// Evidence Grader
Claim grades, A through F
Every major claim in this course gets a transparent grade. Use this dashboard to audit what's established, what's preliminary, and what's hype.
A
Clinically established
B
Supported, context-specific
C
Promising, preliminary
D
Plausible, unproven
E
Popular, weak support
F
Misleading or false
A
FMT is effective for recurrent C. difficile infection
Multiple RCTs, guideline-supported, >85% cure rate.
Module 01 · Why the Microbiome Matters
B
Probiotics prevent antibiotic-associated diarrhea
Strain-specific evidence (S. boulardii, L. rhamnosus GG); not all probiotics are equal.
Module 01 · Why the Microbiome Matters
C
Gut bacteria influence mood via the gut-brain axis
Mechanistically plausible, animal data strong, human RCTs inconsistent.
Module 01 · Why the Microbiome Matters
E
Probiotic supplements cure IBS
Some strains show modest benefit; 'cure' is marketing, not science.
Module 01 · Why the Microbiome Matters
F
Everyone needs a daily probiotic
No evidence supports universal supplementation; may be harmful in some contexts.
Module 01 · Why the Microbiome Matters
E
Microbiome testing kits provide actionable health advice
Consumer kits lack clinical validation and actionable reference ranges.
Module 01 · Why the Microbiome Matters
A
Vaginal birth seeds the neonatal gut microbiome differently than C-section
Consistently replicated; clinical significance of seeding interventions still debated.
Module 02 · Anatomy of the Gut Microbiome
A
Breastfeeding enriches Bifidobacterium in the infant gut
HMOs are a selective substrate for Bifidobacterium spp.
Module 02 · Anatomy of the Gut Microbiome
B
Microbial diversity decreases with aging
Generally supported but confounded by diet, medications, and institutionalization.
Module 02 · Anatomy of the Gut Microbiome
B
Periodontal disease is associated with cardiovascular disease
Strong epidemiological association; causal proof from intervention trials is still building.
Module 03 · The Oral Microbiome
B
Treating periodontitis improves glycemic control in T2DM
Meta-analyses show modest HbA1c reduction (~0.3%) after periodontal treatment.
Module 03 · The Oral Microbiome
C
Mouthwash disrupts beneficial oral bacteria involved in NO production
Emerging evidence; small studies show chlorhexidine reduces oral nitrate reduction and may raise BP.
Module 03 · The Oral Microbiome
D
P. gingivalis causes Alzheimer's disease
Detected in AD brain tissue; causal link is speculative. Cortexyme trial failed.
Module 03 · The Oral Microbiome
B
Quantitative P. gingivalis thresholds (>10⁵ copies/mL) identify active periodontitis requiring SRP
Validated in cohort studies; used in structured biomarker panels with clinical decision rules.
Module 03 · The Oral Microbiome
B
F. nucleatum subsp. animalis is causally linked to colorectal tumorigenesis
Enriched in CRC tissue; FadA/Fap2 mechanisms characterized; subspecies specificity replicated.
Module 03 · The Oral Microbiome
C
Salivary HPV-16 DNA detection screens for oropharyngeal cancer risk
Association strong; screening protocols under development but not yet validated for population use.
Module 03 · The Oral Microbiome
D
Chairside MMP-8 testing replaces periodontal probing
Complements but does not replace probing; sensitivity/specificity insufficient as standalone diagnostic.
Module 03 · The Oral Microbiome
A
L. crispatus dominance is protective against BV and STIs
Consistently replicated across cohorts and meta-analyses.
Module 04 · The Vaginal Microbiome
A
BV increases HIV acquisition risk ~60%
Large prospective cohorts confirm the association; mechanism involves mucosal barrier disruption.
Module 04 · The Vaginal Microbiome
D
Vaginal microbiome transplant (VMT) can treat recurrent BV
Case reports and small pilots only; no RCTs as of 2025.
