Database Query Results : Butyrate, ,

BA, Butyrate: Click to Expand ⟱
Features:

Butyrate = short-chain fatty acid (SCFA; C4) produced by gut microbiota from fermentable fiber; common experimental/therapeutic forms include sodium butyrate (NaBu) and tributyrin (prodrug). Sources: microbiome/colon epithelium physiology, inflammation/IBD–CRC literature, HDAC biology, and colon “butyrate paradox” work.
Primary mechanisms (ranked):
1) HDAC inhibition (esp. when intracellular butyrate accumulates) → histone hyperacetylation, differentiation, cell-cycle arrest, apoptosis; immune-modulatory gene programs. :contentReference[oaicite:0]{index=0}
2) Metabolic fuel vs accumulation (Warburg-dependent “butyrate paradox”): normal colonocytes oxidize butyrate (trophic), whereas Warburg-like colon cancer cells oxidize less → butyrate accumulates and acts as HDACi. :contentReference[oaicite:1]{index=1}
3) GPCR signaling via FFAR2 (GPR43), FFAR3 (GPR41), and GPR109A/HCAR2 → anti-inflammatory epithelial/immune effects (e.g., barrier, IL-18 axis) and context-dependent anti-carcinogenesis. :contentReference[oaicite:2]{index=2}
Bioavailability/PK relevance: systemic butyrate is rapidly absorbed and largely metabolized; most biologic relevance is local (colon lumen/epithelium); oral supplements often aim for colonic delivery (encapsulation/prodrugs). :contentReference[oaicite:3]{index=3}
In-vitro vs oral exposure: many cell studies use ~0.5–5 mM (sometimes higher); these concentrations are primarily plausible locally in the colon lumen, not as sustained systemic plasma levels. :contentReference[oaicite:4]{index=4}
Clinical evidence status: strongest human evidence is GI/RT-supportive contexts (e.g., microencapsulated sodium butyrate during pelvic radiotherapy to reduce/mitigate proctitis symptoms); anticancer efficacy remains largely preclinical/adjunct-hypothesis rather than established RCT antitumor benefit.

Butyrate is a four-carbon, short-chain fatty acid (SCFA) produced during dietary fiber fermentation by microbes in the lower digestive tract.
Butyrate, a short‐chain fatty acid primarily produced by the gut microbiota through the fermentation of dietary fibers.

Pathways:
-Histone Deacetylase (HDAC) Inhibition
-Modulation of Wnt/β-Catenin Signaling
-induce cell cycle arrest.
-G-Protein-Coupled Receptors (GPCRs) Activation
-inhibition of NF-κB
-activate AMPK
-promoting regulatory T-cell (Treg) differentiation

Butyrate (Sodium Butyrate / Tributyrin) — Cancer vs Normal Pathway Effects

Rank Pathway / Axis Cancer Cells (↑ / ↓ / ↔) Normal Cells (↑ / ↓ / ↔) TSF Primary Effect Notes / Interpretation
1 HDAC inhibition → histone acetylation programs ↑ acetylation → ↓ proliferation; ↑ differentiation/apoptosis (dose- & model-dependent) ↑ acetylation (typically homeostatic/anti-inflammatory; high conc. can be growth-inhibitory) R→G Epigenetic reprogramming Canonical mechanism for NaBu in vitro; strong support that butyrate inhibits HDAC activity and alters gene expression. :contentReference[oaicite:6]{index=6}
2 “Butyrate paradox” (Warburg effect dictates fate: fuel vs HDACi) ↓ oxidation → ↑ intracellular butyrate → HDACi phenotype (colon CRC context) ↑ oxidation (fuel) → trophic/proliferative support (colonocytes) R Selective context sensitivity In colon models: normal cells oxidize butyrate; Warburg-like cancer cells accumulate it and show HDACi-driven anti-proliferation. :contentReference[oaicite:7]{index=7}
3 Barrier + anti-inflammatory signaling (epithelium/immune) ↓ pro-inflammatory tumor microenvironment signaling (context-dependent) ↑ barrier integrity; ↓ inflammatory tone P→R→G Mucosal homeostasis Butyrate supports intestinal homeostasis; relevant to inflammation-associated carcinogenesis risk (IBD→CRC axis). :contentReference[oaicite:8]{index=8}
4 GPCR axes: FFAR2/FFAR3, GPR109A (HCAR2) ↔ / ↓ pro-tumor inflammation (context-dependent) ↑ anti-inflammatory signaling (epithelium/immune) P→R Receptor-mediated immunomodulation SCFA receptor signaling contributes to anti-inflammatory and barrier effects; GPR109A implicated in epithelial IL-18/autophagy programs in some models. :contentReference[oaicite:9]{index=9}
5 ROS ↔ (often secondary); ↑ ROS/apoptosis signaling (high concentration only; model-dependent) ↔ or ↓ oxidative stress (indirect; barrier/immune effects) R Stress signaling modulation ROS changes are commonly downstream of metabolic + HDAC-driven programs rather than a primary “direct oxidant” mechanism. :contentReference[oaicite:10]{index=10}
6 NRF2 ↔ (context-dependent; can support resistance if persistently ↑) ↔/↑ cytoprotection (context-dependent) G Adaptive antioxidant response NRF2 directionality varies by model and stress context; interpret as adaptive/secondary unless explicitly demonstrated in a given system. :contentReference[oaicite:11]{index=11}
7 Ca2+ / ER stress–apoptosis coupling ↑ stress signaling (model-dependent) ↔ (not core) R Apoptosis facilitation (subset) Often reported as part of downstream stress/apoptosis cascades with HDACi exposure; not a universal primary axis for butyrate.
8 Ferroptosis ↔ (indirect; model-dependent) ↔ R Lipid-peroxidation sensitivity (indirect) No single canonical “butyrate → ferroptosis” identity across cancers; treat as context-specific/secondary unless explicitly shown.
9 HIF-1α / Warburg metabolism ↔ (indirect; context-dependent) ↔ (indirect) G Metabolic phenotype modulation Most mechanistic centrality comes from the Warburg-dependent “paradox” framing rather than direct HIF targeting. :contentReference[oaicite:12]{index=12}
10 Clinical Translation Constraint Systemic exposure is limited (rapid metabolism); strongest leverage is local colonic delivery/diet–microbiome context; clinical data largely supportive-care (e.g., radiotherapy-associated proctitis), not established tumor-control benefit. — PK / Delivery / Evidence Microencapsulated sodium butyrate has prospective/clinical reports in pelvic RT supportive care; anticancer efficacy remains preclinical/adjunct. :contentReference[oaicite:13]{index=13}

