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Featured Studies

• The effect of low FODMAP diet with and without gluten on irritable bowel syndrome: A double blind, placebo controlled randomized clinical trial
  • 49 IBS patients, randomized to a:
    • Low FODMAP diet w/ gluten-free powder (rice powder) 
    • Or low FODMAP diet w/ gluten powder (5g/d)
  • Both groups had similar rates of:
    • Improved IBS symptoms (-32% gluten vs 49% gluten-free group)
    • Abdominal pain intensity (-45% vs -52%)
    • Abdominal pain frequency (-26% vs -46%)
    • Distension (-29% vs -63%)
  • Commentary: Even though there was a trend towards greater improvement in the gluten-free group, this difference was NOT statistically significant.

• The effectiveness of rotating versus single course antibiotics for small intestinal bacterial overgrowth
  • 223 patients w/ SIBO (by glucose breath test)
  • Patients were treated either with a single antibiotic (quinolone or azole) or rotating antibiotics (quinolone and azole, one after the other) for 10 consecutive days per month for 3 months. 
  • The rotating antibiotic group had higher rate of clinical remission (70% vs 50.8%)
  • Clinical remission was associated with an improvement in quality of life and bloating
  • Commentary: Rotating antimicrobials may be superior for treating SIBO. This study showed an association between the eradication of SIBO and the improvement of quality of life and bloating.

Gastrointestinal Studies

• Efficacy of Probiotics in Rheumatoid Arthritis and Spondyloarthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
  • 13 studies, including 344 patients w/ rheumatoid arthritis (RA) and 197 w/ spondyloarthritis (SpA)
  • Examined effect of lactobacillus and Bacillus probiotics species
  • Probiotic supplementation led to:
    • Decrease in CRP (-3.04 mg/dL) in those w/ RA
    • NO difference in those w/ SpA
  • Commentary: In this meta-analysis, probiotics led to more improvement in those w/ RA as compared to those w/ SpA.

• Predictors of Symptom-Specific Treatment Response to Dietary Interventions in Irritable Bowel Syndrome
  • Aim: Investigate predictors of symptom improvement after dietary change in those w/ IBS
  • 67 IBS patients, randomized to low FODMAP diet or traditional diet x4 weeks
  • Factors associated w/ more symptom improvement:
    • Less severe dysbiosis (per GA-map Dysbiosis test)
    • Higher energy intake at baseline (less food restriction)
  • More psychological distress associated with LESS symptom improvement
  • Commentary: Those who may respond better to a low FODMAP (or another IBS diet) include: those w/ less dysbiosis, less anxiety, and who are able to tolerate more foods at baseline.

• The Effects of One Anastomosis Gastric Bypass Surgery on the Gastrointestinal Tract
  • Prospective study of 32 patients who all had one anastomosis gastric bypass (OAGB) bariatric surgery
  • 6 months after surgery:
    • Increase in SIBO positive (0% to 37%)
      • SIBO was associated w/ lower fiber intake and higher vitamin A deficiency 
    • Increase in exocrine pancreatic insufficiency (0% to 26%)
    • Decrease in microbial diversity
  • Commentary: Relatively high rates of SIBO and exocrine pancreatic insufficiency were found after bariatric surgery at a 6 month follow up.

• Metabolic phenotypes and risk of colorectal cancer: a systematic review and meta-analysis of cohort studies
  • Analysis of 7 cohorts, 760,000 participants
  • Compared with healthy normal-weight people, those w/ obesity and/or have poor metabolic health have a higher rate of colorectal cancer (OR 1.19)
    • This relationship was stronger for males than females
  • Commentary: Being obese or having poor metabolic health is a risk factor for colorectal cancer.

• Fecal microbiota transplant as a potential treatment for Parkinson’s disease – A case series
  • 6 patients w/ Parkinson’s disease, treated with FMT
  • At a 4 week follow up: motor, non-motor, and constipation scores were improved in 5 of 6 patients
  • 1 patient had an adverse event

• Yield of testing for micronutrient deficiencies associated with pancreatic exocrine insufficiency in a clinical setting: An observational study
  • 112 patients w/ suspected maldigestion tested for exocrine pancreatic insufficiency (EPI) and micronutrient deficiencies 
  • 36.6% had EPI
  • Those w/ EPI had a much higher rate of micronutrient deficiencies (41.5% EPI, vs 5.6% non-EPI)
    • Most common micronutrient deficiencies: selenium, magnesium
  • Commentary: Micronutrient deficiencies are relatively common in those w/ EPI.

• Additive effect of probiotics on 5-aminosalicylic acid therapy in patient with ulcerative colitis
  • 118 patients w/ mild-to-moderate ulcerative colitis (UC)
  • Randomized to E. coli Nissle 1917 probiotic or placebo
  • After 8 weeks of supplementation, the probiotic group had:
    • NO difference in IBD symptom score
    • HIGHER clinical response (39.7% vs 21.7%)
    • HIGHER endoscopic remission (46.4% vs 27.1%)
  • Commentary: This study found that the probiotic, E. coli Nissle 1917 was effective in improving UC.

• The role of calcium and vitamin D dietary intake on risk of colorectal cancer: systematic review and meta-analysis of case-control studies
  • 37 studies examining the effect of calcium and Vit D intake on colorectal cancer (CRC) risk
    • 32 studies for calcium: 24,353 CRC cases, 30,650 controls
    • 23 studies for Vit D: 19,076 CRC cases, 36,746 controls
  • Higher dietary intake of calcium was associated w/ lower CRC (OR 0.94) 
  • Higher intake of Vit D was associated with w/ lower CRC (OR 0.96)
  • Commentary: Higher intake of calcium and Vit D was associated with a slightly lower (4-6% reduction) risk of CRC.

