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Featured Study

• Systematic Review and Meta-Analysis: Clinical, Endoscopic, Histological and Safety Placebo Rates in Induction and Maintenance Trials of Ulcerative Colitis
  • 119 placebo-controlled studies of ulcerative colitis
  • Remission rates in the placebo arms:
    • Clinical remission 11%
    • Endoscopic remission 19%
    • Histological remission 15%
  • Commentary: Previously, we have documented a high placebo response rate in IBS studies. Now, we present a notable (although smaller) placebo response rate in IBD studies.

Gastrointestinal Studies

• Effect of antibiotic pretreatment on bacterial engraftment after Fecal Microbiota Transplant (FMT) in IBS-D
  • 44 IBS-D patients randomized to 1 of 4 groups:
    • Single-dose FMT
    • 7 days Ciprofloxacin/Flagyl before FMT
    • 7 days Rifaximin before FMT
    • Placebo FMT
  • Successful FMT engraftment was achieved at a higher rate in the FMT-alone group (16%) compared to Cipro/Flagyl (2.4%) and Rifaximin (5%) groups
  • NO differences in IBS symptom severity or quality of life
  • Commentary: Pre-treatment w/ antibiotics before FMT led to worse engraftment rates. However, no differences of symptoms or quality of life was found. Note how small this study was so statistical significance would be harder to achieve.

• Lack of Effect of Gluten Challenge on Fecal Microbiome in Patients With Celiac Disease and Non-Celiac Gluten Sensitivity
  • 17 celiac and non-celiac gluten sensitivity patients, previously on a gluten-free diet
  • After a 2-week gluten challenge, there was NO change in gut microbiome composition in both groups, despite a worsening in GI symptoms 
  • Commentary: Lab findings do NOT always correlate with symptoms.

• Efficacy of Prucalopride for Chronic Idiopathic Constipation: An Analysis of Participants With Moderate to Very Severe Abdominal Bloating
  • 6 studies
  • Prucalopride (2 mg per day x 3-6 months) led to better improvement in abdominal bloating compared to placebo (62% vs 50% response rate)
  • Commentary: Note the placebo response rate of 50%.

• Impact of synbiotics treatment on bacteremia induced during neoadjuvant chemotherapy for esophageal cancer: A randomised controlled trial
  • 42 esophageal cancer patients requiring chemotherapy and surgical removal of cancer, randomized to:
    • No treatment (control group)
    • Synbiotics 
  • Blood samples collected before and after each chemotherapy session
  • Lymph nodes collected before and after surgical removal of cancer
  • Compared to the control group, treatment with synbiotics led to reduced:
    • Bacteremia (bacteria in blood) (2% vs 15%)
    • Bacteria in lymph nodes (0% vs 35%)
    • GI toxicity during chemotherapy (5% vs 36%)
  • Commentary: Synbiotics led to reductions in bacteremia and GI side effects, both common occurrences in those receiving chemotherapy and surgery for esophageal cancer. Another data point for the gut-immune connection. This study may also suggest probiotic’s safety in those with cancer.

• The influence of probiotics on gastrointestinal tract infections among children attending childcare: A systematic review and meta-analysis
  • 15 RCTs
  • Probiotic supplementation led to an overall reduced risk of GI infections in children by 26% 
  • Commentary: Probiotic use in kids can reduce the risk and duration of GI infections, with some strains offering greater benefit than others.

• A new use of Lactobacillus rhamnosus GG administration in the NICU: colonized vancomycin-resistant enterococcus eradication in the gastrointestinal system
  • 55 newborns in the ICU, colonized by vancomycin-resistant enterococci, randomized to:
    • Antibiotics 
    • Probiotics
  • After 6 months of treatment, the probiotic group had higher eradication rate (95% vs 52%) 
  • Commentary: Probiotics were more effective than antibiotics at clearing an invasive GI pathogen in newborns.

Autoimmunity Study

• Mucocutaneous Manifestations in Autoimmune Gastritis: A Prospective Case-Control Study
  • 60 patients w/ autoimmune gastritis (AIG), 30 healthy controls
  • Compared to healthy controls, patients with AIG had a higher prevalence of mucocutaneous (MC) diseases (66.7% vs 23.3%)
  • In those with AIG, positive Intrinsic Factor (IF) antibodies correlated with higher rates of MC diseases compared to those without IF antibodies (100% vs 58.5%)
  • The most common MC diseases were:
    • 8.3% Sjogren syndrome
    • 8.3% Alopecia areata
    • 6.7% Vitiligo
  • Commentary: Patients with AIG have significantly higher rates of concomitant MC diseases, especially with the presence of IF antibodies.

Thyroid & Hormones Studies

• Determining the Association Between Helicobacter pylori Infection and Treatment-Refractory Hypothyroidism
  • 130 hypothyroid patients treated w/ levothyroxine, categorized into 2 groups: 
    • Euthyroid (TSH < 4.5 mU/L) 
    • Refractory hypothyroid (TSH > 4.5 mU/L) 
  • The presence of H. pylori was tested in all groups (serum IgG)
  • There was NO difference in H. pylori prevalence between both groups (36.2% vs 36.9%)
  • Commentary: No association was found between refractory hypothyroidism and H. pylori infection. However, note that H pylori IgG antibodies are NOT the best way to test for H pylori.

