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Featured Study

Role of probiotics in prevention and treatment of enteric infections: a comprehensive review

• Review of the literature of probiotics used for preventing and treating GI infections
• Remember: dysbiosis makes it more suitable for pathogen growth
• Mechanisms of antimicrobial effects of probiotics
  • “Displace” pathogenic organisms from GI lumen
  • Produce antimicrobial peptides
  • Modulate immune system
  • Improve barrier function
• Clinical outcomes
  • All 3 categories of probiotics shown to improve pediatric diarrhea by 23 hours
  • Increase eradication rate of H pylori
    • “probiotics can be utilized as the first course of anti H. pylori therapy”
  • Multiple anti-parasitic effects

Gastrointestinal Studies

• The Positive Association between Proton Pump Inhibitors and Clostridium Difficile Infection
  • Is there an association between PPI and C. diff infection?
  • 8 meta-analyses and systematic reviews
  • There is a positive relationship between PPI use and C. diff. Infections

• Safety and Efficacy of Probiotic Supplementation in Reducing the Incidence of Infections and Modulating Inflammation in the Elderly with Feeding Tubes: A Pilot, Double-Blind, Placebo-Controlled Study, “IntegPRO”
  • 32 geriatric patients on enteral nutrition, received probiotics or placebo
  • After 60 days of supplementation, the probiotic group had:
    • Less infections (25% vs 44%)
    • Less need of antibiotics (12% vs 37%)
    • No difference in CRP
    • No difference in bowel habits

• Non-responsive celiac disease may coincide with additional food intolerance/malabsorption, including histamine intolerance
  • Up to 30% of celiac patients experience persistent or recurring abdominal complaints despite following an exact gluten-free diet
  • Study of 20 non-responsive, celiac disease patients, with persistent abdominal complaints for 6+ months.
  • Of the 20 non-responsive celiac patients:
    • 18 (90%) had another food intolerance
    • 11 (55%) had histamine intolerance
    • 6 (30%) had H. pylori

• Association between small intestinal bacterial overgrowth and beta-cell function of type 2 diabetes
  • 100 patients w/ type 2 diabetes
  • SIBO+ group had:
    • Higher glucose level at 120 minutes
    • More insulin resistance
  • Commentary: SIBO may be involved in lower levels of insulin release and worse glycemic control.

• Fecal Microbiota Transplantation as Therapy for Treatment of Active Ulcerative Colitis: A Systematic Review and Meta-Analysis
  • 5 studies, 300 patients w/ ulcerative colitis
  • FMT was associated with a higher combined clinical remission
  • FMT delivered via lower GI route was superior to upper GI route
  • NO difference in serious adverse events w/ FMT

• The effect of gluten on skin and hair: a systematic review
  • Review of 42 studies
  • Dermatologic conditions that may respond positively to a gluten-free diet include:
    • Psoriasis
    • Atopic dermatitis
    • Vitiligo

• Cognitive behavioural therapy for refractory irritable bowel syndrome
  • 34 trials
  • There is a positive symptomatic effect of cognitive behavioral therapy on IBS

• Effects of Cannabidiol Chewing Gum on Perceived Pain and Well-Being of Irritable Bowel Syndrome Patients: A Placebo-Controlled Crossover Exploratory Intervention Study with Symptom-Driven Dosing
  • 32 female IBS patients, given 50 mg CBD in chewing gum or placebo
  • NO statistically significant difference in pain scores between CBD and placebo

• Dietary fibre intake and the risk of diverticular disease: a systematic review and meta-analysis of prospective studies
  • What’s the role of fiber in diverticulitis?
  • 5 cohorts, 865,000 participants
  • Dose of fiber intake associated with lower risk of diverticulitis
    • 20 g/day: 3% reduction
    • 30 g/day: 41% reduction
    • 40 g/day: 58% reduction
  • More benefit from fruit fiber than vegetable fiber
  • Commentary: remember that some w/ diverticular disease also have IBS or IBD so you may need to be careful with fiber supplementation.

• Intestinal dysbacteriosis leads to kidney stone disease
  • Dysbiosis is associated with kidney stone development as measured by 16s rRNA markers of various bacterial species

• The effect of faecal microbiota transplantation on abdominal pain, stool frequency, and stool form in patients with moderate-to-severe irritable bowel syndrome: results from a randomised, double-blind, placebo-controlled study
  • 52 patients w/ mod-severe IBS, randomized to FMT capsules or placebo x12 days
  • At 6 month followup, FMT group had NO differences for abdominal pain, stool frequency, stool consistency

• The role of vitamin D in inflammatory bowel disease: a guide for clinical practice
  • Review of Vit. D in IBD
  • D deficiency may be sequelae/result of IBD, rather than a cause
  • Commentary: IBD often leads to malabsorption, which may explain the association w/ Vit. D deficiency

• Association Between Psychological Disorders and Irritable Bowel Syndrome
  • Cross-sectional study of 1,800 participants
  • IBS diagnosis (by ROME III) in 26% of the population
  • Anxiety was significantly more common in participants with IBS compared to participants without IBS (53% vs. 23%)
  • Depression was significantly more common in participants with IBS (50.6% vs. 21.5%)
  • Commentary: IBS is a very common disorder and is associated with poor mental health outcomes.

• Statin use and new-onset of inflammatory bowel disease: A systematic review and meta-analysis of over ten million participants
  • 5 retrospective studies, 10 million participants, 90,000 IBD patients, followed x9 years
  • Overall, statin use was associated with a reduced risk of new-onset IBD (HR = 0.81)
  • Commentary: Statin use may confer a protective effect in reducing the risk of new-onset IBD

Thyroid & Hormone Studies

• Increased Prevalence of Subclinical Hypothyroidism and Thyroid Autoimmunity in Depressed Adolescents: Results From a Clinical Cross-Sectional Study in Comparison to the General Pediatric Population
  • 360 adolescents w/ depression compared to controls
  • Depressed group had higher likelihood of:
    • Thyroid autoimmunity (6% vs 3%)
    • Subclinical hypothyroidism (9% vs 2%)
  • Commentary: Remember, this shows association, not causation. However, those who are infertile and very young MAY benefit from treatment of sub-clinical hypothyroidism.

