Last Updated on August 30, 2018 by Patricia Carter

SUMMARY:   Bottom Line of this post: You want OFF the IBS diseasepan!  WHY? Because — putting aside pain, bowel issues, and bloat — IBS can alter the brain size and function in the emotion and sensory processing areas when having it a long time along with early life stressors [Labus et al., 2017], it is associated with A LOT of diseases, and there are A LOT of surgeries performed inappropriately because of misdiagnosis or poor manangement of IBS!  DISEASES that are associated with IBS  — the listing is NOT  comprehensive — includes:   Type 2 Diabetes, metabolic syndrome, fibromyalgia, chronic fatigue syndrome, IBD, CFS/ME, autism, anxiety, depression, MS, and Parkinson’s.  Inappropriate SURGERIES occurring due to IBS  misdiagnosis includes —  appendectomy, cholecystectomy, ovarian, and hysterectomy.  See below for All of those links. There are lots of ways to get off the IBS diseasespan!  Learn in this post that it is YOUR choice:  IBS, Microbiome, Fodmaps, Probiotics, Mindfulness-based stress reduction, Cognitive behavioral therapy works… or targeted drugs!  Or not drugs — because of the poor efficacy of that current US standard of care:  “The physician should also emphasize the chronic nature of this syndrome [IBS] because nearly 75% of patients continue to have a diagnosis of IBS 5 years later.¹³ ”  [Occhipinti et al., 2012].   “Many different drugs have been suggested for IBS treatment, but their real benefits are very debatable.”  [Bellini et al., 2014].   Don’t be surprised.  In 2012, the FDA changed the endpoints of those drug studies to stop being only one endpoint because of how multi factorial IBS symptomolgy is, and the Bristol Stool Chart — defining what is a ‘normal BM’ (which you’ll learn in this post) — despite being around since 1997, is only now being validated, 2016!  Contrast all this to the UK British Dietetic Association guidelines for IBS — low FODMAP diet is the second-line intervention [Catassi et al., 2017]  [McKenzie et al, 2016]   [UK evidence-based practice guidelines for dietetic management of IBS in adults 2012 PDF]) as it helps about seventy-six percent of IBS patients  [Magge et al., 2012]  [Bohn et al., 2015]   [Staudacher et al., 2011] and yet, it has come under attack with the current US standard of care still NOT recognizing the FODMAP diet (see this post).  A rebuttal to all the rift recently published in 2017, authored by Monash University ressearchers, the creators of the FODMAP diet.  See  [Hill et al., 2017]  To piggyback the diet fix, studies continue to find that probiotics might be something to think about for some cases of IBS — see  [Whiteley, 2016].  Wondering about IBS and what early life stressors might mean?  That group had more history of early life trauma (general trauma (31 items), physical (9 items), emotional (7 items), and sexual abuse (15 items)) AND they had longer duration of IBS symptoms.  [Labus et al., 2017]  While we can’t change our early life stressors, there are lots of ways to tackle IBS using diet, probiotics, mindfulness-based stress reduction, cognitive behavioral therapy and targeted drugs — according to the Monash rebuttal [Labus et al., 2017].  Now you know!  Protect brain size and function, avoid potentially needless surgery and improve your disease status by fixing IBS; LISTEN to your gut!  Unbelievable… check out the global prevalence of IBS:

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DON’T OVERLOOK THE COMMENT SECTION to this post, it adds STUDIES PUBLISHING AFTER I WROTE THIS POST!

IBS is not a condition to ignore.  

Address it & Resolve it considering:  Diet (Fodmaps or similar and probiotics), mindfulness, cognitive behavioral, and/or target drugs because…

• Many diseases, including those crossing the blood-brain-barrier, are associated with the condition, and resolution of the IBS may help prevent or mitigate the disease,

• There are a lot of inappropriate surgeries performed due to misdiagnosis (or poor management) of IBS, and

• It alters the brain emotion and sensory processing areas for those having IBS long term with early life stressors.

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Great animation: What is IBS [Monash University]

Most people don’t even realize their symptoms are IBS — and yet IBS affects up to 10 to 25% of the population, and that has a large margin of error since few get counted via physician visits and the inclusion criteria differs. [Canavan et all., 2014].  I always recommend to jounal!