• Vitamin D supplementation in people with IBS has no effect on symptom severity and quality of life: results of a randomised controlled trial
  • 135 IBS patients, randomized to placebo or Vit D (3,000 IU/d)
  • 60% of participants were vitamin D deficient or insufficient at baseline
  • After 12 weeks, the Vit D group had:
    • Higher Vit D blood levels
    • NO difference in change of IBS symptoms score (-62 vs -75 in placebo)
    • NO difference in quality of life (-7.7 vs -11.3 in placebo)
  • Commentary: This study showed NO beneficial effect of Vit D for IBS.

• Effects of vitamin D supplementation on blood markers in ulcerative colitis patients: a systematic review and meta-analysis
  • 7 studies, 539 participants, examining effect of Vit D on ulcerative colitis
  • Vitamin D supplementation led to:
    • Lower ESR (effect size -1.1)
    • Lower CRP (-0.4)
    • No difference in disease severity
  • Commentary: Vit D supplementation led to improvement of inflammatory markers, but no change in disease activity in those w/ ulcerative colitis.

• The development of the cure of the functional intestinal disorder based on the differences of gut microbiota in aged patients: A randomized clinical trial
  • 60 patients w/ chronic constipation, randomized to:
    • Laxatives only
    • Laxatives + probiotics
  • After 12 weeks, the combined laxative + probiotics group had:
    • No greater improvement in stool frequency or consistency

• Antibiotics for induction and maintenance of remission in ulcerative colitis: systematic review and meta-analysis
  • 13 RCTs, 785 participants
  • Compared to placebo, antibiotic administration resulted in a clinical improvement in those w/ ulcerative colitis (OR 1.74)
  • Commentary: Antimicrobials may improve ulcerative colitis.

• Oral CBD-rich Cannabis Induces Clinical but Not Endoscopic Response in Patients with Crohn’s Disease, a Randomised Controlled Trial
  • 56 patients w/ Crohn’s Disease (CD), randomized to placebo or oral CBD oil
  • After 8 weeks of supplementation, the CBD group had:
    • Lower disease activity
    • More improvement in quality of life
    • NO difference in endoscopic findings
    • NO change in CRP, calprotectin
  • Commentary: CBD supplementation led to improved symptoms and quality of life, with no change in endoscopic findings or inflammatory markers in those w/ CD.

• Lyophilised oral faecal microbiota transplantation for ulcerative colitis (LOTUS): a randomised, double-blind, placebo-controlled trial
  • 35 patients w/ active ulcerative colitis (UC) all had 2 weeks of antibiotics (amoxicillin, metronidazole, and doxycycline)
  • Then randomized to placebo or FMT capsules x8 weeks
  • After 8 weeks, those who responded to the FMT were randomized to withdrawal or continuation of FMT for another 48 weeks
  • After 8 weeks of supplementation, the FMT group had:
    • Higher rate of clinical and endoscopic remission (53% vs 15%)
    • No difference in adverse event rate (67% vs 85%)
  • Those who continued FMT x48 weeks had higher rate of remission (100% vs 0%)
  • Commentary: FMT capsules are beneficial for those w/ UC. However, it looks as though the benefit may be only transitory while the patient is taking FMT.

• The prevalence of small intestinal bacterial overgrowth in diabetes mellitus: a systematic review and meta-analysis
  • 14 studies, 1,417 diabetic patients, 649 healthy controls
  • The pooled prevalence of SIBO in diabetic patients was 29% (OR 2.91 compared to controls)
  • Commentary: Those w/ diabetes have a 2.9x higher risk of SIBO compared to healthy controls.

• Barrett’s esophagus surveillance in a prospective Dutch multi-center community-based cohort of 985 patients demonstrates low risk of neoplastic progression
  • 985 Barrett’s esophagus patients followed x7.9 years
  • 67 patients were diagnosed with high-grade dysplasia or cancer
  • Progression rate to cancer = 0.78% per patient-year
  • Commentary: Risk of progression to pre-cancer or cancer in those w/ Barrett’s esophagus is low.

Thyroid & Hormones Studies

• The effect of dehydroepiandrosterone (DHEA) supplementation on estradiol levels in women: A dose-response and meta-analysis of randomized clinical trials
  • 21 studies, 1,223 participants
  • DHEA supplementation led to higher estradiol levels in women >60 yo (+9.56 pg/mL)
    • Especially when used at 50 mg/d and more than 26 weeks
  • Commentary: DHEA supplementation may improve estradiol levels in post-menopausal women.

• Lipid profile in mild subclinical hypothyroidism: systematic review and meta-analysis
  • 35 studies
  • Mild subclinical hypothyroidism (TSH <10) was associated with poorer cardiometabolic markers:
    • Total Cholesterol (+12.8 mg/dL)
    • LDL-C (+11 mg/dL)
    • Triglycerides (+19.3 mg/dL)
    • HDL-C (-1.8 mg/dL)
  • No difference in ApoB
  • Commentary: Mild subclinical hypothyroidism is associated with a poorer lipid profile.

• Effects of Chronic Suppression or Oversuppression of Thyroid-Stimulating Hormone on Psychological Symptoms and Sleep Quality in Patients with Differentiated Thyroid Cancer
  • Prospective study of 79 healthy controls, 191 patients w/ thyroid cancer on suppressive thyroid medication (thyroid medication meant to suppress TSH below reference range)
  • Compared to healthy controls, those on thyroid suppressive therapy had:
    • More symptoms
    • Worse sleep
  • Those w/ lower TSH had higher anxiety scores
  • Commentary: Over-suppressing TSH is associated with worse sleep and more anxiety.

Diet & Lifestyle Studies

• An Open-Label, Pilot Trial of HRG80™ Red Ginseng in Chronic Fatigue Syndrome, Fibromyalgia, and Post-Viral Fatigue
  • Open-label prospective study of 188 w/ chronic fatigue/fibromyalgia
  • All took red ginseng supplementation
  • After 30 days of supplementation:
    • 67% increase in energy
    • 48% increase in mental clarity
    • 46% improvement in sleep
    • 72% increase in physical stamina
    • 33% decrease in pain
  • Commentary: This study showed that red ginseng supplementation led to a significant improvement in chronic fatigue/fibromyalgia. Note that there was no testing performed before supplementation w/ this adaptogen.

