Butyrate: Missing Link From Gut Health To Full Self

Butyrate is gut health’s most unsung hero! Feed your gut fiber and unleash your microbiome’s supper power to regulate metabolism, inflammation, and mood.

The Nutrient Deficiency that No One is Talking About

A start with a curious question

Can you identify the odd one out? 

A.) Hershey’s Chocolate

B.) Queen bees  

C.) Your gut on an industrialized diet.  

You got it?  OK, hold onto your answer and I’ll explain at the end!

Now on to another question: What if I told you that the majority of people in high income settings have a single nutrient deficiency that has been linked to the majority of diseases that affect our society: gut,[1] cardiovascular,[2] metabolic (e.g. obesity[3] and diabetes[4]), immune (e.g. allergy[5], inflammation[6], and autoimmunity[7]), neurologic (e.g. anxiety,[8] depression,[9] and Alzeheimers[10]), muscle[11] and even cancer?[12] At first it might seem far fetched. Could one nutrient be linked to so much?

Nutrient deficiency:  lesson from developing nations

Consider what happens in the case of a single vitamin deficiency. For example, thiamine/B1 deficiency is a condition that is not uncommon in low and middle income countries where we focused attention at The Bill & Melinda Gates Foundation. It can lead to nerve issues, heart problems, brain abnormalities, and even birth defects.[13] Symptoms include fatigue, irritability, poor memory, loss of appetite, sleep disturbances, abdominal discomfort, and weight loss.[13] It affects multiple body systems and we have a single name for this syndrome (berberi) because we know exactly what causes it.[13] If I started by listing the symptoms above however, you might be equally unsure that a single nutrient deficiency could cause all of this.

Is butyrate the missing link and star molecule of the 21st century?

The truth is, there is a single molecule that only about 5% of people in the US are likely to have enough of daily. And while it may not be a cause of all the diseases listed above, there are growing and intriguing links to each (see references above). The molecule is called butyrate and history might just prove it to be one of the most important molecules of the 21st century. 

So what is butyrate, you might ask? It’s a molecule made by our microbiome from fermentable fiber and is an important link between our diet, gut microbes, and overall health.[14] Butyrate prevents leaky gut,[15] alleviates inflammation,[16] regulates metabolism,[17] contributes to muscle[18] and bone growth,[19] and even helps grow and regulate cells in our brain.[20] You can think of it like your gut microbiome’s superpower!

How fermentable fiber affects the gut microbiome

So how could we have missed such an important molecule and why aren’t we all supplementing it like we do B vitamins in supplements and store bought goods? Part of the reason is because it’s a molecule that comes primarily from the microbiome factories in our lower intestines.[21] It has only been in recent history that we have had the tools to understand the microbiome and the molecules it produces!

As to the reason we don’t get enough? Our gut microbe factories, just like us, need food–and modern food industry practices have been starving microbes of their favorite food, fermentable fiber. Modern food processing removes bran from wheat and rice leaving you with “white bread and white rice”. Plus, the standard American diet involves eating practices that tend to limit whole grains, fruits and vegetables. With all this, only 5% of this country’s population gets enough fiber so it stands to reason that only 5% of the population gets enough butyrate![22]

An intriguing hypothesis

Now I’ll raise what I find to be a most intriguing hypothesis. Could the fiber gap and resulting butyrate deficiency be one of the major factors contributing to many modern diseases? This is not a new hypothesis and indeed was raised by a popular Irish surgeon over fifty years ago, Dr. Denis Burkitt.[23] In some realms like obesity, diabetes, gut disease, and heart disease; it is more than just a correlative connection and a multitude of studies that establish low fiber and butyrate playing a causative role. In other areas that involve the immune system, brain, muscles, and bones there are intriguing correlative connections. That said, studies are still needed to evaluate whether low butyrate might be partially to blame for some of these conditions.

The answer was underneath our noses all along

So now we’ll get back to the odd question at the start! All but C have sufficient butyrate. Hershey’s chocolate contains butyrate in its formula. Hershey’s used a process called lipolysis to help preserve milk in the early days when the dairy farms were far from the factory and has remained an integral part of the special formula.[24,25] It is actually what gives Hershey’s its distinct aroma! Butyrate also turns out to be one of the key microbiome-derived molecules that turns a worker honey bee consuming royal jelly into a queen bee and also gives her special reproductive powers and longevity![26]  The odd one out is C, a gut on an industrialized diet, starving for butyrate.[27]

Online stores or coming soon to a colon in you?

So where can you find this magical molecule? It is present in foods like butter, some cheeses, and even Hershey’s chocolate as you just learned, but in relatively low amounts.[28,29] A number of companies produce butyrate supplements and these may end up being really helpful for some conditions although the research still needs to catch up here. The majority of butyrate that promotes health comes from the lower gut produced by microbes from fermentable fiber.[30] The beauty of this naturally produced butyrate compared to supplements is it’s delivered in the right amounts, at the right time, and in the right place.  