• Are ethnic differences, urinary iodine status, lead and cadmium exposure associated with thyroid autoimmunity and hypothyroid status? A cross-sectional study
  • Cross-sectional study of 2,877 participants
  • The following were associated w/ thyroid autoimmunity
    • Elevated blood lead levels (OR 1.6)
    • Elevated urinary iodine levels (≥300.00 µg/g) (OR 1.5)
    • Elevated blood cadmium levels (OR 1.4)
  • Commentary: High iodine, lead, and cadmium levels may be associated w/ thyroid autoimmunity.

• Pregnancy and Neonatal Outcomes With Levothyroxine Treatment in Women With Subclinical Hypothyroidism Based on New Diagnostic Criteria: A Systematic Review and Meta-Analysis
  • 6 studies, 7,955 pregnant women w/ subclinical hypothyroidism
  • Pregnant women with SCH treated with levothyroxine had a lower risk of:
    • Pregnancy loss (OR 0.55)
    • Preterm birth (OR 0.63)
    • Gestational hypertension (OR 0.78)
  • Commentary: Pregnancy may be a situation where treating SCH is helpful.

• Efficacy and Safety of Nutraceutical on Menopausal Symptoms in Post-Menopausal Women: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial
  • 101 post-menopausal women, randomized to:
    • Placebo
    • Nutraceutical supplement
      • Soy isoflavone (100 mg) 
      • Black cohosh (520 mg) 
      • Chasteberry (400 mg) 
      • Evening primrose oil (500 mg) 
  • After 3 months, compared to placebo, women in the the nutraceutical group experienced less severe:
    • Hot flashes (3 women vs 21 women)
    • Insomnia (6 vs 19)
    • Depression (2 vs 12)
    • Irritability (0 vs 11)
  • Commentary: Herbal nutraceuticals, specifically containing soy isoflavones, black cohosh, chasteberry and evening primrose oil, are effective in the reduction of menopausal symptoms.

• The effect of vitamin D on recurrence of uterine fibroids: A randomized, double-blind, placebo-controlled pilot study
  • 99 women who had undergone uterine fibroid removal, randomized to:
    • Placebo
    • Vitamin D (1,000 IU/day)
  • After 1 year, supplementation with vitamin D led to: 
    • Reduced recurrence of fibroids by 50% 
    • Reduced size of recurrent fibroids (-7.7 mm)
  • Commentary: Vitamin D supplementation was effective in preventing recurrence of fibroids and reducing the size of recurrent fibroids.

Diet & Lifestyle Studies

• Association of Hypoglossal Nerve Stimulation With Improvements in Long-term, Patient-Reported Outcomes and Comparison With Positive Airway Pressure for Patients With Obstructive Sleep Apnea
  • Retrospective study of obstructive sleep apnea (OSA) patient:
    • 85 patients received hypoglossal nerve stimulation (NHS)
    • 217 patients received CPAP therapy
  • After treatment, the NHS group had:
    • Greater improvement of depression score
  • At 1 year follow up, the NHS group had, comparable improvement in:
    • Depression score (29% vs 24% response rate)
    • Comparable improvement in daytime sleepiness (65% vs 55% response rate)
    • Comparable improvement in sleep quality (59% vs 31%)
  • Commentary: This study showed the similar efficacy rate of hypoglossal nerve stimulation to CPAP therapy for those w/ OSA. A device that is more cost-effective and may act in a similar fashion can be found here.

• Resolution of fibromyalgia by controlling obstructive sleep apnea with a mandibular advancement device
  • Case study, 61 y/o female with sleep apnea and fibromyalgia 
  • After 6 months of mandibular advancement device (MAD) therapy, the patient experienced significant reductions in: 
    • Fatigue score (20 vs 3)
    • Fibromyalgia symptom score (78.7 vs 8.1)
    • Depression score (26 vs 2) 
    • Sleep apnea score (69.8 vs 12.6)
  • Commentary: Treatment of sleep apnea with a MAD led to significant improvements in fibromyalgia, depression and energy. Sleep apnea is a common comorbidity in patients with fibromyalgia, so keep sleep apnea in your differential diagnosis. Also, keep in mind this is a case study.

• Frequency of overactive bladder (OAB) and the factors affecting it in patients with obstructive sleep apnea syndrome (OSAS)
  • 255 patients, tested for sleep apnea and overactive bladder (OAB)
  • OAB was present in 66.3% of patients diagnosed with sleep apnea 
  • Commentary: This study suggests an association between sleep apnea and OAB.

• A systematic review for the efficacy of coenzyme Q10 in patients with chronic kidney disease
  • 12 studies
  • CoQ10 supplementation led to:
    • Reduced oxidative stress
    • Decreased CRP (-1.2 mg/dL)
    • Decreased A1C (-0.8%)
    • No effect on cholesterol/lipids
  • Commentary: CoQ10 may have antioxidant and anti-inflammatory properties.

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Featured Study

• Effects of Proton Pump Inhibitors on the Small Bowel and Stool Microbiomes
  • Aim: To compare the microbiomes in PPI and non-PPI users
  • Duodenal aspirates and stool samples from age- and gender-matched 59 PPI users, and 118 non-PPI users
  • The duodenal aspirates of PPI users exhibited:
    • Higher Campylobacteraceae (3.13-fold)
    • Higher Bifidobacteriaceae (2.9-fold)
    • Lower Clostridiaceae (88.24-fold)
  • The stool samples of PPI users exhibited:
    • Higher Streptococcaceae (2.14-fold)
    • Lower Clostridiaceae (2.60-fold)
  • NO difference in SIBO rates (per duodenal aspirate culture)
  • Commentary: This study showed differences in small bowel and large bowel microbiome of PPI vs non-PPI users. However, these differences may be clinically meaningless. No significant differences in SIBO rates were noted between the two groups.

