Podcast Summary

Download Episode

Featured Study

• The D-Health Trial: a randomised controlled trial of the effect of vitamin D on mortality
  • 21,315 participants over 60 years old
  • Randomized to placebo or vitamin D (60,000 IU per month)
  • After 5 years of supplementation and 1,100 recorded deaths, the vitamin D group had:
    • Greater serum vitamin D levels (46 ng/mL vs 30 ng/mL)
    • No difference in overall mortality
    • No difference in cardiovascular disease
    • No difference for cancer
  • Commentary: Administering vitamin D indiscriminately to older individuals did not change the risk of all-cause mortality, cardiovascular disease, or cancer after 5 years of supplementation.

Gastrointestinal Studies

• Smoking has disruptive effects on the small bowel luminal microbiome
  • Cross-sectional study of 24 current smokers, 27 ex-smokers, 27 never smokers
  • Microbiome measured by 16S rRNA sequencing
  • Current smokers had:
    • Lower microbial diversity
    • More abundance of oral and respiratory microbiota
  • Commentary: Smoking is a risk factor for dysbiosis.

• An Open-label, Multicenter Study to Assess the Efficacy and Safety of a Novel Probiotic Blend in Patients With Functional Gastrointestinal Symptoms
  • 188 patients with functional GI disorders all given 5-strain Bifidobacterium/Lactobacillus probiotic
  • After 1 month of supplementation 85% reported overall GI symptom improvement
    • 76% had improved diarrhea
    • 87% had improved bloating
    • 74% had improved constipation frequency, 80% constipation severity
  • Commentary: More support for multi-strain/species probiotics.

• Gut dysbiosis and small intestinal bacterial overgrowth as independent forms of gut microbiota disorders in cirrhosis
  • 47 patients w/ cirrhosis, all tested with lactulose hydrogen breath test 
  • SIBO was diagnosed in 51% of patients
  • Commentary: SIBO is a common diagnosis in patients with liver disease.

• Randomized control trial on the efficacy of Limosilactobacillus reuteri ATCC PTA 4659 in reducing inflammatory markers in acute uncomplicated diverticulitis
  • 119 patients w/ acute diverticulitis, randomized to: 
    • Standard therapy (fluids, bowel rest) + placebo
    • Standard therapy + probiotic
  • After 3 days of treatment, the probiotic group experienced:
    • Reduced CRP (- 59% probiotic vs – 40% placebo)
    • Reduced calprotectin (- 17% vs – 11%) 
    • Shorter hospital stay (76 hours vs 84 hours) 
  • Both groups experienced equal reductions in abdominal pain score (-4 points) 
  • Commentary: Probiotics led to improved inflammatory markers and shorter hospital stay in patients with acute diverticulitis.

• Efficacy of Probiotics for Irritable Bowel Syndrome: A Systematic Review and Network Meta-Analysis
  • 43 RCTs, 5,531 IBS patients treated w/ probiotics
  • Different probiotic strains were evaluated for efficacy 
  • This meta-analysis found that:
    • Bacillus coagulans (soil based probiotic) led to the greatest improvements in IBS symptom scores
    • Length of probiotic therapy (NOT dose) was more influential on clinical outcome in IBS
  • Commentary: This study supports the use of multi-strain/species probiotics in patients with IBS.

• A Nonviable Probiotic in Irritable Bowel Syndrome: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study
  • 389 IBS patients, randomized to placebo or nonviable probiotic (E coli and Enterococcus faecalis)
  • After 26 weeks, similar response rate to abdominal pain and global symptoms
  • Commentary: This study failed to show benefit of a non-viable probiotic in IBS.

• The combined effects of probiotics and restricted calorie diet on the anthropometric indices, eating behavior, and hormone levels of obese women with food addiction : a randomized clinical trial
  • 62 obese women with food addiction
  • Randomized to calorie-restricted diet (-300-500 Cals/d) plus either multi-strain probiotic or placebo
  • After 3 months, the probiotic group had significantly greater reduction in:
    • Weight (-6.7 kg probiotic vs -3.3 kg placebo)
    • BMI (-2.5 vs -1.1)
    • Waist circumference (-8.2 cm vs -6 cm)
    • Body fat percentage (-3.6% vs -1.2%)
    • Hunger score (-11 vs -3.5)
  • Commentary: Probiotics may improve anthropometric markers through a reduction in eating behavior.

• Development of Cancer Among Patients With Pediatric-Onset Inflammatory Bowel Disease: A Meta-analysis of Population-Based Studies
  • 5 studies, 19,812 pediatric patients with IBD, followed up over 283,540 person-years
  • Compared to the general population, pediatric patients with IBD had an increased risk of developing cancers (RR 2.5), specifically:
    • Liver cancer
    • Colorectal cancer
    • Small bowel 
  • Commentary: IBD was associated with an increased risk of gastrointestinal cancers.

• Prevention of Recurrent Childhood Caries with Probiotic Supplements: A Randomized Controlled Trial with a 12-Month Follow-Up
  • 24 preschool children with history of cavities, randomized to: 
    • Placebo
    • Probiotic 
  • After 1 year, there was NO significant difference in recurrence of cavities between groups 
  • Commentary: This small study failed to show a benefit of probiotics on cavity recurrence.

• 16S rRNA and metagenomic shotgun sequencing data revealed consistent patterns of gut microbiome signature in pediatric ulcerative colitis
  • 19 pediatric ulcerative colitis (UC) patients, 23 healthy controls
  • Microbiome analyzed by 16S rRNA sequencing
  • UC patients had:
    • Lower alpha diversity
    • Greater beta diversity
    • Less abundance of Akkermansiaceae, Clostridiaceae, Eggerthellaceae, Lachnospiraceae, and Oscillospiraceae
  • Commentary: Pediatric UC patients had different microbiome signatures as compared to healthy controls.

• Systematic review: Clinical effectiveness of interventions for the treatment of nocturnal gastroesophageal reflux
  • 31 studies on lifestyle modifications for treating nocturnal GERD
  • Success rates of 34-81% (versus 10.4%-51.7% in the placebo group) for:
    • Head of bed elevation (5 studies)
    • Prolonging dinner-to-bed time (2 studies)
    • Left lateral decubitus sleeping position (2 studies)
  • Insufficient evidence for:
    • Nasal CPAP
    • Hypnotics
    • Baclofen
    • Adding bedtime H2 receptor antagonist
  • Commentary: There is good evidence for conservative treatments for nocturnal reflux.

