Is IBS a Gut–Brain–Microbiome Axis Disorder?

IBS is an extremely common gastrointestinal disorder that significantly reduces patient quality of life. Treatment options for IBS have long been limited to symptom management. However, a new understanding of IBS has recently emerged, in which a dysfunctional gut–brain–microbiome axis is responsible for the development and progression of the disorder. Read on to learn how a dysregulated gut–brain–microbiome axis promotes IBS and what therapeutic measures can be used to modulate this axis and reverse the course of the disease.

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What Is the Gut–Brain–Microbiome Axis?

IBS has an extremely high worldwide prevalence; it is estimated to affect between 10 and 25 percent of people in developed countries. Despite its vast influence, an understanding of the pathophysiology of this disorder has remained elusive for many years. (1)

In addition to abdominal pain, bloating, and abnormal bowel movements, IBS adversely impacts brain function and has been linked to psychiatric disorders such as anxiety and depression. Furthermore, research suggests that people with IBS have an altered gut microbiota compared to healthy individuals. These findings have led to the development of a new understanding of IBS, in which the interrelationship between gut symptoms, mental health, and the microbiome is mediated by the gut–brain–microbiome axis.

The gut–brain–microbiome axis connects the body’s central nervous system (CNS), which houses the brain and spinal cord, with the enteric nervous system (ENS) of the gastrointestinal tract. This axis facilitates bidirectional neural, hormonal, and immunological communication between the gut and brain. (2) The microbiome is the third key component of this axis. It serves as an intermediary between the gut and brain, since the microbes it contains produce metabolites that relay messages to both organs. (3) When the gut–brain–microbiome axis is in balance, the digestive system and brain function optimally. Conversely, dysregulation of this axis may initiate IBS and influence its progression and severity.

Is intestinal dysbiosis responsible for the psychological symptoms of IBS? #guthealth #microbiome

The Microbiome Is Altered in IBS

Over the past several years, numerous studies have documented alterations in the gut microbiota of people with IBS relative to healthy people. This has led researchers to postulate that the microbiome may play a key role in the pathogenesis of IBS.

In people with IBS, proportions of specific bacterial groups are altered and the diversity of microbial populations is reduced. Researchers have observed decreased levels of Lactobacilli and Bifidobacteria and an increased prevalence of pathogenic anaerobic organisms such as E. coli and Clostridia in fecal samples from IBS patients. In addition, IBS patients exhibit an increased Firmicutes-to-Bacteroidetes ratio. (4, 5)

There are several factors that may lead to microbiome disruption and the onset of IBS. These include antibiotic use, infection, diet, and stress. Stress is perhaps one of the more insidious factors that contributes to IBS; while dietary changes and treatment for gut infections can be relatively simple to institute, stress is an entirely different beast that must constantly be managed. However, the significance of stress and the psychological toll it creates in IBS cannot be understated, given our understanding of the gut–brain–microbiome axis.

The Psychological Toll of IBS

IBS sufferers have long understood the connection between their gut symptoms and mental health. Indeed, mental health issues such as anxiety and depression are a common comorbidity of IBS. (6) However, this problem has only recently begun to receive the attention it deserves from the medical community, with the scientific discovery of neural links between the gut and brain in the gut–brain–microbiome axis.

Further investigation into the psychological health of IBS patients has found that they exhibit a maladaptive stress response. This includes an exaggerated response to stress and an inability to appropriately shut down the stress response once the stressor is removed. (7) IBS patients also demonstrate visceral hypersensitivity, a condition that increases the level of attention paid to gut symptoms, thus perpetuating anxiety about IBS. (8) There is also evidence that people with IBS may experience stress-related deficits in cognitive function. (9)

The enhanced stress response, anxiety, and altered cognition found in IBS patients may be due in large part to the influence of their gut microbes. There are several mechanisms by which gut microbes affect the gut–brain–microbiome axis. Via the axis, an altered gut microbiota can send neural signals from the gut to the brain, leading to the heightened stress response and increased visceral hypersensitivity characteristic of IBS. This promotes a sustained level of attention to the gut in IBS patients and an inability to “turn off” anxiety surrounding gut symptoms. (10) Gut microbes also alter the availability of tryptophan, an amino acid required to produce the mood-regulating neurotransmitter serotonin. (11) Gut microbes influence the release of immune system mediators and glucocorticoids, which can heighten intestinal pain in IBS. (12, 13) Finally, pathogenic gut microbes can also initiate a proinflammatory state that increases intestinal permeability, resulting in the leakage of neuroactive metabolites from the gut into the CNS, where they have adverse effects on cognition.

Is intestinal dysbiosis responsible for the psychological symptoms of IBS? #guthealth #microbiome

Stress, in turn, has harmful effects on the intestinal microbiota. (14) Stress increases intestinal permeability, allowing bacteria and bacterial antigens to cross the epithelial barrier into the bloodstream, inducing an immune response that alters the microbiome. (15) Stress hormones, including epinephrine and norepinephrine, also increase the virulence of gut pathogens by enhancing the availability of iron, which the pathogens use to fuel their activities. (16, 17) Increased levels of gut pathogens may further exacerbate IBS.