• Role of insulin and insulin resistance in androgen excess disorders
  • High insulin causes androgen excess independent of gonadotropins (LH/FSH) in those w/ PCOS
  • Commentary: treat insulin resistance as a top priority in those w/ PCOS

• Impact of metabolic syndrome on sex hormones and reproductive function: a meta-analysis of 2923 cases and 14062 controls
  • 21 studies, 3,000 Metabolic syndrome (MetS) and 1,400 healthy controls
  • In MALES, MetS cases had a lower level of:
    • testosterone
    • total sperm count
    • sperm concentration
    • sperm normal morphology
    • sperm total motility
  • In FEMALES, MetS cases had:
    • higher level of testosterone
    • No significant difference for:
      • FSH
      • LH
      • estradiol

Autoimmunity Studies

• Rheumatoid arthritis and dietary interventions: systematic review of clinical trials
  • Review of 70 clinical trials
  • Interventions that show benefit:
    • Vitamin D supplementation
    • Dietary sodium restriction
    • Fasting
      • resulted in transient subjective improvements
    • Mediterranean diet
    • Elemental diet
      • Improvement in symptoms but not inflammatory markers

• The risk of fibromyalgia in patients with iron deficiency anemia: a nationwide population-based cohort study
  • 13,000 patients w/ newly diagnosed iron-deficiency anemia (IDA), matched to 13,000 participants without IDA
  • Fibromyalgia rates were significantly higher in the IDA than the non-IDA group (hazards ratio 1.38)
  • Commentary: iron is not only important for oxygen transport, but also neurotransmitter synthesis as well.

Diet & Lifestyle Studies

• Early evidence of efficacy for orally administered SPM-enriched marine lipid fraction on quality of life and pain in a sample of adults with chronic pain
  • 44 adults w/ chronic pain, given fish oil enriched with specialized pro-resolving mediators (SPM)
  • After 4 weeks, SPM supplementation lead to:
  • Reduced pain levels
    • Improved quality of life
    • Improved mood

• Effects of macronutrient intake in obesity: a meta-analysis of low-carbohydrate and low-fat diets on markers of the metabolic syndrome
  • Compare Low Carb (LC) and Low Fat (LF) diets
  • Both the LC and LF diets:
    • Reduce caloric intake at 6 months and 12 months
    • Lead to weight loss
    • Improve metabolic markers
  • Metabolic marker improvements did not depend on weight loss
  • LC and higher fat/protein intake improve metabolic markers independent of weight loss.
    • There is a slight advantage of LC diet over LF diet
  • An increase in protein intake appeared to be most relevant for reducing body weight
  • Increased fat intake and reduced carbohydrate intake appeared to be most relevant for improving metabolic markers
  • Caloric intake was not related to changes in body weight or metabolic markers
  • Commentary: Challenge your confirmation bias- both low carb and low fat diets can work.

• Exercise attenuates bone mineral density loss during diet-induced weight loss in adults with overweight and obesity: A systematic review and meta-analysis
  • 9 studies
  • Diet-induced weight loss led to greater femoral bone loss compared to diet-induced weight loss plus exercise.
    • But, bone loss at the hip and lumbar spine was not affected by exercise during diet-induced weight loss
  • The lack of consistent benefits may be due to the insufficient duration and/or training intensities of most exercise interventions.
  • Commentary: Make sure to have your patients engage in some form of resistance training if they are trying to lose weight.

• Vitamin B12 Supplementation in Diabetic Neuropathy: A 1-Year, Randomized, Double-Blind, Placebo-Controlled Trial
  • 90 patients w/ type 2 diabetes w/ peripheral neuropathy
  • Received 1,000 mg of B12 or placebo
  • After 12 months of supplementation, the B12 group had:
    • Reduced pain
    • Improved neurologic function (e.g. nerve conduction speed)
    • Higher quality of life

• Impact of serum lipoprotein (a) level on coronary plaque progression and cardiovascular events in statin-treated patients with acute coronary syndrome: a yokohama-acs substudy
  • Is Lp(a) an independent factor for plaque progression in statin-treated patients?
  • 100 patients w/ acute coronary syndrome, had intravascular ultrasound at baseline and 10 months
  • Divided in 2 groups: low Lp(a) (<20 mg/dL) and high Lp(a) (>20 mg/dL)
  • At 10 month followup, the low Lp(a) group had significant plaque regression, whereas the high Lp(a) group showed slight plaque progression (-6.8% vs. 2.5%)
  • Survival rate was significantly lower in the high Lp(a) group
  • Commentary: Lp(a) may be an important biomarker to further assess metabolic health.

• The Effects of Curcumin on Diabetes Mellitus: A Systematic Review
  • 16 trials, 1,300 participants w/ type 2 diabetes (T2DM)
  • Curucmin significantly reduces:
    • A1C
    • Fasting blood glucose
    • Triglycerides
    • Total cholesterol
    • LDL-C
    • CRP
    • Systolic and diastolic blood pressure
    • Depression/anxiety
  • Commentary: curcumin may be a useful tool in those w/ T2DM

• Association between plasma retinol levels and the risk of all-cause mortality in general hypertensive patients: A nested case-control study
  • Case-control study in China, 600 all-cause mortality, 600 case controls
  • There was a U-shaped relation of plasma retinol with all-cause mortality
    • All-cause mortality significantly increased in those with plasma retinol less than or greater than 58.3 μg/dL in a dose-dependent relationship
  • Commentary: 58 μg/dL may be an optimal range of serum retinol levels.