Autoimmunity Study

• ​​Serum levels of n-3 and n-6 polyunsaturated fatty acids in patients with systemic lupus erythematosus and their association with disease activity: a pilot study
  • 30 lupus patients, 20 healthy controls
  • Measured serum fatty acids
  • Results:
    • Lupus patients had higher serum linoleic acid (LA) and α-linolenic acid levels 
    • LA levels correlated with higher ANA levels and steroid medication doses
    • EPA and DHA levels correlated with lower anti-dsDNA antibody levels
  • Commentary: This study suggested an association between omega 3 and 6 levels with lupus and associated biomarkers.

Thyroid & Hormones Studies

• Vasomotor menopausal disorders as a possible result of dysfunction of the microbiota-intestine-brain axis
  • 54 women with menopausal vasomotor symptoms, 21 healthy controls
  • Menopausal women with vasomotor symptoms had more dysbiosis:
    • Decrease in Bifidobacterium/Lactobacillus 
    • Increased opportunistic strains (Klebsiella, C. difficile)
  • Commentary: This study highlights the gut-female hormone connection.

• Subclinical hypothyroidism in older individuals
  • Narrative review of subclinical hypothyroidism (SCH)
  • “Studies showed no significantly increased incidence in adverse cardiovascular, musculoskeletal, or cognitive outcomes in individuals aged 65 years or older when serum thyroid-stimulating hormone concentration was 4.5-7.0 mIU/L versus a euthyroid group.”
  • “In older individuals with subclinical hypothyroidism, symptoms of hypothyroidism and cardiac and bone parameters did not improve after levothyroxine treatment.”
  • “Treatment with levothyroxine should be considered for individuals aged 65 years or older with subclinical hypothyroidism when thyroid-stimulating hormone concentration is persistently 7 mIU/L or higher and to not initiate treatment with thyroid-stimulating hormone concentrations of less than 7 mIU/L. Levothyroxine doses should be personalized according to age, comorbidities, and life expectancy.” 
  • Commentary: Take in consideration age and TSH level when deciding to treat SCH or not.

• ​​Influence of phytoestrogens on endometrial thickness: a systematic review and meta-analysis
  • 10 studies, 1,476 patients
  • Phytoestrogen supplementation led to NO change in endometrial thickness even after 2 years

Diet & Lifestyle Studies

• Safety and efficacy of anti-inflammatory therapy in patients with coronary artery disease: a systematic review and meta-analysis
  • 10 RCTs, 60,782 participants
  • Anti-inflammatory therapy lead to reduced risk of:
    • Myocardial infarction (10% reduction)
    • Coronary revascularization (26% reduction) 
  • No difference in cardiovascular death, stroke, or all-cause mortality
  • Commentary: Inflammation is a residual risk factor for cardiovascular disease. Reducing inflammation may lower some but not all risk.

• Metabolic syndrome and pesticides: A systematic review and meta-analysis
  • 12 studies, 6,789 participants
  • 29% had metabolic syndrome
  • Overall exposure to pesticides and their contaminants increased the risk of metabolic syndrome by 30%
  • Commentary: This highlights a key environmental trigger to metabolic dysfunction.

• A novel Wim Hof psychophysiological training program to reduce stress responses during an Antarctic expedition
  • 13 healthy participants, randomized to:
    • Control
    • Wim Hof Method (breathing exercise, cold exposure, meditation) x 20 minutes per day
  • After 2 months, the Wim Hof Method group experienced reduced:
    • Depressive symptoms 
    • Stress response
  • Commentary: Wim Hof Method may be a simple, cost effective option for reducing stress.

Podcast Summary

Download Episode

Featured Study

• Pelvic floor biofeedback is an effective treatment for severe bloating in disorders of gut-brain interaction with outlet dysfunction
  • 156 patients with severe bloating
  • All given 2 weeks of diet changes and balloon expulsion test (evaluating patient’s ability to evacuate a stool)
  • 64 were non-responsive – then given pelvic floor electromyography (EMG) and biofeedback 
    • Specifics on biofeedback:
      • First taught to strain more effectively and to coordinate expulsion efforts with their breathing
      • Then taught to relax pelvic floor muscles during straining through EMG imaging 
  • After biofeedback:
    • 54% had major improvement/cure
    • 100% had at least 50% decrease in bloating severity
  • Commentary: Pelvic floor biofeedback can improve non-responsive bloating.

Gastrointestinal Studies

• Effectiveness of Multistrain Probiotic Formulation on Common Infectious Disease Symptoms and Gut Microbiota Modulation in Flu-Vaccinated Healthy Elderly Subjects
  • 50 elderly participants vaccinated for influenza
  • Randomized to multi-strain probiotic or placebo
  • After 1 month of supplementation, the probiotic group had 78%  less infections (OR 0.22)
  • Commentary: More evidence that probiotics can improve the immune system and help prevent common viral infections.

• Magnesium alginate versus proton pump inhibitors for the treatment of laryngopharyngeal reflux: a non-inferiority randomized controlled trial
  • 50 patients w/ laryngopharyngeal reflux (LPR) symptoms, randomized to: 
    • Omeprazole (20 mg)
    • Or alginate suspension (Gastrotuss®)
  • After 2 months of treatment, both groups had similar reduction in symptoms
  • Commentary: Alginate suspension is non-inferior to PPI therapy for LPR symptoms.

• Efficacy and safety of Bacillus clausii (O/C, N/R, SIN, T) probiotic combined with oral rehydration therapy (ORT) and zinc in acute diarrhea in children: a randomized, double-blind, placebo-controlled study in India
  • 454 hospitalized children (6 mo- 5 years) with acute diarrhea <48 hours 
  • Received standard care and randomized to soil-based probiotic or placebo
  • The probiotic group had:
    • Similar recovery rate (97% probiotic vs 98% placebo)
    • Time to recovery (43 hrs vs 42 hrs)
  • Commentary: There were no benefits of soil-based probiotics in acute diarrhea in this study. However, other studies have suggested a benefit. Also, since only ~20% of patients had nausea/vomiting or abdominal pains, the relative potential benefit was small. 

