A New Holistic Understanding of IBS

IBS is one of the most common disorders of brain-gut interaction globally, with prevalence rates between 5 and 10% for most Western countries and China. In contrast to many chronic non-communicable diseases, such as metabolic, neurological, cardiovascular and some forms of cancer, which we have often discussed in this newsletter, there has been no progressive increase in prevalence during the past 75 years.

“Based on questionnaire data, women are 1.5–3.0 times more likely to have IBS.”

Based on questionnaire data, women are 1.5–3.0 times more likely to have IBS, reflecting a prevalence in women of 14% and in men of 8.9%. However, based on healthcare system utilization, women are up to 2–2.5 times more likely to see a healthcare provider for their symptoms.

Based on the current symptom criteria, IBS is defined by chronically recurring abdominal pain associated with altered bowel habits in the absence of detectable organic disease. IBS symptoms can be debilitating in a small number of patients, but are mild to moderate in the majority of affected individuals. Based on this definition, other frequently associated somatic or visceral pain and discomfort, as well as anxiety and depression are considered so called comorbid conditions.

“IBS is commonly associated with anxiety, depression, and other types of pain…”

The gut-restricted definition of the Rome criteria overlooks the fact that a large number of individuals who meet diagnostic criteria for an anxiety or depressive disorder have IBS and vice versa, and a majority of IBS patients show elevated levels of trait anxiety and neuroticism, or meet diagnostic criteria for an anxiety disorder. Currently, the commonly associated psychiatric and somatic symptoms are generally referred to as comorbidities, separate from the primary GI diagnosis and not present in all patients. However, detailed patient histories, frequently reveal symptoms of abdominal discomfort, anxiety and behavioral disturbances starting in early childhood in a majority of patients.

“IBS has genetic abnormalities in both the brain and in the little brain of the gut…”

A large recent genetic epidemiological study has provided an intriguing explanation for the cooccurrence of abdominal and psychiatric symptoms in IBS patients on the basis of several shared gene alterations (so called single nucleotide polymorphisms or SNIPs). These new findings are consistent with genetic vulnerabilities affecting both the central and the enteric nervous system, and argue against the long held linear pathophysiological concepts that emotional factors may cause IBS symptoms, or that chronic IBS gut symptoms lead to anxiety and depression.

“Traditional understanding of IBS mechanisms has been limited and restricted to gut symptoms…”

Much of research and drug development in IBS patients has been based on descriptive and symptomatic features, rather than on biology-based disease definitions. These definitions suggest a core abnormality shared by all IBS patients (chronic, recurrent abdominal pain) as well as heterogeneity based on self-reports of predominant bowel habit. However, a comprehensive identification of distinct biology-based subgroups of patients including those based on sex, with different underlying pathophysiological components and differential responsiveness to specific therapies, has not been achieved.

In our recently published review article in the prestigious journal Molecular Psychiatry, we discuss the evidence supporting an integrative brain gut microbiome (BGM) model. This model incorporates a large body of evidence from studies on peripheral and central neurobiological disease mechanisms, brain and gut targeted influences of stress and the environment, and results from recently reported large scale genetic analyses with relevance for neuronal dysfunction of the central nervous system and the enteric nervous system (the “little brain” of the gut). The proposed model is consistent with the frequent comorbidity of IBS with other so-called functional gastrointestinal disorders affecting the esophagus, stomach, and other gut areas, and with other chronic pain outside of the gastrointestinal tract, and psychiatric disorders, in particular with anxiety. We also discuss the implications of this model for a better understanding of the biology underlying IBS symptoms and for the development of more effective multidisciplinary treatment approaches.


Dr. Emeran Mayer is a Distinguished Research Professor in the Departments of Medicine, Physiology and Psychiatry at the David Geffen School of Medicine at UCLA, the Executive Director of the G. Oppenheimer Center for Neurobiology of Stress and Resilience and the Founding Director of the Goodman-Luskin Microbiome Center at UCLA.