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Featured Study

The Effectiveness and Safety of Multi-Strain Probiotic Preparation in Patients with Diarrhea-Predominant Irritable Bowel Syndrome: A Randomized Controlled Study

• 50 patients w/ IBS-D given placebo or multi-species probiotic (lactobacillus, bifidobacterium, streptococcus) at 2.5 billion CFU
• After 8 weeks, the probiotic group had:
  • Greater improvement in IBS symptoms
  • Less abdominal pain
  • Better quality of life
• Commentary: This study gives more proof of concept of multi species/strains of probiotics for IBS and other functional GI disorders.

Gastrointestinal Studies

• Chronic giardiasis: a rare cause of exocrine pancreatic insufficiency
  • Case report of patient w/ chronic giardia and exocrine pancreatic insufficiency
  • Symptoms of EPI resolved with treatment of Giardia
  • Commentary: Treat dysbiosis before problems with GI secretions.

• Protective efficacy of probiotics on the treatment of acute rotavirus diarrhea in children: an updated meta-analysis
  • 19 randomized controlled trials, 1,600 children
  • Probiotics (in different categories) can reduce occurrence of acute rotavirus diarrhea in children

• High Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols (FODMAP) Consumption Among Endurance Athletes and Relationship to Gastrointestinal Symptoms
  • Average endurance athlete eats a high FODMAP diet both at baseline and around workouts
  • Commentary: This may be important given the frequent reports of GI symptoms in endurance athletes.

• 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 randomized controlled trials, 1,600 participants w/ IBS, IBD, and other GI symptoms
  • Biophenol (e.g. curcumin, resveratrol) supplementation may improve GI symptoms, inflammation, oxidative stress, and quality of life in patients with IBD and IBS
  • Higher certainty of evidence for peppermint oil for IBS and resveratrol for IBD
  • Commentary: evidence limited by small sample sizes in individual studies

• Measurement of fasting breath hydrogen concentration as a simple diagnostic method for pancreatic exocrine insufficiency
  • 60 patients w/ chronic pancreatitis or pancreatic cancer underwent hydrogen breath test WITHOUT glucose/lactulose
  • Fasting breath hydrogen levels was higher in the exocrine pancreatic insufficiency (EPI) group
    • EPI: 15.70 (1.4 to 77.0) ppm
    • non-EPI group 2.80 (0.7 to 28.2) ppm
  • Fasting breath hydrogen cutoff of 10.7 ppm to diagnose EPI
    • Sensitivity: 73%
    • Specificity 83%
  • Commentary: this study highlights a possible novel diagnostic tool to diagnose EPI. However, this study is limited by small sample size and subjects with a specific diagnosis of either chronic pancreatitis or pancreatic cancer.

• Effects of Probiotics in Preterm Infants: A Network Meta-analysis
  • Are probiotics safe and effective for infants with necrotizing enterocolitis (NEC)?
  • 5 studies, 12,000 preterm infants
  • Probiotics associated with lower rates of mortality and NEC mortality
  • Commentary: Even though many of us do not see preterm infants, this study points to the safety and efficacy of probiotics in high-risk populations.

• Effect of Lactic Acid Bacteria Strains on the Growth and Aflatoxin Production Potential of Aspergillus parasiticus, and Their Ability to Bind Aflatoxin B 1, Ochratoxin A, and Zearalenone in vitro
  • In-vitro study
  • Probiotics can bind to various mycotoxins and reduce mycotoxin production

• Role of Prucalopride in Treating Functional Constipation and Gastroparesis: A Systemic Review
  • 18 studies
  • 2 trials x4 weeks of medication: Prucalopride (1-4 mg/d) showed improvement in gastric emptying and gastroparesis compared to placebo
  • 7 trials x12 weeks of medication: Prucalopride (2-4 mg/d) is effective for chronic constipation
  • Prucalopride is well-tolerated

• Role of a berberine-based nutritional supplement in reducing diarrhea in subjects with functional gastrointestinal disorders
  • Retrospective study of 39 patients w/ functional diarrhea
  • After 30 days of treatment, the berberine treatment significantly reduces diarrhea events by 50-70%.
  • After 90 days, this reduction improves to between 70 and 80%
    • with over 50% achieving normalization of symptoms
  • Commentary: These improvement rates are similar or more than what is seen in Rifaximin trials. Also, berberine was given WITHOUT breath testing.

• Vitamin D3 Supplementation in Diarrhea-Predominant Irritable Bowel Syndrome Patients: The Effects on Symptoms Improvement, Serum Corticotropin-Releasing Hormone, and Interleukin-6 – A Randomized Clinical Trial
  • 88 IBS-D patients w/ Vit. D deficiency randomized to Vit. D 50,000 IU/week or placebo
  • After 9 weeks, the Vit. D group had:
    • Greater improvement in symptoms
    • Less inflammatory markers

• Influence of Combined Eradication and Prokinetic Therapy on Clinical Manifestations, Psychological Status, and Quality of Life of Patients with Functional Dyspepsia- Postprandial Distress Syndrome: Randomized Prospective Study
  • 120 patients with functional dyspepsia and H pylori colonization
  • Randomized to either eradication or eradication + prokinetic (itoprid hydrochloride 50 mg 3x/ day)
  • Combined eradication + prokinetic therapy (in comparison with eradication therapy only) is more effective in the treatment of functional dyspepsia

• Two-day enema antibiotic therapy for parasite eradication and resolution of symptoms
  • 54 patients (≥ 18 years) who were positive for D. fragilis, B. hominis or both
    • Most patients had functional GI symptoms
  • Received triple antibiotics infused over two consecutive days through rectal enema
  • After 6 weeks, 79% of patients cleared the parasites
  • Eradication of parasites associated w/ improvement of clinical outcomes