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Links to the IBS Disease & Surgery Statistics

Most are surprised to learn that many diseases have IBS associations.  Just to put that into perspective, 30–50% of patients diagnosed with IBD [endoscopically in remission] also report IBS-type symptoms.^{3, 4, 5}.  [Ballou et al., 2017].   Check out the list of diseases having known IBS associations — it is not a comprehensive listing:  Type 2 Diabetes  “Given the higher prediabetes occurrence in IBS, IBS may indirectly indicate a higher risk of Type 2 Diabetes.” [Gulcan et al., 2009], metabolic syndrome “The findings suggest that the treatment of irritable bowel syndrome may be a potentially beneficial factor for the PREVENTION  of metabolic syndrome.”  [Guo et al., 2014],  fibromyalgia (49% have IBS), chronic fatigue syndrome (51%), temporomandibular joint disorder (64%), and chronic pelvic pain (50%) [Heitkemper et al., 2015], IBD [Halpin et al., 2012], CFS/ME [Whiteley, 2017], autism [Navarro et al., 2016], anxiety  and depression [Fond et al., 2014] see pdf here, Multiple Sclerosis [Marrie et al., 2015], and Parkinson’s [Mishima et al., 2017].

IBS is complex and multifactorial.  It is “a disruption of the so called “brain-gut axis” that determines changes in the digestive motility and secretion, visceral hypersensitivity, abnormalities of enteroendocrine and immune systems, genetic factors, infections, alterations of the intestinal microbiota and inflammation could play a role in IBS.”  [Bellini et al., 2014].

IBS costs society in terms of medical and loss work absenteeism over $21 billion annually. [Canavan et al., 2014]  As well,  more women (60 to 65%) are affected then men [iffgd, 2016], and lots of inappropriate surgeries due to misdiagnosis occur for IBS suffers.  Some examples include appendectomy, cholecystectomy — 2 to 3 x more likely,  and ovarian  and hysterectomy (twice as likely) occurs 45 to 55% more often in IBS then controls. [Canavan et al, 2014] [iffgd 2016] [Corazziari et al., 2008].

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AND What is a Normal BM?!?

Wondering if you have IBS?  Well.. what does a normal BM look like?  Use the Bristol Stool Chart (BSC) — see TWO versions on the above journal pic — a ‘NORMAL BM’ is rated 3 to 5!  IT FIRST PUBLISHED 1997 [Bristol Stool Chart 1997 PDF], BUT WAS ONLY VALIDATED FOR USE IN THE US IN 2016 BECAUSE IN IBS DRUG CLINICAL TRIALS, “There is little published evidence of efficacy for the most commonly used treatments. Thus, there is an urgent need to conduct clinical trials on existing and novel therapies.”  See [Blake et al, 2016]  [Saps et al, 2016].  If still confused on what is ‘normal’, CHECK OUT A MODIFIED BSC VERSION AT [Lasch et al, 2016].  Honest… I am not making this up… validating the BSC in the US became a scramble because the [FDA Guidance, 2012} changed the “endpoints for clinical IBS trials since prior studies looked at one endpoint which can’t adequately report patient perspective of the complex IBS symptomology”!

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The IBS Microbiome Study including early life stressors

The study: [Labus et al., 2017] Differences in gut microbial composition correlate with regional brain volumes in irritable bowel syndrome.

Cohort:  29 IBS adult patients and 23 healthy controls.  Yes, the small cohort is a limitation of the study but as the study concludes: “the correlations of abundance of certain microbial taxa with early adverse life events and with distinct brain structural changes previously reported in IBS suggest a possible role of gut microbes and their metabolites in the development and shaping of the gut-microbiota-brain axis early in life, confirming results from a previous study [10]... Identifying IBS subgroups based on gut microbiota, their related metabolomic profiles and corresponding brain signatures is likely to play an important role in optimizing therapies in IBS.”

Questionaires used for early life stressors:

•  For background, in mice, early maternal separation induced the brain differences with consequent symptoms similar to IBS [Palma et al., 2015].  Moving to humans, the microbiome/IBS study  [Labus et al., 2017] used The Hospital Anxiety and Depression Scale [HADs] [22], the Patient Health Questionnaire-15 [PHQ] for mood  [23], and the Early Traumatic Inventory–Self Report (ETI-SR) [24] for histories of childhood traumatic and adverse life events that occurred before age 18 years old covering four domains: general trauma (31 items), physical (9 items), emotional (7 items), and sexual abuse (15 items) [24].  Details on the ETI-SR are in the reference section at [Bremner et al., 2011].
• The Catastrophizing subscale from the Coping Strategies Questionnaire assessed levels of catastrophizing [25]. The degree to which subject viewed situations as stressful in the past month was measured by the Perceived Stress Scale [26].
• Medication usage included any of the following: antispasmodic, laxatives, stool softener, fiber supplement, nonsteroidal anti-inflammatory drugs, aspirin, acetaminophen, thyroid medications, antihistamine, or proton pump inhibitors.  [Note… PPIs have a disrupted microbiome — see this post.  The significance is that drugs likely need further stratification when evaluating microbiome.]

Findings:  The IBS microbiomes clustered into two subgroups with those having early childhood trauma clustering together.  This trauma could be influencing how the microbes in our gut interact with our brains as we grow, demonstrating a two-way street between the development of our nervous system and the microscopic residents of our digestive system.