• Gut dysbiosis in severe mental illness and chronic fatigue: a novel trans-diagnostic construct? A systematic review and meta-analysis
  • 19 studies, 2,758 mental illness patients, 1,847 healthy controls
  • Compared to controls, mental illness patients showed increased blood levels of:
    • Zonulin (large effect size) 
    • Lipopolysaccharide (moderate effect size) 
  • Commentary: Markers of leaky gut and dysbiosis were associated with mental illness, highlighting the gut-brain connection. Keep in mind this is an observational study.

• Small intestinal bacterial overgrowth and orocecal transit time in patients of nonalcoholic fatty liver disease
  • 103 NAFLD patients, 49 healthy controls
  • All patients were tested for SIBO w/ lactulose breath test 
  • Compared to healthy controls, NAFLD patients had: 
    • Higher rates of SIBO (58% vs 27%)
    • Longer intestinal-transit time
  • SIBO+ NAFLD patients had slower intestinal-transit time compared to SIBO- NAFLD patients
  • Commentary: SIBO is more common in patients with NAFLD than healthy controls. This highlights the gut-liver connection.

• Effect of early enteral nutrition combined with probiotics in patients with stroke: a meta-analysis of randomized controlled trials
  • Aim: Evaluate the efficacy and safety of elemental diet + probiotics in stroke patients
  • 26 RCTs, 2,216 patients
  • Compared to just elemental diet alone, elemental diet + probiotics resulted in:
    • Lower incidence of of GI complications (71% reduction)
    • Lower risk of infection (73% reduction)
    • Shorter hospital stay (-8.7 days)

• Effect of perioperative probiotic supplements on postoperative short-term outcomes in gastric cancer patients receiving neoadjuvant chemotherapy: A double-blind, randomized controlled trial
  • 66 gastric cancer patients, all had chemotherapy and surgery
  • Randomized to no treatment or probiotics before surgery
  • The probiotic group had:
    • Fewer postoperative infections
    • Less time to first bowel movement
    • Shorter hospital stay
    • Reduced inflammatory markers
  • Commentary: More proof that probiotics can improve cancer-related treatment side effects.

• Psyllium reduces inulin-induced colonic gas production in IBS: MRI and in vitro fermentation studies
  • Cross-over study of 19 patients with IBS
  • Participants ingested a test drink containing either:
    • Inulin (20 g) 
    • Psyllium (20 g) 
    • Inulin (20 g) + psyllium (20 g) 
    • Or dextrose (20 g) (placebo)
  • Breath hydrogen was measured every 30 min with MRI scans hourly for 6 hours
  • Co-administration of psyllium to inulin significantly reduced the inulin-induced rise in colonic gas levels
  • Commentary: Giving psyllium along with inulin can reduce gas production compared to inulin alone. Adding psyllium to other fiber may increase its tolerability in IBS patients.

• Increased prevalence of irritable bowel syndrome in migraine patients: a systematic review and meta-analysis
  • 11 studies, 28,336 migraine patients, 1.5 million healthy controls 
  • Compared to healthy controls, migraine patients had a higher prevalence of IBS (OR 2.5)
  • Commentary: IBS is associated with migraines, highlighting the gut-brain connection.

• Helicobacter pylori Infection and Non-alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis
  • 22 studies, 33,711 patients with H. pylori infection, 83,406 healthy controls
  • Compared to healthy controls, patients with H. pylori were at a higher risk of developing NAFLD (OR 1.2)
  • Commentary: H. pylori may be a minor risk factor for developing NAFLD.

• 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
  • Compared to healthy controls, SIBO was more prevalent in those with diabetes (OR 2.9)
    • Similar prevalence between type 1 (25%) and type 2 (30%) diabetics 
  • Commentary: This highlights the SIBO-metabolic connection.

• Probiotic Mixture Containing Lactobacillus helveticus, Bifidobacterium longum and Lactiplantibacillus plantarum Affects Brain Responses to an Arithmetic Stress Task in Healthy Subjects: A Randomised Clinical Trial and Proof-of-Concept Study
  • 22 healthy subjects, randomized to placebo or probiotic x 4 weeks each, separated by a 4 week washout period
  • All participants underwent fMRI while performing a stressful task
  • Compared to placebo, the probiotic group experienced increased brain activity in areas responsible for reducing stress
  • However, there was NO difference in subjective stress response between groups
  • Commentary: While probiotics led to positive changes in brain function, it did NOT reduce the subjective stress response.

• Small intestinal bacterial overgrowth in patients with inflammatory bowel disease: A case-control study
  • Retrospective study, 86 patients with IBD, 66 healthy controls
  • All participants underwent glucose hydrogen breath tests to assess for SIBO
  • SIBO was more common in: 
    • IBD vs healthy controls (18.6% vs 1.5%)
    • Crohn’s disease vs ulcerative colitis (34.1% vs 4.4%) 
  • Independent risk factors for SIBO in those with IBD included: 
    • Female gender
    • Previous surgery for IBD
  • Commentary: Patients with IBD, specifically Crohn’s disease, had the highest risk of developing SIBO.

• Probiotics’ effect on visceral and subcutaneous adipose tissue: a systematic review of randomized controlled trials
  • 14 studies, 1,523 participants randomized to control or probiotics 
  • Probiotics led to a reduction in:
    • Visceral adipose tissue (-3.6 cm2)
    • Subcutaneous adipose tissue (-2.9 cm2) 
  • Commentary: Probiotics may support healthy body composition.

• A randomised controlled trial of a probiotic and a prebiotic examining metabolic and mental health outcomes in adults with pre-diabetes
  • 129 participants with pre-diabetes, randomized to: 
    • Placebo + control cereal (cornflakes) 
    • Placebo + prebiotic cereal (oat-derived beta-glucan) 
    • Probiotics + control cereal
    • Probiotic + prebiotic cereal
  • After 6 months, there was NO clinically meaningful difference between groups in: 
    • Fasting glucose 
    • Insulin
    • A1c
    • Fasting lipids
    • Blood pressure 
    • Weight 
  • Commentary: This study did NOT find a benefit for probiotics, prebiotics or a combination of them in improving glucose regulation. However, other studies have suggested a benefit.