• Intermittent fasting and continuous energy restriction result in similar changes in body composition and muscle strength when combined with a 12 week resistance training program
  • 34 untrained participants allocated to 12 weeks of resistance training, and randomized to either:
    • Continuous energy restriction (-20% Calories)
    • Or 5:2 intermittent fasting (-70% Calories x2 days, normal Calories x5 days)
  • Both groups ate a moderate amount of protein (>1.4g/kg)
  • After 12 weeks, both groups had improvement of:
    • Lean body mass (+3.7%)
    • Weight (-4.6%)
    • Fat (-24.1%)
    • Muscular strength
  • The continuous energy restriction group had a greater increase in muscle surface area
  • Commentary: When using both resistance training and adequate protein, an intermittent fasting protocol leads to similar improvements in lean body mass, fat loss, and strength as compared to continuous energy restriction.

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Featured Study

• Clinical Outcomes After Discontinuation of Thyroid Hormone Replacement: A Systematic Review and Meta-Analysis 
  • 17 studies, 1,103 patients
  • About 1/3 of patients undergoing thyroid hormone discontinuation remained euthyroid at follow-up (37.2%)
  • Patients with a previous diagnosis of overt hypothyroidism were less likely to remain euthyroid (11.8%) than patients with a prior diagnosis of subclinical hypothyroidism (35.6%)
  • Commentary: A substantial amount of patients on thyroid hormone remain euthyroid after discontinuing thyroid replacement therapy.

Gastrointestinal Studies

• Perturbations in Gut Microbiota Composition in Psychiatric Disorders: A Review and Meta-analysis
  • 34 studies, 1,519 patients w/ psychiatric illness, 1,429 control participants
  • Those w/ a psychiatric illness had a lower microbial diversity and richness in most but not all psychiatric diagnosis
  • Commentary: This highlights the gut-brain connection.

• A Randomized Trial Comparing the Specific Carbohydrate Diet to a Mediterranean Diet in Adults With Crohn’s Disease
  • 194 Crohn’s Disease (CD) patients randomized to mediterranean diet (MD) or specific carbohydrate diet (SCD)
  • After week 6, the SCD group had, NO difference in:
    • Clinical remission rate (46.5% vs 43.5%)
    • Fecal calprotectin remission (34.8% vs 30.8%)
    • CRP remission rate (5.4% vs 3.6%)
  • Commentary: This study showed NO difference between the MD and SCD for improving Crohn’s Disease. This is why we at the clinic follow a step-wise approach for dietary interventions (e.g. first start with a paleo diet before moving to a SCD).

• Evolution of gastroesophageal reflux disease symptoms after bariatric surgery: A dose-response meta-analysis
  • 31 studies, 5,295 patients who had bariatric surgery
  • 63.4% experienced improvement of reflux symptoms
  • More improvements for Roux-en-Y gastric bypass

• Probiotic improves symptomatic and viral clearance in Covid19 outpatients: a randomized, quadruple-blinded, placebo-controlled trial
  • 293 participants w/ symptomatic COVID, randomized to probiotic or placebo
  • After 30 days, the probiotic group had:
    • Higher remission rate (53% vs 28%)
    • Reduced nasopharyngeal viral load
    • Less digestive and non-digestive symptoms
    • Higher IgG and IgM SARS-CoV2 antibodies
  • Commentary: High-quality study suggesting benefits of probiotics for COVID.

• A randomized double-blind placebo-controlled crossover pilot study: Acute effects of the enzyme α-galactosidase on gastrointestinal symptoms in irritable bowel syndrome patients
  • 20 patients w/ IBS, randomized to placebo or α-galactosidase enzyme (Nogasin®, 1200 GaIU/meal) x3 standardized meals, then crossed over to other treatment arm
  • Breath test measured every 30 minutes x7.5 hrs
  • No difference in GI symptoms or hydrogen/methane levels between groups
  • Commentary: In this cross-over pilot study, α-galactosidase enzyme was not superior to placebo.

• A Single Fasting Exhaled Methane Level Correlates With Fecal Methanogen Load, Clinical Symptoms and Accurately Detects Intestinal Methanogen Overgrowth
  • Assessed the viability of using a single fasting breath methane level to diagnose intestinal methanogen overgrowth (IMO)
  • Using the cutoff of ≥10 ppm, a single methane measurement had a:
    • Sensitivity of 86.4% 
    • Specificity of 100% for diagnosing IMO
    • And was associated with constipation
  • Antibiotics led to a decrease of the fasting single methane measurement
  • Single methane measurement was associated with higher stool M. smithii levels
  • Commentary: A single methane breath level may be an accurate predictor of IMO, and correlates w/ M. smithii levels in the stool. 
  • Dr. Ruscio has been critical of some of Rao’s work on probiotics, however this study deserves praise as it has much clinical relevance.

• Regular Use of Proton Pump Inhibitor and the Risk of Inflammatory Bowel Disease: Pooled Analysis of 3 Prospective Cohorts
  • Pooled analysis of 3 cohorts, including 647,407 participants
  • Regular use of PPIs consistently showed a significantly positive association with both Crohn’s Disease and Ulcerative Colitis (HR 1.42)

• Systematic review with meta-analysis: the accuracy of serological tests to support the diagnosis of coeliac disease
  • 113 studies, 28,338 participants
  • Accuracy of celiac disease tests measured:
    • IgA anti-tissue transglutaminase:
      • Sensitivity: 90.7%
      • Specificity: 87.4%
    • IgA endomysial antibodies:
      • Sensitivity: 88%
      • Specificity: 99.6%
  • Commentary: tTG IgA is more sensitive, and endomysial IgA is more specific for assessing celiac disease.

