Butyrate is an essential short-chain fatty acid (SCFA) that has been extensively studied over the past few decades, primarily due to its potent ability to modulate histone deacetylase (HDAC) activity and regulate epigenetics. Butyrate has become increasingly important in the field of cancer research due to its potential to modulate the expression of cancer-related genes and pathways, as well as its ability to act as an anti-inflammatory and anti-carcinogenic agent. Butyrate is a four-carbon SCFA that is produced by the microbial fermentation of dietary fiber in the colon. It is then absorbed and utilized by the colonic epithelial cells for energy production. It has been shown to have several beneficial effects on the human body, including acting as an anti-inflammatory and anti-carcinogenic agent.
Butyrate production is mainly dependent on the composition of the gut microbiome.
Butyrate:
- can modulate histone deacetylase (HDAC) activity and epigenetic regulation
- can induce cell growth inhibition in different types of cancer cells.
- is anti-inflammatory {ref│ref│ref}
- is an immunomodulator {ref}
- SIRT3 inhibitor {ref}
- dictates ferroptosis sensitivity through FFAR2-mTOR signaling {study|study}
- preferentially induces apoptosis in glycolytic cells {ref}
- prevents anaerobic glycolysis and promotes normal oxidative glycolysis (epigenetically) {ref}
- is a modulator of redox signaling {ref}
- reduces endotoxin levels {ref│ref}
- reduces plasma glucose {ref}
- inhibits the growth of E. coli {ref}
- mitigates clinical and pathological features of C. difficile {ref}
- decreases the production of ammonia by inhibiting the growth of ammonia-producing bacteria e.g. H. pylori produces unusually large amounts of urea-derived ammonium
- GPR109A is a tumor suppressor in the mammary gland, and the pharmacological induction of this gene in tumor tissues, followed by its activation with agonists, could be an effective therapeutic strategy to treat breast cancer. {ref}
Synergistic/Anti-Cancer: In most contexts, especially extra-intestinal cancers.
Antagonistic/Pro-Cancer: Butyrate is an energy source for certain colorectal cancer cells, particularly under specific genetic and hypoxic conditions. This warrants caution in CRC therapeutic strategies involving direct high-dose butyrate supplementation.
For immunotherapy combinations, the current evidence suggests synergy. However, careful consideration of cancer type (especially when it comes to CRC), dose, and delivery method is crucial. Promoting a butyrate-producing microbiome through diet is likely a safe strategy for improving immunotherapy outcomes in many cancers.
Synergy
- →Artemisinin {study}
- →Vitamin D {study/study}
- →Aloe Vera
- →DHA (docosahexaenoic acid)
- →Curcumin {study}
- →Quercetin
- →Acetylcarnitine {ref}
- →Zinc (HDAC is a zinc dependent mechanism)
- →Aspirin {ref}
- →Lovastatin {study}
- →Capsicum chinense (Habanero chili pepper)
- →Phytate
- →Melatonin
- →Niacin
- →EGCg {ref}
- →Xylo-oligosaccharide {ref} anti-inflammatory
- →Glycerol {ref}
- →Metformin {ref}
- →Selenite {study}
Supplements and pharmaceutical drugs: Tributyrin (Butycaps) {ref}, Sodium/Calcium/Potassium/Magnesium Butyrate, Intrinsa Genoma Nutritionals (contains magnesium, butyric acid, caprylic acid🛈), Pendulum Glucose Control *
You can also increase butyrate by eating enough fiber (fruits and vegetables), type III resistant starch {ref}, short-chain fructo-oligosaccharides, xylo-oligosaccharides (XOS), herbs and herbal teas such as (green) tea {ref}, PHGG, senna {study}, licorice, ginger {study}, Triphala {ref}; honey, psyllium husk, berberine, orange juice {ref}, kombucha, coffee, chlorella, butter/ghee, taurine, curcumin, modified citrus pectin, kelp, walnuts {ref}, yacon, carrot, cooled potato, exercise, riboflavin {ref}
I wonder if it might be beneficial to do a one-time 7 day-course of a broad-spectrum antibiotic first and then start with the foods and supplements as mentioned above. A sort of reset: out with the old, in with the new.