Gastrointestinal Studies

• The Impact of Helminth Infection on the Incidence of Metabolic Syndrome: A Systematic Review and Meta-Analysis
  • 14 studies
  • Natural helminth infection was associated with: 
    • 46% reduced risk of type 2 diabetes
    • 56% reduced risk of metabolic syndrome 
  • Commentary: Another data point for the connection between the gut microbiome and metabolic health. Note that these studies were observational in nature.

• Role of Probiotics for Recurrent UTIs in the Twenty-First Century: a Systematic Review of Literature
  • 9 studies, 772 patients 
  • Two studies showed probiotics reduced the risk of recurrent UTIs
    • The remaining studies (7 studies) showed inconclusive results
  • Commentary: There are mixed results on the use of probiotics for prevention of recurrent UTIs.

• Pre-Digested Protein Enteral Nutritional Supplementation Enhances Recovery of CD4 + T Cells and Repair of Intestinal Barrier in HIV-Infected Immunological Non-Responders
  • 36 patients w/ AIDS, non-responsive to current antiviral therapy
  • All received a pre-digested protein drink (i.e. elemental diet) once per day in addition to their current diet
  • After 3 months, treatment led to:
    • Improved immune function (Increased WBC, neutrophils, CD4+)
    • Reduced intestinal permeability markers (LPS, D-lactate, DAO) 
    • Increased body weight 
  • Commentary: Using a pre-digested protein drink (e.g. elemental diet drink) as a meal replacement led to improved immune function, reduced markers of intestinal permeability, and weight gain. This supports our clinical observation that using elemental diets exclusively is NOT always necessary, but rather a hybrid approach can provide clinically meaningful benefits.

• Lifestyle interventions can reduce the risk of Barrett’s esophagus: a systematic review and meta-analysis of 62 studies involving 250,157 participants
  • 62 studies
    • 250,157 healthy controls
    • 22,608 cases of Barrett’s esophagus (BE)
  • Risk factors for developing BE include:
    • Less sleep (RR 1.7)
    • Proton pump inhibitors use (RR 1.6)
    • Smoking (RR 1.3)
    • Alcohol (RR 1.2)
  • The following was associated w/ reduced BE risk: 
    • Fiber (RR 0.9)
    • Aspirin (RR 0.7)
    • Vitamin C (RR 0.6)
    • Folate (RR 0.4)
  • Commentary: Dietary quality can affect BE risk.

• SER-109, an Oral Microbiome Therapy for Recurrent Clostridioides difficile Infection
  • 182 chronic C. diff patients w/ current infection, randomized to one of the following after antibiotic treatment:
    • Placebo
    • SER-109 (new medication containing Firmicutes spores)
  • After 2 months, the recurrence rate in the treatment group was lower compared to placebo (12% vs 40%) 
  • Commentary: A novel spore-based probiotic medication led to reduction in recurrence of C. diff infections.

• Measurement of the serum zonulin levels in patients with acne rosacea
  • 30 patients w/ rosacea, 31 healthy controls
  • Serum zonulin was significantly higher in those w/ rosacea (18.5 vs 13.2 ng/mL)
  • Commentary: This highlights the gut-skin connection.

• Dynamic changes of intestinal flora in patients with irritable bowel syndrome combined with anxiety and depression after oral administration of enterobacteria capsules
  • 18 IBS-D patients w/ anxiety and/or depression, randomized to placebo or FMT capsules
  • After 3 months, the FMT group had:
    • Improved IBS symptoms (291 to 144)
    • Better stool consistency (Bristol stool type 6 to 4)
    • Reduced anxiety scores (18 to 8)
    • Reduced depression score (22 to 18)
    • Increased microbial diversity
  • Commentary: This highlights important gut-brain connection and the ability of gut-focused therapies to improve mood.

• Gut-brain axis dysfunction underlies FODMAP-induced symptom generation in irritable bowel syndrome
  • Cross-over study of 13 IBS patients and 13 healthy controls
  • Randomized to 1 of 3 intragastric infusions:
    • Fructans (FODMAP)
    • Glucose
    • Or saline 
  • Abdominal MRI was performed before, 1 hr, and 2 hrs post-infusion
  • The fructan (FODMAP) group had:
    • More cramps, pain, flatulence and nausea compared to glucose
    • Increased small bowel motility and ascending colonic gas in both IBS patients and healthy controls
  • Commentary: This study showed that an intragastric infusion of FODMAPs (fructans) lead to GI symptoms, increased bowel motility, and increased gas production. Dr. Ruscio wanted me to mention this partially contradicts the ‘slow motility underlies IBS/SIBO hypothesis’.

• Evidence supporting safe diagnosis of coeliac disease in children with antitissue transglutaminase titre ≥5 times upper limit of normal
  • 722 children w/ biopsy-confirmed celiac disease (CD) 
  • Anti-tissue transglutaminase (tTG-IgA) levels were assessed in all children
  • 99.5% of children with tTG-IgA ≥ 5x the upper normal limit also had biopsy-confirmed CD 
  • Commentary: tTG-IgA ≥ 5x the upper normal limit is highly predictive of a positive CD diagnosis.