• A 2-strain mixture of Lactobacillus acidophilus in the treatment of irritable bowel syndrome: A placebo-controlled randomized clinical trial
  • 80 patients w/ IBS, randomized to multi-strain lactobacillus probiotic or placebo
  • After 8 weeks, probiotic group had
    • Less flatulence
    • Overall, better IBS symptom score
  • No difference in abdominal discomfort between groups
  • Commentary: More proof of multi-strain/species probiotics

• Contrasting Clinician and Insurer Perspectives to Managing Irritable Bowel Syndrome: Multilevel Modeling Analysis
  • Modeling potential cost-savings for treating IBS
  • Routinely using low risk IBS treatments (e.g. low FODMAP diet, cognitive behavior therapy, etc) before medications resulted in per-patient cost savings of $9,000 for IBS-D and $3,000 for IBS-C over 1 year to insurers
  • Health outcomes similar for med-first vs diet-first approach
  • “In NO scenario were prescription drugs routinely more cost-effective than global IBS treatments”

• How the North American Consensus Protocol Affects the Performance of Glucose Breath Testing for Bacterial Overgrowth Versus a Traditional Method
  • Compared North American (rise in hydrogen >20 ppm, >10 ppm methane anytime) vs Modified Rome criteria for diagnosing SIBO (rise in hydrogen or methane >12 ppm)
  • North American Consensus criteria had:
    • Better accuracy for diagnosing SIBO
    • More GI symptoms during testing
  • Commentary: the North American Consensus may be a better criteria to use to diagnose SIBO.

• Saccharomyces boulardii CNCM I-745: A Non-bacterial Microorganism Used as Probiotic Agent in Supporting Treatment of Selected Diseases
  • Review; evaluating the efficacy of S. boulardii
  • S boulardii has shown usefulness in managing:
    • H pylori
      • increases eradication rate and decreases diarrhea during antimicrobial therapy
    • Antibiotic-associated diarrhea
    • diff infection
    • IBD
      • limited evidence
    • IBS
      • reduced symptoms and better quality of life

Thyroid & Hormone Studies

• The rationale for selenium supplementation in patients with autoimmune thyroiditis, according to the current state of knowledge
  • In euthyroid, subclinical, or overt hypothyroid autoimmune thyroid patients, selenium supplementation is associated with:
    • Decreased TPO Ab
    • Lower TSH
    • Decreased fT4/fT3 ratio
    • Reduced oxidative stress/inflammation
    • Better quality of life
    • Better thyroid ultrasound structure

• Subtle Thyroid Dysfunction Is Not Associated with Cognitive Decline: Results from the ELSA-Brasil
  • 4,5000 adults >55 years old without OVERT hypothyroidism at baseline
  • Thyroid function and hormone levels were NOT associated with cognitive decline during 4 years of follow-up
  • Commentary: In those without overt hypothyroidism, thyroid hormones do not correlate to cognitive function.

• The effectiveness of coenzyme Q10, vitamin E, inositols, and vitamin D in improving the endocrine and metabolic profiles in women with polycystic ovary syndrome: a network Meta-analysis
  • 23 studies, 1,300 participants
  • Vitamin E, CoQ10, and inositol all effective for treating PCOS
  • Inositol had best results

Diet & Lifestyle Studies

• The associations of phthalate biomarkers during pregnancy with later glycemia and lipid profiles
  • Higher urinary phthalate concentrations during pregnancy were associated with worse metabolic function at 8 year followup after delivery
    • Higher insulin
    • Higher A1C
    • More insulin resistance
    • Lower HDL-C
    • Higher triglycerides
  • Commentary: remember, phthalates are found in food and synthetic products such as cleaning products, detergents, plastics, flooring material, fragrances, and nail polish.

• Diabetes Mellitus Increases Risk of Incident Dementia in APOEɛ4 Carriers: A Meta-Analysis
  • 12 studies, 16,000 participants
  • In ApoE4 carriers, diabetes increased dementia risk an additional 35%

• Nutrient composition of mealtimes and its association with the energy intake of subsequent meals among Mexican adults
  • Foods associated with less energy intake:
    • Fiber
    • Protein
  • Commentary: I have found that prioritizing protein intake is one of the most impactful first-line recommendations for improving a patient’s nutrition.

• Environmental factors and risk of multiple sclerosis: Findings from meta-analyses and Mendelian randomization studies
  • Factors associated with multiple sclerosis
    • Smoking
    • History of EBV
    • High BMI in childhood/adolescence

• Effect of icosapent ethyl on progression of coronary atherosclerosis in patients with elevated triglycerides on statin therapy: final results of the EVAPORATE trial
  • 80 patients on statin w/ elevated triglycerides, given EPA or placebo
  • After 18 months of supplementation, the EPA group had:
    • reduced atheroslcerotic plaque volume by 17% (while in the placebo group plaque volume more than doubled )
  • Commentary: In those with high triglyceride levels, EPA supplementation may prevent and even reduce atheroslcerotic plaque.

• Chronic disruption of circadian rhythm with mistimed sleep and appetite – an exploratory research
  • Those with jet lag (circadian disruption) had higher appetite and made poorer food choices compared to those with just sleep deprivation

• Associations of accumulated selected persistent organic pollutants in adipose tissue with insulin sensitivity and risk of incident type-2 diabetes
  • Organochlorine pesticide and polychlorinated biphenyl (PCB) concentrations were analyzed in adipose tissues samples in those with type 2 diabetes
  • Positive dose-dependent relationships between toxin levels and T2DM risk
  • Commentary: The higher the toxin levels in an individual, the higher their likelihood of developing T2DM is.