• A low FODMAP diet reduces symptoms in treated celiac patients with ongoing symptoms – a randomized controlled trial
  • 70 celiac disease patients w/ persistent symptoms, randomized to low FODMAP diet, or gluten-free diet (control)
  • After 4 weeks, the low FODMAP diet had:
    • Lower IBS symptoms 
    • Less celiac disease symptom score 
  • Commentary: Those w/ celiac disease and persistent symptoms may benefit from a low FODMAP diet.

• Frequency of Celiac Disease in Patients With Chronic Diarrhea
  • Cross-sectional study of 188 patients w/ chronic diarrhea (>3 months)
  • Celiac disease was found in 12.2% of the individuals
  • 21% of those w/ a family history of celiac disease developed the disease
  • Commentary: A small (but notable) portion of those w/ chronic diarrhea may have diarrhea, especially if there is a family history of the disease.

Autoimmunity Study

• Human Herpesvirus 6 Infection and Risk of Chronic Fatigue Syndrome: A Systematic Review and Meta-Analysis
  • 11 studies
  • Human herpesvirus 6 infection was associated w/ chronic fatigue

Thyroid & Hormones Studies

• Vitamin D and thyroid disorders: a systematic review and Meta-analysis of observational studies
  • Examine the relationship between vitamin D levels and thyroid disorders
  • Serum vit D levels were significantly lower in those with:
    • Autoimmune thyroid disease (-3.1 ng/dL)
    • Hashimoto’s (-6.1 ng/dL)
    • Hypothyroidism (-13.4 ng/dL)
  • No difference in those w/ Graves’ disease
  • Commentary: This study showed lower Vit D levels in those w/ thyroid dysfunction, except for Graves’ disease.

• The effect of vitamin D supplementation on clinical symptoms and metabolic profiles in patients with endometriosis
  • 60 women w/ endometriosis, randomized to Vit D (50,000 IU every 2 weeks) or placebo
  • After 12 weeks of supplementation, the Vit D group had:
    • Reduced pelvic pain
    • Reduced CRP (-0.64 mg/L)
    • Increase in total antioxidant capacity
  • Commentary: Vit D may be beneficial for those w/ endometriosis.

• Effect of the phthalates exposure on sex steroid hormones in the US population
  • 16 urinary phthalate metabolites and serum sex hormones measured in 1,768 adults
  • Higher phthalate levels were associated w/ lower serum testosterone levels in males
  • Commentary: Toxic burden may contribute to sex hormone dysfunction. Unfortunately, the effect size was unavailable in this study. 

Diet & Lifestyle Studies

• Sleep disordered breathing as a risk factor for unnecessary pacemaker implantation
  • 207 patients w/ cardiovascular disease at high risk for sleep disordered breathing (SDB)
  • SDB confirmed in 84.5% (36% had severe SDB)
  • Severe SDB was a predictor of the following during sleep:
    • Third-degree AV block (OR 11.6)
    • Second-degree AV block type 2 (Mobitz) (OR 4.5)
    • Sinus bradycardia below 40 bpm (OR 3)
  • Commentary: SDB may be a risk factor for heart arrhythmias. 

• Improvements in Cognitive Function and Quantitative Sleep EEG in OSA after Six Months of CPAP Treatment
  • 162 sleep apnea patients, measured cognitive function and EEG measurements before and after CPAP
  • After 6 months of CPAP therapy
    • ALL cognitive domains improved
    • Enhanced EEG measurements
  • Commentary: Treating sleep disordered breathing may improve cognitive function.

• A High Protein Diet Is More Effective in Improving Insulin Resistance and Glycemic Variability Compared to a Mediterranean Diet-A Cross-Over Controlled Inpatient Dietary Study
  • 16 obese women, randomized to high protein (HP) or Mediterranean diet x10 days, then crossed over to the other diet x10 days
  • Compared to the Mediterranean diet, the HP diet led to:
    • Lower insulin (-7  µIU/mL)
    • Less insulin resistance (HOMA-IR -1.8)
    • Less glycemic variability

• Effects of Periodization on Strength and Muscle Hypertrophy in Volume-Equated Resistance Training Programs: A Systematic Review and Meta-analysis
  • 35 studies comparing periodized vs non-periodized strength training
  • Periodized strength training had:
    • Better 1-rep max strength (effect size 0.31) in trained participants
    • NO difference in muscle hypertrophy
  • Commentary: Following a periodized (change in volume and intensity over time) strength training program may be better, as compared to non-periodized training. However, this may not make a big difference in an untrained population. 
  • Dr. Ruscio wanted to make the connection that periodization might make exercise unnecessarily complicated, much like some practices in GI and FM care.

• 3-Week passive acclimation to extreme environmental heat (100± 3 °C) in dry sauna increases physical and physiological performance among young semi-professional football players
  • 36 male football players, randomized to no therapy or sauna therapy (3x/week for 9 total sessions)
  • The sauna group had:
    • Decreased body weight and body fat
    • Increased hamstring flexibility and work capacity
    • Better respiratory fitness
  • Commentary: Sauna therapy may have beneficial effects for fitness, too.

Podcast Summary

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Featured Study

• Small Intestinal Bacterial Overgrowth in Subclinical Hypothyroidism of Pregnant Women
  • 224 pregnant women w/ subclinical hypothyroidism (SCH), 196 euthyroid pregnant women
  • Lactulose breath test and thyroid function tests performed in all women
  • Pregnant women w/ SCH had:
    • HIGHER rate of SIBO (57% vs 32%)
    • Higher CRP (7.8 vs 4.7)
    • More GI symptoms
    • Higher TPO antibodies (32 vs 11)
    • Higher TSH (5.9 vs 5.3) and lower fT4 (13.5 vs 14.1)
  • Commentary: SIBO is associated w/ SCH.