Autoimmunity Studies

• Systematic Review and Meta-analysis on the Association of Occupational Exposure to Free Crystalline Silica and Rheumatoid Arthritis
  • 12 studies
  • Exposure to free crystalline silica (FCS) was associated with a higher risk of rheumatoid arthritis (OR 1.94)
  • Commentary: Exposure to FCS almost doubled the risk of rheumatoid arthritis. FCS exposure can be from cutting bricks, concrete work, mining, etc. This highlights environmental triggers to autoimmunity.

• Association between systemic lupus erythematosus and disruption of gut microbiota: a meta-analysis
  • 11 studies, 373 systemic lupus erythematosus (SLE) patients, 1,288 healthy controls 
  • Patients with SLE had lower gut microbiome diversity compared to healthy controls (small effect size)

Thyroid & Hormones Studies

• Obesity is associated with subclinical hypothyroidism in the presence of thyroid autoantibodies: a cross-sectional study
  • Cross sectional study of 2,505 participants
  • Prevalence:
    • 11.5% had obesity
    • 6.6% had subclinical hypothyroidism (SCH)
    • 17.6% had TPO Abs
  • Obesity was associated with a higher risk of SCH (OR 2.2) only in those with TPO Abs

• Preliminary Observation of the Changes in the Intestinal Flora of Patients With Graves’ Disease Before and After Methimazole Treatment
  • 18 untreated Graves’ disease (GD) patients, 10 euthryoid GD patients treated with methimazole, 11 healthy controls
  • All had 16S rRNA stool sampling
  • Results:
    • Abundance of Bifidobacterium was associated with higher levels of TRAb, TgAb, and TPOAb
    • Microbiome diversity was lower in both GD patient groups compared to healthy controls
    • Methimazole treatment significantly altered microbiome composition
  • Commentary: This highlights the gut-thyroid connection. Methimazole may function partially through changes in the gut.

• The impact of omega-3 polyunsaturated fatty acids on primary dysmenorrhea: a systematic review and meta-analysis of randomized controlled trials
  • 5 RCTs on women with primary dysmenorrhea
  • Omega-3 polyunsaturated fatty acids led to a reduction in severity of primary dysmenorrhea symptoms (large effect size)

Diet & Lifestyle Studies

• Effect of high dose vitamin D supplementation on indices of sarcopenia and obesity assessed by DXA among older adults: A randomized controlled trial
  • 248 overweight older adults (>65 years) with baseline low serum Vitamin D level of 10-30 ng/mL
  • All received calcium (1 g/d) plus:
    • Low dose Vit D (600 IU/d)
    • High dose Vit D (3,750 IU/d)
  • After 12 months, NO difference in:
    • Muscle mass
    • Muscle strength
    • Fat mass
    • Sarcopenia

• Egg Consumption and Risk of All-Cause and Cause-Specific Mortality: A Systematic Review and Dose-Response Meta-Analysis of Prospective Studies
  • 32 cohort studies, 2.2 MILLION participants
  • Comparing highest vs. lowest egg intake categories was NOT associated with the risk of:
    • Mortality from all-causes
    • Cardiovascular disease
    • Or stroke
  • However, it was associated with a higher risk of cancer mortality (RR 1.2)
  • Commentary: While nutritional epidemiology is hard to interpret, this large study found NO association between egg consumption and heart disease risk.

• Characteristics of hypertension and arterial stiffness in obstructive sleep apnea: A Scandinavian experience from a prospective study of 6408 normotensive and hypertensive patients
  • 6,408 participants w/ suspected sleep apnea, referred for sleep apnea testing 
  • 35% of patients tested positive for sleep apnea
  • Hypertension was more prevalent in those diagnosed with sleep apnea compared to no sleep apnea (71% vs 48%) 
  • Commentary: Sleep apnea is a common diagnosis that is associated with increased risk of hypertension.

• Can omega-3 fatty acids be beneficial in pediatric NAFLD? A systematic review and meta-analysis
  • 6 RCTs, 378 pediatric patients w/ NAFLD
  • Compared to placebo, omega-3 fatty acid supplementation improved: 
    • Liver enzymes
    • Liver steatosis (demonstrated by ultrasound) 
    • BMI 
  • Commentary: Omega-3 fatty acids may be beneficial for NAFLD.

• Basal Serum Diamine Oxidase Levels as a Biomarker of Histamine Intolerance: A Retrospective Cohort Study
  • Retrospective study on 146 patients w/ histamine intolerance (HIT) symptoms 
  • Serum diamine oxide (DAO) levels were measured and categorized by:
    • Low (< 3 U/mL)
    • Moderate (3-10 U/mL)
    • High (> 10 U/mL) 
  • Compared to the high DAO group, those with low DAO experienced:
    • More frequent HIT symptoms (87% vs 29%) 
    • More severe HIT symptoms
  • After 6-8 months of treatment w/ low histamine diet and/or DAO supplementation, patients with moderate DAO levels showed the greatest response to treatment 
  • Commentary: DAO levels correlated with HIT symptom frequency and severity, however response to treatment was greatest in those with moderate levels of DAO.

Podcast Summary

Download Episode

Featured Study

• Low FODMAP Diet and Probiotics in Irritable Bowel Syndrome: A Systematic Review With Network Meta-analysis
  • 76 RCTs, 8,058 participants
  • Both lactobacillus/bifidobacterium and soil-based probiotics were effective in reducing IBS symptoms:
    • Bacillus species (RR 5.67)
    • Lactobacillus (RR 1.74)
    • Bifidobacterium (RR 1.76) 
  • The combination of Bifidobacterium, Lactobacillus, and Streptococcus (RR 1.50) was the most effective among all the treatment combinations
  • Commentary: This high-quality meta-analysis showed benefit of both lactobacillus/bifidobacterium and soil-based probiotics in improving IBS. It also highlights the superiority of multi-species probiotics.

Gastrointestinal Studies

• Association Between Psychosocial Disorders and Gastroesophageal Reflux Disease: A Systematic Review and Meta-analysis
  • 9 studies, 1.5 million participants
  • GERD was associated with a higher risk of anxiety/depression/mood disorders (OR 2.57)
  • Commentary: This highlights the gut-brain connection.