Module 04 · The Vaginal Microbiome
E
Probiotic supplements restore vaginal Lactobacillus
Oral probiotics rarely colonize the vagina; vaginal application has mixed results.
Module 04 · The Vaginal Microbiome
B
S. aureus colonization drives AD flares
Consistently associated; precedes flares in longitudinal data; bacteriotherapy trials underway.
Module 05 · The Skin Microbiome
B
C. acnes strain diversity explains acne susceptibility
Supported by genomic studies; ribotype RT4/RT5 associated with severe acne.
Module 05 · The Skin Microbiome
D
Topical probiotics treat acne and eczema
Phase I/II; promising for AD (R. mucosa), minimal data for acne.
Module 05 · The Skin Microbiome
B
Gut microbiota influence brain function and behavior
Strong animal evidence; human data mostly observational.
Module 06 · The Gut-Brain Axis
C
FMT from depressed donors transfers depressive behavior in mice
Replicated in gnotobiotic models; human translation unclear.
Module 06 · The Gut-Brain Axis
E
Probiotics effectively treat clinical depression
Human RCTs show small, inconsistent effects; no strain is clinically recommended.
Module 06 · The Gut-Brain Axis
E
Gut dysbiosis causes autism
GI symptoms common in ASD; causal link unestablished. Confounded by diet and medication.
Module 06 · The Gut-Brain Axis
B
The vagus nerve is required for some probiotic behavioral effects
Vagotomy abolishes L. rhamnosus JB-1 effects in mice; human evidence indirect.
Module 06 · The Gut-Brain Axis
B
Chronic stress causes gut dysbiosis
Consistent animal data; human studies show associations with reduced Lactobacillus.
Module 06 · The Gut-Brain Axis
C
Early-life microbiome perturbation affects neurodevelopment
Animal models strong; human birth cohort data preliminary.
Module 06 · The Gut-Brain Axis
C
Truncal vagotomy reduces Parkinson's disease risk
Epidemiological data suggests ~40% reduction; confounded by indication bias.
Module 06 · The Gut-Brain Axis
B
Gut microbiome composition predicts response to anti-PD-1 immunotherapy
Replicated in melanoma, NSCLC cohorts; specific taxa vary by study but pattern is consistent.
Module 07 · Immune Regulation & the Microbiome
C
FMT from immunotherapy responders improves non-responder outcomes
Small trials show signals; larger Phase II underway.
Module 07 · Immune Regulation & the Microbiome
B
Reduced microbial diversity in childhood increases allergy risk
Supported by birth cohort studies; hygiene hypothesis framework.
Module 07 · Immune Regulation & the Microbiome
C
Specific probiotics prevent allergies in infants
L. rhamnosus GG shows some benefit in high-risk infants; not generalizable to all probiotics.
Module 07 · Immune Regulation & the Microbiome
B
IgA coating patterns distinguish pathobionts from commensals
IgA-seq identifies inflammation-driving bacteria; replicated in IBD cohorts.
Module 07 · Immune Regulation & the Microbiome
C
Trained immunity is partly microbiome-driven
Mechanistically plausible; β-glucan and BCG evidence strong, direct microbiome contribution inferred.
Module 07 · Immune Regulation & the Microbiome
B
Microbiome composition affects vaccine immunogenicity
Geographic variation in oral vaccine efficacy correlates with microbiome differences; interventional data emerging.
Module 07 · Immune Regulation & the Microbiome
B
Salivary MMP-8 detects active periodontitis with clinically useful accuracy
Sensitivity ~76–83%, specificity ~68–73% across validation studies; PerioSafe/ORALyzer commercially available.
Module 07 · Immune Regulation & the Microbiome
C
Salivary cytokine panels (IL-6, TNF-α) predict systemic cardiovascular risk
Correlations observed in cohort studies; not yet validated as standalone cardiovascular predictors.
Module 07 · Immune Regulation & the Microbiome
A
Dietary fiber intake increases SCFA production
Well-established from feeding studies; dose-response relationship documented.