• Disturbed gastric motility in patients with long-standing diabetes mellitus
  • 23 diabetic patients, 15 healthy controls
  • Gastric emptying was significantly delayed in diabetic patients, and was associated with higher rates of GI symptoms compared to healthy controls (52% vs 20%) 
  • Commentary: Diabetes is associated with slower gastric motility and increased GI symptoms.

Thyroid & Hormones Studies

• Effects of Thyroperoxidase Antibody and Thyroglobulin Antibody on Maternal and Neonatal Outcomes in Pregnant Women
  • 296 pregnant women, classified into 4 groups according to thyroid antibody status in first trimester:
    • 97 women: TPOAb+/TgAb-
    • 35 women: TPO-/Tg+
    • 85 women: TPO+/Tg+
    • 79 women: TPO-/Tg-
  • Followed thyroid status x2-3 years postpartum
  • TPOAb (OR 2.3) and TgAb (OR 3.1) had a higher rate of postpartum thyroiditis:
    • 6.3% TPO-/Tg-
    • 16.5% TPO+/Tg-
    • 22.9% TPb-/Tg+
    • 35.3% TPO+/Tg+
  • Those w/ TgAbs were more likely to have thyroid dysfunction at a 2-3 year followup
  • Commentary: In summary, both TPO and Tg antibodies were associated w/ a higher rate of postpartum thyroiditis. In addition, the presence of antibodies was associated w/ higher rates of thyroid dysfunction at a 2-3 year followup. Getting TgAb on top of TPOAb may add additional prognostic value to pregnancy-related outcomes than TPOAb alone.

• Effect of selenium on thyroid autoimmunity and regulatory T cells in patients with Hashimoto’s thyroiditis: A prospective randomized-controlled trial
  • 90 Hashimoto’s thyroiditis patients, randomized to selenium (200 mcg/d) or no treatment
  • After 6 months, the selenium group had significantly reduced: 
    • Anti-TPO (-28.4 vs 0 IU/ml)
    • Anti-Tg (-48.8 vs +18.3 IU/ml)
    • TSH (-0.2 vs +0.5 mIU/L)
  • NO difference between groups noted for fT3 and fT4 
  • Commentary: Selenium is useful for reducing thyroid antibodies in patients with Hashimoto’s thyroiditis. However, note the small effect size.

• Elevated Levels of Circulating Biomarkers Related to Leaky Gut Syndrome and Bacterial Translocation Are Associated With Graves’ Disease
  • Intestinal permeability markers (LPS, I-FABP, zonulin, and D-lactate) measured in 91 Graves’ Disease (GD) patients and 44 healthy controls
  • All intestinal permeability markers were higher in GD patients compared to healthy controls
  • Intestinal permeability markers were associated with:
    • Lower TSH
    • Higher fT4 
    • Higher antibody levels
    • More eye symptoms
  • Commentary: This highlights the gut-thyroid connection, especially in the context of autoimmune thyroid disease.

• Prevalence and predictors of adequate treatment of overt hypothyroidism – a population-based study
  • Prospective study of 113 newly diagnosed overt hypothyroid patients
  • Followed x10 years
  • After 10 years, only 68% were biochemically euthyroid
  • Risk factors for remaining hypothyroid include:
    • Age
    • Smoking
    • Higher TSH at diagnosis
    • Higher BMI
  • Commentary: This study showed that a substantial amount of overt hypothyroid patients are inadequately treated at a long-term followup. Those who are older, have a history of smoking, higher BMI, or had higher TSH at diagnosis may need more attention to their thyroid labs after starting treatment.

• ​​Dietary Modification for Reproductive Health in Women With Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis
  • 20 RCTs, 1,113 PCOS patients
  • Dietary modifications lead to significant improvements in:
    • Fertility outcomes
    • Reduced testosterone and androgens
    • Less hirsutism (e.g. facial hair growth)
  • Low carb diets and low calorie diets were superior
  • Commentary: Dietary changes can lead to significant changes in PCOS.

Diet & Lifestyle Studies

• Effect of omega-3 fatty acids supplementation on cardio-metabolic and oxidative stress parameters in patients with chronic kidney disease: a systematic review and meta-analysis
  • 13 trials
  • Omega-3 fatty acids improved oxidation markers with a moderate effect size
  • Commentary: Omega-3 fatty acids can be considered as antioxidants.

• Impact of Cold-Water Immersion Compared with Passive Recovery Following a Single Bout of Strenuous Exercise on Athlet ic Performance in Physically Active Participants: A Systematic Review with Meta-analysis and Meta-regression
  • 52 studies
  • After a single bout of intense exercise, compared to passive recovery, cold water immersion (CWI) led to improvements in:
    • Creatinine kinase (marker of muscle breakdown)
    • Muscle soreness
    • Perceived feeling of recovery 
  • NO improvements were noted on strength after CWI
  • Commentary: CWI may be an effective tool for recovery after intense exercise.

• The association of co-morbid insomnia and sleep apnea with prevalent cardiovascular disease and incident cardiovascular events
  • 4,160 participants, followed x11 years
  • Having both insomnia + obstructive sleep apnea (OSA) was associated w/ a 2x higher risk of cardiovascular disease
    • However, after adjusting for other variables (e.g. weight), this association was not found
  • Commentary: This study showed NO increased risk of cardiovascular disease in those w/ sleep apnea after correcting for other confounding variables.