So hats off to fermentable fiber, the microbes that consume it, and building a more butyraceous bottom and body! See blog on fiber for the science behind the best fermentable fibers for helping your body produce butyrate. Spoiler alert:  resistant starch might be key.[31]

More Articles and Resources

If you enjoyed this article, please feel free to visit gutbites.org where you’ll find more practical food and microbiome digests to improve gut health and lift your whole self! Would love to hear your comments below too!

1. Jamka M, Kokot M, Kaczmarek N, Bermagambetova S, Nowak JK, Walkowiak J. The Effect of Sodium Butyrate Enemas Compared with Placebo on Disease Activity, Endoscopic Scores, and Histological and Inflammatory Parameters in Inflammatory Bowel Diseases: A Systematic Review of Randomised Controlled Trials. Complement Med Res. 2021;28: 344–356. doi:10.1159/000512952

2. Amiri P, Hosseini SA, Ghaffari S, Tutunchi H, Ghaffari S, Mosharkesh E, et al. Role of Butyrate, a Gut Microbiota Derived Metabolite, in Cardiovascular Diseases: A comprehensive narrative review. Front Pharmacol. 2021;12: 837509. doi:10.3389/fphar.2021.837509

3. Coppola S, Avagliano C, Calignano A, Berni Canani R. The Protective Role of Butyrate against Obesity and Obesity-Related Diseases. Molecules. 2021;26. doi:10.3390/molecules26030682

4. Arora T, Tremaroli V. Therapeutic Potential of Butyrate for Treatment of Type 2 Diabetes. Front Endocrinol . 2021;12: 761834. doi:10.3389/fendo.2021.761834

5. Yip W, Hughes MR, Li Y, Cait A, Hirst M, Mohn WW, et al. Butyrate Shapes Immune Cell Fate and Function in Allergic Asthma. Front Immunol. 2021;12: 628453. doi:10.3389/fimmu.2021.628453

6. Cleophas MCP, Ratter JM, Bekkering S, Quintin J, Schraa K, Stroes ES, et al. Effects of oral butyrate supplementation on inflammatory potential of circulating peripheral blood mononuclear cells in healthy and obese males. Sci Rep. 2019;9: 775. doi:10.1038/s41598-018-37246-7

7. Takahashi D, Hoshina N, Kabumoto Y, Maeda Y, Suzuki A, Tanabe H, et al. Microbiota-derived butyrate limits the autoimmune response by promoting the differentiation of follicular regulatory T cells. EBioMedicine. 2020;58: 102913. doi:10.1016/j.ebiom.2020.102913

8. Duan C, Huang L, Zhang C, Zhang L, Xia X, Zhong Z, et al. Gut commensal-derived butyrate reverses obesity-induced social deficits and anxiety-like behaviors via regulation of microglial homeostasis. Eur J Pharmacol. 2021;908: 174338. doi:10.1016/j.ejphar.2021.174338

9. Qiu J, Liu R, Ma Y, Li Y, Chen Z, He H, et al. Lipopolysaccharide-Induced Depression-Like Behaviors Is Ameliorated by Sodium Butyrate via Inhibiting Neuroinflammation and Oxido-Nitrosative Stress. Pharmacology. 2020;105: 550–560. doi:10.1159/000505132

10. Fernando WMADB, Martins IJ, Morici M, Bharadwaj P, Rainey-Smith SR, Lim WLF, et al. Sodium Butyrate Reduces Brain Amyloid-β Levels and Improves Cognitive Memory Performance in an Alzheimer’s Disease Transgenic Mouse Model at an Early Disease Stage. J Alzheimers Dis. 2020;74: 91–99. doi:10.3233/JAD-190120

11. Davis JA, Collier F, Mohebbi M, Pasco JA, Shivappa N, Hébert JR, et al. The associations of butyrate-producing bacteria of the gut microbiome with diet quality and muscle health. Gut Microbiome. 2021;2. doi:10.1017/gmb.2021.2

12. Wang W, Fang D, Zhang H, Xue J, Wangchuk D, Du J, et al. Sodium Butyrate Selectively Kills Cancer Cells and Inhibits Migration in Colorectal Cancer by Targeting Thioredoxin-1. Onco Targets Ther. 2020;13: 4691–4704. doi:10.2147/OTT.S235575

13. Wiley KD, Gupta M. Vitamin B1 Thiamine Deficiency. StatPearls. Treasure Island (FL): StatPearls Publishing; 2021. Available: https://www.ncbi.nlm.nih.gov/pubmed/30725889

14. Wang M, Wichienchot S, He X, Fu X, Huang Q, Zhang B. In vitro colonic fermentation of dietary fibers: Fermentation rate, short-chain fatty acid production and changes in microbiota. Trends Food Sci Technol. 2019;88: 1–9. doi:10.1016/j.tifs.2019.03.005