• Effects of Different Vitamin D Supplementation Schemes in Post-Menopausal Women: A Monocentric Open-Label Randomized Study
  • 107 post-menopausal women with low Vit. D assigned to 4 different Vit D regiments:
    • Cholecalciferol single
    • Cholecalciferol monthly
    • Cholecalferol weekly
    • Calcifediol weekly
  • Weekly dosing is better than monthly dosing
  • Calcifediol is more effective and faster compared to cholecalciferol in increasing Vit. D levels and is associated with a greater improvement of muscular function

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Featured Study

Romanian Guidelines for Nonpharmacological Therapy of IBS

• A low FODMAP diet may be offered to IBS patients to improve abdominal pain, bloating, and/or diarrhea, for a minimum of 4 weeks (elimination phase). If no symptom improvement occurs within 4 weeks, the diet should be stopped.
• In IBS  patients where symptoms improved during the elimination phase,  recommend gradual reintroduction of  FODMAPs  (during the next  3  months)  to identify triggers,  followed by a personalized diet.
• Soluble fibers are recommended for overall symptom improvement in patients with mild to moderate  IBS  symptoms, especially in type IBS-C.
• Soluble fibers are well tolerated, have a low cost, and therefore represent a reasonable first-line treatment in IBS.
• No recommendation can be made regarding the gluten-free  diet  in  patients  with IBS.
• The assessment of HLA DQ2/8 for GFD in IBS-D is not recommended.
• Recommend peppermint oil to improve overall symptoms, as well as abdominal pain in IBS patients.
• Recommend the use of probiotics as an alternative therapy in trials of limited duration.
• Physical exercise may be useful in Regular exercise can help manage some symptoms in IBS and can be a primary treatment in IBS-C.
• Psychotherapy should be considered for people with IBS who do not respond to pharmacological treatments after 12 months and who develop a refractory IBS.

Gastrointestinal Studies

• Micronutrient deficiencies in children with coeliac disease; a double-edged sword of both untreated disease and treatment with gluten-free diet
  • 15 micronutrients analyzed in 100 blood samples of newly diagnosed Celiac Disease patients and patients on gluten-free diet (GFD)
  • At diagnosis, deficiencies of the following micronutrients were noted:
    • vitamins E (88%)
    • B1 (71%)
    • D (24%)
    • K (21%)
    • A (20%)
    • B6 (12%)
    • ferritin (79%)
    • zinc (33%)
  • After 12 months of GFD, repletion of vitamins E, K, B6, and B1 was observed
  • BUT, vitamins D, A, and zinc did not change significantly post-diagnosis.
  • Increased tTg-IgA Abs at follow-up were associated with low vitamins A and B1
  • Commentary: Several micronutrient deficiencies in CD respond to a GFD but others (A, D, zinc) need to be monitored long-term and supplemented where indicated.

• Multi-Strain Probiotics: Synergy among Isolates Enhances Biological Activities
  • “While single-strain probiotics are beneficial to health, multi-strain probiotics might be more helpful because of synergy and additive effects among the individual isolates.”

• Blastocystis sp. Carriage and Irritable Bowel Syndrome: Is the Association Already Established?
  • Is Blastocystis hominis colonization associated w/ IBS?
  • Cross-sectional analysis of 36 IBS patients, 36 controls
  • Blastocystis hominis measured using PCR and microscopic evaluation
  • When comparing the presence of Blastocystis sp. between asymptomatic subjects and IBS patients, no significant difference was noted

• The Effectiveness of Probiotic Lactobacillus rhamnosus and Lactobacillus casei Strains in Children with Atopic Dermatitis and Cow’s Milk Protein Allergy: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study
  • 150 children with atopic dermatitis and cow’s milk protein allergy
  • All received cow milk protein elimination diet +/- probiotic
  • After 3 months, the probiotic group had:
    • Greater improvement in symptoms (odds ratio 2.56)

• The influence of rifaximin on diverticulitis rate and quality of life in patients with diverticulosis
  • Prospective study of 250 patients w/ diverticulitis
  • 150 received Rifaxmin prophylaxis
  • Rifaximin group had:
    • No difference in diverticulitis rate at 6 months
    • But, lower rate of diverticulitis at 6-12 months
    • Higher quality of life
  • Other findings: Rifaxmin can be safely given for prevention of diverticulitis every 3 months
  • Commentary: Antimicrobial therapy is effective for improving diverticulitis and quality of life.

• Effect of rose oil on Gastroesophageal Reflux Disease in comparison with omeprazole: A double-blind controlled trial
  • 70 patients with GERD
  • Randomized to omeprazole (PPI) or rose oil
  • Rose oil was equivalent to PPI in reducing GERD symptoms

• Do Antibiotics Cause Obesity Through Long-term Alterations in the Gut Microbiome? A Review of Current Evidence
  • Association w/ increased odds of obesity/overweight if:
    • antibiotics during the first 6 months of life
    • repeated exposure to antibiotics for ≥ 3 courses
    • treatment with broad-spectrum antibiotics

• Diagnosing Coeliac Disease During Mass-Screening of General Paediatric Population: Is Biopsy Avoidable?
  • In those with DQ2/DQ8 positive, a tTG-IgA titer above 10x upper limit of normal had a sensitivity & specificity of 100% to correctly diagnose Celiac Disease
  • Commentary: A tTG-IgA above 10x upper limit of normal may be sufficient to diagnose Celiac Disease without a biopsy in those who are DQ2/DQ8 positive. However, more evidence may be necessary.

• Gallbladder motility in children with celiac disease before and after gluten-free diet
  • Gallbladder function is impaired in at least 16% of children with Celiac Disease at diagnosis and is reversible with gluten-free diet.
  • Commentary: This may be one mechanism behind fat-malabsorption in Celiac Disease.