Module 08 · Metabolomics & Short-Chain Fatty Acids
A
Butyrate is essential for colonocyte health and barrier integrity
Mechanistically validated; butyrate-deficiency models show barrier breakdown.
Module 08 · Metabolomics & Short-Chain Fatty Acids
B
Elevated TMAO predicts cardiovascular events
Prospective cohort data consistent; causal mechanism still debated.
Module 08 · Metabolomics & Short-Chain Fatty Acids
D
TMAO testing should guide dietary counseling
No guideline recommends TMAO measurement; clinical utility unestablished.
Module 08 · Metabolomics & Short-Chain Fatty Acids
B
Propionate supplementation reduces appetite and weight gain
RCT (Chambers 2015) showed reduced energy intake and intra-abdominal fat over 24 weeks.
Module 08 · Metabolomics & Short-Chain Fatty Acids
C
IPA is neuroprotective in Alzheimer's disease
Animal model data; human epidemiological association (reduced IPA in cognitive decline); no interventional data.
Module 08 · Metabolomics & Short-Chain Fatty Acids
C
Modifying gut microbial metabolism slows CKD progression
Preclinical data strong; AST-120 trials mixed; dietary intervention trials ongoing.
Module 08 · Metabolomics & Short-Chain Fatty Acids
A
Shotgun metagenomics provides species-level resolution
Well-validated against cultured isolates; strain resolution depends on read depth and reference database.
Module 09 · Sequencing & Diagnostics
F
Consumer microbiome kits provide actionable health guidance
No clinical validation, no FDA-cleared test, no consensus reference ranges.
Module 09 · Sequencing & Diagnostics
A
DNA extraction method significantly affects results
MBQC demonstrated this is a major source of between-study variance.
Module 09 · Sequencing & Diagnostics
A
Long-read sequencing provides species-level microbiome resolution
Validated against cultured isolates; full-length 16S resolves what amplicons cannot.
Module 09 · Sequencing & Diagnostics
A
Culturomics can isolate previously 'unculturable' organisms
Lagier 2016: 247 new species isolated; replicated across labs.
Module 09 · Sequencing & Diagnostics
B
Single-cell genomics reveals clinically relevant strain heterogeneity
Identifies resistance gene variants invisible to bulk metagenomics; clinical utility emerging.
Module 09 · Sequencing & Diagnostics
A
Standardized DNA extraction and bioinformatics pipelines are essential for reproducible clinical microbiome results
MBQC demonstrated these are the largest sources of between-study variance; standardization efforts ongoing.
Module 09 · Sequencing & Diagnostics
A
Microbiome sequencing data qualifies as health data under GDPR Article 9
Legal consensus; requires explicit consent, DPIAs, and DPAs for compliant processing.
Module 09 · Sequencing & Diagnostics
A
S. boulardii prevents antibiotic-associated diarrhea
Multiple meta-analyses of RCTs support this; NNT ~10.
Module 10 · Probiotics, Prebiotics & Synbiotics
A
L. rhamnosus GG prevents pediatric AAD
Strain-specific evidence from >20 RCTs.
Module 10 · Probiotics, Prebiotics & Synbiotics
E
Probiotics cure IBS
Some strains improve specific symptoms; no strain cures IBS.
Module 10 · Probiotics, Prebiotics & Synbiotics
F
Higher CFU count means better probiotics
No dose-response relationship established for most strains; marketing, not science.
Module 10 · Probiotics, Prebiotics & Synbiotics
F
Probiotics colonize the gut permanently
Most transit through; colonization is person-specific and temporary.
Module 10 · Probiotics, Prebiotics & Synbiotics
D
Postbiotics are as effective as live probiotics
Conceptually promising; few head-to-head RCTs comparing killed vs live preparations.
Module 10 · Probiotics, Prebiotics & Synbiotics
E
Probiotics are safe for everyone
Generally safe in healthy adults; bacteremia and fungemia reported in immunocompromised/ICU patients.