• Relationship between CPAP termination and all-cause mortality: a French nationwide database analysis
  • 88,007 patients w/ sleep apnea and prescribed CPAP therapy
  • Compared to patients who stopped CPAP therapy within 1 year, continual CPAP therapy beyond 1 year was associated with: 
    • Lower risk of all-cause mortality (HR 0.6)
    • Lower incident of heart failure (HR 0.7)
  • Commentary: Consistent CPAP use for sleep apnea is associated with a reduced risk of all-cause mortality. Keep in mind this is an observational study.

• Assessment of Laryngopharyngeal Reflux and Obstructive Sleep Apnea: A Population-Based Study
  • 701 participants, evaluated for laryngopharyngeal reflux (LPR) and sleep apnea
    • 17% diagnosed with LPR
    • 38.5% diagnosed with sleep apnea
  • In those diagnosed with sleep apnea, 45.4% also had LPR
  • Commentary: A significant percentage of participants were diagnosed with sleep apnea, which was associated with an increased risk of LPR.

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Featured Study

• A systematic review and meta-analysis on the prevalence of non-malignant, organic gastrointestinal disorders misdiagnosed as irritable bowel syndrome
  • Looking at the rate of the following conditions in those originally diagnosed with IBS:
    • Bile acid diarrhea (BAD), 7 studies, 597 participants
    • Carbohydrate malabsorption (CM), 39 studies, 10,115 participants
      • E.g. lactose or fructose intolerance
    • Microscopic colitis (MC), 17 studies, 5,068 participants
    • Pancreatic exocrine insufficiency (PEI), 2 studies, 478 participants
    • And small intestinal bacterial overgrowth (SIBO), 48 studies, 6,779 participants
  • The following diagnoses were correctly identified in those w/ an original diagnosis of IBS:
    • CM – 54%
    • BAD – 41%
    • SIBO – 19% (glucose BT), 49% (lactulose BT)
    • PEI – 4.6%
    • MC – 3%
  • Commentary: This study showed a notable prevalence of organic disorders in those w/ a past diagnosis of IBS. BAD, SIBO and food intolerances (e.g. lactose intolerance) are the most common types of missed diagnosis. Keep these differential diagnoses in mind next time you see a patient that looks to have IBS. 

Gastrointestinal Studies

• Fecal Microbiota Transplantation for Severe or Fulminant Clostridioides difficile Infection: Systematic Review and Meta-analysis
  • 10 studies, 240 patients studying FMT for severe or fulminant C. diff infection (CDI)
  • FMT had a resolution rate of 88% within 4 weeks
    • Only 1.6-2.0 FMT administrations was needed to achieve resolution 
  • Rate of those who required additional antimicrobials after FMT:
    • 50% for severe CDI 
    • 67% for fulminant CDI
  • Commentary: FMT is very effective for severe CDI. However, additional antibiotics may be required after FMT to achieve full resolution.

• Rifaximin Modulates the Gut Microbiota to Prevent Hepatic Encephalopathy in Liver Cirrhosis Without Impacting the Resistome
  • Prospective study, 21 patients w/ liver cirrhosis in remission from hepatic encephalopathy (HE)
  • All were treated w/ Rifaximin (400 mg TID), stool samples collected throughout the study
  • After 3 months, there were significant improvements in:
    • Blood ammonia (54.1 to 25.6 µmol/L)
    • Cognitive function
  • Rifaximin treatment did NOT reduce microbiota diversity
  • Commentary: Rifaximin treatment led to improved cognition and significant reductions in blood ammonia.

• Effect of synbiotic supplementation on migraine characteristics and inflammatory biomarkers in women with migraine: Results of a randomized controlled trial
  • 69 women w/ migraine, randomized to placebo or synbiotic
  • After 3 months of supplementation, the probiotic group lead to greater improvement in:
    • Migraine frequency (-1.02 vs -0.30/month)
      • No change in duration or severity 
    • Need for pain medication (-7.5% vs +27.5%)
    • Gastrointestinal symptoms (-35% vs -2.5%)
    • Zonulin level (-4.12 vs +0.85 ng/ml)
    • hs-CRP level (-0.43 vs -0.09 mg/l)
  • Commentary: Probiotic supplementation was beneficial for migraines and need for pain medications.

• Efficacy of Fecal Microbiota Transplantation in Irritable Bowel Syndrome Patients: An Updated Systematic Review and Meta-Analysis
  • 19 studies using FMT in IBS patients
  • Compared to placebo, FMT led to:
    • Improvement of quality of life 
    • No difference in IBS symptom severity
  • Commentary: While FMT is an effective tool for C. diff. Infection, it remains a last line therapy for managing IBS.

• Gut microbiota in patients with Alzheimer’s disease spectrum: a systematic review and meta-analysis
  • 11 studies, 427 Alzheimer’s Disease (AD) patients, 378 healthy controls
  • Measured microbiota composition
  • Patients with AD showed significantly reduced microbiota diversity as compared to healthy controls
    • No difference in those w/ just mild cognitive impairment
  • Commentary: This meta-analysis suggests a correlation between lower microbiota diversity and AD. However, note that this study is observational in nature and thus, we cannot infer causality yet.

• Functional gastrointestinal and somatoform symptoms five months after SARS-CoV-2 infection: A controlled cohort study
  • Cohort study of 164 SARS-CoV-2 infected patients and 183 healthy controls
  • After a 5 month follow up, the SARS-CoV-2 patients had a higher rate of:
    • Loose stools (RR 1.88)
    • Chronic fatigue (RR 2.24)
    • Other medically unexplained symptoms (RR 3.62)
  • Commentary: Chronic symptoms such as loose stools can be common in those recovering from SARS-CoV-2.