• Antibiotic treatment for small intestinal bacterial overgrowth: Is a cocktail better than a single?
  • Expert narrative review
  • Study noted:
    • 223 patients w/ SIBO using GHBT
    • Given single antibiotic (quinolone or azole) or rotating antibiotics (quinolone and azole, one after the other) for ten days every month x3 months
    • Rotating antibiotics had:
      • More SIBO resolution (70% vs. 51%)
      • More improvement in bloating
      • Better quality of life
    • Commentary: Rotating antibiotics may be better than a single antibiotic at remediating SIBO.

• Celiac disease in pediatric patients according to HLA genetic risk classes: a retrospective observational study
  • HLA-DQ2/DQ8 alleles were NOT associated with any specific symptoms in those with Celiac disease

Thyroid & Hormone Studies

• Investigating the prevalence of primary thyroid dysfunction in obese and overweight individuals: Tehran thyroid study
  • 5,000 participants
  • Higher prevalence of hypothyroidism in obese participants
    • Overall hypothyroidism (11.6% vs 8%)
    • Overt hypothyroidism (4% vs 1%)
    • Subclinical hypothyroidism (7.6% vs 7%)
    • TPOAb positivity (17% vs 12%)
  • No difference in hyperthyroidism

• The Status of Iodine Nutrition after Removing Iodized Salt in High Water Iodine Regions: A Cross-sectional Study in China
  • Cross-sectional analysis of 1,300 adults in 4 regions in China with different iodine concentrations in water
  • High iodine concentration in water associated with higher prevalence of:
    • Thyroid autoimmunity
    • Subclinical hypothyroidism
    • Thyroid nodules
    • Thyroid dysfunction
  • High urinary iodine concentration associated with more:
    • Thyroid nodules
    • Thyroid dysfunction
  • Iodine concentrations still elevated in high iodine areas even after discontinuation of iodized salt
  • Commentary: Too much iodine is also harmful to the thyroid. Removing iodized salt may not be sufficient to prevent harmful effects of too much iodine.

Diet & Lifestyle Studies

• Association Between Age at Diabetes Onset and Subsequent Risk of Dementia
  • 10,000 participants followed x32 years
  • Younger age at onset of diabetes was significantly associated with higher risk of subsequent dementia

• Changes in lipoprotein particle subclasses, standard lipids, and apolipoproteins after supplementation with n-3 or n-6 PUFAs in abdominal obesity: A randomized double-blind crossover study
  • What do different fatty acids do to cholesterol markers?
  • Receive either high dose fish oil (3-4 g/d) or omega 6 fatty acid (15-20g/d) x7 weeks w/9-week washout phase
  • Omega 3 vs omega 6 results
    • VLDL cholesterol (-38% vs +16%)
    • ApoB (+0.4% vs -6%)
    • Triglycerides (-16% vs -2.6%)
    • Total cholesterol (-0.3% vs -4.4%)
  • Commentary: Omega 3 fatty acids at 3-4 g/d had significant reduction in VLDL-C and Tgs with no difference in ApoB or total cholesterol. Overall, omega 6 fatty acids had relatively little impact on cholesterol or triglyceride content.

• Type 2 diabetes preventive effects with a 12-months sardine-enriched diet in elderly population with prediabetes: An interventional, randomized and controlled trial
  • 150 prediabetic participants, randomized to eat sardines 2x/wk
  • After 12 months, the sardine group had:
    • Less participants diagnosed with overt diabetes
    • Increased HDL-C
    • Reduced triglycerides
    • Reduced blood pressure
    • Reduced HOMA-IR (insulin resistance)
    • More red blood cell omega 3 fatty acids
  • Commentary: The inclusion of cold-water fish (like sardines) can be an effective strategy to prevent cardiometabolic disease.

• High-Protein, Low-Glycaemic Meal Replacement Decreases Fasting Insulin and Inflammation Markers: A 12-Month Subanalysis of the ACOORH Trial
  • 450 obese patients
  • Intervention group ate higher protein, low carb meals
  • After 12 months, the high protein group had:
    • Significantly higher reductions in insulin (-3.3 µU/mL vs. -1.6 µU/mL)
    • Greater weight loss weight (-6.1 kg vs. -3.2 kg)
    • Lower inflammation markers

• The role of resveratrol on heavy metal-induced oxidative stress
  • Resveratrol can modulate the oxidative stress exerted by arsenic, cadmium, copper, and iron

• Medium-chain fatty acids lower postprandial lipemia: A randomized crossover trial
  • Compared to animal fat (lard, butter), coconut oil leads to LESS of an increase in postprandial lipids/cholesterol

• The Association between Vitamin D Status and Autism Spectrum Disorder (ASD): A Systematic Review and Meta-Analysis
  • Children with reduced maternal or neonatal vitamin D had 54% higher likelihood of developing autism

• Inverse association between dietary vitamin A intake and new-onset hypertension
  • 12,000 participants followed over 6 years
  • Those with higher vitamin A intake had a significantly lower risk of new-onset hypertension
  • Commentary: Vitamin A rich foods include:
    • Liver
    • Eggs
    • Milk
    • Most yellow, red, and orange vegetables (not as bioavailable as animal sources)

Podcast Summary

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Featured Study

• British Society of Gastroenterology guidelines on the management of irritable bowel syndrome
  • Recommendations for IBS patients:
    • No breath testing
    • No food sensitivity (IgG) test
    • CRP, calprotectin, celiac serology for first time workup
    • Workup for bile acid malabsorption if nocturnal diarrhea or history of cholecystectomy
    • Low FODMAP diet for 1st line therapy
    • Endorses trial of non-strain specific probiotics for up to 12 weeks before deciding benefit vs no benefit
    • Endorses peppermint oil for global symptoms

Gastrointestinal Studies

• Anti-Helicobacter pylori treatment can effectively improve the clinical remission rates of irritable bowel syndrome: A controlled clinical trial meta-analysis
  • 10 studies, 650 patients with IBS, about 50% with H. pylori
  • Anti-H. pylori treatment can effectively improve the clinical remission rates of IBS patients.