• One subgroup of IBS was indistinguishable from the healthy control cohort.
• The other IBS subgroup differed and had an altered gut microbiota.  As well, an area of the brain associated with pulling together the body’s sensory information was slightly bigger in this group. The front part of the insular cortex – an area associated with keeping certain body functions in balance as well as dealing with emotions and cognitive functions  was slightly smaller as was the ventral prefrontal regions.  This cohort also had more history of early life trauma based on a psychological evaluation called the Early Traumatic Inventory–Self Report (ETI-SR) Inventory, and a longer duration of IBS symptoms.  “A history of early life trauma has been shown to be associated with structural and functional brain changes and to alter gut microbial composition. It is possible that the signals the gut and its microbes get from the brain of an individual with a history of childhood trauma may lead to lifelong changes in the gut microbiome. These alterations in the gut microbiota may feed back into sensory brain regions, altering the sensitivity to gut stimuli, a hallmark of people with IBS.”  — Gut microbes linked to brain structure in people with irritable bowel syndrome, May 2017 UCLA Newsroom article.  It was postulated that “different kinds of bacteria in the gut could be producing chemicals that influence the brain’s development during childhood. Traumatic experiences early in life could affect the brain, which in turn influences the kinds of microbes that grow in the gut. These in turn could influence the brain’s development”.— Bacteria Could Be Responsible For Shifts in Brain Structure in People With IBS, ScienceAlert May 2017.

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Future — IBS clinical therapeutics

Your Choice:  IBS, Microbiome, Fodmaps, Probiotics, Mindfulness-based stress reduction, Cognitive behavioral therapy and/or targeted drugs?!?

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Part 1:  Diet (Fodmaps & Probiotics)

“Analysis of a person’s gut microbiota may become a routine screening test for people with IBS in clinical practice, and future, therapies such as certain diets [low FODMAPS perhaps  [Occhipinti et al., 2012]] and probiotics may become personalized based on an individual’s gut microbial profile.” [Labus et al., 2017]

Diet (Fodmaps)

• What are FODMAPs?  FODMAPs are food substrates that are poorly absorbed and therefore fermentable by the gut microbiota. The acronym stands for Fermentable Oligo-, di-, Monosaccharides And Polyols. FODMAP substrates are ubiquitous prebiotics in the diet that are difficult to digest for everyone, they are additive, and when in excess for your unique physiology, can cause digestive symptoms.  “There is an accumulating body of evidence, based on observational and comparative studies, and on randomized-controlled trials that supports the notion that FODMAPs trigger gastrointestinal symptoms in patients with functional bowel disorders.” [Shepherd et al., 2013].
• The FODMAP diet is not intended to be long-term therapy.  From Monash University (the creator of the Low FODMAP diet):  “A low FODMAP diet will reduce the intake of foods high in fibre and natural prebiotics, which in turn may impact of the growth of certain bacteria in the gut.  This is why we advise against following a strict low FODMAP diet  unnecessarily.  Typically consume low FODMAP 2-6 weeks, then re-introduce FODMAPs in a deliberate process to learn tolerance levels using a FODMAP knowledgeable professional.” Source: Monash University, Dietary Fibre and natural prebiotics for gut health: FAQs.   The below chart lists some prebiotic FODMAPs that beneficially feed the microbiome.
• A FODMAP re-introduction guideline can be found at:  Metagenics, Patient Information: Low FODMAP Diet for Irritable Bowel Syndrome. 

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• The efficacy of the elimination phase of the low-FODMAP diet for overall gastrointestinal symptom relief in adult patients with IBS has been seen in randomized, controlled trials; a blinded, randomized, rechallenge study; and observational studies that have been reviewed in detail elsewhere^3,4 as well as in a meta-analysis.⁵ These studies have shown that 50% to 86% of patients have a clinically meaningful response to the low-FODMAP diet. In contrast, the success of maintenance (the reintroduction phase of the diet) has been studied less (in only a few observational studies).^6,7 Due to the difficulties of designing an appropriately blinded, randomized, longer-term, interventional study, the evidence base for maintenance will likely remain less solid. [Hill et al,, 2017],
• Dr. Gibson, the creator of the FODMAP diet, estimates that overall ~10% of the population may be FODMAP-sensitive.  The book, The Complete Low-FODMAP Diet: A Revolutionary Plan for Managing IBS and Other Digestive Disorders, by Drs. Sue Shepherd and Peter Gibson is a reference guide and road map for the low-FODMAP diet.

