Mental Health Archives

Protecting your gut-brain axis with probiotics

Mental Health, Probiotics / By @drHoberman

Do you realize how strong the connection between your brain and intestines, which is better known as the gut-brain axis, really is?

For example, you may feel that connection painfully or positively when you’re feeling anxious about an event out of your control, experiencing a fender-bender, taking a pop test, going on a first date or making an important presentation at your job.

The physical feelings you’re experiencing in your gut are the direct result of your brain releasing chemicals traveling through the bloodstream or the major nerve pathways. Those messages could be painful (no second date) or positive (you aced the presentation) depending on how your individual gut-brain axis reacts to the outcome.

Some health experts believe the dysfunction of the gut-brain axis may explain several health problems, ranging from fatigue and brain fog to something as simple as toenail fungus.

One of the best and simplest ways to maintain a healthy, balanced gut-brain axis—taking a multi-species probiotic—is at the heart of a recent University of Michigan study about the connection between stress and irritable bowel syndrome (IBS) on mice.

Researchers discovered mice produced chemicals called inflammasomes to maintain good gut health. However, when stressed, a corticotropin-releasing hormone (CRH) produced by mice blocked the benefits of those inflammasomes, while changing the composition of their guts, leading to intestinal inflammation. The good news: Mice pretreated with probiotics experienced reduced intestinal inflammation, by reversing the inhibition of inflammasomes.

So, how do these positive results affect folks dealing with IBS? Although researchers say that stress doesn’t cause IBS, it alters gut-brain interactions that lead to diarrhea, problems with appetite and chronic or severe gut pain.

“The effect of stress could be protected with probiotics which reverse the inflammation of the inflammasomes,” says John Kao, senior study author and an associate professor of medicine at the University of Michigan. “This study reveals an important mechanism for explaining why treating IBS patients with probiotics makes sense.”

The important takeaway from this study regarding probiotics: Your body is under constant attack externally (bad bacteria is lurking everywhere) and internally (too many things to do and not enough time to do them). Taking a probiotic is the safest, most effective way to maintain the balance that protects and preserves a healthy gut-brain axis.

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Probiotics May Battle IBS-Induced Stress

Mental Health, Probiotics / By @drHoberman

You may recall a recent study I posted about the possibilities of an anxiety-free future by taking probiotics. Those possibilities are looking a little more like probabilities, based on the results of a University of Michigan study on irritable bowel syndrome (IBS).

Although stressful emotions aren’t the primary cause of IBS, they can alter brain-gut interactions that trigger the intestinal inflammation that spurs diarrhea, belly pains (severe or chronic) or a loss of appetite.

In tests on mice, University of Michigan scientists discovered that stress may suppress an important element called an inflammasome, which is needed to maintain healthy gut microbes. The good news: Probiotics reversed the suppressive effect in these animals.

“This study reveals an important mechanism for explaining why IBS patients with probiotics makes sense,” said senior study author, gastroenterologist and associate professor of internal medicine at the University of Michigan John Y. Kao, M.D.

During the course of the study, researchers found inhibiting inflammosomes changed gut composition, resulting in intestinal inflammation. However, pretreating some rats with probiotics reduced inflammation in animals with stress-induced, small bowel inflammation.

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A Possible Anxiety-Free Future With Probiotics

Drug interactions, Mental Health / By @drHoberman

For many, new stresses may arise as the result of the New Year. From New Year’s resolutions to the upcoming tax season, stress and anxiety can take a toll on the body. Recently, researchers looked at how stress and anxiety directly affect the gut-brain axis.

A new study on mice conducted by an international team of researchers found a connection between probiotics, stress and anxiety. Researchers divided the mice into two groups, one being fed a Lactobacillus rhamnosus-filled broth, a bacterium found in EndoMune Advanced, and the other a bacteria-free broth. Conclusions drawn from the study suggest that those that drank the Lactobacillus rhamnosus-filled broth were less stressed and produced less corticosterone, a stress hormone, when reacting to a nerve-racking event.

