# Monarch Initiative Dismech Microbiome Curation > Microbiome Curation Skill - Skill: `tomevault-io/monarch-initiative-dismech-microbiome-curation` (Agent Skill, multi-file: 2 files) - Install (CLI): `npx skillmds@latest add tomevault-io/monarch-initiative-dismech-microbiome-curation` - Raw SKILL.md: https://api.skillmd.com/api/skills/tomevault-io/monarch-initiative-dismech-microbiome-curation/raw - Safety review: pending (external: skill-scanner PASS, skillspector PASS) - Works with: Claude Code, Claude.ai, OpenAI Codex - Category: Coding & Dev Tools - Author: tomevault-io (https://skillmd.com/u/tomevault-io) - Updated: 2026-09-17 - Page: https://skillmd.com/skills/tomevault-io/monarch-initiative-dismech-microbiome-curation --- # Microbiome Curation Skill ## Overview Curate microbiome-related pathophysiology entries with ecological depth beyond simple taxa +/- lists. Focus on: - Ecological concepts (diversity, stability, keystone taxa) - Causal chains from dysbiosis to clinical manifestations - Metabolic consequences (SCFA, bile acids) - Integration with BugSigDB and primary literature ## When to Use - Adding microbiome dysbiosis entries to disorders - Curating pathophysiology for IBD, C. diff, obesity, metabolic diseases - Decomposing "microbiome dysbiosis" into causal graph nodes - Adding ecological concepts (Anna Karenina, colonization resistance) - Linking microbial metabolites to host pathophysiology ## Key Principle: Graph Structure Over Monolithic Entries **DO NOT** create single entries bundling all microbiome effects: ```yaml # BAD - monolithic entry - name: Microbiome Dysbiosis description: > Reduced diversity with depletion of Firmicutes and expansion of pathobionts, leading to decreased SCFA and barrier dysfunction. ``` **DO** decompose into atomic nodes with `downstream` edges: ```yaml # GOOD - causal graph - name: Loss of Microbial Diversity downstream: - target: Loss of Keystone SCFA Producers - target: Increased Microbial Community Instability - name: Loss of Keystone SCFA Producers downstream: - target: Decreased Butyrate Production - name: Decreased Butyrate Production downstream: - target: Impaired Colonocyte Energy Metabolism - name: Impaired Colonocyte Energy Metabolism downstream: - target: Epithelial Barrier Dysfunction ``` This enables: 1. Shared nodes across disorders 2. Explicit feedback loops 3. Targeted therapeutic entry points 4. Evidence on specific causal steps ## Ecological Dimensions of Dysbiosis ### Beyond Taxa +/- BugSigDB captures increased/decreased taxa, but ecology is richer: | Dimension | What it captures | Example | |-----------|------------------|---------| | **Taxonomic** | Which species +/- | Faecalibacterium, E. coli | | **α-Diversity** | Richness/evenness | Shannon index | | **β-Diversity** | Inter-individual variability | Anna Karenina effect | | **Functional** | Pathway capacity | Butyrate synthesis genes | | **Metabolic** | Actual output | Fecal SCFA concentrations | | **Network** | Community structure | Keystone taxa, modularity | | **Stability** | Resilience | Alternative stable states | ### Anna Karenina Principle > "All healthy microbiomes are alike; each dysbiotic microbiome is dysbiotic in its own way." Dysbiosis often manifests as **increased stochasticity** rather than consistent shift to specific taxa. ```yaml - name: Increased Microbial Community Instability description: > Anna Karenina effect - dysbiotic microbiomes show increased inter-individual variability and temporal instability. The community loses resilience and may occupy an alternative stable state that resists therapeutic intervention. notes: > This increased stochasticity complicates biomarker discovery and explains heterogeneous treatment responses. downstream: - target: Loss of Microbial