• Fecal Microbiota Transplantation from Overweight or Obese Donors in Cachectic Patients with Advanced Gastroesophageal Cancer: A Randomized, Double-blind, Placebo-Controlled, Phase II Study
  • 24 cachectic patients w/ metastatic gastroesophageal cancer randomized to :
    • Allogenic FMT (healthy obese donor) 
    • Or autologous FMT, prior to palliative chemotherapy
  • Allogenic FMT led to:
    • NO improvement of cachexia rates
    • Less disease severity at 3 months
    • Better overall survival (365 vs 227 days, HR 0.38)
  • Commentary: This fascinating study found that a FMT from healthy obese donors improved upper GI cancer survival rates.

• Probiotics for treatment of chronic constipation in children
  • 14 RCTs, 1,127 pediatric patients w/ constipation
  • Compared to placebo, probiotics alone or in combination with other constipation therapies (e.g magnesium oxide or laxatives) did NOT lead to improved constipation 
  • Constipation was improved with the use of synbiotics (RR  2.3) 
  • Commentary: Synbiotics, not probiotics, were effective in improving constipation.

• The risk of dementia in patients with inflammatory bowel disease: a systematic review and meta-analysis
  • 7 studies, 65,454 dementia patients
  • Compared to the general population, IBD was associated with increased risk of:
    • Dementia (RR 1.3) 
    • Alzheimer’s (RR 2.7)
  • Commentary: IBD is associated with an increased risk of dementia and Alzheimer’s disease, highlighting the gut-brain connection.

• A Randomized Pilot Study to Compare the Effectiveness of a Low FODMAP Diet vs Psyllium in Patients With Fecal Incontinence and Loose Stools
  • 37 patients w/ fecal incontinence and loose stool, randomized to:
    • Low FODMAP diet (LFD) 
    • Psyllium (6 g/d) 
  • After 1 month the LFD group had:
    • More improvement of fecal incontinence severity score (-6.8 LFD vs -3.3 psyllium)
    • NO significant difference in proportion of patients who experienced >50% reduction in fecal incontinence episodes (38.9% LFD vs 50% psyllium)
  • Both groups experienced similar improvements in quality of life 
  • Commentary: Both LFD and psyllium led to improvements in quality of life and fecal incontinence frequency, while LFD led to greater improvements in severity of fecal incontinence.

• Group Cognitive-Behavioral Therapy With Interoceptive Exposure for Drug-Refractory Irritable Bowel Syndrome: A Randomized Controlled Trial
  • 107 drug-refractory IBS patients, randomized to:
    • No treatment
    • Cognitive behavioral therapy (CBT) 
  • After 2.5 months, the CBT group experienced: 
    • Reduced IBS symptom score (-115.8 CBT vs -29.7 control) 
    • Improved quality of life (+20.1 vs -0.2) 
  • Commentary: CBT is an effective therapy for drug-refractory IBS.

• The Effects of Prebiotics, Synbiotics, and Short-Chain Fatty Acids on Respiratory Tract Infections and Immune Function: A Systematic Review and Meta-Analysis
  • 58 studies
  • Compared to placebo, the frequency of respiratory tract infections (RTIs) were reduced with:
    • Prebiotics (OR 0.7)
    • Synbiotics (OR 0.7)
  • Prebiotics were more effective at preventing RTIs in infants and children compared to adults
  • Commentary: Prebiotics and synbiotics may have a protective role against URTs, providing greater benefit to infants and children compared to adults.

• Associations between proton pump inhibitors and Alzheimer’s disease: A nested case-control study using a Korean nationwide health screening cohort
  • 17,225 Alzheimer’s disease (AD) patients, 68,900 controls
  • Prior PPI use was associated with increased AD in both current (OR 1.3) and past (OR 1.1) users
  • Longer duration of PPI use was also associated with an increased risk of AD:
    • <30 days (OR 1.1)
    • 30-90 days (OR 1.2)
    • >90 days (OR 1.3)
  • Commentary: Longer-term use of PPIs is associated with a small increased risk of AD.

• Effect of Open-label Placebo on Children and Adolescents With Functional Abdominal Pain or Irritable Bowel Syndrome: A Randomized Clinical Trial
  • 30 pediatric patients w/ IBS or functional abdominal pain, openly randomized to:
    • Placebo x 3 weeks followed by 3 weeks of no treatment
    • No treatment x 3 weeks followed by placebo
  • Compared to no treatment, placebo led to:
    • Reduced pain scores (40 placebo vs 45 no treatment)
    • Fewer rescue medications needed (2 vs 3.8 pills)
  • Commentary: Placebo can have a significant effect on GI symptoms even in pediatric patients.

• Fecal microbiota transplant improves cognition in hepatic encephalopathy and its effect varies by donor and recipient
  • Open-label study of 10 hepatic encephalopathy patients treated w/ 5 rounds of FMT
  • After 7 weeks, FMT led to:
    • NO change in liver disease scores
    • Improved cognition scores (+3.1)
  • Commentary: This small study shows FMT improves cognitive function in patients w/ hepatic encephalopathy. Keep in mind there was no control group and patients knew they were receiving treatment.

• Effect of Probiotics on the Frequency of CD4+ T-Cells in HIV-Infected Children and Adolescents: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
  • 3 studies on pediatric patients w/ HIV randomized to control or probiotics
  • Probiotic group had greater improvement in CD4+ T-cell counts with NO adverse effects
  • Commentary: Probiotic supplementation has a positive effect on improving immune function in a very high risk cohort.

• A systematic review and meta-analysis on the efficacy of probiotics for bacterial vaginosis
  • 18 studies, 1,651 patients w/ bacterial vaginosis (BV)
  • Compared to antibiotics alone, antibiotics + probiotic led to: 
    • Lower recurrence rate (RR 0.4) 
    • Greater cure rate (1.2)
  • Compared to placebo, probiotics led to: 
    • Lower recurrence rate (RR 0.3)
    • Greater cure rate (RR 10) 
  • Compared to antibiotics, probiotics led to: 
    • Lower recurrence rate (RR 0.3)
    • Greater cure rate (RR 1.3) 
  • Probiotic treatment for 1-3 months led to greater clinical outcomes compared to <1 month
  • Commentary: Probiotic supplementation for 1-3 months improved clinical outcomes in patients with BV. Note the lower recurrence rate and greater cure rates when comparing probiotics alone vs antibiotics + probiotics

• The effect of multistrain synbiotic and vitamin D3 supplements on the severity of atopic dermatitis among infants under 1 year of age: a double-blind, randomized clinical trial study
  • 81 infants w/ atopic dermatitis (AD), randomized to:
    • Routine treatment (corticosteroids, antihistamines, emollients)
    • Synbiotics + routine treatment 
    • Vitamin D (1,000 IU/day) + routine treatment
  • After 2 months, AD scores were similarly reduced in BOTH synbiotic (-14) and vitamin D (-12) groups compared to routine treatment alone
  • Commentary: Probiotics and vitamin D are beneficial therapies for AD, and likely the combination of the two therapies would have a synergistic effect.