Clearly, an imbalanced gut microbiome and an unhappy brain walk hand in hand. The complex relationship between the gut, brain, and microbiome in IBS creates a vicious cycle of intestinal symptoms, stress, and poor mental health. To break this vicious cycle, we must repair the gut–brain–microbiome axis.

Repairing the Gut–Brain–Microbiome axis to Treat IBS

To successfully treat IBS, we need to employ strategies that address each component of the gut–brain–microbiome axis. Modulation of the axis with dietary changes, prebiotics, probiotics, select antibiotics, and stress-reduction strategies offers a holistic means of treating IBS.

Diet and Prebiotics

Significant positive changes can be induced in the gut–brain–microbiome axis through the implementation of dietary modifications and prebiotic supplementation. One dietary approach that has received substantial attention in the treatment of IBS is the low-FODMAP diet. Briefly, gut bacteria metabolize FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols), which include various types of fermentable dietary fibers, into short-chain fatty acids (SCFAs). High levels of two SCFAs, acetic acid and propionic acid, have been associated with gastrointestinal symptoms, anxiety, depression, and reduced quality of life in IBS patients. (18) Reducing dietary intake of FODMAPs can lower levels of these SCFAs and therefore alleviate IBS symptoms. (19, 20)

However, research on the low-FODMAP diet for IBS conflicts with other studies suggesting that prebiotics, a type of fermentable fiber, improve both gut- and brain-related symptoms of IBS. The regular consumption of fructooligosaccharides (FOSs) has been found to reduce gastrointestinal symptoms and improve quality of life markers such as anxiety and sleep in people with functional bowel disorders. (21) Prebiotics also offer brain-health benefits; the intake of galactooligosaccharides (GOSs) increases hippocampal levels of brain-derived neurotrophic factor, a protein involved in normal brain function, and NMDA receptors, which regulate brain plasticity and memory. (22) More research is needed to understand the divergent responses to low-FODMAP diets and prebiotics in IBS patients. Clinically, practitioners should encourage patients to experiment with FODMAPs and prebiotics and find what works best for them.

Probiotics

Probiotics are another promising treatment option for IBS, since they modulate both the gut and the brain components of the gut–brain–microbiome axis. Supplementation with Bifidobacterium infantis has been found to improve gut-related symptoms of IBS by reducing abdominal pain and bloating and normalizing bowel movements, while also inducing antidepressant effects through the augmentation of plasma tryptophan levels, increasing levels of the “feel good” neurotransmitter, serotonin. (23, 24) Bifidobacterium animalis is effective for promoting intestinal motility and reducing abdominal discomfort in IBS-C patients. (25) Lactobacillus acidophilus supplementation reduces visceral hypersensitivity in IBS by activating opioid and cannabinoid receptors, thus ameliorating intestinal pain and reducing hypervigilance to gastrointestinal sensations. (26) Finally, probiotic strains that repair the intestinal barrier may reduce the leakage of neuroactive metabolites from the gut into the systemic circulation, protecting brain function. (27)

Antibiotics

Mark Pimentel, a noted small intestinal bacterial overgrowth (SIBO) researcher, has found that up to 85 percent of IBS patients have SIBO. (28) However, other research suggests that this may be an overestimation, due to the high false positive rate associated with the lactulose breath test used to diagnose SIBO. (29) While not a cure-all, the eradication of SIBO using specific antibiotics, such as rifaximin, may benefit some cases of IBS. (30)

Stress Reduction

Chronic stress perpetuates the vicious cycle of IBS by altering the gut microbiota, increasing gut pathogen virulence, and promoting intestinal permeability. The implementation of stress reduction strategies is crucial for breaking the cycle and restoring health to the gut–brain–microbiome axis. While there are many stress-reducing practices to choose from, three in particular—yoga, exercise, and mindfulness meditation—have demonstrated IBS-specific benefits.

Yoga has exploded in popularity in recent years and has become the subject of extensive scientific investigation. A recent study found that a yoga practice consisting of postures and breathing exercises beneficially modulates gut and brain function by reducing sympathetic nervous system activity and increasing parasympathetic activity, making it an effective remedial therapy for IBS. (31)

A generalized exercise program may also benefit the gut–brain–microbiome axis and reduce symptoms of IBS. Exercise increases gastrointestinal motility, reduces intestinal gas retention, relieves stress, and increases the number of beneficial microbial species in the gut. (32, 33)

Finally, mindfulness training is another beneficial stress reduction strategy for IBS. Mindfulness training (MT) promotes nonreactive awareness to emotional and sensory experiences, such as gastrointestinal symptoms, and has been found to beneficially alter pain processing. An eight-week course of mindfulness training in women with IBS significantly reduced gut-focused anxiety and abdominal pain, thus breaking the vicious cycle between stress and intestinal symptoms. (34, 35)

A diagnosis of IBS no longer needs to be vague and frustrating for your patients. Our newfound knowledge of the gut–brain–microbiome axis, and the variety of treatments that can be used to modulate it, offers IBS patients the possibility of a full recovery.