Anxiety and IBS – Two Sides of the Same Coin?

For as long as I can remember in my career as a gastroenterologist (30+ years) every new publication and every presentation about IBS which affects around 10% of the population has always started with the same caveats: IBS is a diagnosis based on (regularly changing) “subjective symptom criteria”, the pathophysiology is “incompletely understood” and available treatments are “unsatisfactory”.

“Commonly used IBS treatments, ranging from dietary exclusion, motility modulating drugs to psychoactive medications, are largely ineffective…”

The commonly used IBS treatments, ranging from dietary exclusion, motility modulating drugs to psychoactive medications, are largely ineffective (in most clinical trials they performed not better than 10% above placebo) and their variety (targeting smooth muscle, water secretion, gut microbes) reflects the uncertain etiology of the syndrome. Even though behavioral therapies have proven more effective than most medications, they have not been widely accessible even though web-based versions of cognitive behavioral therapy (CBT), gut directed hypnosis and mindfulness-based stress reduction are rapidly becoming available.

Considering the number of efforts and funding invested in research studies aimed at identifying the cause of the syndrome and demonstrating effectiveness of a variety of medications (largely unsuccessful), it is surprising that the list of these caveats has remained virtually unchanged over more than 3 decades. Another recurrent theme in scientific and clinical meetings has been the debate about whether IBS is a gut disorder (a “real disease”) or is related to alterations in the brain (“just psychological symptoms”). Recent epidemiological data suggested that, in individuals developing both IBS and psychological features, the former preceded the latter in two thirds of cases and the latter preceded the former in one third. However, in my own practice, a thorough history taking reveals psychological factors often dating back to infancy in the majority of patients presenting with IBS symptoms, even those with so called post infectious IBS.

“IBS has finally been officially recognized as a disorder of altered brain gut interactions”

The good news is that after decades of these fruitless arguments and debates, and based on overwhelming clinical and scientific evidence, IBS has finally been officially recognized as a disorder of altered brain gut interactions.

A recent study by a large group of investigators in the UK and US, provides new and strong evidence supporting the brain gut disorder concept. (Even though there have been many previous studies in smaller groups of patients that had already strongly implicated the brain gut disorder concept). The new study was based on the hypothesis that identifying genes (so called single nucleotide polymorphisms or SNPs) that increase the likelihood of IBS (so called susceptibility genes) could highlight the mechanisms that are responsible for the symptoms. The investigators conducted a genome-wide association study (probing every one of the 20,000 genes making up the human genome) with 53,400 cases of individuals meeting IBS symptom criteria and 433,201 healthy controls and then replicated their findings of significant associations in a database from the genetic testing company 23andMe (205,252 IBS cases and 1,384,055 healthy controls). IBS subjects were identified using a digestive health questionnaire that was administered to cases in the database of the UK Biobank together with a battery of tests for digestive, psychological and pain symptoms and combined identified cases with IBS with independent cohorts.

“IBS showed the strongest genome-wide overlap with anxiety, neuroticism, depression…”

Their study identified and confirmed six genetic susceptibility loci (genes that increase the likelihood for IBS). Four of these genes were associated with mood and anxiety disorders, are expressed in the nervous system (brain and enteric nervous system), or both. Mirroring these genetic associations, they also found strong genome-wide correlation between the risk of IBS and psychological traits. IBS showed the strongest genome-wide overlap with anxiety, neuroticism, depression, and schizophrenia. Even though based on clinical symptoms, anxiety scores correlated with IBS severity and 34.3% of cases with IBS had sought or had been treated for anxiety versus 16.1% of controls the genetic correlation (between susceptibility genes for IBS and psychological syndromes) appeared quantitatively even greater. Additional analyses performed on this massive dataset suggested that these associations between genes, GI symptoms and symptoms of altered mood and affect was a consequence of shared pathogenic pathways for both groups of disorders, rather than, for example, anxiety or depression causing abdominal symptoms.

“…anxiety and IBS symptoms can be viewed as two sides of the same coin…”

The sheer size of this study, the confirmation of the initial findings in a second large data set, and the use of rigorous epidemiological and genetic methodology will make it difficult to challenge these findings. The results from the study confirm the genetic basis of IBS as a brain gut disorder, in which neither psychological symptoms produce GI symptoms, nor chronic GI symptoms lead to anxiety or depression. As I have always explained to my patients, anxiety and IBS symptoms can be viewed as two sides of the same coin, or in other words, whatever happens in the brain is mirrored in the gut and vice versa. The new study will make this concept even easier to explain.

The sharing of similar susceptibility genes between IBS and psychological symptoms may also explain the recent explosion of public interest in gut health and gut-friendly diets in a time of worldwide increases in anxiety and depression. Some people are responding to the stresses posed by the COVID-19 pandemic and political divisiveness with belly pain and altered bowel habits, while others experience anxiety, and a third group experiences both. The brain gut disorder concept also implies that the best treatment for the majority of IBS patients is multipronged, aiming both at the brain (with CBT, hypnosis, or mindfulness-based stress reduction) and at the gut (with a healthy gut friendly diet) at the same time.

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 and the Executive Director of the G. Oppenheimer Center for Neurobiology of Stress and Resilience at UCLA.