Thyroid & Hormones Study

• Randomized Clinical Trial: Probiotics Alleviated Oral-Gut Microbiota Dysbiosis and Thyroid Hormone Withdrawal-Related Complications in Thyroid Cancer Patients Before Radioiodine Therapy Following Thyroidectomy
  • 39 thyroid cancer patients undergoing thyroidectomy and thyroid medication withdrawal, randomized to:
    • Placebo
    • Probiotics (lacto/bifido + soil based)
  • After 1 month, compared to placebo, the probiotic group experienced less thyroid hormone withdrawal symptoms, including:
    • Constipation (9% probiotics vs 63% placebo)
    • Fatigue (30% vs 63%)
    • Weight gain (35% vs 69%)
    • Dry mouth (30% vs 69%) 
  • Commentary: Probiotics led to improvements in hypothyroid symptoms associated with thyroid medication withdrawal. This illustrates the gut-thyroid connection, and how improving gut health with probiotics can positively impact thyroid symptoms.

Diet & Lifestyle Studies

• Dose-Dependent Effect of Supervised Aerobic Exercise on HbA 1c in Patients with Type 2 Diabetes: A Meta-analysis of Randomized Controlled Trials
  • 26 trials, 1,253 participants
  • Cach 30 minutes of aerobic exercise lowered A1C by -0.22%
  • Aerobic exercise also:
    • Decreased antidiabetic medications by 13 per 100 patients 
    • Increased hypoglycemic reactions by 10 per 100 patients 
  • Commentary: Aerobic exercise is an effective strategy to manage hyperglycemia.

• Nocturnal nasal congestion is associated with uncontrolled blood pressure in patients with hypertension comorbid obstructive sleep apnea
  • 326 patients newly diagnosed obstructive sleep apnea (OSA) classified as:
    • 66 with controlled hypertension
    • 209 with uncontrolled hypertension
    • 51 with severe resistant hypertension
  • Nocturnal nasal congestion was independently associated with:
    • Uncontrolled hypertension (OR 2.09)
    • Severe resistant hypertension (OR 2.96)
  • Commentary: Nasal congestion may block proper respiration at night and contribute to OSA.

• Effect of Intermittent Fasting Diet on Glucose and Lipid Metabolism and Insulin Resistance in Patients with Impaired Glucose and Lipid Metabolism: A Systematic Review and Meta-Analysis
  • 10 studies, 359 participants w/ metabolic syndrome treated with various intermittent fasting protocols 
  • Intermittent fasting led to improvements in: 
    • Fasting glucose (-2.7 mg/dl) 
    • Insulin (-13.2 mIU/L)
    • Insulin resistance (HOMA-IR) (-0.3) 
    • Weight loss (-5.5 lbs) 
    • Waist circumference (-2.2 cm) 
    • Total cholesterol (-6.8 mg/dl) 
    • LDL-C (-3.9 mg/dl)
    • Systolic blood pressure (-2.5 mmHg) 
  • NO significant improvements noted in A1c, triglycerides or HDL-C were observed
  • Commentary: Intermittent fasting was most beneficial for improving insulin and weight loss, with less significant effects on lipids and fasting glucose.

• Dose-related meta-analysis for Omega-3 fatty acids supplementation on major adverse cardiovascular events
  • 19 RCTs, 97,709 participants randomized to:
    • Control
    • Omega 3 supplement (doses <1 g/day to ≥3 g/day)
  • Overall, omega-3 supplementation was NOT associated with a reduced rate of:
    • All-cause mortality
    • Cardiac death
    • Myocardial infarction
    • Stroke 
  • However, omega 3 supplementation at 2g/day was associated with reduced cardiac mortality (RR 0.5) 
  • Commentary: Omega 3 supplementation at 2 g/day was associated with lower cardiac mortality, however other doses did NOT show cardiovascular benefit.

• Sleep apnea and the risk of dementia: A systematic review and meta-analysis
  • 11 studies, 1.3 million participants
  • Sleep apnea was associated with an increased risk of:
    • Neurocognitive disorder (HR 1.4)
    • Alzheimer’s disease (HR 1.2)
    • Parkinson’s disease (HR 1.5)
    • Lewy-body dementia (HR 2.0) 
  • Commentary: This large study shows an association between sleep apnea and dementia. Keep in mind this is an observational study.

• The effects of docosahexaenoic acid supplementation on cognition and well-being in mild cognitive impairment: A 12-month randomised controlled trial
  • 60 older adults 60-90 y/o, randomized to placebo or DHA (1.5 g/day) 
  • After 1 year, NO improvement in cognitive function was observed
  • Commentary: This study did NOT find benefit of DHA supplementation on  cognitive function in older adults.

• Myofunctional therapy for OSA: a meta-analysis
  • 15 studies, 237 sleep apnea patients treated with myofunctional therapy 
  • Myofunctional therapy led to improved:
    • Sleep apnea scores (large effect size) 
    • Lowest oxygen saturation (moderate effect size)
    • Sleepiness scores (large effect size) 
  • Commentary: Myofunctional therapy is an effective therapy option for patients with sleep apnea.

• Effect of Sleep Extension on Objectively Assessed Energy Intake Among Adults With Overweight in Real-life Settings: A Randomized Clinical Trial
  • 80 overweight participants sleeping < 6.5 hours per night, randomized to: 
    • No change in sleep duration (control group)
    • Increase sleep duration by 1.2 hours
  • After 2 weeks, compared to control, the sleep extension group experienced:
    • Decrease calorie intake (-155 vs +114.9 calories/day)
    • Greater weight loss (-1 vs +0.8 lbs)
  • Commentary: Increasing sleep duration leads to reduced calorie intake and subsequent weight loss in this short-term study.