• Figure out if it is Gluten or FODMAP Intolerance!  The FODMAP gold standard of food intolerance testing (ie, food exclusion to achieve symptom resolution followed by gradual food reintroduction and subsequent symptom induction to identify tolerance)³⁵ is important because often gluten is not the dietary culprit contrary to many thinking otherwise.  “Randomized studies have shown that there is a lack of gluten specificity in the induction of symptoms in the vast majority of patients with self-reported NCGS.^32–34   Another trial of 36 patients experienced improvement in gastrointestinal symptoms when placed on a low-FODMAP diet during the run-in period, but none had repeatedly consistent exacerbation of symptoms specifically on ingestion of FODMAP-depleted gluten during the blinded rechallenge phases.³¹ One logical interpretation of these studies is that the FODMAP reduction associated with avoidance of wheat, rye, and barley—all high in FODMAPs—led to partial response, and more extensive FODMAP restriction further improved that response.”  See  [Hill et al,, 2017] for reference links.
• IBS, Food Intolerances, and SIBO.  FODMAPS may work since 75.6%, 37.8% and 13.3% of  [IBS] patients had fructose, lactose malabsorption or small intestinal bacterial overgrowth respectively.  [de Roest et al 2013]  [Barrett et al., 2007].
• Disease and FODMAPs — IBD.  The FODMAP diet successfully manages over 86% of IBS/IBD patients, having partial (54%) or full (32%) efficacy.  Satisfaction with dietary management was seen in 83 (70%) IBS patients and 24 (55%) IBD patients. Eighty-four percent of patients lived on a modified low FODMAP diet (LFD), where some foods rich in FODMAPs were reintroduced, and 16% followed the LFD by the book without deviations. WHEAT, DAIRY products, and ONIONS were the foods most often NOT reintroduced by patients. [Maagaard et al., 2016].
• Disease and FODMAPs —Diabetes.  The Joslin Diabetes Center, a teaching and research affiliate of Harvard Medical School, recommends trying FODMAP for diabetes! Have IBS [and Diabetes]? Try FODMAPs.
• Genetic predisposition and IBS. There may be a subset of patients that are genetically predisposed to IBS due to mutations in the gene encoding the enzyme sucrase-isomaltase which is responsible for the digestion of small carbohydrates from sugars and starches called disaccharides.  15Phe is a common sucrase-isomaltase polymorphism. “A significant decrease in the enzymatic activity of sucrase-isomaltase would be compatible with poor carbohydrate digestion in the intestine, possibly leading to malabsorption and bowel symptoms,” Hassan Naim, PhD.  [Henström et al,, 2016] and see this Healio article. 
• Fructose and children under 10 years age:  “Children under the age of 10 years have a reduced capacity to absorb fructose. It would be important to assess whether young children with IBS are consuming a high-FODMAP diet with excessive amounts of fruit/fruit products, dairy/dairy products, and wheat/wheat products. Furthermore, it would also be important to assess whether normalizing—that is, limiting portions of fruit, dairy, and wheat to reduce dietary intake of FODMAPs—results in symptom resolution.”  [Hill et al., 2017]

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Probiotics — They Work Well for IBS!

The study.  [Zhang et al., 2016]   Meta analysis of 21 randomized controlled trials (RCTs) that compared  many probiotics including different types of Lactobacillus acidophilus and Lactobacillus rhamnosus  including  VSL#3 with placebo.

Conclusion:  “Probiotics are an effective pharmacological therapy in IBS patients.  Single probiotics, a low dose, and a short treatment duration were more effective with respect to overall symptom response and quality of life.”  Some probitoic(s) worked very well but we don’t know enough about which ones used under which circumstances because the authors did not analyze “the effects of individual probiotic species”.

Practically,  Try many different whole food probiotics. You’ll find those in the refrigerated section, or try making your own and see how you feel — see my Pinterest Ferment Board for starters.  Always start     S—L—O—W!   Here is the link for how I make SCD Yogurt – the FODMAP lactose is eliminated in this recipe since the long ferment time renders the yogurt lactose-free.  Regarding the inflammatory casein protein, it is said that the recipe changes the protein to more digestible, but different milks can also be trialed to decrease the inflammatory nature of casein. If you find you still cannot tolerate yogurt, try non-dairy ferments such as those in the below pic.  Note too:  You should try those non-dairy ferments anyway because all ferments contain differing probiotic bacteria and more is better when it comes to talking microbiome diversity.

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Part 2:  Mindfulness-based stress reduction, cognitive behavioral therapy and/or targeted drugs?!?

Intro:  Health psychology and gastroenterology have become increasingly aligned over the last several decades because: “There is strong evidence that cognitive behavioral therapy; hypnotherapy; and mindfulness-based therapy directly target physiological processes by reducing arousal of the autonomic nervous system, decreasing the stress-response, and even reducing inflammation. This physiologic effect is largely due to the so-called brain-gut axis, which explains in part the common gastrointestinal consequences of stress and anxiety. Although the brain-gut axis is particularly important in the treatment of IBS [and ALL diseases having IBS associations], it is also relevant among patients with IBD, especially when considering the increased likelihood of an IBD flare in the context of chronic stress.^{84, 85} ”  [Ballou et al., 2017].