Diversity description: Feedback loop - instability promotes further diversity loss evidence: - reference: PMID:28836573 supports: SUPPORT snippet: "The result is an 'Anna Karenina principle' for animal microbiomes, in which dysbiotic individuals vary more in microbial community composition than healthy individuals." ``` ### Keystone Taxa Low-abundance species with high network connectivity: | Taxon | Role | Loss Consequence | |-------|------|------------------| | *Faecalibacterium prausnitzii* | Butyrate producer, anti-inflammatory | ↓ SCFA, ↑ inflammation | | *Akkermansia muciniphila* | Mucin degrader, cross-feeding hub | Barrier dysfunction | | *Clostridium scindens* | 7α-dehydroxylation (bai operon) | Loss of colonization resistance | | *Roseburia* spp. | Butyrate producer | ↓ SCFA | ### Colonization Resistance (C. diff model) ```yaml - name: Loss of Colonization Resistance description: > The healthy microbiome prevents pathogen colonization through nutrient competition, niche exclusion, and antimicrobial production. Antibiotic disruption removes these barriers. notes: > Key taxa: Lachnospiraceae, Ruminococcaceae, Collinsella. C. scindens provides bile acid-mediated resistance via bai operon. downstream: - target: Pathogen Germination and Expansion - name: Loss of Secondary Bile Acid Production description: > Depletion of 7α-dehydroxylating bacteria (C. scindens, C. hylemonae) prevents conversion of primary to secondary bile acids. Primary bile acids promote pathogen germination; secondary bile acids inhibit it. downstream: - target: Pathogen Germination and Expansion ``` ## SCFA Pathway Template Common pattern for butyrate-related mechanisms: ```yaml - name: Loss of Keystone SCFA Producers description: > Depletion of butyrate-producing Firmicutes, particularly Faecalibacterium prausnitzii, Roseburia spp., and Eubacterium rectale. These keystone taxa support community structure through cross-feeding. notes: > F. prausnitzii is anti-inflammatory; its supernatant reduces colitis in animal models. Primary butyrate producers use the acetyl-CoA pathway. downstream: - target: Decreased Butyrate Production - name: Decreased Butyrate Production description: > Reduced fecal SCFA concentrations, particularly butyrate. Butyrate is the primary energy source for colonocytes (~70% of energy) and exerts anti-inflammatory effects via HDAC inhibition and GPR109A signaling. biological_processes: - preferred_term: Short-chain Fatty Acid Metabolism term: id: GO:0046459 label: short-chain fatty acid metabolic process downstream: - target: Impaired Colonocyte Energy Metabolism - name: Impaired Colonocyte Energy Metabolism description: > Colonocytes deprived of butyrate shift from beta-oxidation to glycolysis, causing energy deficit. This impairs tight junction maintenance, mucus production, and epithelial renewal. cell_types: - preferred_term: Colonic Epithelial Cell term: id: CL:0011108 label: colon epithelial cell downstream: - target: Epithelial Barrier Dysfunction ``` ## Pathobiont Expansion Template ```yaml - name: Pathobiont Expansion description: > Bloom of opportunistic pathobionts (adherent-invasive E. coli, Fusobacterium, Enterobacteriaceae) that exploit niches vacated by depleted commensals. Promote inflammation through LPS and epithelial invasion. downstream: - target: Mucosal Inflammation description: LPS and pro-inflammatory molecules - target: Epithelial Barrier Dysfunction description: Direct epithelial invasion and tight junction disruption evidence: - reference: PMID:26185088 supports: SUPPORT snippet: "This is often characterized by an increased relative abundance of facultative anaerobic bacteria (e.g., Enterobacteriaeceae, Bacilli) and, at the same time, depletion of obligate anaerobic bacteria." ``` ## BugSigDB