The Importance of Butyrate in Postviral Conditions
The previous blog post on the carnivore diet sparked some very interesting discussion on the topic of butyrate. This post, then, is a nice segue. Go back and read Carnivore on this blog or more in-depth on Health Rising, if you haven’t already.
In postviral illnesses like ME/CFS and long COVID (and also in fibromyalgia), the gut microbiome is disrupted. Studies show reduced microbial diversity, a loss of beneficial bacteria, and lower levels of short-chain fatty acids. Among these changes, low butyrate levels may be one of the most important and overlooked factors affecting recovery.
Butyrate is a compound produced by gut bacteria when they ferment dietary fiber. It plays a central role in gut health, immune balance, energy metabolism, and even sleep regulation. In people with postviral conditions, these systems are often impaired, and restoring butyrate may help support them.
While it is not a fast-acting solution, gradually increasing butyrate through nutrition and microbiome repair may offer steady, long-term benefits. In this article, we will look at what butyrate is, why it matters for people with ME/CFS and long COVID, and how to support its production safely and effectively.
What Is Butyrate?
Butyrate (or butyric acid) is a short-chain fatty acid (SCFA) produced when certain gut microbes ferment dietary fibers. It’s a major energy source for colonocytes, the cells that line the colon, and plays critical roles in:
Maintaining intestinal barrier integrity
Regulating immune responses
Modulating inflammation and oxidative stress
Influencing sleep and mood via gut-brain signaling
Butyrate Producers Are Depleted in Postviral Illness
Multiple studies have now confirmed that postviral conditions are associated with a decline in butyrate-producing microbes such as Faecalibacterium prausnitzii and Roseburia spp.
A 2021 metabolomics study in long COVID found decreased SCFA production and disrupted microbial metabolism (Nagy-Szakal et al., 2021).
In ME/CFS, similar findings were reported as far back as 2016, with reduced diversity and lower levels of F. prausnitzii (Giloteaux et al., 2016).
These microbial shifts correlate with disease severity and immune abnormalities.
This suggests that butyrate deficiency isn’t a coincidence. It may be a contributing factor to ongoing symptoms.
Is All Butyrate the Same?
Not exactly. There are multiple sources and forms of butyrate, each with different implications for gut and systemic health.
Microbially produced butyrate (made when gut bacteria ferment dietary fiber) is the most beneficial. It’s produced directly in the colon, where it nourishes colonocytes, supports the gut barrier, and regulates immune function. Just as importantly, the fermentation process that produces butyrate also feeds a diverse, resilient microbial ecosystem.
In contrast, tributyrin, the form of butyrate found in grass-fed butter and ghee, is absorbed primarily in the small intestine. While it may offer systemic anti-inflammatory effects, it doesn’t reach the colon in meaningful amounts (Canani et al., 2011; Sivaprakasam et al., 2021). It also doesn’t support the growth of beneficial microbes, meaning it’s not a replacement for fiber-driven fermentation.
Supplemental butyrate, such as sodium butyrate or butyrate salts, may offer benefits in certain cases, but again, absorption patterns vary, and these products often bypass the colon entirely unless formulated for delayed release. Some can be used topically (via enema) in conditions such as ulcerative colitis.
Lastly, isobutyrate, a branched-chain fatty acid, is produced from the microbial breakdown of amino acids like valine on high-protein diets, like carnivore. While sometimes described as a “butyrate alternative,” it lacks many of butyrate’s beneficial effects and is often associated with the production of harmful byproducts like ammonia and p-cresol (Windey et al., 2012). Isobutyrate may still appear in SCFA profiles, but it’s not necessarily a sign of a healthy gut environment.
Butyrate’s Role Beyond the Gut
Butyrate’s benefits extend far beyond the colon. It influences mitochondrial function, modulates the immune system, and even plays a role in brain health. A 2023 study in Cell Metabolism found that disruptions in SCFA metabolism (including butyrate) were linked to immune dysregulation and fatigue in people with long COVID, underscoring how changes in gut-derived metabolites can have wide-reaching effects (Wu et al., 2023).
Mitochondria
Butyrate supports mitochondrial biogenesis and oxidative phosphorylation. This can enhance energy production in tissues with high metabolic demands (like muscle and brain), which is particularly relevant for patients experiencing post-exertional malaise and chronic fatigue.
Immune System
It promotes regulatory T-cell development and helps dampen chronic inflammation. This immunomodulatory effect can aid in calming overactive immune responses frequently observed in postviral syndromes.
Brain and Mood
Butyrate crosses the blood-brain barrier, where it may reduce neuroinflammation and improve brain-derived neurotrophic factor (BDNF) signaling, contributing to better cognitive function and mood stability.
Sleep
Butyrate may also influence sleep quality—a major concern for people with ME/CFS and long COVID, where non-restorative sleep is a core and persistent symptom.
Animal studies show that butyrate can enhance non-REM (deep) sleep, possibly by acting on the hypothalamus and influencing thermoregulation and sleep-promoting pathways (Szentirmai & Kapás, 2019). These effects suggest that butyrate may help support more restorative sleep, though human research is still emerging.
How to Support Butyrate Production
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Rather than supplementing directly, the best approach is to feed the microbes that make butyrate. This means:
Resistant starches (green bananas, cooked/cooled potatoes or rice, legumes if tolerated)
Low-FODMAP vegetables for those with sensitivities
Polyphenols (berries, tea, cocoa, olive oil, herbs) to selectively fuel beneficial microbes
Reintroduction protocols that slowly reintroduce fiber after restrictive phases, such as using an elimination diet
Avoiding excessive protein-only diets, which promote isobutyrate and other less desirable metabolites
References
Giloteaux L, Goodrich JK, Walters WA, et al. Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome. Microbiome. 2016;4(1):30. doi:10.1186/s40168-016-0171-4
Nagy-Szakal D, Barupal DK, Lee B, et al. Insights into myalgic encephalomyelitis/chronic fatigue syndrome phenotypes through comprehensive metabolomics. Sci Rep. 2021;11(1):14329. doi:10.1038/s41598-021-93859-7
Wu H, Aguilar EG, Tian L, et al. Inflammatory and metabolic signatures in post-acute sequelae of SARS-CoV-2 infection (PASC). Cell Metab. 2023;35(1):28–46.e5. doi:10.1016/j.cmet.2022.12.001
Windey K, De Preter V, Verbeke K. Relevance of protein fermentation to gut health. Mol Nutr Food Res. 2012;56(1):184–196. doi:10.1002/mnfr.201100542
Windey K, De Preter V, Verbeke K. Relevance of protein fermentation to gut health. Mol Nutr Food Res. 2012;56(1):184–196. doi:10.1002/mnfr.201100542
Sivaprakasam S, Prasad PD, Singh N. Short-chain fatty acid transporters: Role in colonic homeostasis. Curr Opin Pharmacol. 2021;61:111–118. doi:10.1016/j.coph.2021.10.001
Stilling RM, van de Wouw M, Clarke G, Stanton C, Dinan TG, Cryan JF. The neuropharmacology of butyrate: The bread and butter of the microbiota-gut-brain axis? Neurochem Int. 2016;99:110–132. doi:10.1016/j.neuint.2016.06.011
Szentirmai É, Kapás L. Butyrate, a metabolite of intestinal bacteria, enhances sleep. Sci Rep. 2019;9(1):7035. doi:10.1038/s41598-019-43314-3