Note:  This section focuses on IBD studies since there are a lot of them!

Realize if it works for IBD patients that also have IBS, it should work for IBS alone, or other diseases also having IBS.  

Due to the length of this post, I cannot go into depth in this section.  Search Pubmed for further evidence insights for your disease of interest.  Given that this is new areas of research, try the info presented herein to see if it works for you.  What do you have to lose except IBS symptoms!  Help others; share your excperience and research in the comments!

• Cognitive Behavior Therapy, Hypnotherapy, Mindfulness-based therapy, Psychodynamic and Interpersonal therapies.  The evidence is supporting conceptualization of both IBS and IBD in a biopsychosocial model for symptom and gut inflammation mitigation.  Among patients with IBS, psychological interventions can serve as stand-alone therapies to decrease physical GI symptoms and improve overall functioning. Among patients with IBD, psychological interventions complement and may even optimize existing medical interventions in an effort to improve quality of life, medical adherence, and to help patients cope with the effects of a chronic illness.. There is a high rate of comorbidity between IBS and IBD, with 30–50% of patients diagnosed with IBD [endoscopically in remission] also reporting IBS-type symptoms.^{3, 4, 5}.  [Ballou et al., 2017].  A 2017 meta-analysis found short term benefit for cognitive therapy especially for IBD quality of life, anxiety and depression; the authors noted that continued treatment may provide long term benefit. [Gracie et al, 2017].
• Gut hypnotherapy.  Compelling data have been presented to suggest that gut hypnotherapy can reduce rectal mucosal inflammatory responses (IL-6, IL-13, TNF-α, substance P, and histamine) in patients with ulcerative colitis after just one session of hypnotherapy.⁶³   [Ballou et al., 2017].  Gut hypnotherapy had similar response as FODMAP for GI symptom relief BUT it had superior improvement in psychological indices and should be considered as an alternative to diet if available.  See [Hill et al., 2017] for references.  A starting place to learn what gut hypnotherapy (and other mind modalities) are is [Palsson, 2012 pdf “Hypnosis Treatment of Irritable Bowel Syndrome”].  Generally, the protocol is 7 scripted sessions, delivered word-for-word in 30–40 minutes by a therapist with accompanying audio recording script for a shorter daily home practice by the patient.  Details of imagery and mantra can be found in [Palsson et al., 2015].  Response rates in clinical trials have ranged from 53% to 94%.  Benefit was maintained at 6-, 10-, or 12-month follow-ups in different studies.  Later studies found success using only audios at home — DIY treatment — and that included DIY home treatment success using shorter audios for children! [Rutten et al, 2014]  and Hypnosis CDs noninferior to hypnotherapist for children with IBS, functional abdominal pain, 2017.
• “Subgroups of people with IBS distinguished by brain and microbial signatures may show different responsiveness to brain-directed therapies such as mindfulness-based stress reduction, cognitive behavioral therapy and targeted drugs.”  — See the “Impact” section of Gut microbes linked to brain structure in people with irritable bowel syndrome, May 2017 UCLA Newsroom article.
• Because psychological support is not currently part of clinical care, “Books (such as “Master Your IBS: An 8-Week Plan Proven to Control the Symptoms of IBS” ⁸⁹ or “Controlling IBS the Drug Free Way”⁹⁰) could bridge existing gaps in psychosocial care for GI disorders.”  [Ballou et al., 2017].  Note:  I have not read these but included them since [Ballou et al., 2017] specifically did so.
•  How effective are drugs for IBS?  Seems not very: “The physician should also emphasize the chronic nature of this syndrome [IBS] because nearly 75% of patients continue to have a diagnosis of IBS 5 years later.¹³ ”  [Occhipinti et al., 2012].  The [FDA Guidance, 2012} changed the endpoints for clinical IBS trials since prior studies looked at one endpoint which can’t adequately report patient perspective of the complex IBS symptomology.  From [Bellini et al., 2014], “Many different drugs have been suggested for IBS treatment, but their real benefits are very debatable. Based on the multifaceted pathophysiology of the disease, it is unlikely that drugs acting on a single receptor and/or a unique pathophysiologic mechanism would be able to provide any substantial therapeutic gain over a placebo in this disease, for which the placebo response rate is approximately 40%[14]. Essentially, we are still far from having discovered the magic bullet capable of treating all IBS symptoms. Although many papers have been published on this syndrome in recent years, up to now, many fundamental questions remain unanswered about its pathophysiology, diagnosis and therapy.”

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Conclusion

IBS is not a condition to ignore.  