Gastrointestinal Studies

• Monocytosis Is a Biomarker of Severity in Inflammatory Bowel Disease: Analysis of a 6-Year Prospective Natural History Registry
  • Prospective study of 1,290 patients with IBD (64.1% with Crohn’s disease; 35.9% with ulcerative colitis)
  • Followed over 6 years
  • Monocytosis (high monocytes on CBC) was found in 399 (30.9%) of patients with IBD 
    • 29.3% with Crohn’s disease
    • 33.9% with ulcerative colitis
  • Monocytosis was associated with:
    • Elevated CRP and ESR levels
    • Anemia
    • Worse quality of life
    • Longer time on biologic medications
    • Higher financial costs
    • Increased risk of hospitalization
  • Commentary: High monocytes can be an indicator of higher disease activity in those w/ IBD. 

• A randomized controlled trial to evaluate the effect of influenza vaccination and probiotic supplementation on immune response and incidence of influenza-like illness in an elderly population in Indonesia
  • 554 healthy elderly adults, randomized to:
    • Flu vaccine + probiotic
    • Flu vaccine + placebo
    • Probiotic + placebo
    • Placebo + placebo
  • The addition of probiotics to the flu vaccine had NO effect of influenza antibody titers
  • Incidence of flu-like illness was NOT different between the probiotic group vs non-probiotic group
  • Commentary: This study showed NO effect of probiotics for the flu.

• Clinical Factors Associated With Positive Stool PCR for Gastrointestinal Pathogens in Celiac and Inflammatory Bowel Disease
  • Retrospective of 92 w/ Celiac Disease and 174 w/ IBD
  • All had PCR stool test to examine for GI pathogens
  • Those w/ positive GI pathogen:
    • Celiac Disease patients were more likely to:
      • Have diarrhea (OR 2.6)
      • Have extra-intestinal symptoms (OR 2.5)
    • IBD patients were more likely to:
      • Be on steroids (OR 2.2)
      • Have extra-intestinal symptoms (OR 2.6)
      • Use PPI (OR 4.1)
  • Commentary: Those w/ GI pathogens were more likely to have more complications of either Celiac Disease or IBD.

• Fecal Microbiota Transplant for Clostridioides Difficile Infection Is Safe and Efficacious in an Immunocompromised Cohort
  • Retrospective study of 77 immunocompromised patients (62% had IBD)
  • All had FMT
  • Overall cure rate was 87%
  • 12 patients received FMT for recurrent C. diff infection
    • 3-month survival rate was 92%
    • 11.7% had serious adverse events
  • Commentary: FMT is both safe and effective for immunocompromised patients. 

• Hydrogen and methane breath test results are negatively associated with IBS and may reflect transit time in post-surgical patients
  • 525 glucose breath tests performed over 3 years in post-surgical patients
  • 16% positive for hydrogen, 8% positive for methane
  • Patients w/ IBS (HR 0.17) and those with a higher body mass index (HR = 0.93) were LESS likely to have a positive test
  • Patients who underwent the test post-surgically were more likely to have a positive test (HR 2.76)
  • Commentary: This study contradicts the most recent meta-analysis that shows an association between IBS and SIBO. 

• Mediterranean Diet Adherence in People With Parkinson’s Disease Reduces Constipation Symptoms and Changes Fecal Microbiota After a 5-Week Single-Arm Pilot Study
  • 8 Parkinson’s Disease (PD) patients, 8 healthy controls all put on Mediterranean diet
  • After 5 weeks:
    • Less constipation for those w/ PD
    • No difference in intestinal permeability between 2 groups

• Proton pump inhibitors and risk of gastric cancer: population-based cohort study
  • Prospective study of 973,281 new PPI users, and 193,306 new H2 blocker users
  • Followed ~5 years
  • The use of PPIs was associated with a 45% increased risk of gastric cancer compared with the use of H2 blockers (HR 1.45)
  • The number needed to harm was:
    • 2,121 for 5 years after starting treatment
    • 1,191 for 10 years after starting treatment
  • Commentary: Compared to H2 blockers (e.g. Pepcid), PPI use was associated w/ a higher risk of gastric cancer, although the absolute risk is low.

• Association Between Proton Pump Inhibitor Use and Biliary Tract Cancer Risk: A Swedish Population-Based Cohort Study
  • 738,881 participants who’ve used PPI therapy for >6 months
  • Followed x5.3 years
  • Those who had been on PPIs were more likely to have the following compared to non-PPI users:
    • 206 (0.03%) developed gallbladder cancer 
    • 265 (0.04%) extrahepatic bile duct cancer
    • 131 (0.02%) intrahepatic bile duct cancer 
  • Commentary: Longer-term PPI use may increase the risk of gallbladder and bile duct cancer.

• Proton pump inhibitor use and risk of depression and anxiety in children: nationwide cohort study
  • 29,320 pairs of PPI users and non-users among children aged 7-17 years
  • Kids who started PPI therapy had a higher rate of depression and anxiety (HR 2.61)
  • Higher risk for longer use of PPI use
  • Commentary: PPI use was associated w/ an increased risk of depression and anxiety in children. This highlights the gut-brain connection. However, causation CANNOT be inferred from this study.

• Regular use of proton pump inhibitors and risk of type 2 diabetes: results from three prospective cohort studies
  • Prospective analysis of 204,689 participants free of diabetes 
  • 10,105 cases of type 2 diabetes identified over 2.1 million person-follow up-years
  • Regular PPI users had a 24% higher risk of diabetes than non-users (HR 1.24)
  • Longer duration of PPI use was associated with higher diabetes risk
    • PPI use 0-2 years (no increased risk)
    • PPI use >2 years (HR 1.26)
  • Commentary: PPIs may have a dose-dependent effect on diabetes risk.

