^{Sources (sidenote: Ford AC, Sperber AD, Corsetti M, et al. Irritable bowel syndrome. Lancet. 2020 Nov 21;396(10263):1675-1688 )}

What causes irritable bowel syndrome?

The causes of irritable bowel syndrome are complex, and not yet fully identified. IBS is thought to be triggered by a combination of different factors, the importance of which varies from person to person ²: genetic predisposition, certain medical histories and treatments, stress, diet, etc.

The most well-known risk factor for IBS is a history of acute intestinal infection: 10% of people with IBS believe their problems began after such an episode, for example viral gastroenteritis, traveler’s diarrhea or diverticulitis (sidenote: Diverticulitis Diverticulitis is an inflammation or infection of the diverticula, small folds (hernias) in the inner wall of the colon.  https://www.cancer.gov/publications/dictionaries/cancer-terms/def/diverticulitis ) ^1,4,5. The risk of developing IBS seems to be quadrupled after one year following this type of infection ¹.

^{Sources (sidenote: SNFGE. Syndrome de l’intestin irritable (SII) [Irritable bowel syndrome (IBS)]. June 2018. CNPHGE.  Syndrome de l’intestin irritable [Irritable bowel syndrome]. )}

Recent research is increasingly suggesting that the gut microbiota play a key role in the development of IBS ^6,7. Experts have even recognized an imbalance in the composition of the gut microbiota, or dysbiosis, as a plausible cause of IBS ⁵. Antibiotic-induced dysbiosis has also been associated with the development of IBS ¹.

The scientific community is also showing strong interest in the role of diet in IBS. Over 60% of IBS patients say their symptoms appeared or worsened after eating ^8,9. This is labeled as bowel hypersensitivity. The presence of certain food compounds (wheat, milk, etc.) appears to trigger an exaggerated reaction in the gut, which can be immune-related ^10,11. Moreover, dietary habits often disturb the gut microbiota and cause abnormal fermentation of ingested food, thought to play a crucial role in intestinal distension ¹⁰.

IBS is also triggered by traumatic or distressing events (bereavement, divorce, abuse, conflict, etc.), and by acute or chronic stress and other psychological disorders such as depression or anxiety ^1,2,7. These appear to exert a negative impact on the enteric nervous system (sidenote: The enteric nervous system The enteric nervous system (ENS) is the nervous system of the gut. It is composed of a network of neurons that line the walls of the gastrointestinal tract and controls the sensory, motor and secretory activity of the digestive system. Watson C., Kirkcaldie M., Paxinos G. The brain: an introduction to functional neuroanatomy – Chapter 4 - Peripheral nerves. Academic Press, 2010. 43-54 ) , which controls motor function, the mucosal barrier, sensory function and intestinal secretions ¹.

Could poor communication between the gut and brain explain IBS?

Does the gut-brain axis mean anything to you? The brain communicates with the enteric nervous system in both directions: what happens in the brain affects the gut, and vice versa. But that is not all: neurons in the gut are linked directly to the gut microbiota, which also maintains bidirectional communication with our hormonal and immune systems.

IBS disturbances cause:

What are the main symptoms of IBS?

According to well-established criteria, IBS is characterized by the simultaneous presence of several symptoms, involving abdominal pain and bowel dysfunction. These symptoms must be sufficiently frequent and long-standing (>1 day/week in the past 3 months) ^13,14:

• Recurrent abdominal pain (at least 1 day a week);
• Painful defecation;
• Bloating;
• Change in stool consistency;
• Change in stool frequency.

Some clarification and explanation may be useful!

Abdominal pain is manifested by spasms, burning sensations, tightness and bloating. It occurs around the navel, in the lower abdomen, and can appear to follow the course of the colon. The pain is associated with defecation, and can be aggravated or relieved by the emission of gas or stools ².

Abnormalities in stool consistency and frequency range from stools that are too soft and/or too frequent (as in diarrhea) to stools that are too hard and/or too infrequent (as in constipation). There may be alternating periods of diarrhea and constipation. These transit disorders are sometimes accompanied by other types of discomfort, including an urgent need to pass stools, presence of mucus in stools or an impression of incomplete stool evacuation ⁵.