Although it is not conclusive that probiotics can replace medications for anxiety or stress, the study initiates the idea that alternative treatments, like probiotics, for anxiety or stress disorders may exist in the future. Read the full study and its implications here.

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Celebrate Holiday Gut Health

Digestive Health, Mental Health / By @drHoberman

The holiday season is upon us and that means traveling, eating rich foods and celebrating with family and friends. With all these activities, there is no time to have an unhappy tummy. Taking a daily probiotic can help maintain the normal intestinal activity despite the changes in diet, hectic schedule and travel.

Dependent upon the vacation destination, traveler’s diarrhea can be a problem. Studies have found that probiotics can help enhance normal intestinal immunity and maintain the good bacteria to help in our digestion. In addition, probiotics can lessen the risk of contracting traveler’s diarrhea by 30-40%; therefore, everyone should make it part of their “travel insurance.”

Traveling and visiting family and friends does increase the risk of picking up cold and flu viruses. By taking a daily probiotic, it can lessen the risk of catching these infections, especially for children.

The bottom line is, enjoy the holidays and consider taking a daily dose of EndoMune Advanced. If you have children, give them an EndoMune Jr. It may help to protect their GI and respiratory systems.

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Probiotics – Helping You Think Happy Thoughts?

Mental Health, Probiotics / By @drHoberman

A recent study analyzing the effect of gut bacteria and probiotics on brain activity may have positive implications for individuals. Although still in the most preliminary stages of analysis and evaluation, scientists have discerned a link between the presence of probiotics in the diet and muted mental reactions to outside negative stress or stimuli.

Read the full article for details on how the study was conducted and when these hypotheses may gain enough support to become proven facts.

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Study Links Crohn’s and Ulcerative Colitis to Antibiotic Use

Disease, Healthy Aging, Mental Health / By @drHoberman

Many physicians are hesitant to prescribe antibiotics for many reasons. In fact, it’s not uncommon for physicians to use antibiotics as a last option for treatment. Those who are hesitant to prescribe antibiotics now have one more reason – Crohn’s Disease and Ulcerative Colitis (Here is more information on “What Is Colitis?“).

A new study published in the American Journal of Gastroenterology has found that people who are prescribed larger amounts of antibiotics have a higher risk for inflammatory bowel diseases (IBD). Crohn’s Diease and Colitis are the most common forms of IBD and can cause inflammation in the intestines, which then can cause abdominal pain, diarrhea and weight loss.

The article can be found at length at the American College of Gastroenterology website.

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New Study Reveals Danger of Sack Lunches

Children’s Health, Mental Health / By @drHoberman

It is back to school time. While you are out shopping for school clothes and supplies, I want to encourage you to consider adding EndoMune to your shopping list.

Over the years I have written a number of newsletters that discuss the benefit of probiotics for children. Topics have included: lessening the risk of infectious diarrhea, preventing cold and flu symptoms and avoiding antibiotic related diarrhea.

This month I want to discuss a new reason for giving your child a daily probiotic: foodborne illnesses.

An interesting study⁽¹⁾ was published this month in the respected medical journal, Pediatrics. The study discussed the risk of foodborne illnesses in sack lunches prepared at home for preschool children going to day care centers. The researchers wanted to determine the temperature of the perishable foods during the morning hours prior to lunchtime.

What Causes Foodborne Illnesses?

Before diving into the findings of the article, I would like to make some general comments about how contaminated foods cause intestinal infections that lead to symptoms of nausea, vomiting, diarrhea, fever and abdominal pain.

Most foodborne infections are undiagnosed and unreported, although the Centers for Disease Control and Prevention estimates that every year about 76 million people in the United States become ill from contaminated foods. Of these people, about 5,000 die⁽²⁾.

Almost half of the reported foodborne illnesses occur in children, with the majority occurring in children under age 15 years. Frightening, right?

Children are at high risk for foodborne illness for several reasons: immature immune system, reduced stomach acid to kill harmful bacteria, and low body weight – which means a lower dose of pathogen is required to cause injury⁽³⁾.