• ​Effect of N-acetylcysteine on remission maintenance in patients with ulcerative colitis: A randomized, double-blind controlled clinical trial
  • 168 ulcerative colitis (UC) patients on high-dose steroids and mesalamine
  • Randomized to placebo or NAC (800 mg) and all patients had steroids tapered
  • After 16 weeks of supplementation, the NAC group had:
    • Less patients experience relapse (6 vs 19)
    • Lower CRP, ESR
    • Lower calprotectin
  • Commentary: NAC may be a useful therapy for those w/ UC.

• Food Elimination in the Management of Refractory Chronic Rhinosinusitis: A Pilot Study
  • 16 patients w/ chronic rhinosinusitis eliminated foods based off of IgE food allergy test
  • After 12 weeks, there was a significant reduction in symptoms
  • Commentary: Note that they used IgE testing (not IgG testing commonly used in popular food sensitivity tests).

• Chronic Intestinal Pseudo-Obstruction Is Associated with Intestinal Methanogen Overgrowth
  • Retrospective study of 494 patients, all had glucose breath test
  • 7.7% had intestinal pseudo-obstruction (rare motility disorder of dilated small bowel in the absence of mechanical obstruction)
  • Prevalence of methane-positive SIBO was much higher in those w/ intestinal pseudo-obstruction (53% vs 12%)
  • No difference in hydrogen SIBO between the 2 groups
  • Commentary: Methane-positive SIBO can contribute to reduced GI motility.

• Diagnostic yield of esophagogastroduodenoscopy in France
  • Survey of 342 gastroenterologists, including 2,735 endoscopies
  • Most common findings on endoscopy:
    • 32.8% normal
    • 20.9% gastritis
    • 18.1% hiatal hernia
    • 13.7% esophagitis
    • 4% Barrett’s esophagus
    • 2.9% peptic ulcer
    • 0.7% malignancy
  • Commentary: The majority of endoscopies are normal. Only a small fraction find malignancy.

• Does Probiotic Consumption Enhance Wound Healing? A Systematic Review
  • 4 studies, 348 participants
  • All studies reported positive effects of probiotics improving wound healing
  • NO adverse effects

• Probiotic Supplementation for Promotion of Growth in Children: A Systematic Review and Meta-Analysis
  • 79 RCTs of probiotics used in kids 0-5 years old 
  • Probiotics had a small effect on increasing weight (effect size 0.26) and height (effect size 0.16)
  • This beneficial effect was only seen in low-middle income countries (not in high-income countries)
  • Commentary: Probiotics may be able to improve weight and height in kids who may be predisposed to malnutrition (e.g. kids who live in low-middle income countries).

• Association between Brachyspira and irritable bowel syndrome with diarrhoea
  • 62 IBS patients, 31 healthy controls all had mucosal samples from sigmoid biopsy
  • Brachyspira colonization was higher in the IBS group compared to healthy controls (31% vs 0%)
  • Commentary: The spirochete Brachyspira was found more commonly in IBS patients compared to healthy controls. 

• The Effect of Rice vs. Wheat Ingestion on Postprandial Gastroesophageal Reflux (GER) Symptoms in Patients with Overlapping GERD-Irritable Bowel Syndrome (IBS)
  • Randomized crossover study in 21 patients with overlapping GERD-IBS 
  • Evaluated GERD symptoms after rice noodles (low FODMAP, gluten-free) w/ wheat noodles (high FODMAP, gluten), w/ 1-week washout period
  • Wheat noodles were associated with: 
    • More reflux symptoms
    • Higher H2 and CH4 breath test levels
  • Commentary: Low FODMAP/gluten-free meals led to less intestinal gas levels and less reflux symptoms. A low FODMAP diet may be effective for reflux/GERD.

• Six vs 12 Sessions of Gut-focused Hypnotherapy for Irritable Bowel Syndrome: A Randomized Trial
  • 448 IBS patients, randomized to 6 or 12 sessions of hypnotherapy
  • No difference in those achieved >50% reduction in IBS symptoms (79% in 6 session group, 74% in 12 session group)
  • Commentary: 6 sessions of hypnotherapy were non-inferior to 12 sessions in improving IBS symptoms.

• Impaired intestinal barrier function in type 2 diabetic patients measured by serum LPS, Zonulin, and IFABP
  • 90 patients w/ type 2 diabetes (T2D), 28 healthy controls
  • All intestinal permeability markers were HIGHER in the T2D group compared to the healthy controls
    • Levels of elevation were associated w/ worse metabolic health
  • Commentary: This highlights the gut-metabolic connection and the importance of foundational dietary practices for gut health.

• Rifaximin or Saccharomyces boulardii in heart failure with reduced ejection fraction: Results from the randomized GutHeart trial
  • Open-label study of 151 patients w/ heart failure (w/ reduced ejection fraction), randomized to:
    • S. boulardii (500 mg BID)
    • Rifaximin (550 mg BID)
    • Or standard of care only
  • After 3 months of treatment, no difference in:
    • Ejection fraction
    • Microbial diversity
    • CRP levels
  • Commentary: It’s surprising that there were no differences in microbial diversity, which makes us hesitant about the accuracy of this study.

Thyroid & Hormones Study

• Hyperthyroidism in Graves’ disease causes sleep disorders related to sympathetic hypertonia
  • Prospective study of :
    • 22 newly diagnosed Graves’ Disease (GD) with untreated hyperthyroidism
    • 20 previously diagnosed with GD with normal thyroid function
    • And 30 healthy controls
  • Newly diagnosed GD patients started treatment and all followed x12 months
  • At 12 month follow-up:
    • Sleep quality was worse in untreated GD group
    • Higher fT4 levels were associated with worse sleep quality
    • Sleep quality improved by treating the GD group
  • Commentary: Sleep quality can be impaired by hyperthyroidism and improved by treating it.