IBS symptoms vary in severity from person to person, and over time in the same person ^3,5. They can range from being inconvenient to very disabling, with severe forms of IBS affecting 20-25% of patients ³. Generally speaking, they affect personal, social and professional quality of life ^1,3.

Only physicians can diagnose IBS, once they have successfully ruled out another digestive disorder ². There is no diagnostic test for IBS as yet, so physicians rely on patients’ descriptions of symptoms; the results of clinical examinations and imaging carried out in people with IBS are generally normal ³.

Which disorders and conditions are associated with IBS?

Generally speaking, people with IBS are more likely to suffer from certain disorders and conditions.

• Other digestive disorders: In over 20% of cases, IBS is accompanied by bloating, flatulence ⁴, nausea or heartburn ¹⁶. Some people are also intolerant of certain foods ⁵.
• Psychological disorders: Not only can psychological factors play a role in causing IBS, but a proportion of sufferers may also develop psychological disorders as a result of IBS ¹, for example anxiety, stress, depression, insomnia or eating disorders ⁵.
• Genitourinary disorders: IBS may be accompanied by pelvic pain, urinary disorders, pain during intercourse in women and erectile dysfunction in men ^4,5.
• Endometriosis: Studies have shown that women with endometriosis are three times more likely to develop IBS ¹⁷.
• General disorders: Some people with IBS experience fatigue, lethargy, headaches and/or muscle pain ^2,4,5. IBS is more common in people with fibromyalgia and chronic fatigue ¹.

How to treat your IBS?

Although painful and challenging to live with in everyday life, IBS is a benign disorder ². Despite this, IBS symptoms should be relieved as soon as possible to improve quality of life ³. Your physician will give you lifestyle tips and recommend an optimal combination of specific medications and alternative solutions.

Good nutritional habits can alleviate IBS symptoms ^6,18:

• eat meals at regular times and avoid skipping meals;
• avoid “pantagruelian” meals and spicy or greasy dishes;
• chew food well;
• drink enough fluids;
• limit alcohol, caffeine and tobacco;
• engage in regular physical activity.

Medication

Some IBS symptoms can be improved by taking physician-prescribed medication, for example antispasmodics, intestinal transit regulators, laxatives in case of IBS-C, antidiarrheals in case of IBS-D, and sometimes antidepressants ⁹. But these drugs are not effective in everyone ¹⁶, and to date none have been shown to relieve all IBS symptoms.

Mind-body therapies

Mind-body therapies (sidenote: Mind-body therapies Mind-body therapies are practices that focus on the relationships between the body, brain, mind and behavior and their effects on health and disease. Wahbeh H, Elsas SM, Oken BS. Mind-body interventions: applications in neurology. Neurology. 2008;70(24):2321-2328 ) can reduce pain and discomfort associated with bowel disorders, particularly in people in whom stress and anxiety can exacerbate symptoms. Examples include cognitive-behavioral therapy (sidenote: Cognitive-behavioral therapy A type of psychotherapy where therapists help patients to identify the impact of their dysfunctional thoughts (incorrect, negative) on their behavior and well-being. Cuijpers P, Smit F, Bohlmeijer E, et al. Efficacy of cognitive–behavioural therapy and other psychological treatments for adult depression: meta-analytic study of publication bias. The British Journal of Psychiatry. 2010;196(3):173-178 InformedHealth.org [Internet]. Cologne, Germany: Institute for Quality and Efficiency in Health Care (IQWiG); 2006. Cognitive behavioral therapy. 2013 Aug 7 [Updated 2016 Sep 8] ) , hypnosis, meditation, relaxation and biofeedback (sidenote: Biofeedback A method for learning how to control certain bodily functions, such as heart rate, blood pressure and muscle tension, using a special device. It can help control pain. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/biofeedback ) ¹⁶.

Diets

Many people with IBS find that certain foods improve or aggravate their symptoms, but they are not the same for everyone. Modifying the diet can therefore improve IBS symptoms, but this should always be done with the help of a health professional (physician, dietician), to work out a personalized solution and prevent any nutritional imbalance ¹⁶.

For example, your physician can help you detect any foods that “don’t work for you” (milk, wheat, legumes, etc.), to then limit their intake ⁹. You can also include more fiber in your diet if you have IBS-C, although not in excess to avoid increased risk of pain and bloating ⁶.