There are three important factors when considering food safety: (1) type of food, (2) stored temperature, and (3) time exposed to unsafe temperature.

Bacteria that cause foodborne illnesses like Salmonella and E. coli grow rapidly in certain types of foods. Meat, poultry, fish, dairy products and cut fruits and vegetables are most likely to carry these bacteria.

If the bacteria are present when the food is prepared, then refrigerating the food to below 40°F prevents the bacteria from multiplying and causing an infection. Additionally, cooking foods to a temperature greater 165°F will kill any bacteria in food. Once cooked, the hot foods need to stay at a safe temperature of greater than 140° F prior to serving or refrigerated to less than 40°F for storing.

When perishable foods like chicken salad or bologna sandwiches are left in the “danger” temperature zone of 40°F to 140°F for greater than two hours, the harmful bacteria rapidly multiply. When this happens, the foods must be discarded due to risk of contamination by bacteria and toxins, which can cause mild to life threatening intestinal infections.

Pediatrics Study: Sack Lunches at Risk of Bacteria Proliferation

This brings us back to the study. The objective was to measure the temperature of the foods in preschool-aged children’s sack lunches. Using non-contact temperature guns, the researchers tested 705 lunches that contained a total of 1,361 perishable foods. The temperature was measured 90 minutes before lunchtime.

The results were astounding: Only 22 or 1.6% of the 1361 perishable food items were in a safe temperature zone. Overall, 97.4% of meats, 99% of dairy, and 98.5% of vegetables were in the danger zone.

The researchers found that the use of thermally insulated bags with ice packs only marginally improved the number of perishable foods in the safe temperature zone.

So what is a parent to do?

Here are some recommendations:

Wash hands and use clean cutting boards and knives.
Use safe foods like peanut butter (if allowed), raw, cooked or dry fruit and raw vegetables.
Consider making a meat sandwich of turkey or roast beef the night before and putting in the freezer using bags designed for freezing. It will take 3 to 3.5 hours for the sandwich to thaw.
Soups, stews and chili make a hearty lunch. To use them in a packed lunch, heat to boiling and put in a sterilized thermos bottle.

Finally, I recommend giving your child a high quality probiotic like EndoMune Junior.

Studies have shown that probiotics are able to defend the human intestinal tract against harmful bacteria. The probiotic bacteria stimulate the immune response, prevent pathogens from adhering to the intestinal lining cells and produce antibacterial proteins⁽⁴⁾.

There has been increasing evidence in the last 10 years for the benefit of probiotics in preventing and treating acute diarrhea in children. A number of studies have found that giving probiotics versus a placebo to children in day care facility can statistically lessen the risk of having an episode of diarrhea^(6,7).

Take Home Message

Given the results of the study on food temperature in school lunch bags, I would think it would be a good idea to give EndoMune Jr to lessen the risk of experiencing a bout of foodborne gastroenteritis.

Eat healthy, exercise and live well!
Dr. Hoberman

References

(1) Temperature of Foods Sent by Parents of Preschool-aged Children. Almansour FD, Sweitzer SJ, Magness AA.
(2) Food-related illness and death in the United States.Mead, P., L. Slutsker, V Ddietz et al.Emerg Infect Dis, Sept-Oct 1999, 56(No. 53).
(3) Children and microbial foodborne illness.Buzbym H>C. Food Revuewm 2001l 24⁽²⁾:32-7.
(4) Use of probiotics in children with acute diarrhea. Szajewska H, Mrukowicz JZ. Paediatr Drugs. 2005;7⁽²⁾:111-22
(5) Probiotics for treatment of acute diarrhoea in children: randomised clinical trial of five different preparations. Canani RB, Cirillo P, Terrin G, Cesarano L, Spagnuolo MI, De Vincenzo A, Albano F, Passariello A, De Marco G, Manguso F, Guarino A. BMJ. 2007 Aug 18;335(7615):340
(6) Efficacy of probiotics in prevention of acute diarrhoea: a meta-analysis of masked, randomised, placebo-controlled trials. Sazawal S, Hiremath G, Dhingra U, Malik P, Deb S, Black RE. Lancet Infect Dis. 2006 Jun;6⁽⁶⁾:374-82
(7) Probiotics for children with diarrhea: an update. Guandalini S.J Clin Gastroenterol. 2008 Jul;42 Suppl 2:S53-7

