairment of gut microbiota –and affecting the gut-brain axis.1,3,5

The gut-brain-gut axis facilitates bidirectional communication between these organs via the sympathetic, parasympathetic, autonomic, and enteric nervous systems, using neuroendocrine and neuroimmune pathways. These feedback systems allow for modulation of gastrointestinal tract activity (motor, sensory and/or secretory).3

Stress-related disturbances to these finely-tuned pathways have been reported to increase sensitivity to pain,enhance pain perception and promote visceral pain disorders, including irritable bowel syndrome (IBS).1, 6

Unlike other types of visceral pain disorders, IBS, which manifests with abdominal pain, bloating, nausea, urgency, and incomplete evacuation, is not associated with structural and/or histological abnormalities, or activation of mechanical nociceptive receptors in visceral organs, but with modifications in central pain neurocircuitry, leading to a top-down experience of visceral pain.1,6,7

According to the Rome III diagnostic criteria for IBS, an IBS diagnosis can be reached when changes in bowel function (eg, urgency, incomplete evacuation) and consistency (eg, constipation-predominant IBS; diarrhea-predominant IBS; IBS mixed; and un-subtyped IBS) occur in conjunction with gastrointestinal pain and/or discomfort for at least 3 days per month over a minimum of 3 consecutive months.7

In the present study, 12 subjects were recruited (6 healthy controls and 6 patients with IBS) to participate in a positron emission tomography (PET) study.8 in order to assess whether affected cerebral blood flow.8

Anticipation and/or experience of noxious visceral events activated the anterior cingulate cortex involved in pain processing in control subjects and the left prefrontal cortex, a region associated with cognitive and affective responses to pain, as well as affective disorders in IBS patients.8,10 An estimated 20-60% of patients with IBS have comorbid anxiety and/or depression.1,11,12 

In another study, microbiota-deficient rats were transplanted with fecal microbiota from individuals with major depression (n=34) or healthy controls (n=33).13

Three days post-transplantation, microbiota from the depressed group had reduced diversity, and increased levels of proinflammatory markers (interleukin [Il]-6, P =.009; Il-8, P =.021; tumor necrosis factor-α, P =.022; C-reactive protein, P =.001), compared to those exposed those exposed to healthy subject microbiomes.

These results implicate the gut microbiota in the manifestation of depressive symptomatology (including anxiety and anhedonia), via the neuro-endocrine and immune systems of the gut-brain axis.

Based on these and other studies showing significant overlap between affective disorders and IBS, psychotropic treatments such as selective serotonin reuptake inhibitors and tricyclic antidepressants are indicated by the American College of Gastroenterology and the National Institute for Health and Care Excellence as a second-line therapy for IBS.7

Because of the heterogeneous nature of IBS, its treatment will likely be multimodal, and require lifestyle changes (eg, dietary modifications and physical activity), psychotherapy/psychopharmacology, as well as restoration of the gut microbiota’s balance.7

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