Diet & Lifestyle Studies

• Effects of a Very Low-Carbohydrate High-Fat Diet and High-Intensity Interval Training on Visceral Fat Deposition and Cardiorespiratory Fitness in Overfat Individuals: A Randomized Controlled Clinical Trial
  • 91 overweight participants, randomized to one of four groups:
    • high-intensity interval training (HIIT)
    • very low-carb diet (VLCD)
    • combined HIIT + VLCD 
    • or control 
  • After 12 weeks, VLCD and combined HIIT + VLCD had greater reduction in:
    • Visceral adipose tissue and body fat
    • Waist/hip circumference
    • Lean mass
  • Commentary: A combined diet and exercise program may be superior compared to just one in isolation. 

• The effects of Silymarin on the features of cardiometabolic syndrome in adults: A systematic review and meta-analysis
  • 11 RCTs
  • Silymarin led to significant improvement in:
    • Fasting blood glucose ( -17.96 mg/dL)
    • A1C (-1.25%)
    • Total cholesterol (-17.5 mg/dL)
    • Triglycerides (-25.7 mg/dL)
    • LDL-C (-10.5 mg/dL)
    • HDL-C (+3.4 mg/dL)
  • No difference in BMI
  • Commentary: Silymarin is associated with improvement in most cardiometabolic markers.

• Effect of Long-term Supplementation With Marine Omega-3 Fatty Acids vs Placebo on Risk of Depression or Clinically Relevant Depressive Symptoms and on Change in Mood Scores: A Randomized Clinical Trial
  • 18,353 adults randomized to:
    • Vitamin D3 (2000 IU/d)
    • Omega-3 fatty acids (1 g/d)
    • Or placebo
  • After an average of 5.3 years of supplementation, no difference in mood or depression risk

Podcast Summary

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Featured Studies

• 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. Ruscio wanted to add he has mixed emotions about prokinetics. He quickly checked this study and had his hesitancy reinforced by this quote:
      • “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.

• On-demand Versus Continuous Maintenance Treatment of Gastroesophageal Reflux Disease With Proton Pump Inhibitors: A Systematic Review and Meta-analysis
  • Aim: Compare on-demand (occasional use) vs continuous PPI therapy
  • 11 studies
  • Compared with continuous PPI therapy, on-demand therapy showed similar outcomes
    • Especially in non-erosive reflux or mild reflux disease types
  • However, in severe esophagitis, continuous PPI therapy was superior. 
  • Commentary: Given the potential adverse effect profile of PPIs, on-demand (occasional) PPI therapy may be preferential for milder versions of reflux

Gastrointestinal Studies

• Dental Caries Occurrence in Inflammatory Bowel Disease Patients: A Systematic Review and Meta-Analysis
  • 6 studies
  • Those w/ IBD had higher rate of dental caries compared to healthy controls

• The effects of probiotic/synbiotic supplementation compared to placebo on biomarkers of oxidative stress in adults: a systematic review and meta-analysis of randomized controlled trials
  • 31 trials, 1,681 participants
  • Probiotics/synbiotics resulted in:
    • Increased total antioxidant capacity
    • Increased glutathione
  • Commentary: Probiotics can exert antioxidant effects.

• Glutamine Supplementation Enhances the Effects of a Low FODMAP Diet in Irritable Bowel Syndrome Management
  • 50 IBS patients, randomized to:
    • Low FODMAP diet + placebo
    • Low FODMAP diet + glutamine (15 g/d)
  • After 6 weeks, the low FODMAP diet + glutamine group had significant improvement in IBS symptoms (58% reduction)
    • Improvement in IBS-severity score of more than 45% was observed in 88% (vs 60% in low FODMAP + placebo)
  • Commentary: Adding glutamine supplementation to a low FODMAP diet is superior to a low FODMAP diet alone. This is one of the mainstays of our clinic model.

• 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. 

• Regular use of proton-pump inhibitors and risk of stroke: a population-based cohort study and meta-analysis of randomized-controlled trials
  • Prospective study of 492,479 participants
  • Documented 5,182 incidents of strokes over 3.1 million person-years of follow-up
  • Regular PPI users had a 16% higher risk of stroke than non-users (HR 1.16, 95% CI 1.06 to 1.27)
  • Commentary: Stroke is now identified as a potential adverse effect of PPI (along w/ enteric infections, fractures, and diabetes).

• Impact of 12-week exercise program on biomarkers of gut barrier integrity in patients with coronary artery disease
  • 41 participants, measured gut permeability markers before and after exercise program
  • After 12 week exercise program (aerobic exercise and resistance training):
    • Increase in cardiorespiratory fitness (VO2 max) was associated with lower gut permeability levels
  • Commentary: A foundational practice such as regular exercise can lead to improved gut health.

• Effect and Tolerability of a Nutritional Supplement Based on a Synergistic Combination of β-Glucans and Selenium- and Zinc-Enriched Saccharomyces cerevisiae (ABB C1 ®) in Volunteers Receiving the Influenza or the COVID-19 Vaccine: A Randomized, Double-Blind, Placebo-Controlled Study
  • 72 participants, randomized to one of the following treatment given after COVID or flu vaccine:
    • Placebo 
    • Or combined supplementation of S. cerevisiae probiotic, selenium, and zinc
  • After 30 days of supplementation, the combined supplementation group had greater increases in IgG and IgM antibodies following the vaccine
  • No adverse effects
  • Commentary: A probiotic-containing supplement can improve the immune response to a viral vaccine.

• Role of Glucose Breath Test for Small Intestinal Bacterial Overgrowth in Children and Adolescents With Functional Abdominal Pain Disorders in Korea
  • 68 kids w/ functional abdominal pain given glucose breath test
  • 20.6% had SIBO
  • Loose stools were more common in those w/ SIBO compared to those without SIBO
  • Commentary: SIBO is not uncommon in children w/ functional abdominal pain. This study showed a correlation between SIBO and symptoms.

• Mast Cell Activation Disorder and Postural Orthostatic Tachycardia Syndrome: A Clinical Association
  • 69 patients w/ POTS for >4 months
  • 64% had additional non-orthostatic symptoms (migraine, allergies, skin rash, or GI symptoms)
  • Of these patients, 66% had at least 1 lab abnormality suggesting MCAS
    • 52% had elevated histamine markers
  • Commentary: MCAS and histamine intolerance may be a contributing factor to POTS.