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Tax Season Can Lead to Stress and IBS

Healthy Aging, Mental Health / By @drHoberman

April is a wonderful time of the year. Spring is nature’s way of saying, “let’s party.”⁽¹⁾

Planting new flowers and watching the first blossoms of the year are very joyful and relaxing activities, especially after enduring the cold gray days of winter.

Unfortunately, despite its beauty, April can sometimes be stressful for various reasons. At the forefront of many people’s mind is the need to file taxes. Or, you may be waiting to hear where your children will be going to school next year, or if they will find a job. If you happen to be one of those millions of people experiencing stress this season, you may want to consider taking a probiotic after you read this month’s newsletter.

Stress Causes Changes in Bacteria

Two very interesting articles were published in March. These articles investigated how stress can adversely affect the healthy bacteria of intestines^(2,3) .

In my practice of gastroenterology, I would see many patients who had ongoing symptoms of abdominal pain and change in stool habits. Despite comprehensive evaluations, no specific cause could be found for many of the patients. As a result, they would be labeled with the diagnosis of “Irritable Bowel Syndrome” (IBS).

At the time, it was thought that the symptoms of IBS were frequently due to stress. The common therapies included medications that combined an antispasmodic and a mild tranquilizer like Librax, Donnatal or Bentyl. These medications were treating the symptoms, but not the cause of stress. If medical researchers can determine the cause of the symptoms, then better therapy can be developed.

Immune System and Stress Regulation

The intestines contain 70% of our immune cells. It’s these cells that are responsible for monitoring the bacteria entering our system. Harmful bacteria stimulate the intestines to release inflammatory mediators (cytokines) in an effort to destroy the harmful bacteria. An increase in these mediators can result in intestinal inflammation, which in turn causes the symptoms of IBS.

One study⁽³⁾ published in March measured the level of inflammatory cytokines in 30 patients with IBS and in 30 normal controls. The level of cytokines were much higher in the IBS group – indicating there is a link between IBS and cytokines.

The other study⁽²⁾ investigated the intestinal bacteria in mice before and after they were exposed to a stressful situation. Following exposure to the stress, there was a change in the composition of the intestinal bacteria. With this change came an increase in harmful bacteria, which then induced the immune system to release inflammatory cytokines.

These research studies help to understand the cause of IBS symptoms. Now, the question is how to decrease the inflammation induced by stress. Doing this will be a giant step toward “treating” the symptoms of IBS.

Fortunately, scientific studies^(4,5) have already demonstrated that giving probiotics can reduce the immune system release of inflammatory cytokines, thereby easing IBS symptoms.

Take Home Message

If you are experiencing some stress and GI symptoms, consider taking a high quality probiotic like EndoMune so you can fully enjoy this springtime.

Eat healthy, exercise and live well!
Dr. Hoberman

References:

(1) Quote by Robin Williams

(2) Exposure to a social stressor alters the structure of the intestinal microbiota: implications for stressor-induced immunomodulation. Bailey MT, Dowd SE, Galley JD, Hufnagle AR, Allen RG, Lyte M. Brain Behav Immun. 2011 Mar;25⁽³⁾:397-407

(3) Altered peripheral toll-like receptor responses in the irritable bowel syndrome. McKernan DP, Gaszner G, Quigley EM, Cryan JF, Dinan TG. Aliment Pharmacol Ther. 2011 May;33⁽⁹⁾:1045-52.