Address it & Resolve it considering:  Diet (Fodmaps or similar and probiotics), mindfulness, cognitive behavioral, and/or target drugs because

• Many diseases, including those crossing the blood-brain-barrier, are associated with the condition, and resolution of the IBS may help prevent or mitigate the disease,

• There are a lot of inappropriate surgeries performed due to misdiagnosis (or poor management) of IBS, and

• It alters the brain emotion and sensory processing areas for those having IBS long term with early life stressors.

Best in health through awareness.  References are below my signature!

♥Last updated: August 30, 2018 at 7:22 am  added the FODMAPs Re-Introduction Guideline from Metagenics, Patient Information: Low FODMAP Diet for Irritable Bowel Syndrome.  Prior update Sept 5, 2017, was for minor editorial changes and to add the reminder DON’T OVERLOOK THE COMMENT SECTION to this post, it adds STUDIES PUBLISHING AFTER I WROTE THIS POST!  Prior update corrected SUMMARY section to read that the  Bristol Stool Chart has been around from 1997 (not 1999) since it FIRST PUBLISHED in 1997 [Bristol Stool Chart 1997 PDF].

References in order of appearance:

1. [Labus et al., 2017]  Differences in gut microbial composition correlate with regional brain volumes in irritable bowel syndrome, 2017.
2. [Occhipinti et al., 2012]  Irritable Bowel Syndrome: A Review and Update, 2012.  “The physician should also emphasize the chronic nature of this syndrome [IBS] because nearly 75% of patients continue to have a diagnosis of IBS 5 years later.¹³ “
3. [Bellini et al., 2014] Irritable bowel syndrome: A disease still searching for pathogenesis, diagnosis and therapy. “A disruption of the so called “brain-gut axis” that determines changes in the digestive motility and secretion, visceral hypersensitivity, abnormalities of enteroendocrine and immune systems, genetic factors, infections, alterations of the intestinal microbiota and inflammation could play a role in IBS… Many different drugs have been suggested for IBS treatment, but their real benefits are very debatable. Based on the multifaceted pathophysiology of the disease, it is unlikely that drugs acting on a single receptor and/or a unique pathophysiologic mechanism would be able to provide any substantial therapeutic gain over a placebo in this disease, for which the placebo response rate is approximately 40%[14]. Essentially, we are still far from having discovered the magic bullet capable of treating all IBS symptoms. Although many papers have been published on this syndrome in recent years, up to now, many fundamental questions remain unanswered about its pathophysiology, diagnosis and therapy.”
4. [Catassi et al., 2017]  The Low FODMAP Diet: Many Question Marks for a Catchy Acronym
5. [ McKenzie et al, 2016]  British Dietetic Association systematic review and evidence-based practice guidelines for the dietary management of irritable bowel syndrome in adults (2016 update).  In the UK, FODMAPS is the second-line dietary treatment for IBS.  The first-line is healthy eating.
6. UK evidence-based practice guidelines for the dietetic management of irritable bowel syndrome (IBS)
   in adults PDF.  The first British Dietetic Association (BDA) guidelines for the dietary management of irritable bowel syndrome (IBS) in adults was published in 2012.
7. [Magge et al., 2012] Low-FODMAP Diet for Treatment of Irritable Bowel Syndrome. 76% of IBS are helped on FODMAP.
8. [Bohn et al., 2015] Diet low in FODMAPs reduces symptoms of irritable bowel syndrome as well as traditional dietary advice: a randomized controlled trial.
9. [Staudacher et al., 2011] Comparison of symptom response following advice for a diet low in fermentable carbohydrates (FODMAPs) versus standard dietary advice in patients with irritable bowel syndrome.
10. IBS: FODMAPS, STOMACH MICROBIOME, RIFAXIMIN ANTIBIOTIC TREATMENT, SERIOUSLY?!?
11. [Hill et al., 2017] Controversies and Recent Developments of the Low-FODMAP Diet, 2017.
12. [Whiteley, 2016] On probiotics and irritable bowel syndrome (IBS)Gut microbes linked to brain structure in people with irritable bowel syndrome, May 2017 UCLA Newsroom article.
13. [Canavan et al., 2014] The epidemiology of irritable bowel syndrome 2014.  IBS affects up to 10 to 25% of the population.
14. [Ballou et al., 2017] Psychological Interventions for Irritable Bowel Syndrome and Inflammatory Bowel Diseases.
15. [Gulcan et al., 2009]   Increased frequency of prediabetes in patients with irritable bowel syndrome.  “Given the higher prediabetes occurrence in IBS, IBS may indirectly indicate a higher risk of Type 2 Diabetes.”
16. [Guo et al., 2014] Irritable bowel syndrome is positively related to metabolic syndrome: a population-based cross-sectional study. “The findings suggest that the treatment of irritable bowel syndrome may be a potentially beneficial factor for the prevention of metabolic syndrome.”
