Supporting Fatigue Through Improving Gut Health
Introduction
Fatigue is a common and often debilitating symptom, affecting approximately 25% of the UK population.1 It impacts not only individuals with chronic or acute health conditions—such as post-viral infections, cancer, depression, multiple sclerosis, and fibromyalgia—but also seemingly healthy individuals.2 Many people who experience fatigue also report related symptoms like brain fog, poor concentration, muscle aches, non-refreshing sleep, and chronic inflammation.3
Fatigue is frequently described as a lack of energy, physical or mental exhaustion, and reduced endurance.4 While the exact cause of fatigue is not fully understood, one major factor is the impaired function of mitochondria—the energy-producing powerhouses within our cells.4 When mitochondria become affected by excess inflammation and oxidative stress, their ability to generate ATP (adenosine triphosphate), the body's main energy currency, is compromised.5 By enhancing mitochondrial function and lowering free radical damage, we can improve energy production and alleviate fatigue symptoms.
The Mitochondria-Microbiome Axis: A New Understanding of Fatigue
Recent studies have uncovered a fascinating connection between fatigue, gut health, and mitochondrial function. Individuals experiencing fatigue often present with gut imbalances, known as dysbiosis, where harmful bacteria outnumber beneficial microbes.6 Emerging research suggests that the gut microbiome—the diverse community of bacteria living in our intestines—can directly communicate with mitochondria within our cells.7 This interaction, known as the mitochondria-microbiome axis, appears to play a crucial role in modulating energy production, immune health, and even cognitive function.7
This connection between gut bacteria and mitochondria makes sense when you consider that, about two billion years ago, mitochondria were essentially bacteria themselves.8 Over time, these primitive bacteria entered host cells and evolved into the mitochondria we know today, creating a symbiotic relationship where both host and bacteria benefited.9 This ancient bond continues to play a vital role in the balance between gut health and cellular energy production.
How Mitochondria Activity Affects Gut Health
Mitochondria are essential not only for energy production but also for regulating levels of free radicals—molecules that, in excess, can damage cells and tissues. Although free radicals are a natural byproduct of metabolism and have important cellular roles, too many can lead to oxidative stress, which contributes to ageing and diseases like Parkinson’s, diabetes, and cancer.10
Thankfully, the body produces antioxidants to counteract free radical damage, and we can further support this process through eating a diet rich in vitamins A, C, D, zinc, and polyphenols.11 However, when free radical damage outpaces antioxidant defences, mitochondrial function declines, resulting in reduced ATP production (and thus more fatigue) and increased oxidative stress.10 This damage doesn’t just affect cellular energy—it can also disrupt the diversity and health of our gut bacteria.10
In turn, poor mitochondrial function may compromise gut integrity, weakening the intestinal lining and impairing digestion.10 This intricate relationship highlights how mitochondrial health directly influences gut microbiota diversity and overall digestive function.
The Gut Microbiome's Role in Supporting Mitochondrial Health and Energy
The mitochondria-microbiome axis is bidirectional: just as mitochondrial activity affects gut health, the gut microbiome plays a key role in regulating mitochondrial function and energy production.9 Beneficial gut bacteria produce several vital compounds, known as metabolites, that influence mitochondrial health.9 Three key metabolites—butyrate, urolithin A, and lactic acid—are particularly important:9
Butyrate: This short-chain fatty acid (SCFA) is produced by the fermentation of prebiotic fibres (such as garlic, onions, leeks, and asparagus) in the gut. Butyrate is a primary energy source for colon cells and helps maintain the health of the intestinal lining.9 It also supports mitochondrial energy production.6
Urolithin A: Produced by Lactobacilli and Bifidobacteria from polyphenols found in foods like walnuts, raspberries, strawberries, and pomegranates,12 urolithin A enhances mitochondrial energy output and capacity.9,13
Lactic acid: Also produced by Lactobacilli and Bifidobacteria, lactic acid supports the growth of bacteria that produce butyrate and urolithin A. A derivative, lactate, serves as a fuel source for mitochondria in muscles, especially during endurance exercise, providing a vital energy boost.14
How Good Gut Health Supports Energy and Mitochondrial Health
Beneficial gut bacteria have shown to positively influence energy metabolism—the process by which our bodies generate energy from nutrients.6 These microbes can enhance nutrient absorption, produce SCFAs like butyrate, convert food into antioxidant-rich metabolites like urolithin A, inhibit harmful bacteria, and support the integrity of the intestinal lining.6
Here are a few notable studies highlighting how beneficial gut bacteria can improve energy metabolism:
A strain of Lactobacillus plantarum given to mice improved exercise endurance by increasing the metabolism of proteins to branch-chain amino acids (BCAAs), which are vital for muscle energy.15
In a human study, Lactobacillus plantarum was found to enhance endurance by accelerating nutrient metabolism during exercise.16 Participants derived more energy from fatty acid oxidation (using fats for fuel rather than carbohydrates), a significant advantage for athletes.