(4) The role of microbiota and probiotics in stress-induced gastro-intestinal damage.Lutgendorff F, Akkermans LM, Söderholm JD. Curr Mol Med. 2008 Jun;8⁽⁴⁾:282-98

(5) Therapies aimed at the gut microbiota and inflammation: antibiotics, prebiotics, probiotics, synbiotics, anti-inflammatory therapies.Quigley EM.Gastroenterol Clin North Am. 2011 Mar;40⁽¹⁾:207-22

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Probiotics Recommended for Nursing Home Residents

Healthy Aging, Mental Health, Probiotics / By @drHoberman

Over the years, I have written a number of newsletters that discuss the benefits of probiotics for children and adults. This month will focus on the older generation, an important topic since there are currently 11.4 million people living in nursing homes in the United States ⁽¹⁾. This figure includes 14% of the population older than 84.

For anyone who has loved ones in nursing homes and is concerned for their well-being, there are numerous reasons I recommend all nursing home patients take probiotics.

Scenario One: Hospitalization

A recurring story is that of a functioning senior citizen living at home who fractures a hip due to a fall or experiences a stroke. The following series of events is likely to happen:

Upon injury, 9-1-1 is called.
The individual becomes a hospitalized patient.
The patient is required to take medications, including antibiotics.
The antibiotics adversely affect the gastrointestinal tract.
The individual is now at risk of developing hospital-acquired infections like Clostridia difficile and methicillin-resistant staph infections.
Eventually, the patient improves and is transferred to a rehab unit or nursing home.

The seniors may have had normal intestinal function prior to hospitalization, but with all the medications and change in activity level, constipation and diarrhea become real problems. These disorders can severely affect quality life and health of the people within the nursing homes.

For instance, other healthy nursing home residents are now at risk of being exposed to surface areas that have become contaminated by the arrival of the recently hospitalized patients.

This scenario is one reason to consider giving probiotics to healthy nursing home residents. Should a resident be exposed, the probiotics can prevent harmful bacteria from colonizing the intestines and causing damage.

Scenario Two: General Aging Process

Another main reason to give probiotics has to do with the changes that occur in the normal intestines as they age. Due to reduction in acid production, enzyme secretions, reduced intestinal immunity and slowed motility, the healthy intestinal bacteria population is reduced. This change in the intestinal microflora contributes to the risk of diarrhea and constipation.

According to the Administration of Aging ⁽²⁾, among healthy adults 65 years of age and older, 26% of men and 34% of women experience constipation. These numbers increase drastically for elderly people living in nursing homes – more than 80% suffer from constipation. Medications, immobility, and dementia are all contributing factors for this increase.

Residents of nursing homes have a much higher risk of developing infectious diarrhea. In the United States, nursing home residents are four times more likely to die from gastroenteritis than those living outside nursing homes. Additionally, of all deaths occuring from diarrheal disease, nursing home residents account for 17.5% ^(3,4).

The physicians and nursing staff are very aware of the health risks associated with severe constipation and diarrhea. Unfortunately, nursing home patients often require medications that can slow intestinal motility, damage the lining cells, and disrupt the healthy balance of the intestinal bacteria. As a result, severe intestinal disorders can occur despite good medical care.

Probiotics Improve Constipation and Diarrhea

During the last three years, there have been several reports published that found that probiotics improved constipation and diarrhea in nursing home residents ^(5,6,7). The research protocols were similar; One group of residents received probiotics containing Lactobacillus and/or Bifidobacteria, and the other group received a placebo. The research findings revealed that the frequency and consistency of the stools improved in the groups treated with probiotics, as compared to the control groups ^(5,6,7).

After considerable review of the literature, I have come to the conclusion that giving nursing home residents daily probiotics can help to improve intestinal function, quality of life, and lessen the risk of serious health issues.

The real concern in medicine is that we “do no harm.” Probiotics, fortunately, have an excellent safety profile. It is worth noting, though, that there have been rare reports of infections due to probiotics in seriously immune-compromised patients ⁽⁹⁾.

Take Home Message

If you have a loved one in a nursing home, ask the health care provider to consider giving them a probiotic. The daily dosage should be at least 10 billion and contain multiple strains of Lactobacillus and Bifidobacteria, like EndoMune Advanced.