Module 10 · Probiotics, Prebiotics & Synbiotics
F
Probiotics prevent ventilator-associated pneumonia
PROSPECT trial (n=2,650) definitively negative; prior small studies were misleading.
Module 10 · Probiotics, Prebiotics & Synbiotics
C
Colonization verification testing improves probiotic prescribing outcomes
Mechanistically sound; Zmora 2018 demonstrated person-specific colonization resistance; clinical outcome studies pending.
Module 10 · Probiotics, Prebiotics & Synbiotics
F
Most probiotic adverse events are captured by existing pharmacovigilance systems
Supplements bypass MedWatch/EU pharmacovigilance; vast majority of AEs go unreported.
Module 10 · Probiotics, Prebiotics & Synbiotics
F
Probiotic prophylaxis is safe in severe acute pancreatitis
PROPATRIA trial (Lancet 2008) showed increased mortality (16% vs 6%); contraindicated.
Module 10 · Probiotics, Prebiotics & Synbiotics
B
Strain attribution by whole-genome sequencing of patient isolate vs product lot is the gold standard for confirming probiotic-related infection
ANI ≥99.9% match supports causation; recommended in published case reports and required for regulator escalation.
Module 10 · Probiotics, Prebiotics & Synbiotics
A
Many Lactobacillus rhamnosus and L. casei strains are intrinsically resistant to vancomycin
Well-established (CLSI/EUCAST); empiric therapy for suspected Lactobacillus bacteremia should be ampicillin or penicillin G ± gentamicin, not vancomycin.
Module 10 · Probiotics, Prebiotics & Synbiotics
A
FMT cures recurrent C. difficile infection in >85% of cases
Multiple RCTs; guideline-recommended after ≥2 recurrences.
Module 11 · Fecal Microbiota Transplantation
C
FMT induces remission in ulcerative colitis
Pooled-donor, intensive protocols show benefit; effect sizes modest, durability uncertain.
Module 11 · Fecal Microbiota Transplantation
C
FMT converts immunotherapy non-responders to responders
Small Phase I/II trials show signals; larger trials needed.
Module 11 · Fecal Microbiota Transplantation
F
FMT is safe without screening
Transmitted MDR infections reported; rigorous donor screening is mandatory.
Module 11 · Fecal Microbiota Transplantation
B
Donor strain engraftment predicts FMT clinical response in IBD
Strain-tracking studies in UC show correlation; replicated across cohorts.
Module 11 · Fecal Microbiota Transplantation
C
Super donors exist and can be identified
Outcome clustering by donor observed in UC trials; predictive biomarkers under investigation.
Module 11 · Fecal Microbiota Transplantation
D
FMT durably improves metabolic disease
Transient insulin sensitivity gains (Vrieze 2012); effects not durable; no clinical indication.
Module 11 · Fecal Microbiota Transplantation
A
Antibiotics cause lasting microbiome changes
Longitudinal studies confirm incomplete recovery at 6+ months for some taxa.
Module 12 · Antibiotics & Dysbiosis
C
Early childhood antibiotics increase obesity risk
Epidemiological association; confounded by infection severity, diet, and other factors.
Module 12 · Antibiotics & Dysbiosis
E
Co-prescribing probiotics prevents all antibiotic side effects
S. boulardii prevents AAD specifically; not a blanket solution.
Module 12 · Antibiotics & Dysbiosis
E
Generic probiotics always help after antibiotics
Suez 2018 showed they can delay microbiome recovery; only strain-specific evidence supports specific uses.
Module 12 · Antibiotics & Dysbiosis
C
Autologous FMT accelerates post-antibiotic recovery
Small studies show faster diversity restoration; no large RCT with clinical outcome data.
Module 12 · Antibiotics & Dysbiosis
B
Nitrofurantoin has minimal gut microbiome impact
Pharmacokinetic rationale (renal excretion) supported by microbiome studies showing minimal disruption.