17. [Heitkemper et al., 2015]  Overlapping Conditions in Women With Irritable Bowel Syndrome, 2015.  Fibromyalgia (49% have IBS), chronic fatigue syndrome (51%), temporomandibular joint disorder (64%), and chronic pelvic pain (50%).
18. [Halpin et al., 2012] Prevalence of symptoms meeting criteria for irritable bowel syndrome in inflammatory bowel disease: systematic review and meta-analysis. 2012.  See too [Whiteley, 2017)  Intestinal dysbiosis, irritable bowel syndrome and ME/CFS.  “ Outside of the observations that particular types of bacteria seem to be more or less prevalent in cases of CFS/ME (yet again) I was rather more interested in the finding that over 40% of the cohort also met criteria for IBS. I say that on the basis that I’ve already talked about ‘abdominal discomfort syndrome’ as a feature of some CFS/ME (see here) alongside findings that certain foods *might* also play a role in the bowel symptoms accompanying CFS/ME (see here).
19. [Whiteley, 2017] Intestinal dysbiosis, irritable bowel syndrome and ME/CFS.
20. [Navarro et al., 2016]  Can probiotics benefit children with autism spectrum disorders?
21.  [Fond et al., 2014]  Anxiety and depression comorbidities in irritable bowel syndrome (IBS): a systematic review and meta-analysis. Dec 2014. See pdf here.  Patients with IBS had significantly higher levels of anxiety and depression than healthy controls. Anxiety and depression symptomatology should be systematically checked and treated in IBS patients, as psychological factors are important moderators of symptom severity, symptom persistence, decisions to seek treatment, and response to treatment.
22. [Marrie et al., 2015]  The incidence and prevalence of comorbid gastrointestinal, musculoskeletal, ocular, pulmonary, and renal disorders in multiple sclerosis: A systematic review. 2015.
23. [Mishima et al., 2017] The Prevalence of Constipation and Irritable Bowel Syndrome in Parkinson’s Disease Patients According to Rome III Diagnostic Criteria.  May 2017. The prevalence of constipation in PD patients has been reported in multiple studies, and ranged from 28.7 to 64.9%, based on various definitions of constipation [3, 5, 14]. The prevalence of constipation in PD patients in our cohort (27.1%) was lower than that in studies using other definitions for constipation. The result suggested that Rome III diagnostic criteria may more strictly define the diagnosis of constipation. Rome III diagnostic criteria are widely used and are currently the gold standard for the diagnosis of functional gastrointestinal disorders; however, few studies have investigated functional gastrointestinal disorders in the PD population using these criteria [3, 15, 16].
24. [Bristol Stool Chart 1997 PDF]  First published: Lewis SJ, Heaton KW (1997) Stool form scale as a useful guide to intestinal
    transit time. Scandinavian Jorunal of Gastroenterology 32: 920–4
25. [Blake et al, 2016] Validity and reliability of the Bristol Stool Form Scale in healthy adults and patients with diarrhoea-predominant irritable bowel syndrome. “There is little published evidence of efficacy for the most commonly used treatments. Thus, there is an urgent need to conduct clinical trials on existing and novel therapies.”
26. [Saps et al, 2016]  Recommendations for pharmacological clinical trials in children with irritable bowel syndrome: the Rome foundation pediatric subcommittee on clinical trials.
27. [Lasch et al, 2016]  Development of a New Instrument to Assess Stool Form and Consistency in Irritable Bowel Syndrome with Diarrhea  the modified version of Bristol Stool Chart if still confused.
28. [FDA Guidance, 2012} Guidance for Industry Irritable Bowel Syndrome — Clinical Evaluation of Drugs for Treatment.   FDA changed the endpoints for clinical IBS trials since prior studies looked at one endpoint which can’t adequately report patient perspective of the complex IBS symptomology.
29. [iffgd, 2016] IFFGD, Facts about IBS, 2016. 60% to 65% of individuals who report IBS in the community are female, 35% to 40% are male.  The cost to society in terms of direct medical expenses and indirect costs associated with loss of productivity and work absenteeism is considerable – estimates range from $21 billion or more annually.
30. [Corazziari et. al., 2008]  Gallstones, cholecystectomy and irritable bowel syndrome (IBS) MICOL population-based study. IBS patients are more likely than others to have their gall bladder removed unnecessarily and with no positive effect on their IBS symptoms.  IBS have an increased risk of cholecystectomy that is not due to an increased risk of gallstones, but rather to abdominal pain, awareness of having gallstones, and inappropriate surgical indications.
31. [Palma et al., 2015] Microbiota and host determinants of behavioural phenotype in maternally separated mice, July 2015