• Delayed Gastric Emptying is Not Associated with a Microbiological Diagnosis of Small Intestinal Bacterial Overgrowth
  • 73 participants underwent gastric emptying study and small bowel culture
    • There was NO significant association between a microbiological diagnosis of SIBO and delayed gastric emptying by scintigraphy
  • Commentary: Gastric transit time different from small bowel transit time

• Probiotics supplementation improves hyperglycemia, hypercholesterolemia, and hypertension in type 2 diabetes mellitus: An update of meta-analysis
  • 13 studies, 800 participants over 8 countries
  • Probiotics had a statistically significant reduction in:
    • Fasting blood sugar (-0.9 mg/dL)
    • Insulin resistance (-0.43)
    • Total cholesterol (-0.19 mg/dL)
    • Triglycerides (-0.23 mg/dL)
    • Systolic (-5.6 mmHg) and diastolic blood (-3.4 mmHg) pressure
  • These effects were more pronounced with multi-species strains of probiotics given for at least 8 weeks
  • Commentary: Don’t get statistically significant confused with clinically significant.

• Effects of probiotic therapy on cardio-metabolic parameters and autonomic modulation in hypertensive women: A randomized, triple-blind, placebo-controlled trial
  • 40 women with hypertension
  • After 8 weeks, the probiotic group had:
    • Reduced fasting glucose (-10.3 mg/dL)
    • Reduced Total cholesterol (-23.6 mg/dL)
    • Increased HDL-C (+6.5 mg/dL)
    • Reduced systolic blood pressure (-5 mmHg)
    • Improvement in autonomic function

• AGA Clinical Practice Update on Small Intestinal Bacterial Overgrowth: Expert Review
  • Expert review by 3 authors, including Dr. Pimentel
  • Consensus
    • SIBO= lab abnormality
    • Elevated folate and B12 deficiency can occur from SIBO
    • Management should revolve around fixing underlying cause
    • Diarrhea (not bloating) has strongest association to SIBO
    • Calprotectin has no utility for identifying SIBO
    • SIBO = >10^3 CFU/mL

• Antimicrobial resistance surveillance of Clostridioides difficile in Australia, 2015-18
  • 1,000 C. diff strains collected over 3 years
  • All strains were susceptible to metronidazole, fidaxomicin, rifaximin, and amoxicillin/clavulanate (Augmentin)
  • Resistance to:
    • Vancomycin: 5.7%
    • Ceftriaxone: 19%
    • Clindamycin: 85%

• The effect of pro/synbiotics on postoperative infections in colorectal cancer patients: A systematic review and meta-analysis
  • 19 studies, 2,000 participants
  • Compared with the control group, the pro/synbiotics group had reduced total postoperative infections

• Association of Diabetes and Dental Caries Among U.S. Adolescents in the NHANES Dataset
  • NHANES analysis of 25 million US adolescents
  • Diabetic adolescents were more than twice as likely to experience dental caries compared to nondiabetic adolescents

• The Specific Carbohydrate Diet and Diet Modification as Induction Therapy for Pediatric Crohn’s Disease: A Randomized Diet Controlled Trial
  • 18 pediatric patients with Crohn’s disease
  • Randomized to:
    • Specific carbohydrate diet
    • Modified specific carbohydrate diet
    • Or whole food diet
  • After 12 weeks
    • CRP reduced in all groups
    • Symptoms improved in all groups

Thyroid & Hormone Studies

• The correlation between selenium levels and autoimmune thyroid disease: A systematic review
  • 17 studies, 2,000 participants w/ either Graves’ or Hashimoto’s
  • Selenium supplementation associated with:
    • Reduced fT3
    • Reduced fT4
    • Reduced TPO Abs
    • No change in TSH or Tg-Abs
  • Commentary: On average, selenium supplementation leads to a reduction in fT3, fT4, and TPOAbs, with NO change in TSH or Tg-Abs

• Metformin does not improve insulin sensitivity over hypocaloric diets in women with polycystic ovary syndrome: A systematic review of 12 studies
  • No benefit to adding Metformin to hypocaloric diet for fasting glucose, insulin, or insulin resistance
  • Commentary: Diet and lifestyle measures should be 1st line for PCOS.

Autoimmunity Studies

• Dietary Intake Assessment, Severity of Symptoms, and Pain in Women with Fibromyalgia
  • Lower fibromyalgia symptom score associated with higher intake of the following nutrients:
    • Phosphorous
    • Iron
    • Zinc
    • B1
    • B6
    • Folate
    • Vitamin C
  • Commentary: Inverse relationship between fibromyalgia symptoms and nutrient density.

Diet & Lifestyle Studies

• Coffee Consumption and the Risk of All-Cause and Cause-Specific Mortality in the Korean Population
  • 170,000 participants
  • participants who consumed > 3 cups/day had a reduced risk of all-cause mortality (HR 0.79)
  • Participants who consumed <3 cups/day had a reduced risk of CVD mortality

• Cadmium exposure and risk of adverse pregnancy and birth outcomes: A systematic review and dose-response meta-analysis of cohort and cohort-based case-control studies
  • 18 prospective studies
  • Maternal cadmium exposure resulted in significant:
    • Reduction in birth weight
    • Reduction in head circumference
    • Increased blood/urine cadmium levels

• The effect of curcumin and zinc co-supplementation on glycemic parameters in overweight or obese pre-diabetic subjects: A phase 2 randomized, placebo-controlled trial with a multi-arm, parallel-group design
  • 84 participants given 500 mg curcumin, 30 mg zinc, or both
  • No difference in physical activity or dietary intake
  • Only zinc and zinc + curcumin groups had decreased BMI compared to the placebo
  • All 3 groups had improved:
    • Fasting glucose
    • A1C
    • Insulin sensitivity