15. Kelly CJ, Zheng L, Campbell EL, Saeedi B, Scholz CC, Bayless AJ, et al. Crosstalk between Microbiota-Derived Short-Chain Fatty Acids and Intestinal Epithelial HIF Augments Tissue Barrier Function. Cell Host Microbe. 2015;17: 662–671. doi:10.1016/j.chom.2015.03.005

16. Siddiqui MT, Cresci GAM. The Immunomodulatory Functions of Butyrate. J Inflamm Res. 2021;14: 6025–6041. doi:10.2147/JIR.S300989

17. Zhang L, Liu C, Jiang Q, Yin Y. Butyrate in Energy Metabolism: There Is Still More to Learn. Trends Endocrinol Metab. 2021;32: 159–169. doi:10.1016/j.tem.2020.12.003

18. Walsh ME, Bhattacharya A, Sataranatarajan K, Qaisar R, Sloane L, Rahman MM, et al. The histone deacetylase inhibitor butyrate improves metabolism and reduces muscle atrophy during aging. Aging Cell. 2015;14: 957–970. doi:10.1111/acel.12387

19. Tyagi AM, Yu M, Darby TM, Vaccaro C, Li J-Y, Owens JA, et al. The Microbial Metabolite Butyrate Stimulates Bone Formation via T Regulatory Cell-Mediated Regulation of WNT10B Expression. Immunity. 2018;49: 1116–1131.e7. doi:10.1016/j.immuni.2018.10.013

20. Silva YP, Bernardi A, Frozza RL. The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication. Front Endocrinol . 2020;11: 25. doi:10.3389/fendo.2020.00025

21. Zhu L-B, Zhang Y-C, Huang H-H, Lin J. Prospects for clinical applications of butyrate-producing bacteria. World J Clin Pediatr. 2021;10: 84–92. doi:10.5409/wjcp.v10.i5.84

22. Quagliani D, Felt-Gunderson P. Closing America’s Fiber Intake Gap: Communication Strategies From a Food and Fiber Summit. Am J Lifestyle Med. 2017;11: 80–85. doi:10.1177/1559827615588079

23. O’Keefe SJ. The association between dietary fibre deficiency and high-income lifestyle-associated diseases: Burkitt’s hypothesis revisited. Lancet Gastroenterol Hepatol. 2019;4: 984–996. doi:10.1016/S2468-1253(19)30257-2

24. Azzara CD, Campbell LB. Off-Flavors of Dairy Products. In: Charalambous G, editor. Developments in Food Science. Elsevier; 1992. pp. 329–374. doi:10.1016/B978-0-444-88558-6.50018-0

25. Finding the flavor of chocolate. [cited 11 May 2022]. Available: https://www.psu.edu/news/research/story/finding-flavor-chocolate/

26. Anderson KE, Ricigliano VA, Mott BM, Copeland DC, Floyd AS, Maes P. The queen’s gut refines with age: longevity phenotypes in a social insect model. Microbiome. 2018;6: 108. doi:10.1186/s40168-018-0489-1

27. Jacobson DK, Honap TP, Ozga AT, Meda N, Kagoné TS, Carabin H, et al. Analysis of global human gut metagenomes shows that metabolic resilience potential for short-chain fatty acid production is strongly influenced by lifestyle. Sci Rep. 2021;11: 1724. doi:10.1038/s41598-021-81257-w

28. Paszczyk B, Łuczyńska J. The Comparison of Fatty Acid Composition and Lipid Quality Indices in Hard Cow, Sheep, and Goat Cheeses. Foods. 2020;9. doi:10.3390/foods9111667

29. Woo AH, Lindsay RC. Stepwise Discriminant Analysis of Free Fatty Acid Profiles for Identifying Sources of Lipolytic Enzymes in Rancid Butter1. J Dairy Sci. 1983;66: 2070–2075. doi:10.3168/jds.S0022-0302(83)82052-9

30. Medawar E, Haange S-B, Rolle-Kampczyk U, Engelmann B, Dietrich A, Thieleking R, et al. Gut microbiota link dietary fiber intake and short-chain fatty acid metabolism with eating behavior. Transl Psychiatry. 2021;11: 500. doi:10.1038/s41398-021-01620-3

31. McOrist AL, Miller RB, Bird AR, Keogh JB, Noakes M, Topping DL, et al. Fecal butyrate levels vary widely among individuals but are usually increased by a diet high in resistant starch. J Nutr. 2011;141: 883–889. doi:10.3945/jn.110.128504

One response to “Butyrate: Missing Link From Gut Health To Full Self”

  1. Dr. Matthew Durham Avatar
    Dr. Matthew Durham

    After writing a book on Fatty Liver (Fatty Liver Protocol) I’m not a fan of large amounts of fruit. I think the sweet spot for most folks is a high protein, moderate fat, low carb diet including lots of veggies, some berries and occasional fruit.

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