Dysbiosis and Low FODMAP, Plus Other Research Updates

Efficacy of fecal microbiota transplantation for patients with irritable bowel syndrome at three years after transplantation

• 125 IBS patients randomized to: 
  • Placebo
  • Single FMT 
• After 3 years, patients who received FMT experienced:
  • Higher response rates (68% FMT vs  27% placebo)
  • Less fatigue
  • Greater quality of life 
  • NO side effects
• Commentary: FMT led to long-term, sustained improvement in patients with IBS. 

 

Exocrine Pancreatic Insufficiency is Undiagnosed in Some Patients with Diarrhea-Predominant Irritable Bowel Syndrome Using the Rome IV Criteria

• 140 patients with IBS-D, all tested for exocrine pancreatic insufficiency (EPI)
  • Fecal elastase-1 <100 µg/g was considered positive
• In the 5% of patients that tested positive for EPI, dyspepsia was the most common symptom
• Treatment with pancreatic enzymes led to improved:
  • IBS severity
  • Abdominal pain 
  • Bloating
  • Stool consistency
• Commentary: EPI is relatively rare (5%) in patients with IBS-D, however it may be an important differential diagnosis to consider in patients with non-responsive diarrhea and dyspepsia.

 

Internet-Delivered Cognitive Behavioral Therapy in Patients With Irritable Bowel Syndrome: Systematic Review and Meta-Analysis

• 9 RCTs on patients with IBS
• Internet-based cognitive behavioral therapy (CBT) led to improved: 
  • IBS symptoms (moderate effect size) 
  • Quality of life (moderate effect size) 
• Commentary: Internet-based CBT may be a cost-effective treatment option for patients with IBS. 

 

The effectiveness of microencapsulated sodium butyrate at reducing symptoms in patients with irritable bowel syndrome

• 2,990 IBS patients, treated with sodium butyrate (150 mg twice/day) 
• After 3 months, butyrate led to improved: 
  • Abdominal pain (5/10 severity → 2/10 severity) 
  • Gas (6 → 2) 
  • Diarrhea (5 → 2) 
  • Constipation (4.5 → 2.5)
  • Stool urgency (4 → 1.5) 
  • Nausea (1.5 → 0.5)
  • Quality of life (6.6/10 → 3.6/10) 
• 94% of participants reported they would continue using butyrate 
• Commentary: Butyrate supplementation led to improvements in IBS symptoms. Keep in mind there was no placebo group, and we know there is a strong placebo-response in this patient population. 

 

A Low-FODMAP Diet Provides Benefits for Functional Gastrointestinal Symptoms but Not for Improving Stool Consistency and Mucosal Inflammation in IBD: A Systematic Review and Meta-Analysis

• 9 studies, 446 participants with IBD 
• Compared to control groups, the low FODMAP diet (LFD) led to improved:
  • IBD symptom score (large effect size) 
  • Crohn’s disease symptom score (large effect size) 
• LFD did NOT improve:
  • Stool consistency 
  • Ulcerative colitis symptom score 
  • Fecal calprotectin 
• Commentary: LFD led to improved overall symptoms of IBD, but NOT stool consistency or fecal calprotectin. 

 

The prevalence of intestinal dysbiosis in patients referred for antireflux surgery

• Retrospective study of 104 patients referred for reflux correction surgery
• All had lactulose breath test for SIBO
• 39.4% had SIBO, 35.6% had methanogen overgrowth
• Those w/ dysbiosis were more likely to have:
  • Bloating (75% vs 49%)
  • Belching (60% vs 34%)
• Commentary: SIBO may be a contributing factor to reflux. 

 

This study found dysbiosis was more frequent in subjects positive for anti-CdtB antibodies, but antibodies did not discriminate. 

• It also found antibodies in 64% of healthy controls. 
• This strengthens previous mention that dysbiosis could be an underlying cause of antibodies. 

Piggy backing off of Joe’s study

• 67 IBS patients randomized to standard IBS or Low FOD diet x4 weeks
• GA-map Dysibosis test performed at baseline could discriminate who would be likely to benefit from Low FOD diet
  • Non-responders to a low FODMAP diet (but not a traditional IBS diet) had higher DI scores than responders at baseline 
• A low FODMAP intervention was associated with an increase in Dysbiosis Index (DI) scores in 42% of patients; while decreased DI scores were recorded in 33% of patients following a traditional IBS diet. → how can we account for this discrepancy between lab results and clinical outcomes (in other words, their test got worse but we have plenty of evidence that suggests a LFD helps)

 

Long-Term Effects of a Web-Based Low-FODMAP Diet Versus Probiotic Treatment for Irritable Bowel Syndrome, Including Shotgun Analyses of Microbiota: Randomized, Double-Crossover Clinical Trial

• Cross-over study of 34 IBS patients, 6 healthy controls
• Randomized to probiotic (VSL#3) or low FODMAP diet x4 weeks, then cross-over to the other intervention
• Results:
  • 55% response rate for LFD
  • 62% response rate for probiotics
  • No difference in IBS symptom reduction between two groups (-127 LFD, -130 probiotics)
  • Response to treatment was NOT able to be predicted using metagenomic microbiome sequencing
• Commentary: This study (although small) shows the efficacy of both probiotics and a LFD for IBS. It also suggests that changes in the microbiota are not predictive of treatment success. 