• The Relationship of Severity of Autism with Gastrointestinal Symptoms and Serum Zonulin Levels in Autistic Children
  • 56 kids w/ autism, 55 healthy controls
  • Serum zonulin levels were significantly higher in kids w/ autism (24.5 vs 21.8 ng/mL)
  • Higher serum zonulin was associated with more GI symptoms (33 vs 23 ng/mL)  and higher autism severity (20 vs 36 ng/mL)
  • Commentary: Highlights the gut-brain connection.

• The low FODMAP diet for IBS; A multicentre UK study assessing long term follow up 
  • 205 IBS patients on a low FODMAP diet, followed x3.7 years
  • Adequate symptom relief was noted in 60% of individuals at long term follow up
  • Commentary: A long-term low FODMAP diet has a high response rate.

• Fecal microbiota transplantation for induction of remission, maintenance and rescue in patients with corticosteroid-dependent ulcerative colitis: a long-term follow-up real-world cohort study
  • 27 ulcerative colitis (UC) patients on steroids, all given 3 FMT administrations along w/ standard care
  • Responders were given maintenance FMT every 6 months
  • After a ~6 month followup:
    • Improved UC severity score (6.4 to 2.8)
    • Clinical remission w/o steroids in 48%
    • Histological response seen in 38%
  • Those receiving maintenance FMT had a lower rate of relapse
  • Commentary: FMT is effective for UC. Maintenance FMT Q6 months may improve long-term outcomes.

• Irritable bowel syndrome and long-term risk of cancer: a prospective cohort study among 0.5 million adults in UK Biobank
  • Prospective study of 449,595 participants, 22,338 (5.0%) w/ IBS
  • After a ~12 year follow up, IBS patients had a lower rate of:
    • Digestive cancer (HR 0.79)
    • Colon cancer (HR 0.75)
    • Rectal cancer (HR 0.68)
    • Cancer-related mortality (HR 0.83) 
  • Commentary: IBS does NOT increase rates of GI cancer and is actually associated w/ a LOWER rate of GI cancer.

• Lactobacillus rhamnosus CNCM I-3690 decreases subjective academic stress in healthy adults: a randomized placebo-controlled trial
  • 92 healthy college students who had to give public speech, randomized to placebo drink or probiotic drink
  • After 4 weeks, the probiotic group had:
    • Less stress/anxiety scores
    • Similar increase in salivary cortisol
  • Commentary: This study showed that probiotics improved perceived stress scores INDEPENDENT of cortisol levels.

• Risk factors for the development of esophageal candidiasis among patients in community hospital
  • 7,736 patients w/ esophageal candidiasis (EC) who had endoscopy
  • Risk factors for EC included:
    • Type 2 diabetes (OR 1.52)
    • PPI (OR 1.7)
    • Atrophic gastritis (OR 1.6)
    • History of gastrectomy (OR 2.3)
    • Advanced gastric cancer (OR 4.7)
  • Commentary: Note that atrophic gastritis, PPI use, and type 2 diabetes are risk factors for EC.

• Systematic review with meta-analysis: The prevalence, risk factors and outcomes of upper gastrointestinal tract Crohn’s disease
  • 26 studies
  • Prevalence of upper GI tract involvement in those w/ Crohn’s disease was 13%
    • 56% involved the stomach
  • Commentary: Remember that Crohn’s disease can also affect the upper GI tract including the upper small bowel, stomach, and oral cavity.

Thyroid & Hormones Study

• Screening of Organ-Specific Autoantibodies in a Large Cohort of Patients with Autoimmune Thyroid Diseases
  • 1,502 patients w/ autoimmune thyroid disease
  • Most common autoantibodies other than thyroid antibodies were:
    • 7% Parietal cell antibodies
    • 2.8% anti-glutamic acid decarboxylase (found in brain and pancreas)
  • tTg-IgA and anti-mitochondrial antibodies found <1%
  • Commentary: There is a notable rate of parietal cell antibodies in those w/ autoimmune thyroid disease.

Diet & Lifestyle Studies

• Weight reduction added to CPAP decreases blood pressure and triglyceride level in OSA: systematic review and meta-analysis
  • 8 RCTs, 2,627 obstructive sleep apnea (OSA) patients
  • Randomized to CPAP alone or CPAP + weight loss therapy
  • CPAP + weight loss led to greater reduction in systolic blood pressure (-8.9 mmHg greater reduction)
  • Commentary: Don’t forget the power of weight loss in those w/ OSA.

• The effects of collagen peptide supplementation on body composition, collagen synthesis, and recovery from joint injury and exercise: a systematic review
  • 15 RCTs
  • Collagen protein supplementation led to improvement in:
    • Reducing joint pain
    • Improve joint functionality

• Low-carbohydrate versus balanced-carbohydrate diets for reducing weight and cardiovascular risk
  • Cochrane database analysis of low (50-150 g/d) to balanced (45-65%) carbohydrate diets
  • 61 RCTs, 6,925 participants
  • In overweight and obese participants, low-carb diets result in little to no difference in change in body weight over 3-9 months (mean difference -1.07 kg additional weight loss)
  • Little to no change in LDL-C or A1C
  • Commentary: Weight loss, independent of what kind of diet what used, results in improvement in many metabolic markers. Low carb diets can work but so can other types of diets.