(*) What specific bacteria help create butyrate?
There are many species of bacteria that either contribute to the butyrate-making process or are responsible for the actual production of butyrate.
Some of the most common species who are responsible for producing butyrate:
- Faecalibacterium prausnitzii (belongs to Clostridium leptum cluster)
- Eubacterium rectale (belongs to Clostridium coccoides cluster)
- Roseburia spp. (Roseburia faecis, Roseburia inulinivorans, Roseburia intestinalis, and Roseburia hominis)
- Clostridium butyricum
- Clostridium beijerinckii
- Eubacterium spp. (Eubacterium hallii)
- Anaerostipes spp. (Anaerostipes butyraticus, Anaerostipes caccae, and Anaerostipes hadrus)
- Butyricicoccus pullicaecorum {study}
Additionally, species of bacteria in the Bifidobacterium genus are known to help break carry out the first steps in fiber digestion, providing molecules to the gut microbiome that the above species can use to make butyrate.
References & Sources
- First trial to prove a diet supplement can prevent hereditary cancer
- The niacin/butyrate receptor GPR109A suppresses mammary tumorigenesis by inhibiting cell survival
- Effect of sodium butyrate on estrogen receptor and epidermal growth factor receptor gene expression in human breast cancer cell lines
- Synergistic effects of sodium butyrate and cisplatin against cervical carcinoma in vitro and in vivo NaB combined with cisplatin inhibited tumor growth, and reversed EMT process through up-regulating E-cadherin in Vivo
- GPR109A Is a G-protein–Coupled Receptor for the Bacterial Fermentation Product Butyrate and Functions as a Tumor Suppressor in Colon{study}
- Searching for the Magic Bullet Against Cancer: The Butyrate Saga
- Butyrate Makes Macrophages “Go Nuclear” against Bacterial Pathogens
- The association between gut butyrate-producing bacteria and non-small-cell lung cancer {study}
- The Effect of Probiotics on the Production of Short-Chain Fatty Acids by Human Intestinal Microbiome {ref}
- Sodium Butyrate Selectively Kills Cancer Cells and Inhibits Migration in Colorectal Cancer by Targeting Thioredoxin-1 {ref}
- Butyrate-induced partial remission of acute myelogenous leukemia in a child {ref}
- Sodium butyrate promotes apoptosis in breast cancer cells through reactive oxygen species (ROS) formation and mitochondrial impairment {ref}
- Different effects of sodium butyrate on cancer and normal prostate cells {ref}
- The effect of sodium butyrate as a histone deacetylase inhibitor on the gene expression of Bid in HT-29 human colorectal cancer cell line
- Targeting Histone Deacetylases for Cancer Therapy: From Molecular Mechanisms to Clinical Implications {study}
- Plant extracts as natural modulators of gut microbiota community structure and functionality
- Cross sectional evaluation of the gut-microbiome metabolome axis in an Italian cohort of IBD patients{ref} phospholipids pathways role in cancer
- The Role of Butyrate in Attenuating Pathobiont-Induced Hyperinflammation
- THE SHIKIMATE PATHWAY, THE MICROBIOME, AND DISEASE
- Study discovers link between cancer and autism "patients who have been diagnosed with an autism spectrum disorder (ASD) have a higher burden of mutations in cancer-promoting oncogenes, but actually have lower rates of cancer."
- Dysbiotic bacteria in the gastrointestinal tract of individuals with autism produce butyrate that drives the mitochondria to become overactive and very sensitive to oxidative stress.
- Image reference: https://www.cmghjournal.org/article/S2352-345X(18)30034-1/fulltext
- Yacon (Smallanthus sonchifolius) as a Food Supplement: Health-Promoting Benefits of Fructooligosaccharides
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