TSF legend: P: 0–30 min (primary/rapid effects) | R: 30 min–3 hr (acute signaling + stress responses) | G: >3 hr (gene-regulatory adaptation; phenotype outcomes)
Scientific Papers found: Click to Expand⟱
1032- BA,    Gut microbiome-derived butyrate inhibits the immunosuppressive factors PD-L1 and IL-10 in tumor-associated macrophages in gastric cancer
- in-vivo, GC, AGS
GutMicro↑, PD-L1↓, IL10↓, TumCG↓,
1080- BA,    Butyrate suppresses Cox-2 activation in colon cancer cells through HDAC inhibition
- in-vitro, CRC, HT-29
HDAC↓, TNF-α↓, COX2↓,
1224- BA,    Intratumor microbiome-derived butyrate promotes lung cancer metastasis
- in-vivo, Lung, NA
TumCG↑, H19↑, HDAC2↓,
2047- BA,    Sodium butyrate inhibits migration and induces AMPK-mTOR pathway-dependent autophagy and ROS-mediated apoptosis via the miR-139-5p/Bmi-1 axis in human bladder cancer cells
- in-vitro, CRC, T24/HTB-9 - in-vitro, Nor, SV-HUC-1 - in-vitro, Bladder, 5637 - in-vivo, NA, NA
HDAC↓, AntiTum↑, TumCMig↓, AMPK↑, mTOR↑, TumAuto↑, ROS↑, miR-139-5p↑, BMI1↓, TumCI?, E-cadherin↑, N-cadherin↓, Vim↓, Snail↓, cl‑PARP↑, cl‑Casp3↑, BAX↑, Bcl-2↓, Bcl-xL↓, MMP↓, PINK1↑, PARK2↑, TumMeta↓, TumCG↓, LC3II↑, p62↓, eff↓,
2050- BA,    The Role of Sodium Phenylbutyrate in Modifying the Methylome of Breast Cancer Cells
- in-vitro, BC, MCF-7
eff↑, HDAC↓, TumCG↓,
3236- EGCG,  BA,    Molecular mechanisms for inhibition of colon cancer cells by combined epigenetic-modulating epigallocatechin gallate and sodium butyrate
- in-vitro, Colon, RKO - in-vitro, Colon, HCT116 - in-vitro, Colon, HT29
Apoptosis↑, TumCCA?, HDAC1↓, DNMT1↓, survivin↓, HDAC↓, P21↑, NF-kB↑, γH2AX↑, ac‑H3↑, DNAdam↑,

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 6

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

PARK2↑, 1,   ROS↑, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 1,   PINK1↑, 1,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,  

Cell Death ⓘ

Apoptosis↑, 1,   BAX↑, 1,   Bcl-2↓, 1,   Bcl-xL↓, 1,   cl‑Casp3↑, 1,   survivin↓, 1,  

Transcription & Epigenetics ⓘ

H19↑, 1,   ac‑H3↑, 1,  

Autophagy & Lysosomes ⓘ

LC3II↑, 1,   p62↓, 1,   TumAuto↑, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   DNMT1↓, 1,   cl‑PARP↑, 1,   γH2AX↑, 1,  

Cell Cycle & Senescence ⓘ

P21↑, 1,   TumCCA?, 1,  

Proliferation, Differentiation & Cell State ⓘ

BMI1↓, 1,   HDAC↓, 4,   HDAC1↓, 1,   HDAC2↓, 1,   mTOR↑, 1,   TumCG↓, 3,   TumCG↑, 1,  

Migration ⓘ

E-cadherin↑, 1,   miR-139-5p↑, 1,   N-cadherin↓, 1,   Snail↓, 1,   TumCI?, 1,   TumCMig↓, 1,   TumMeta↓, 1,   Vim↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   IL10↓, 1,   NF-kB↑, 1,   PD-L1↓, 1,   TNF-α↓, 1,  

Drug Metabolism & Resistance ⓘ

eff↓, 1,   eff↑, 1,  

Clinical Biomarkers ⓘ

GutMicro↑, 1,   PD-L1↓, 1,  

Functional Outcomes ⓘ

AntiTum↑, 1,  
Total Targets: 47

Pathway results for Effect on Normal Cells:


Total Targets: 0

Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:50  Target#:%  State#:%  Dir#:%
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