32. [Bremner et al., 2011]  Psychometric Properties of the Early Trauma Inventory–Self Report, 2011. The ETI-SR follows the ETI (Bremner et al., 2000) format of four domains of childhood traumatic events: general trauma (31 items), physical (9 items), emotional (7 items), and sexual abuse (15 items). Physical abuse is defined as physical contact, constraint, or confinement, with intent to hurt or injure. Emotional abuse is verbal communication with the intention of humiliating or degrading the victim. Sexual abuse is unwanted sexual contact performed solely for the gratification of the perpetrator or for the purposes of dominating or degrading the victim.
33. Hearburn Drugs, Dementia, Alzheimer’s Risk to All? T2D, Is it the Canary in the Coal Mine!?!  PPIs have a disrupted microbiome — see this post; medications may need to be further stratified when evaluating microbiome.
34. Gut microbes linked to brain structure in people with irritable bowel syndrome, May 2017 UCLA Newsroom article.
35. Bacteria Could Be Responsible For Shifts in Brain Structure in People With IBS, ScienceAlert May 2017.
36. [Shepherd et al., 2013] Short-Chain Carbohydrates and Functional Gastrointestinal Disorders.  Summary of accumulating body of evidence, based on observational and comparative studies, and on randomized-controlled trials that supports the notion that FODMAPs trigger gastrointestinal symptoms in patients with functional bowel disorders.
37. Monash University, Dietary Fibre and natural prebiotics for gut health: FAQs. 
38. A FODMAP re-introduction guideline can be found at:  Metagenics, Patient Information: Low FODMAP Diet for Irritable Bowel Syndrome.
39. [Maagaard et al., 2016] Follow-up of patients with functional bowel symptoms treated with a low FODMAP diet.  The FODMAP diet successfully manages over 86% of IBS/IBD patients, having partial (54%) or full (32%) efficacy.  From the study: “Satisfaction with dietary management was seen in 83 (70%) IBS patients and 24 (55%) IBD patients. Eighty-four percent of patients lived on a modified low FODMAP diet (LFD), where some foods rich in FODMAPs were reintroduced, and 16% followed the LFD by the book without deviations. Wheat, dairy products, and onions were the foods most often not reintroduced by patients.”
40. Have IBS? Try FODMAPs. The Joslin Diabetes Center, a teaching and research affiliate of Harvard Medical School, recommends trying FODMAP for diabetes.
41. The book, The Complete Low-FODMAP Diet: A Revolutionary Plan for Managing IBS and Other Digestive Disorders, by Drs. Sue Shepherd and Peter Gibson is a reference guide and road map for the low-FODMAP diet.
42. [de Roest et al., 2013] The low FODMAP diet improves gastrointestinal symptoms in patients with irritable bowel syndrome: a prospective study, 2013 and see [Barrett et al., 2007] Clinical Ramifications of Malabsorption of Fructose and Other Short-chain Carbohydrates, 2007.  FODMAPS works since 75.6%, 37.8% and 13.3% of [IBS] patients had fructose, lactose malabsorption or small intestinal bacterial overgrowth respectively.
43. [Henström et al, 2016]  Functional variants in the sucrase–isomaltase gene associate with increased risk of irritable bowel syndrome, see here for full text.  Also see the Healio article,  IBS linked to genetic defects in carbohydrate digestion.
44. [Zhang et al, 2016]  Effects of probiotic type, dose and treatment duration on irritable bowel syndrome diagnosed by Rome III criteria: a meta-analysis. June 2016.  Review discusses evidence, from human and animal studies, of a potential role of probiotics in the treatment of gastrointestinal symptoms in children with autism.
45. CLA GRASSFED SCD YOGURT BENEFITS, CYTOKINE STUDIES: ERIVAN & WHOLE FOODS 365.  Link for how I make SCD Yogurt.
46. Pubmed search for science literature.
47. [Gracie et al, 2017] Effect of psychological therapy on disease activity, psychological comorbidity, and quality of life in inflammatory bowel disease: a systematic review and meta-analysis.  
48. [Palsson, 2012 pdf, “Hypnosis Treatment of Irritable Bowel Syndrome”] is a start for understanding gut hypnotherapy and other mind modaltities.
49. [Palsson, 2015]  Hypnosis and Guided Imagery Treatment for  Gastrointestinal Disorders: Experience With Scripted Protocols Developed at the University of North Carolina.  Response rates in clinical trials have ranged from 53% to 94%, and the therapeutic benefits have been shown to be well
    maintained at 6-, 10-, or 12-month follow-ups in different studies.
50. [Rutten et al, 2014] Gut-directed hypnotherapy in children with irritable bowel syndrome or functional abdominal pain (syndrome): a randomized controlled trial on self exercises at home using CD versus individual therapy by qualified therapists 
51. Hypnosis CDs noninferior to hypnotherapist for children with IBS, functional abdominal pain, 2017.