 

A Systematic Review and Meta-analysis of Randomized Control Trials: Combination Treatment With Proton Pump Inhibitor Plus Prokinetic for Gastroesophageal Reflux Disease

• 16 studies, 1,446 participants w/ GERD
  • 727 receiving PPI only
  • 719 receiving PPI + prokinetic
• The PPI + prokinetic resulted in greater improvement of GERD symptoms regardless of prokinetic type or GERD severity
• No difference in quality of life or adverse effects
• Commentary: PPI + prokinetic is superior to PPI alone in those w/ GERD.
  • Dr. Rusico wanted to add he has mixed emotions about prokinetics.  He quickly checked this study and had his hesitancy reinforced by this quote
    • 4 In Asia, the most commonly used prokinetics are mosapride, itopride, and domperidone. However, another prokinetic agent, cisapride, has been withdrawn from the market owing to its association with fatal heart arrhythmia
  • We aim to treat dysmotility further upstream, although still lacking robust data to support our approach. 

 

A Meta-Analysis of Microbial Therapy Against Metabolic Syndrome: Evidence From Randomized Controlled Trials

• 42 RCTs examining effect of microbial therapy (probiotics, prebiotics, FMT) for improving metabolic syndrome
• Microbial therapy resulted in:
  • Reduced waist circumference (effect size -0.26)
  • Reduced fasting glucose (effect size -0.35)
  • Reduced total cholesterol (effect size -0.36)
  • Reduced LDL-C (effect size -0.42)
  • Reduced triglycerides (effect size -0.38)
  • Increased HDL-C (0.28)
  • No change in A1C or systolic blood pressure
• Commentary: This meta-analysis suggested that GI therapies can improve most metabolic parameters w/ a small effect size. 

 

Effect of continuous positive airway pressure on gastroesophageal reflux in patients with obstructive sleep apnea: a meta-analysis

• 10 studies, 272 patients w/ sleep apnea
• CPAP therapy reduced reflux symptoms
  • More reduction w/ longer use of CPAP
• Commentary: Given that reflux is common in those w/ sleep apnea, treating sleep disordered breathing may be an important part of getting optimal GI health improvement. 

 

Feasibility of a low FODMAPs diet without initial dietician intervention in the management of patients with irritable bowel syndrome: a prospective study

• 35 IBS patients, all given low FODMAP diet handout
• After 6 weeks: 
  • 52% followed LFD regularly
  • 28% sometimes followed
  • 20% barely/did not follow
• All symptoms (except constipation) decreased significantly
• 77% reported symptom satisfaction
• Commentary: This study showed a large response rate despite a lack of full diet adherence. This is why we at the clinic do not push our patients into 100% compliance with diets – this can often lead to anxiety and unwarranted fear around food. 

 

Effectiveness of Crohn’s Disease Exclusion Diet for Induction of Remission in Crohn’s Disease Adult Patients

• 32 Crohn’s Disease patients put on Crohn’s Disease Exclusion Diet (50% of calories and elemental diet (50% of calories)
• After 3 months:
  • Clinical remission in 82%
  • Lower calprotectin
• Commentary: A CDED + partial elemental dieting has a very notable positive effect on those w/ Crohn’s Disease. 

 

Psychological Interventions for Irritable Bowel Syndrome: A Meta-Analysis of Iranian Randomized Trials

• 20 RCTs
• Psychological interventions (e.g. meditation, relaxation) had a large effect size at improving:
  • IBS symptom severity ( effect size -1.2)
  • Anxiety (-0.97)
  • Depression (-0.86)
  • Quality of life (-0.64)
• Commentary: Addressing limbic imbalances can be a very impactful line of therapy for improving IBS. 

 

Helicobacter Pylori CagA Virulence Gene and Severe Esophagastroduodenal Diseases: Is there an association?

• Gastric biopsies from 117 patients w/ various esogastroduodenal diseases
• H pylori detected in 66% of patients, 80.5% had cagA virulence gene
• The cagA gene was NOT associated w/ severity of disease
• Commentary: Contrary to popular belief, the cagA virulence gene was not associated with upper GI disease severity in this study.

• Elemental Heal
• Dr. Ruscio’s, DC Resources