Eat healthy, exercise and live well!
Dr. Hoberman

References:

(1) National Center for Health Statistics. Health, United States, 2009: with special feature on
medical technology. Hyattsville, MD, 2010.

(2) Sources: Data releases from the web sites of the National Center for Health Statistics; and from the Bureau of Labor Statistics web site

(3) Mortality due to gastroenteritis of unknown etiology in the United States. Frenzen PD.J Infect Dis. 2003 Feb 1;187⁽³⁾:441-52. Epub 2003 Jan 24

(4) Clin Infect Dis. 2010 Oct 15;51⁽⁸⁾:907-14.Surveillance for outbreaks of gastroenteritis in long-term care facilities, Australia, 2002-2008. Kirk MD, Fullerton KE, Hall GV, Gregory J, Stafford R, Veitch MG, Becker N

(5) Efficacy of Lactic Acid Bacteria (LAB) supplement in management of constipation among nursing home residents. 1)Sources: Data releases from the web sites of the National Center for Health Statistics; and from the Bureau of Labor Statistics web site

(6) Fermented cereal with specific bifidobacteria normalizes bowel movements in elderly nursing home residents. A randomized, controlled trial.Pitkala KH, Strandberg TE, Finne Soveri UH, Ouwehand AC, Poussa T, Salminen S.J Nutr Health Aging. 2007 Jul-Aug;11(4):305-11

(7) Clostridium difficile in the long-term care setting. Makris AT, Gelone S.J Am Med Dir Assoc. 2007 Jun;8⁽⁵⁾:290-9. Review

(8) Probiotics and the nursing home: should we give bacteria for breakfast?Morley JE.J Am Med Dir Assoc. 2009 Jul;10⁽⁶⁾:365-7.

(9) Safety assessment of probiotics for human use.Sanders ME, Akkermans LM, Haller D, Hammerman C, Heimbach J, Hörmannsperger G, Huys G, Levy DD, Lutgendorff F, Mack D, Phothirath P, Solano-Aguilar G, Vaughan E.Gut Microbes. 2010 May;1⁽³⁾:164-185. Epub 2010 Mar 4.

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Probiotics are Effective Treatment for Pediatric IBS

Children’s Health, Mental Health, Women’s Health / By @drHoberman

If you’re a parent, then you are probably familiar with the phrase, “My stomach hurts!”

This is often a self limited problem, but some children do experience recurrent abdominal pain which is often diagnosed as Irritable Bowel Syndrome (IBS).

A recently published study examined the benefits of probiotics for alleviating the symptoms of IBS in children⁽¹⁾. IBS is a common problem in pediatrics, and no safe and effective treatment has been available up until now⁽²⁾.

Suspected Causes of IBS

The symptoms of abdominal bloating, gas, pain and change in stools are very common in both children and adults. Once appropriate tests have ruled out any underlying disorder like ulcers, colitis, or celiac disease, the diagnosis is often IBS.

Between 5 to 20% of kids have IBS, and about one in five adults do, too. It’s not fun, but the good news is that IBS doesn’t lead to more serious problems. It is more about quality of life for the child and the family.

Since the cause is not really known, and the symptoms can vary, IBS can be hard to treat.

Over the years a variety of theories have been offered to explain IBS symptoms in children. These have included emotional stress, intestinal hypersensitivity, altered intestinal motility, dietary intolerances and genetics^(3,4).

In the last several years there has been a shift in the paradigm, and now alterations in the intestinal bacteria are thought to be a major factor leading to IBS.

We are all familiar with the term “food poisoning” — a bout of infectious diarrhea due to the consumption of harmful bacteria in contaminated foods or drinks.

Researchers in the area of IBS noted that many of the people who developed symptoms of IBS had experienced a recent episode of food poisoning⁽⁵⁾. It was theorized that the infection caused a disruption of the healthy intestinal bacteria resulting in ongoing intestinal inflammation and GI symptoms⁽⁶⁾.