• Efficacy and safety of exogenous beta-hydroxybutyrate for preventive treatment in episodic migraine: A single-centred, randomised, placebo-controlled, double-blind crossover trial
  • 41 patients w/ episodic migraines, randomized to:
    • Placebo
    • Beta-hydroxybutyrate (BHB)
  • After 3 months, BHB led to NO significant difference in: 
    • Migraine days 
    • Migraine intensity 
  • Commentary: BHB was not effective in improving migraines.

Podcast Summary

Download Episode

Featured Studies

• Probiotics supplementation in patients with colorectal cancer: a systematic review of randomized controlled trials
  • 23 RCTs of patients w/ colorectal cancer (CRC), randomized to placebo or probiotics
  • Compared to placebo, probiotics led to improvements in: 
    • Quality of life
    • Reduced postoperative infections 
    • Chemotherapy side effects 
    • Surgical outcomes
    • Reduced hospital stays
    • Reduced risk of death
  • Commentary: Probiotics led to improved clinical outcomes and quality of life in patients with CRC.

• Probiotics and synbiotics for preventing postoperative infectious complications in colorectal cancer patients: a systematic review and meta-analysis
  • Assessing the impact of probiotics/synbiotics on infections in those who had surgery for colon cancer
  • 14 RCTs, 1,566 patients
  • Probiotic/synbiotics significantly reduced the risk of developing postoperative infectious complications by 37% (RR 0.63)
  • Commentary: Probiotics may reduce the risk of abdominal surgery related infections. 

Final Commentary: These studies show 1) the benefit of probiotics in those with colon cancer and 2) the safety of probiotics in those with cancer.

Gastrointestinal Studies

• The Effects of Probiotic Supplementation on Clinical Symptom, Weight Loss, Glycemic Control, Lipid and Hormonal Profiles, Biomarkers of Inflammation, and Oxidative Stress in Women with Polycystic Ovary Syndrome: a Systematic Review and Meta-analysis of Randomized Controlled Trials
  • 11 RCTs of patients w/ PCOS
  • Probiotic supplementation led to reduced:
    • BMI
    • Fasting glucose
    • Insulin
    • Insulin resistance (HOMA-IR) 
    • Triglycerides
    • Hirsutism
    • Testosterone 
    • C-reactive protein
  • Probiotics did NOT improve DHEA-S, LDL-C or HDL-C
  • Commentary: Probiotics may be an effective therapy for PCOS by improving metabolic and hormonal markers.

• Clinical and Histologic Remission in an Adult Crohn’s Disease Patient Following the Specific Carbohydrate Diet and Its Impact on Healthcare Costs
  • Case study, Crohn’s disease patient treated with specific carbohydrate diet (SCD)
  • Treatment with SCD led to: 
    • Reduced fecal calprotectin (493 ug/g to 70 ug/g) after 3 months
    • Normal endoscopy w/ biopsy after 1 year 
    • NO symptoms for 3 years while on the diet
  • Healthcare costs for this patient reduced from $42,688 prior to SCD to $2,797/year while on SCD
  • Commentary: Treating Crohn’s disease w/ SCD led to significant improvements in clinical and laboratory findings while also being more cost-effective. Keep in mind this is a case study.

• The seroprevalence of celiac disease in patients with symptoms of irritable bowel syndrome: A cross-sectional study in north of Iran
  • 475 IBS patients, all tested for Celiac disease (tTG-IgA and tTG-IgG)
  • 6.5% of IBS patients tested positive for Celiac disease 
  • Commentary: While more common than the general population, Celiac disease is rare even among IBS patients.

• Role of Lactobacillus plantarum 299v versus Placebo in symptomatic improvement of irritable bowel syndrome patients
  • 108 IBS patients, randomized to placebo or probiotics
  • After 6 months, NO significant difference in IBS symptoms were observed between groups
  • Commentary: While this study showed no benefit for probiotics on IBS symptoms, there are many other studies that do show benefit.

• Alcohol consumption and risk of inflammatory bowel disease among three prospective US cohorts
  • Prospective study, 237,835 participants
  • NO association was found between alcohol consumption and risk of ulcerative colitis or Crohn’s disease

• Long-Term Efficacy and Safety of Rifaximin in Japanese Patients with Hepatic Encephalopathy: A Multicenter Retrospective Study
  • 215 cirrhosis patients, treated w/ rifaximin long-term
  • After 12 months of treatment w/ rifaximin, NO serious adverse events occurred, including no changes in:
    • Liver enzymes
    • Kidney function
    • Electrolyte balance
  • 5% of patients experienced diarrhea, which improved by reducing the rifaximin dose or giving probiotics 
  • Commentary: Rifaximin appears to be safe long-term with minimal side effects.

• Randomized study of prevention of gastrointestinal toxicities by nutritional support using an amino acid-rich elemental diet during chemotherapy in patients with esophageal cancer (KDOG 1101)
  • 71 esophageal cancer patients randomized to no treatment or elemental diet
  • After 9 weeks, the elemental diet group had no difference in chemotherapy side effects
  • Commentary: Other studies have suggested that the elemental diet can reduce the risk of oral mucositis. 

• AGA Clinical Practice Update on the Role of Diet in Irritable Bowel Syndrome: Expert Review
  • Expert opinion review on dietary management of IBS
  • “The low-FODMAP diet is currently the most evidence-based diet intervention for IBS.”
  • Commentary: The AGA recommends a low FODMAP diet for IBS

• Fecal microbiota transplantation in alcohol-associated acute-on-chronic liver failure: an open-label clinical trial
  • Open-label study of 33 patients w/ severe alcoholic hepatitis randomized to standard care or single FMT
  • After 90 days, the FMT group had:
    • Better survival (54% vs 25%)
    • Resolved hepatic encephalopathy in 100% of cases (vs 57%)
    • Similar adverse effects
    • Decreased inflammatory marker IL-1 (-21% vs +27%)
  • Commentary: Targeting GI health is a way to improve liver dysfunction, even when severe.

• Skin microbiome alterations in seborrheic dermatitis and dandruff: A systematic review
  • 12 studies, 706 w/ seborrheic dermatitis (SD), 379 healthy controls
  • Compared the healthy controls, those w/ SD had more Malassezia (type of yeast) species 
    • Malassezia was associated with increased itching
  • Commentary: Dysbiosis can also be found on the skin.