Module 12 · Antibiotics & Dysbiosis
A
Dietary fiber increases SCFA production and supports gut health
Well-established; feeding studies confirm dose-response.
Module 13 · Diet & the Microbiome
B
Fermented foods increase microbial diversity
Stanford RCT (Wastyk 2021) showed increased diversity; longer-term effects unknown.
Module 13 · Diet & the Microbiome
C
Artificial sweeteners disrupt the gut microbiome
Suez 2014 showed effects in mice and some humans; replication and clinical significance debated.
Module 13 · Diet & the Microbiome
D
Personalized nutrition based on microbiome testing works
PREDICT studies show individual variation; no validated clinical implementation yet.
Module 13 · Diet & the Microbiome
A
EEN is as effective as corticosteroids for pediatric Crohn's remission
Multiple RCTs; ~80% remission rate; ECCO/ESPGHAN first-line recommendation.
Module 13 · Diet & the Microbiome
A
Diet changes the microbiome within 24 hours
David 2014 (Nature): measurable shifts within 1 day; major changes by day 3-4.
Module 13 · Diet & the Microbiome
B
Ketogenic diet reduces gut SCFA production
Consistent finding across studies; clinical significance for long-term colon health uncertain.
Module 13 · Diet & the Microbiome
B
Intestinal permeability is measurable and clinically relevant in specific diseases
Real phenomenon in celiac, IBD, critical illness; clinical implications for other conditions uncertain.
Module 14 · Controversies & Myths
F
'Leaky gut syndrome' is a recognized medical diagnosis
Not in any guideline; wellness marketing term.
Module 14 · Controversies & Myths
F
Detox supplements remove toxins from the gut
No mechanism, no evidence; your liver and kidneys detoxify.
Module 14 · Controversies & Myths
F
Systemic candida overgrowth is common in healthy people
Candidemia is a medical emergency in immunocompromised patients; the 'candida diet' has no basis.
Module 14 · Controversies & Myths
D
SIBO breath testing accurately diagnoses bacterial overgrowth
Sensitivity/specificity ~60-70%; oro-cecal transit confounds lactulose test; overdiagnosis is common.
Module 14 · Controversies & Myths
F
Microbiome age tests predict health outcomes
Statistical correlation with chronological age; no evidence of clinical utility or actionability.
Module 14 · Controversies & Myths
F
Social media microbiome advice is generally reliable
Dominated by oversimplification, false causation, and commercial conflicts.
Module 14 · Controversies & Myths
C
Akkermansia muciniphila supplementation improves metabolic parameters
Phase I/II shows safety and modest improvements in insulin sensitivity; larger trials needed.
Module 15 · Emerging Therapies & Precision Microbiome Medicine
C
Phage therapy can eliminate drug-resistant infections
Compassionate-use case series are promising; RCTs are scarce.
Module 15 · Emerging Therapies & Precision Microbiome Medicine
D
Engineered bacteria can deliver drugs in the GI tract
Proof-of-concept in Phase I/II; efficacy and safety not yet established.
Module 15 · Emerging Therapies & Precision Microbiome Medicine
E
Microbiome profiling enables precision medicine today
Conceptually appealing; clinically premature. No validated implementation exists.
Module 15 · Emerging Therapies & Precision Microbiome Medicine
D
CRISPR-armed probiotics can selectively eliminate resistant bacteria
Proof-of-concept in vitro and animal models; Phase I beginning; human safety/efficacy unknown.
Module 15 · Emerging Therapies & Precision Microbiome Medicine
A
Gut bacteria significantly metabolize common pharmaceuticals
Zimmermann 2019: 2/3 of 271 drugs metabolized; clinical implications for digoxin, levodopa, irinotecan established.
Module 15 · Emerging Therapies & Precision Microbiome Medicine
B
Oral pathobionts contribute to gut disease
F. nucleatum in CRC tissue, Klebsiella driving gut Th1 inflammation — replicated across cohorts.
Module 15 · Emerging Therapies & Precision Microbiome Medicine