• Randomized comparison of self-monitored blood glucose (BGM) versus continuous glucose monitoring (CGM) data to optimize glucose control in type 2 diabetes
  • 114 type 2 diabetics, randomized to either finger stick blood glucose measurements (4 times daily) or CGM (24/7)
  • After 4 months, the CGM group had:
    • More A1C reduction (-1.1% vs -0.8%)
    • Reduced hypoglycemic episodes
    • Similar improvements in glucose variability
  • Commentary: CGM may lead to better awareness and thus, improved glycemic control. 

Podcast Summary

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Featured Study

• Effect of Open-label Placebo on Children and Adolescents With Functional Abdominal Pain or Irritable Bowel Syndrome
  • Crossover study of 30 pediatric patients w/ functional abdominal pain or IBS
  • 1 week observation prior to being randomized to either no treatment or an open-label placebo (patients knew it was a placebo)
  • Patients were in control or placebo for 3 weeks before switching to the other group
  • At the end of the study, the open-label placebo group had:
    • Less pain scores (40 vs 45)
    • Took about ½ the amount of rescue medications as the control group (2 vs 3.8 pills)
  • Commentary: A placebo response can be powerful, even if the patient knows it is placebo. This study highlights the strong mind-gut connection in IBS and the high placebo response rate in IBS literature.

Gastrointestinal Studies

• Prebiotic Galacto-Oligosaccharides Impact Stool Frequency and Fecal Microbiota in Self-Reported Constipated Adults: A Randomized Clinical Trial
  • 132 adults w/ constipation, randomized to:
    • Placebo
    • Low dose Galacto-Oligosaccharides prebiotic (GOS) (5.5 g/d)
    • Or high dose GOS (11 g/d)
  • After 3 weeks of supplementation, there was NO significant difference between the 3 groups
  • Commentary: GOS did NOT lead to improvement in those w/ constipation.

• Probiotic supplement attenuates chemotherapy-related cognitive impairment in patients with breast cancer: a randomised, double-blind, and placebo-controlled trial
  • 159 breast cancer patients on chemotherapy, randomized to placebo or probiotics
  • Compared to the placebo group, the probiotic group had improved cognitive function 
  • Commentary: Another data point for the gut-brain axis.

• ​​Efficacy of Bacillus clausii UBBC – 07 spores in the amelioration of oral mucositis in head and neck cancer patients undergoing radiation therapy
  • 46 patients who had radiation, randomized to standard care plus either placebo or soil-based probiotic (in an oral suspension)
  • After 30 days supplementation, the probiotic group had:
    • Increased time to develop mucositis (10 vs 8 days)
    • Reduced time to remission (12 vs 14 days)
    • Less severe mucositis (0 vs 2 patients)
    • No adverse effects
  • Commentary: This is another data point suggesting that probiotics are beneficial to prevent radiation-induced mucositis. Note that the probiotic was administered in an oral-suspension.

• Low FODMAPs diet or usual dietary advice for the treatment of refractory gastroesophageal reflux disease: An open-labeled randomized trial
  • Open-label study of 31 GERD patients refractory to PPI therapy
  • Randomized to standard diet (low-fat diet, head of bed elevation) or low FODMAP diet
  • After 30 days, there was NO significant difference of response rate between the two groups (37.5% vs 20%)
  • Commentary: Even though the differences were NOT statistically significant, there was a trend towards low FODMAP being superior.

• Gluten-free diet in postural orthostatic tachycardia syndrome (POTS)
  • Retrospective study of 20 patients w/ POTS and without Celiac disease who followed a gluten-free diet 
  • 11 patients had MCAS, 8 had hypermobile Ehlers-Danlos syndrome
  • After 4 weeks of a gluten-free diet, patients had improved POTS symptom score (-34% reduction)
  • Commentary:  This study introduces bias by having patients fill out a pre-questionnaire AFTER the study is done.

• Association between helicobacter pylori infection and subclinical atherosclerosis: A systematic review and meta-analysis
  • 18 studies, 6,776 participants w/ H pylori, and 7,795 participants without H pylori
  • H. pylori positive subjects is significantly associated with increased subclinical atherosclerosis (per CIMT score)
  • Commentary: H pylori is associated w/ subclinical atherosclerosis, highlighting the gut-cardiovascular connection.

• Effects of probiotic supplementation on abdominal pain severity in pediatric patients with irritable bowel syndrome: a systematic review and meta-analysis of randomized clinical trials
  • 7 RCTs, 441 pediatric patients w/ IBS
  • Probiotic supplementation led to a significant reduction in abdominal pain in pediatric patients with IBS 
  • Greater benefit for:
    • Children <10 yo
    • Taking probiotics 4+ weeks
  • Commentary: Probiotics are effective in pediatric IBS.

• Dyspepsia in children: organic or functional? Experience in a tertiary care hospital
  • Retrospective study of 100 children w/ dyspepsia
  • Most common underlying causes:
    • 54% – Esophagitis or erosive gastropathy
    • 12% – H pylori
    • 12% – SIBO
    • 20% – functional dyspepsia
  • Commentary: This study found that it is common for functional dyspepsia to have an underlying cause.

• Adjunctive Probiotics Alleviates Asthmatic Symptoms via Modulating the Gut Microbiome and Serum Metabolome
  • 55 asthma patients, all took inhaled steroids and randomized to either placebo or probiotic
  • After 3 months, the probiotic group had greater symptom relief
  • Commentary: Probiotics may be helpful for asthma.