• 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. 

• A Randomized Clinical Trial of Fecal Microbiota Transplant for Alcohol Use Disorder
  • 20 patients w/ alcohol use disorder and cirrhosis randomized to placebo enema or FMT enema
  • At 2 weeks follow-up:
    • Alcohol cravings reduced significantly in 90% of FMT versus 30% in placebo
    • FMT had reduced serum inflammatory markers
  • At 6 month followup, placebo had HIGHER rates of serious adverse events (8 vs 2)  
  • Commentary: FMT may help improve alcohol cravings and have lower adverse events compared to placebo.

• Probiotics Supplementation on Cardiac Remodeling Following Myocardial Infarction: a Single-Center Double-Blind Clinical Study
  • 44 patients with myocardial infarction who underwent percutaneous coronary intervention 
  • Randomized to probiotic or placebo
  • After 3 months, the probiotic group had:
    • Reduced markers of cardiac remodeling
    • Greater improvements in echocardiogram findings
  • Commentary: Probiotics may have beneficial effects on cardiac remodeling, suggesting a gut-heart connection.

Autoimmunity Study

• Efficacy and Safety of N-Acetylcysteine for the Management of Chronic Pain in Adults: A Systematic Review and Meta-Analysis
  • 9 studies, 863 participants w/ chronic pain
  • N-acetylcysteine did not reduce pain intensities 
  • Commentary: NAC may not have benefits for chronic pain.

Thyroid & Hormones Studies

• Elevated Levels of Circulating Biomarkers Related to Leaky Gut Syndrome and Bacterial Translocation Are Associated With Graves’ Disease
  • 91 patients w/ Graves’ Disease, 44 healthy controls
  • Measured markers of intestinal permeability
  • Graves’ Disease patients had higher levels of intestinal permeability as compared to healthy controls
  • Higher gut permeability levels were associated with:
    • Higher antibody levels
    • Lower TSH, higher fT4/fT3
    • More symptoms
  • Commentary: Another data point for the gut-thyroid connection.

• Carotid Intima-Media Thickness in Patients with Subclinical Hypothyroidism: A Prospective Controlled Study
  • 54 total participants: 
    • 18 with subclinical hypothyroidism (SCH) 
      •  Median TSH 6.15 µIU/ml
    • 18 with overt hypothyroidism (OH)
    • 18 healthy controls 
  • Carotid Intima-Media thickness (CIMT) measured in all participants
  • Levothyroxine given to those w/ SCH
  • Higher CIMT in SCH compared to healthy controls
  • There was a decreased CIMT after levothyroxine treatment in those w/ SCH
  • Commentary: Even w/ a TSH <10, those w/ SCH had:
    • A higher CIMT
    • Reduced CIMT scores after starting levothyroxine
    • This is why research suggests considering levothyroxine in those w/ SCH who have a TSH between 7-10 and are younger.

• Lower serum testosterone concentrations are associated with a higher incidence of dementia in men: The UK Biobank prospective cohort study
  • 159,411 elderly men followed x7 years
  • 826 developed dementia
  • Lower total testosterone was associated with a higher risk of dementia (HR 1.43)

• Effects of vitamin D treatment on thyroid function and autoimmunity markers in patients with Hashimoto’s thyroiditis-A meta-analysis of randomized controlled trials
  • 6 RCTs, 258 participants w/ Hashimoto’s
  • Vitamin D supplementation resulted in:
    • Reduced TPO Abs (-158.2)
    • No difference in TSH, fT4, fT3
  • Commentary: Another data point suggesting a benefit of Vitamin D for thyroid autoimmunity.

Diet & Lifestyle Studies

• The effect of vitamin D and exercise on balance and fall risk in postmenopausal women: A randomised controlled study
  • RCT of postmenopausal women 50-70 y/o
  • Women w/ low Vit D (<25nmol/L) randomized to 3 groups:
    • Vit D supplementation
    • Core and balance exercises
    • Vit D + exercises
  • Compared to 40 women w/ normal Vit D levels w/ no intervention
  • After 8 weeks, all groups had improvement of balance and quality of life

• Evaluation of mandibular advancement device placement based on levels of TNF-alpha in participants with obstructive sleep apnea: A clinical study
  • 20 patients w/ mild-to-moderate OSA given customized mandibular advancement device (MAD)
  • After 6 months:
    • Reduced inflammatory levels (TNF-alpha)
    • Reduced daytime sleepiness
  • Commentary: MAD can improve sleep apnea and reduce inflammation.

• Effects of a six-month low-carbohydrate diet on glycemic control, body composition and cardiovascular risk factors in patients with type 2 diabetes: an open-label RCT
  • Open label study of 71 type 2 diabetics, randomized to low carb (20% carbs)  or standard diet (higher carbs)
  • After 6 months, the low carb group: 
    • Decreased carb intake by 30%
    • Lower A1C (-2.8%)
    • Reduced weight (-4 kg more than control)
    • No change in lipids or blood pressure
    • No episodes of severe hypoglycemia
  • Commentary: A low carb diet (<20% carbs) is both safe and effective for type 2 diabetics.

• Comparison of the efficacy of intranasal ketamine versus intravenous ketorolac on acute non-traumatic headaches: a randomized double-blind clinical trial
  • 140 participants w/ headache randomized to IV ketorolac or intranasal ketamine (0.75 mg/kg, max 75 mg)
  • After 30 minutes, intranasal ketamine group had greater improvements in symptom severity
  • Side effects (fatigue, dizziness, general discomfort, nausea, increased heart rate, and hypertension) were significantly higher in the ketamine group
  • Commentary: Intranasal ketamine may have superior effects to improving headache compared to an IV NSAID medication, but has a greater risk of side effects.