Of the diets tested scientifically, the low FODMAPS diet (Fermentable Oligosaccharides, Disaccharides, Monosaccharides and Polyols), seems to give the best results in relieving IBS ^6,16 although it does not work for everyone ². FODMAPs are sugars that are poorly absorbed in the small intestine and ferment through the action of gut microbiota bacteria. This fermentation exacerbates bloating and pain in people with IBS.

The diet consists in significantly reducing intake of foods rich in FODMAPs, which are foods containing lactose, certain cereals, certain fruits and vegetables, synthetic sweeteners, processed foods, etc. It can be restrictive, it requires supervision by a physician, and must be monitored for 4 to 6 weeks. If symptoms improve, foods containing FODMAPs are then gradually reintroduced one by one. In this way it will be possible to determine which food(s) aggravate your symptoms and avoid them ^2,19.

Probiotics, prebiotics and fecal microbiota transplantation

Various studies have highlighted the importance of the gut microbiota in the occurrence of IBS, and shown differences in the composition of gut microbiota between affected and healthy individuals ⁵. Solutions may therefore be proposed to modulate the gut microbiota, with the aim of improving IBS symptoms ²⁰.

According to experts, prebiotics are a promising option. Studies show that they have an overall positive effect on IBS symptoms by acting on various mechanisms, such as visceral hypersensitivity and intestinal motility ⁹. Probiotics can strengthen the colonic barrier, reduce inflammation and improve gut immunity, for example ²⁰. Some may even act on the gut-brain axis and improve depressive symptoms ⁹. All these effects appear to be beneficial to well-being: in a recent study, consumption of a strain of bifidobacteria reduced symptom severity and improved quality of life in 60% of people with IBS in 30 days ²¹.

Studies on the effect of symbiotics on IBS, which combine probiotics and prebiotics, are also underway ⁹, and initial testing of fecal microbiota transplantation has yielded encouraging results in some patients with IBS who have seen an improvement in both symptoms and quality of life ¹.

BMI 23.11

How many people suffer from IBS?

Prof. Premysl Bercik: Data differ between countries, but it is estimated that IBS affects around 5 to 10% population globally. ² Women are almost twice as likely as men to have IBS. They also report more fatigue and psychological distress. For both men and women, IBS can develop at any age, but its onset is often between age of 20 and 30.

The quality of life of IBS patients is severely affected, interfering with their everyday life, frequently resulting in missing work or school. ³

What triggers IBS symptoms? Why do I develop IBS?

P.-B.: IBS is a complex disorder, its genesis is likely multifactorial and not fully understood. In general, it stems from impaired gut–brain interaction, a bidirectional communication between the digestive tract and the central nervous system. There are several peripheral mechanisms involved in IBS, including intestinal hypersensitivity, altered bowel motility, increased intestinal permeability and low-grade inflammation. In the brain, the signals from the bowel may be incorrectly interpreted and further magnified, and then the brain sends erroneous signals to the gut. During the last decade, increasing attention has been given to gut microbiota as a key player in IBS ^4,5.

What is the scientific evidence for the involvement of the gut microbiota in IBS?

P.-B.: There are several lines of evidence that implicate microbiota in IBS:

• First, bowel infection (gastroenteritis) is the strongest risk factor for IBS, with 11-14% of patients developing chronic symptoms after acute infection with pathogenic bacteria (Salmonella, E. coli or Campylobacter infection). ⁶
• Second, clinical studies showed that microbiota-directed treatments affect IBS symptoms. Indeed, certain antibiotics improve symptoms in some patients with IBS, while in asymptomatic individuals they can trigger IBS symptoms. Specific probiotics were shown to improve symptoms of IBS, such as abdominal pain, diarrhea or bloating, although there is currently no consensus on which probiotics to recommend in clinical practice. ²
• Third, gut microbial composition and metabolic activity differ between IBS patients and healthy individuals, and associate not only with bowel symptoms, but also with anxiety and depression. However, the results from individual studies vary and there seems to be no unique microbial profile that could be attributed to IBS. ⁷
• Finally, and most importantly, several studies have shown that gut dysfunction and associated anxiety can be transferred through microbiota transplantation from IBS patients into germ-free mice. ^8,9,10

You’ve talked about gut-brain interaction. Is there a microbiota-gut-brain axis?