• Highly Bioavailable Curcumin Derivative Ameliorates Crohn’s Disease Symptoms: A Randomized, Double-Blind, Multicenter Study
  • 30 patients w/ mild-to-moderate Crohn’s Disease, randomized to placebo or curcumin (Theracurmin® 360 mg/day)
  • After 3 months of supplementation, the curcumin group had:
    • Higher clinical remission rates (40% vs 0%)
    • Reduced endoscopic remission rate (15% vs 0%)
    • No adverse effects
  • Commentary: Another data point suggesting curcumin may be helpful in IBD.

• A high potency multi-strain probiotic improves glycemic control in children with new-onset type 1 diabetes mellitus: A randomized, double-blind, and placebo-controlled pilot study
  • 90 kids w/ newly diagnosed type 1 diabetes, randomized to placebo or high-dose multi-strain probiotics (112 billion CFU)
  • After 3 months, the probiotic group had:
    • Decreased A1C (-5.1% vs -3.8%)
    • Higher number of those who achieved remission
    • No adverse effects
  • Commentary: Probiotics can help glycemic control in those w/ type 1 diabetes.

Autoimmunity Study

• ​​Probiotic supplementation improves clinical outcomes and quality of life indicators in patients with plaque psoriasis: A randomized double-blind clinical trial
  • 50 patients w/ plaque psoriasis, randomized to control or probiotic drink
  • After 8 weeks, the probiotic group had:
    • Improved mood
    • Improved quality of life
    • Reduced symptom score
    • Increased antioxidant capacity
    • Decreased CRP (-1.6 vs +0.9)
  • Commentary: Probiotics improved quality of life, symptoms, and inflammatory markers in those w/ psoriasis.

Thyroid & Hormones Study

• Efficacy of Ginger Supplementation in Relieving Persistent Hypothyroid Symptoms in Patients with Controlled Primary Hypothyroidism: A Pilot Randomized, Double-Blind, Placebo-Controlled Clinical Trial
  • 60 hypothyroid patients on thyroid replacement therapy but with persistent symptoms despite normal TSH
  • Randomized to placebo or ginger supplementation (500 mg BID)
  • After 30 days, the ginger group had:
    • Improved total symptom score (8.6 vs 15.8)
    • Decreased body weight (-2.4 vs +1 kg)
    • Improved TSH (-0.9 vs +0.95)
    • Lower fasting glucose (-11.6 vs +7)
    • Improved triglycerides (-57 vs +40)
    • Improved total cholesterol (-19 vs +10)
  • Commentary: Ginger supplementation may improve some hypothyroid symptoms and lead to improvement in some metabolic markers.

Diet & Lifestyle Studies

• The Inclusion of Folic Acid in Weekly Iron-Folic Acid Supplements Confers no Additional Benefit on Anemia Reduction in Nonpregnant Women: A Randomized Controlled Trial in Malaysia
  • 311 nonpregnant women randomized to supplemental iron plus either:
    • No folic acid
    • Low dose folic acid (0.4 mg)
    • High dose folic acid (2.8 mg)
  • 84% had low baseline folate levels
  • After 16 weeks of supplementation, all groups had a reduction in anemia (RR 0.65) and iron deficiency (OR 0.3)
    • NO difference between the 3 groups
  • Commentary: Despite low baseline folate levels, the addition of folic acid on top of iron supplementation did NOT improve anemia or iron deficiency rates.

• Oral myofunctional therapy for the treatment of temporomandibular disorders: A systematic review
  • 4 trials
  • 3 of the 4 trials showed benefit of myofunctional therapy to improve TMJ disorder
  • Commentary: At the clinic, we consider using MFT for sleep apnea which has been associated w/ TMJ.

• Traumatic brain injuries among veterans and the risk of incident dementia: A systematic review & meta-analysis
  • 13 studies, 7.1 million participants
  • History of TBI was associated with an increased risk of:
    • All-cause dementia (HR 1.95)
    • Vascular dementia (HR 2.02)
  • NO increased risk of Alzheimer’s disease
  • Commentary: There was significant heterogeneity in this meta-analysis. However, there is a mild association between TBI and dementia.

• Cardiovascular and metabolic effects of a mandibular advancement device and continuous positive airway pressure in moderate obstructive sleep apnea: a randomized controlled trial
  • 54 patients w/ moderate obstructive sleep apnea
  • Randomized to mandibular advancement device (MAD) or CPAP
  • After 12 months of therapy:
    • NO significant improvement in cardiovascular risk factors 
    • Sleep apnea severity significantly reduced with both MAD and CPAP
      • There were NO significant differences between the two groups
  • Commentary: MAD therapy was just as effective as CPAP therapy for improving sleep apnea.

• Continuous Glucose Monitoring With Low-Carbohydrate Nutritional Coaching to Improve Type 2 Diabetes Control: Randomized Quality Improvement Program
  • 185 patients w/ type 2 diabetes randomized to standard care or personalized nutrition coaching to include:
    • Eating < 100g/day of carbohydrates
    • Use a continuous glucose monitor (CGM) 
  • After 12 months, in participants who followed nutrition coaching (only 33%), A1c was 1.1% lower
  • Commentary: CGM use may lead to improved HbA1c by helping participants more effectively stick with dietary recommendations through increased self-accountability.