Recent studies have supported this association and identified post-infectious irritable bowel syndrome (PI-IBS) as a disorder due to a previous bout of infectious gastroenteritis. Approximately 30% of individuals with IBS can date the onset of their symptoms following an episode of gastroenteritis⁽⁷⁾.

Pediatric Medical Studies

In February of this year, a study⁽⁸⁾ was published that documented for the first time that exposure to acute gastroenteritis in childhood is associated with an increased risk of IBS in early adulthood. There was an outbreak of infectious gastroenteritis due to drinking contaminated city water. Children were followed for 8 years after the exposure. The children who had a bout of gastroenteritis had a greater than fourfold increase in IBS compared with unexposed children.

This now brings us back to the new medical article that I mentioned at the beginning of this newsletter. The study⁽¹⁾ enrolled children 4 to 18 years of age who fulfilled the criteria for IBS. The children received a probiotic or a placebo. A daily record of their symptoms was maintained. At the end of the study, the results were reviewed.

The group receiving probiotics had a better than 50% improvement in their symptoms of abdominal pain, and bloating compared to the placebo group. There was also an improvement in the passage of stools. Additionally, no adverse effects were noted in the group taking probiotics.

In 2008, a review article⁽²⁾ on medications to ease the symptoms of IBS in children stated, “The lack of clear evidence of effectiveness for any of the recommended drugs suggests that there is little reason for their use outside of clinical trials.” The new study on childhood IBS, though, does show that probiotics are effective.

Take Home Message

If your child has IBS, probiotics may help to ease their symptoms. Fortunately, there have been no adverse effects associated with their use. Consider using EndoMune Jr for children less than 8 years of age and EndoMune Advanced for older children. It won’t hurt, and it certainly may help!

Eat healthy, exercise and live well!
Dr. Hoberman

(1) VSL#3 improves symptoms in children with irritable bowel syndrome: a multicenter, randomized, placebo-controlled, double-blind, crossover study.Guandalini S, Magazzù G, Chiaro A, La Balestra V, Di Nardo G, Gopalan S, Sibal A, Romano C, Canani RB, Lionetti P, Setty M.J Pediatr Gastroenterol Nutr. 2010 Jul;51⁽¹⁾:24-30.

(2) Pharmacological interventions for recurrent abdominal pain (RAP) and irritable bowel syndrome (IBS) in childhood.Huertas-Ceballos A, Logan S, Bennett C, Macarthur C. Cochrane Database Syst Rev. 2008 Jan 23;⁽¹⁾.

(3) Irritable bowel syndrome: epidemiology, diagnosis and treatment: an update for health-care practitioners.Grundmann O, Yoon SL.J Gastroenterol Hepatol. 2010 Apr;25⁽⁴⁾:691-9. Epub 2010 Jan 13.

(4) Pathogenesis of IBS: role of inflammation, immunity and neuroimmune interactions.Ohman L, Simrén M.Nat Rev Gastroenterol Hepatol. 2010 Mar;7⁽³⁾:163-73. Epub 2010 Jan 26. Review.

(5) The irritable colon syndrome. A study of the clinical features, predisposing causes, and prognosis in 130 cases.CHAUDHARY NA, TRUELOVE SC. Q J Med. 1962 Jul;31:307-22.

(6) Bacillary dysentery as a causative factor of irritable bowel syndrome and its pathogenesis . Wang LH , Fang XC , Pan GZ . Gut 2004 ; 53 : 1096 – 101.

(7) Postinfectious irritable bowel syndrome–a meta-analysis.Halvorson HA, Schlett CD, Riddle MS.Am J Gastroenterol. 2006 Aug;101⁽⁸⁾:1894-9; quiz 1942.

(8) An Outbreak of Acute Bacterial Gastroenteritis Is Associated With an Increased Incidence of Irritable Bowel Syndrome in Children Marroon Thabane, Marko Simunovic, Noori Akhtar-Danesh, Amit X Garg, William F Clark, Stephen M Collins, Marina Salvadori, John K Marshall The American Journal of Gastroenterology 105, 933-939 (23 February 2010).

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