P.-B.: The gut-brain axis involves immune, neural and hormonal signaling and growing evidence suggests that the gut microbiota plays a key role in this communication. Although most data have been obtained from animal studies, many clinical studies support this concept. ¹¹ Just to mention few, sudden changes in behavior have been described in patients treated with antibiotics. A recent population-based study found that use of antibiotics in early childhood is associated with an increased risk of developing mental health disorders in later life. The most obvious case comes from patients with end-stage liver disease (cirrhosis), diagnosed with hepatic encephalopathy. (sidenote: Hepatic encephalopathy (HE) Hepatic encephalopathy (HE) refers to changes in the brain that occur in patients with advanced, acute (sudden) or chronic (long-term) liver disease. It is one of the major complications of cirrhosis. https://britishlivertrust.org.uk/information-and-support/living-with-a-liver-condition/liver-conditions/hepatic-encephalopathy/ ) These patients display altered behavior and cognition which improve quickly and dramatically after administration of antibiotics or laxatives, or fecal microbiota transplantation ¹². And multiple studies found that the microbial profiles differ between patients with psychiatric disorders and healthy individuals. ¹³

Can we modulate the gut microbiota to improve mental health?

P.-B.: In animal models, certain probiotics have shown beneficial effects on behavior and brain chemistry, suggesting they could be used therapeutically in mental disorders. The results of the few clinical studies completed so far suggest that probiotics, if used as an adjunctive treatment, improve symptoms in patients with major depressive disorder. ¹³ And our recent pilot study found that probiotic treatment improved depression scores and bowel symptoms in patients with IBS, and changed their brain activation patterns. ¹⁴ Altogether, this suggest that some probiotics could be helpful not only for patients with functional bowel disorders, but also for those with mental health issues. However, this needs to be confirmed by larger rigorous clinical studies.

^BMI-23.14

Unlike the genome, which is inherited from our parents and is stable, the microbiota is seeded at birth, and then changes over time under the influence of diet and lifestyle, and, more surprisingly, the people we spend time with. So say the results of a study which analyzed a large panel of metagenomic data covering four continents. The study included 9,715 microbiota samples in total, 7,646 from stools and 2,069 from saliva.

Greater geographical distance means less microbial sharing

The first finding was that person-to-person strain sharing follows a gradient based on geographical distance, shared environments and kinship. Overall, looking at the gut microbiota, the highest rates of person-to-person strain sharing are between mothers and their offspring aged 0-3 years (34%), followed by individuals (≥4 years of age) in the same household (12%), non-cohabiting adult twins (8%), and finally adults living in the same town but not under the same roof (8%). According to the authors, this shared microbial profile between individuals in the same town is due to physical interactions between the individuals and their shared environment. On the contrary, individuals living under different roofs and in different towns have a very low strain sharing rate.

Maternal transmission under the microscope

To better understand maternal transmission, 3,598 samples from 711 mother-child pairs were analyzed. They show a progressive decrease in intestinal strain sharing rates from 65% at Day 1 to 50% at 1 week, 47% at 1 year, 27% between 1 and 3 years, 19% up to 18 years, and 14% up to 30 years. This gradual decline in gut strain sharing is likely associated with reduced physical proximity and access to new environments. However, strain sharing remained significant later in life, with offspring at 50-85 years of age still sharing 16% of gut strains with their mother, even if they no longer live under the same roof.

As for the oral microbiota, data from the US and Fiji shows a very different dynamic: mother-child sharing rates increase with the child’s age, especially after 3 years of age, coinciding with the increasing accumulation of microbe species in the oral microbiota. However, strain sharing between a young child and mother (30%) or father (24%) remains lower than between partners (38%), due to the intimacy between the latter.

Low influence of divergent lifestyles on microbiota transmission

Lastly, lifestyle (Western or otherwise) had a much lower-than-expected impact on microbiota transmission dynamics, with the rates of strain sharing between individuals remarkably similar across countries. The greater richness of microorganisms observed in non-westernized communities does not therefore seem caused by an increased transmission from other members of the household. Instead, this tendency may be due to interactions with their environment, as well as diets and lifestyles that favor microbial diversity.

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