A 2022 study on Lactobacillus salivarius in rats with Parkinson’s disease found that this beneficial gut bacteria improved mitochondrial activity in both the brain and muscles.17 It increased levels of antioxidants, altered SCFA production in the gut, restored muscle mass, and improved motor function. The researchers suggested that the probiotic helped recover energy metabolism and reduced oxidative stress.
Conclusion
The intricate relationship between the mitochondria and the gut microbiome offers a compelling new angle in understanding and managing fatigue. This dynamic link suggests that improving gut health can have a direct and positive impact on mitochondrial function, and consequently, energy levels.
Emerging evidence indicates that supporting the gut microbiome through consuming fermented foods and prebiotic fibres to feed the gut microbiome, could improve energy metabolism and support mitochondrial health.
Although more research is needed, the early findings are encouraging. By supporting both gut and mitochondrial health through diet, lifestyle, and targeted supplementation, we may be able to better manage fatigue and improve overall well-being.
References
1 Hackett KL, Lambson RL, Strassheim V, Gotts Z, Deary V, Newton JL. A concept mapping study evaluating the UK’s first NHS generic fatigue clinic. Health Expect 2016; 19: 1138–49.
2 Billones R, Liwang JK, Butler K, Graves L, Saligan LN. Dissecting the fatigue experience: A scoping review of fatigue definitions, dimensions, and measures in non-oncologic medical conditions. Brain Behav Immun Health. 2021; 15. DOI:10.1016/j.bbih.2021.100266.
3 Fatigue and Mitochondrial Dysfunction - Dr. Jennifer Kessmann. https://www.drjenniferkessmann.com/fatigue-and-mitochondrial-dysfunction/ (accessed Nov 22, 2022).
4 Filler K, Lyon D, Bennett J, et al. Association of mitochondrial dysfunction and fatigue: A review of the literature. BBA Clin. 2014; 1: 12–23.
5 Wood E, Hall KH, Tate W. Role of mitochondria, oxidative stress and the response to antioxidants in myalgic encephalomyelitis/chronic fatigue syndrome: A possible approach to SARS-CoV-2 ‘long-haulers’? Chronic Dis Transl Med 2021; 7: 14.
6 Li Y, Li J, Xu F, et al. Gut microbiota as a potential target for developing anti-fatigue foods. Crit Rev Food Sci Nutr 2021. DOI:10.1080/10408398.2021.1983768.
7 Han B, Lin CCJ, Hu G, Wang MC. ’Inside Out’- a dialogue between mitochondria and bacteria. FEBS J 2019; 286: 630–41.
8 Rossmann MP, Dubois SM, Agarwal S, Zon LI. Mitochondrial function in development and disease. Dis Model Mech 2021; 14. DOI:10.1242/DMM.048912.
9 Franco-Obregón A, Gilbert JA. The Microbiome-Mitochondrion Connection: Common Ancestries, Common Mechanisms, Common Goals. mSystems 2017; 2. DOI:10.1128/MSYSTEMS.00018-17.
10 Ballard JWO, Towarnicki SG. Mitochondria, the gut microbiome and ROS. Cell Signal 2020; 75: 109737.
11 Liu Z, Ren Z, Zhang J, et al. Role of ROS and Nutritional Antioxidants in Human Diseases. Front Physiol 2018; 9. DOI:10.3389/FPHYS.2018.00477.
12 Muku GE, Murray IA, Espín JC, Perdew GH. Urolithin A Is a Dietary Microbiota-Derived Human Aryl Hydrocarbon Receptor Antagonist. Metabolites 2018; 8. DOI:10.3390/METABO8040086.
13 Singh A, Andreux P, Blanco W, Auwerx J, Rinsch C. Urolithin A, a Gut Microbiome Derived Metabolite Improves Mitochondrial and Cellular Health: Results from a Randomized, Placebo-controlled, Double-blind Clinical Trial (FS09-06-19). Curr Dev Nutr 2019; 3: 2061.
14 Garrote GL, Abraham AG, Rumbo M. Is lactate an undervalued functional component of fermented food products? Front Microbiol 2015; 6: 1–5.
15 Xu M, Kitaura Y, Ishikawa T, et al. Endurance performance and energy metabolism during exercise in mice with a muscle-specific defect in the control of branched-chain amino acid catabolism. PLoS One 2017; 12: e0180989.
16 Huang WC, Pan CH, Wei CC, Huang HY. Lactobacillus plantarum ps128 improves physiological adaptation and performance in triathletes through gut microbiota modulation. Nutrients 2020; 12: 1–15.
17 Nurrahma BA, Tsao SP, Wu CH, et al. Probiotic Supplementation Facilitates Recovery of 6-OHDA-Induced Motor Deficit via Improving Mitochondrial Function and Energy Metabolism. Front Aging Neurosci 2021; 13. DOI:10.3389/FNAGI.2021.668775.