• The effects of selenium plus probiotics supplementation on glycemic status and serum lipoproteins in patients with gestational diabetes mellitus: A randomized, double-blind, placebo-controlled trial
  • 60 patients w/ gestational diabetes mellitus, randomized to:
    • Placebo
    • Selenium (200 mcg/d) + probiotics 
  • After 6 weeks, compared to placebo, selenium + probiotics led to improved:
    • Fasting glucose (-4.5 vs 1.2 mg/dl) 
    • Insulin (-1.4 vs -0.2 μIU/mL)
    • Triglycerides (-16.6 vs +14.9 mg/dl) 
    • Total cholesterol (-24.2 vs +4.5 mg/dl) 
    • LDL-C (-20.8 vs -0.2 mg/dl) 
  • Commentary: Probiotics + selenium led to improvements in metabolic and lipid markers, especially LDL-C and triglycerides.

• Can Probiotics Supplementation Improve Glycemic and Renal Status in Diabetic Nephropathy? A Systematic Review and Meta-Analysis of Clinical Trials
  • 7 studies, 340 patients w/ diabetic nephropathy
  • Probiotics led to improved:
    • Fasting glucose (-19.1 mg/dL)
    • Insulin resistance (HOMA-IR) (-1.8)
    • Creatinine (-0.2 mg/dl) 
  • NO improvements in GFR, blood urea nitrogen, A1c or insulin were observed
  • Commentary: Probiotics led to an improvement in fasting glucose and insulin resistance without a change in kidney function.

• The effect of gastric acid suppression on probiotic colonization in a double blinded randomized clinical trial
  • 30 healthy participants randomized to placebo or PPI x 6 weeks
    • At weeks 2-6, all participants started probiotics 
  • Probiotics prevented PPI-induced microbial changes 
  • Commentary: Probiotics may be a useful treatment in those also taking PPIs to reduce microbiome disruption.

• Sleep positional therapy for nocturnal gastroesophageal reflux: a double-blind, randomized, sham-controlled trial
  • 100 nocturnal reflux patients, asked to sleep in left lateral decubitus position
  • Randomized to:
    • Sham: wearable device that vibrated during first 20 minutes 
    • Intervention: wearable device that vibrated when patient sleeping on right side
  • The intervention group had:
    • Less time sleeping on right side (2% vs 24%)
    • More time sleeping on left side (61% vs 39%)
    • More patients that had >50% reduction in symptoms (44% vs 20%)
  • Commentary: A wearable device that helps patients sleep on the left side can improve nocturnal reflux.

• Lactobacilli reduce recurrences of vaginal candidiasis in pregnant women: a randomized, double-blind, placebo-controlled study
  • 78 pregnant women w/ recurrent vaginal candidiasis, randomized to placebo or probiotic (Lactobacillus)
  • After 8 weeks, the probiotic group had:
    • Reduced irritation and discharge
    • Reduced impairment of daily activities
    • Reduced emotional/social stress
    • Less constipation
  • Commentary: Remember that probiotics have antimicrobial properties.

• Randomized Controlled Trial of Cognitive-Behavioral and Mindfulness-Based Stress Reduction on the Quality of Life of Patients With Crohn Disease
  • 116 mild-moderate Crohn Disease patients, randomized to no treatment or cognitive behavioral therapy (CBT)
  • After 3 months, the CBT group had:
    • Reduced disease activity
    • Increased quality of life
    • Reduced fatigue
    • Reduced CRP
    • Reduced calprotectin
  • Commentary: Stress management is an important aspect of helping IBD patients.

• Efficacy and safety of biophenol-rich nutraceuticals in adults with inflammatory gastrointestinal diseases or irritable bowel syndrome: A systematic literature review and meta-analysis
  • 23 RCTs in IBS, ulcerative colitis (UC), and Crohn Disease (CD)
  • Compared with placebo, biophenol-rich nutraceuticals:
    • Improved GI symptoms in all conditions (medium effect size)
    • Reduced CRP in UC and CD (-1.6 mg/dL)
    • Only resveratrol improved quality of life
  • Most amount of evidence for:
    • Resveratrol in UC and CD
    • Peppermint oil in IBS
  • Biophenol nutraceuticals like resveratrol and peppermint oil may help w/ IBS and IBD.

Thyroid & Hormones Study

• Vitamin B12 (Cobalamin) Deficiency in Overt and Subclinical Primary Hypothyroidism
  • 133 patients, categorized by: 
    • Healthy control
    • Subclinical hypothyroid
    • Overt hypothyroid
  • NO difference in prevalence of B12 deficiency between all 3 groups
  • Among hypothyroid patients with B12 deficiency, 7.5% also had intrinsic factor antibodies present 
  • Commentary: Overt or subclinical hypothyroidism is not associated with B12 deficiency.

Diet & Lifestyle Studies

• Association between long-term exposure to PM 2.5 and hypertension: A systematic review and meta-analysis of observational studies
  • Examining the association between long-term exposure to particulate matter with a diameter of ≤2.5 μm (PM2.5) and hypertension
  • 27 studies, 42 million participants
  • Each dose increment in PM2.5 was significantly associated with the risks of hypertension incidence (RR = 1.21)
  • Commentary: PM2.5 comes primarily from combustion. Fireplaces, car engines, and coal- or natural gas–fired power plants are all major PM2.5 sources. This meta-analysis strengthens the relationship between air pollution and hypertension.

• The effect of 4-h versus 6-h time restricted feeding on sleep quality, duration, insomnia severity and obstructive sleep apnea in adults with obesity
  • 49 adults w/ obesity randomized to:
    • 4-h time restricted feeding (TRF)
    • 6-h TRF
    • Normal diet
  • After 8 weeks, the TRF group had :
    • Similar loss of weight (-3.9 kg 4-h vs -3.4 kg 6-h)
    • NO improvement of sleep quality or insomnia
    • NO change in sleep quantity
    • NO improvement in sleep apnea symptoms
  • Commentary: 4- and 6-h TRF have no effect on sleep quality, duration, insomnia severity, or the risk of obstructive sleep apnea

• Prevalence of insomnia and insomnia symptoms following mild-traumatic brain injury: A systematic review and meta-analysis
  • 19 studies, 95,195 participants w/ mild traumatic brain injury (TBI) 
  • Estimates of 71.7% of participants w/ mild TBI experience insomnia symptoms  
  • Commentary: Insomnia symptoms are higher in those with a history of mild TBI.