Research Briefs for Practitioners – April 2022 - Dr. Michael Ruscio, DNM, DC
Future of Functional Medicine Review Clinical Newsletter

Research Briefs for Practitioners – April 2022

by Dr. Ruscio, DNM, DC, Gavin Guard, PA-C, MPAS, CISSN, Pn1, and the Ruscio Institute for Functional Medicine Clinical Team

Medically reviewed & fact checked by a
board-certified doctor
Medically reviewed & fact checked by a
board-certified doctor
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Episode 48

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Featured Study


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Gastrointestinal Studies

  • Effect of antibiotic pretreatment on bacterial engraftment after Fecal Microbiota Transplant (FMT) in IBS-D
    • 44 IBS-D patients randomized to 1 of 4 groups:
      • Single-dose FMT
      • 7 days Ciprofloxacin/Flagyl before FMT
      • 7 days Rifaximin before FMT
      • Placebo FMT
    • Successful FMT engraftment was achieved at a higher rate in the FMT-alone group (16%) compared to Cipro/Flagyl (2.4%) and Rifaximin (5%) groups
    • NO differences in IBS symptom severity or quality of life
    • Commentary: Pre-treatment w/ antibiotics before FMT led to worse engraftment rates. However, no differences of symptoms or quality of life was found. Note how small this study was so statistical significance would be harder to achieve.
  • Impact of synbiotics treatment on bacteremia induced during neoadjuvant chemotherapy for esophageal cancer: A randomised controlled trial
    • 42 esophageal cancer patients requiring chemotherapy and surgical removal of cancer, randomized to:
      • No treatment (control group)
      • Synbiotics 
    • Blood samples collected before and after each chemotherapy session
    • Lymph nodes collected before and after surgical removal of cancer
    • Compared to the control group, treatment with synbiotics led to reduced:
      • Bacteremia (bacteria in blood) (2% vs 15%)
      • Bacteria in lymph nodes (0% vs 35%)
      • GI toxicity during chemotherapy (5% vs 36%)
    • Commentary: Synbiotics led to reductions in bacteremia and GI side effects, both common occurrences in those receiving chemotherapy and surgery for esophageal cancer. Another data point for the gut-immune connection. This study may also suggest probiotic’s safety in those with cancer.

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Autoimmunity Study

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

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Thyroid & Hormones Studies

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

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Diet & Lifestyle Studies

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

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Episode 47

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Featured Study

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

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Gastrointestinal Studies

  • Pre-Digested Protein Enteral Nutritional Supplementation Enhances Recovery of CD4 + T Cells and Repair of Intestinal Barrier in HIV-Infected Immunological Non-Responders
    • 36 patients w/ AIDS, non-responsive to current antiviral therapy
    • All received a pre-digested protein drink (i.e. elemental diet) once per day in addition to their current diet
    • After 3 months, treatment led to:
      • Improved immune function (Increased WBC, neutrophils, CD4+)
      • Reduced intestinal permeability markers (LPS, D-lactate, DAO) 
      • Increased body weight 
    • Commentary: Using a pre-digested protein drink (e.g. elemental diet drink) as a meal replacement led to improved immune function, reduced markers of intestinal permeability, and weight gain. This supports our clinical observation that using elemental diets exclusively is NOT always necessary, but rather a hybrid approach can provide clinically meaningful benefits.
  • SER-109, an Oral Microbiome Therapy for Recurrent Clostridioides difficile Infection
    • 182 chronic C. diff patients w/ current infection, randomized to one of the following after antibiotic treatment:
      • Placebo
      • SER-109 (new medication containing Firmicutes spores)
    • After 2 months, the recurrence rate in the treatment group was lower compared to placebo (12% vs 40%) 
    • Commentary: A novel spore-based probiotic medication led to reduction in recurrence of C. diff infections.
  • Gut-brain axis dysfunction underlies FODMAP-induced symptom generation in irritable bowel syndrome
    • Cross-over study of 13 IBS patients and 13 healthy controls
    • Randomized to 1 of 3 intragastric infusions:
      • Fructans (FODMAP)
      • Glucose
      • Or saline 
    • Abdominal MRI was performed before, 1 hr, and 2 hrs post-infusion
    • The fructan (FODMAP) group had:
      • More cramps, pain, flatulence and nausea compared to glucose
      • Increased small bowel motility and ascending colonic gas in both IBS patients and healthy controls
    • Commentary: This study showed that an intragastric infusion of FODMAPs (fructans) lead to GI symptoms, increased bowel motility, and increased gas production. Dr. Ruscio wanted me to mention this partially contradicts the ‘slow motility underlies IBS/SIBO hypothesis’.

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Thyroid & Hormones Studies

  • Effects of Thyroperoxidase Antibody and Thyroglobulin Antibody on Maternal and Neonatal Outcomes in Pregnant Women
    • 296 pregnant women, classified into 4 groups according to thyroid antibody status in first trimester:
      • 97 women: TPOAb+/TgAb-
      • 35 women: TPO-/Tg+
      • 85 women: TPO+/Tg+
      • 79 women: TPO-/Tg-
    • Followed thyroid status x2-3 years postpartum
    • TPOAb (OR 2.3) and TgAb (OR 3.1) had a higher rate of postpartum thyroiditis:
      • 6.3% TPO-/Tg-
      • 16.5% TPO+/Tg-
      • 22.9% TPb-/Tg+
      • 35.3% TPO+/Tg+
    • Those w/ TgAbs were more likely to have thyroid dysfunction at a 2-3 year followup
    • Commentary: In summary, both TPO and Tg antibodies were associated w/ a higher rate of postpartum thyroiditis. In addition, the presence of antibodies was associated w/ higher rates of thyroid dysfunction at a 2-3 year followup. Getting TgAb on top of TPOAb may add additional prognostic value to pregnancy-related outcomes than TPOAb alone.
  • Prevalence and predictors of adequate treatment of overt hypothyroidism – a population-based study
    • Prospective study of 113 newly diagnosed overt hypothyroid patients
    • Followed x10 years
    • After 10 years, only 68% were biochemically euthyroid
    • Risk factors for remaining hypothyroid include:
      • Age
      • Smoking
      • Higher TSH at diagnosis
      • Higher BMI
    • Commentary: This study showed that a substantial amount of overt hypothyroid patients are inadequately treated at a long-term followup. Those who are older, have a history of smoking, higher BMI, or had higher TSH at diagnosis may need more attention to their thyroid labs after starting treatment.

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Diet & Lifestyle Studies

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

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Episode 46

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Featured Study

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

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Gastrointestinal Studies

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

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Diet & Lifestyle Studies

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

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Episode 45

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Featured Study

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

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Gastrointestinal Studies

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

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Autoimmunity Study


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Thyroid & Hormones Study


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Diet & Lifestyle Studies


Discussion

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