Integration ### When to Reference BugSigDB - Identifying which taxa are commonly reported +/- in a condition - Validating that your keystone taxa match published signatures - Finding PMIDs for evidence ### How to Search BugSigDB ```bash # Web interface open "https://bugsigdb.org/w/index.php?search=ulcerative+colitis" # R/Bioconductor # library(bugsigdbr) # sigs <- getSignatures(condition = "ulcerative colitis") ``` ### Adding BugSigDB Notes ```yaml - name: Loss of Colonization Resistance notes: > Metagenomics studies consistently show CDI patients have depleted Lachnospiraceae, Ruminococcaceae, and Collinsella spp. compared to controls. BugSigDB signatures confirm depletion of these protective taxa. ``` ## Key References ### Ecological Concepts | Concept | PMID | Citation | |---------|------|----------| | Anna Karenina principle | 28836573 | Zaneveld et al. 2017, Nat Microbiol | | Diversity/stability | 22972295 | Lozupone et al. 2012, Nature | | Alternative stable states | [search for recent] | Microbiome journal | ### IBD Microbiome | Topic | PMID | Citation | |-------|------|----------| | F. prausnitzii | 18936492 | Sokol et al. 2008, PNAS | | IBD meta-analysis | 25307765 | Walters et al. 2014, FEBS Lett | | Dysbiosis patterns | 26185088 | Stecher 2015, Microbiol Spectr | ### C. diff / Colonization Resistance | Topic | PMID | Citation | |-------|------|----------| | bai operon | 32179626 | Reed et al. 2020, J Bacteriol | | C. scindens | 28066726 | Studer et al. 2016, Front Cell Infect Microbiol | | Toxin mechanism | 15831824 | Voth & Ballard 2005, Clin Microbiol Rev | ## Ontology Terms ### Biological Processes (GO) ```bash uv run runoak -i sqlite:obo:go search "short-chain fatty acid" uv run runoak -i sqlite:obo:go search "microbiome" ``` | Process | GO ID | |---------|-------| | SCFA metabolic process | GO:0046459 | | Modification by symbiont | GO:0044003 | | Inflammatory response | GO:0006954 | ### Cell Types (CL) | Cell | CL ID | |------|-------| | Colon epithelial cell | CL:0011108 | | Goblet cell | CL:0000160 | | Neutrophil | CL:0000775 | ### Organisms (NCBITaxon) ```bash uv run runoak -i sqlite:obo:ncbitaxon search "Faecalibacterium" ``` **Note:** Do NOT use NCBITaxon in `cell_types` - microbial taxa are not cell types. Include taxa in `description` or `notes` fields instead. ## Validation ```bash # Full validation just validate kb/disorders/MyDisorder.yaml # Check references just validate-references kb/disorders/MyDisorder.yaml # Generate HTML to visualize causal graph uv run python -m dismech.render kb/disorders/MyDisorder.yaml open pages/disorders/MyDisorder.html ``` ## Common Patterns by Disorder Type ### IBD (UC, Crohn's) 1. Loss of Microbial Diversity 2. Loss of Keystone SCFA Producers (F. prausnitzii) 3. Pathobiont Expansion (AIEC, Fusobacterium) 4. Decreased Butyrate → Colonocyte Energy Deficit 5. Barrier Dysfunction 6. Anna Karenina instability (feedback) ### C. diff Infection 1. Antibiotic-Induced Microbial Depletion 2. Loss of Colonization Resistance 3. Loss of Secondary Bile Acid Production 4. C. difficile Germination and Expansion 5. Toxin Production → Epithelial Death + Neutrophil Recruitment 6. Pseudomembranous Colitis ### Obesity / Metabolic Syndrome 1. Firmicutes/Bacteroidetes ratio shift 2. Increased Energy Harvest 3. Altered Bile Acid Metabolism 4. Gut Barrier Permeability 5. Metabolic Endotoxemia (LPS) 6. Low-grade Inflammation ## Integration with Other Skills - **dismech-terms**: For ontology lookups (GO, CL, UBERON) - **dismech-references**: For validating PMID snippets - **cancer-curator**: Some cancers have microbiome components (colorectal) --- > Converted and distributed by [TomeVault](https://tomevault.io/claim/monarch-initiative) — claim your Tome and manage your conversions.