• Effect of low salicylate diet on clinical and inflammatory markers in patients with aspirin exacerbated respiratory disease – a randomized crossover trial
  • 7 participants w/ aspirin-exacerbated respiratory disease (AERD)
  • Randomized to high or low salicylate diet for 1 week then cross-over to other intervention
  • Low salicylate group had
    • No difference in urinary creatinine, salicylate, or leukotriene levels
    • But had improved symptoms

• Free Radical Oxidation of Lipids as an Indicator of the Effectiveness of CPAP Therapy in Apnea Syndrome
  • CPAP therapy reduced lipid oxidation

• A 1:1 matched case-control study on dietary protein intakes and hip fracture risk in Chinese elderly men and women
  • 1,000 sex and age-matched cohorts of newly diagnosed hip fractures
  • The highest quartile of protein intake was associated with lower risk of hip fracture in dose-dependent response for both men and women
  • More of an effect in elderly with dietary calcium intake <400 mg/d
  • Commentary: Higher protein intake may be necessary for elderly.

• Improvement in Cardiometabolic Risk Factors During Smoking Cessation Treatment in Patients with Type 2 Diabetes: A Retrospective Cohort Study
  • 250 type 2 diabetics in smoking cessation program
  • 34% successfully quit smoking at 3 months
  • After smoking cessation
    • Decreased fasting glucose (10 mg/dL)
    • Decreased A1C (0.3%)
    • Reduced systolic and diastolic blood pressure (4.6, 3 mmHg)
    • Reduced total cholesterol (8 mg/dL)
    • No change in body weight
  • Commentary: Smoking cessation is associated with improved cardiometabolic biomarkers INDEPENDENT of weight loss.

• Exercise for Weight Loss: Further Evaluating Energy Compensation with Exercise
  • 3-arm RCT of overweight adults
    • 6 training sessions/wk
    • 2 training sessions/wk
    • Sedentary control
  • Measured energy expenditure, ghrelin, leptin, insulin
  • The 6 sessions/wk group expended more energy and exercised longer per week than the 2 sessions/wk group, resulting in greater fat loss
  • Commentary: Find an exercise routine your patients enjoy and can be consistent with.

• The effect of a 6-month ketogenic medium-chain triglyceride supplement on plasma cardiometabolic and inflammatory markers in mild cognitive impairment
  • 9 participants with mild cognitive impairment
  • Given ketogenic medium-chain triglycerides (30 g/d), no change in diet
  • After 6 months, the MCT group had no effect on cardiometabolic or inflammatory markers
  • Commentary: Ketogenic supplements by themselves may have minimal effects on cardiometabolic biomarkers if no changes are made to diet/lifestyle.

• High sensitivity C-reactive protein (hsCRP): Its relationship with metabolic syndrome and Framingham Risk Score
  • Cross-sectional study of 83 patients
  • Measured CRP and cardiovascular risk score (via Framingham risk calculator)
  • CRP was increased in patients with high BMI, waist circumference, presence of metabolic syndrome, and cardiovascular disease risk

• Natural Products and Extracts as Xanthine Oxidase Inhibitors: A Hope for Gout Disease?
  • Quercetin, resveratrol, and berberine act as xanthine oxidase inhibitors and may be able to reduce uric acid and prevent gout attacks

• Oxidative stress parameters and antioxidants in patients with bipolar disorder: Results from a meta-analysis comparing patients, including stratification by polarity and euthymic status, with healthy controls
  • Patients with bipolar disorder have significantly higher uric acid which may be a sign of oxidative stress

• The effect of brown rice compared to white rice on adiposity indices, lipid profile, and glycemic markers: A systematic review and meta-analysis of randomized controlled trials
  • 13 RCTs comparing brown vs white rice
  • Brown rice may lower weight more but had no additional beneficial effect on lipid or glycemic markers compared to white rice

• The Psychological and Physical Effects of Forests on Human Health: A Systematic Review of Systematic Reviews and Meta-Analyses
  • 11 studies
  • forest-based interventions are beneficial to the:
    • cardiovascular system
    • immune system
    • mental health (in the areas of stress, depression, anxiety, and negative emotions)

• Weight-loss-independent benefits of exercise on liver steatosis and stiffness in Japanese men with NAFLD
  • Men w/ Non-Alcoholic Fatty Liver Disease given exercise regimen x3 months
  • Exercise regimen reduced liver steatosis by 9.5% and liver stiffness by 6.8% per 1% weight loss

• Treatment of NAFLD with intermittent calorie restriction or low-carb high-fat diet: A randomized controlled trial
  • 74 patients with fatty liver
  • Randomized to standard care, intermittent fasting, or low carb-high fat (LCHF) diet
  • After 12 weeks, the intermittent fasting (2 days per week of very low-calorie diet (500 Cals/d)) and LCHF diet had more % weight loss and improved liver stiffness
  • Intermittent fasting had improved levels of LDL-C and tolerated better than LCHF diet

• Constrained Total Energy Expenditure and Metabolic Adaptation to Physical Activity in Adult Humans
  • Does more exercise = more calories burned?
  • 330 adults in free-living conditions in 5 different populations
  • Total energy expenditure (calories burned) measured by doubly labeled water method
  • Results:
    • Fat-free mass accounted for #1 determinant of calories burned
    • Physical activity only accounted for 7% of variability of the calories burned
    • Resting metabolic rate was NOT associated with physical activity
    • Amount of calories burned increased with increasing physical activity but plateaued at upper range of physical activity
    • Reduced non-physical activity (less fidgeting, sitting instead of standing, reduced reproduction) may be the reason that energy expenditure stays the same despite increased activity
  • Commentary: In other words, you cannot run marathons to eat Oreos and expect to lose weight. Pursue lean body mass increase to yield sustained results for body composition.