Part of the MGBA Series
What are Prebiotics?
We’ll start out this gut-healing series with prebiotics. They are one half of the psychobiotic treatment plan, and can be defined as chemical compounds that directly benefit our gut when consumed.
Though you may not have heard of prebiotics, you’ve probably heard of the term “dietary fiber.” It is important to distinguish that dietary fiber is a larger umbrella term that encompasses prebiotics; thus, all prebiotics are dietary fibers, but not all dietary fibers qualify as prebiotics. Dietary fiber has to meet three specific qualifications to count as a prebiotic:
- It cannot be digested in the early stages of the digestive tract (such as the mouth and stomach).
- It has to be consumed (fermented) by the intestinal microbes.
- It must selectively benefit the good microbes in the body.
Some examples of prebiotics include substances like fructan, indigestible polysaccharides, galacto-oligosaccharides (GOS), and fructo-oligosaccharides (FOS).
You might also see prebiotics referred to as fermentable fibers, based on the fermentation process they go through in your gut. When you eat prebiotics, you’re not actually eating for you—at least not how you might think. Instead, prebiotics are digested by your gut microbiome. While some of the food you eat—like protein and carbs—is digested and absorbed by your body, prebiotics are a snack for your microbes. When microbes consume prebiotics, this process is called fermentation.
What Do Prebiotics Do?
Prebiotics have two main impacts on the body: altering microbiome composition and creating postbiotics.
Consuming prebiotics can impact the composition of microbes in your gut. In the first article of this series, we talked about how there is a careful balance of good and bad microbes in the gut. There is only so much surface area in the gut, so good microbes and bad microbes have to fight for living space where they can. Eating prebiotics is kind of like giving the good microbes a special boost; since prebiotics are food for good microbes only, they selectively help good microbes grow. As good microbes grow, this naturally leaves less space for bad microbes in our gut.
As good microbes ferment prebiotics, they produce substances that can benefit your body. This can include substances such as hydrogen, methane, carbon dioxide, short-chain fatty acids (SCFAs) and lactate, all of which can impact your health. These substances are the main avenues through which microbes positively impact health.
Take the example of SCFAs. They are water-soluble, meaning they can easily exit the gut and enter your bloodstream. SCFAs provide important fuel for the brain and muscles and can also increase absorption of minerals and vitamins in the digestive tract. Even more importantly, SCFAs in your gut contribute to a hostile environment for bad microbes, making it harder for them to grow. Thus, the production of SCFAs through fermentation helps to prevent harmful bacteria from living in your gut. SCFAs can also regulate your immune system’s activity and help your body produce more immune cells.
The consumption of fiber (including prebiotics) is associated with many health benefits including improved cardiovascular health, control of type II diabetes, regular GI tract movements, and weight regulation. Unfortunately, most commonly-consumed foods in current global diets are relatively low in dietary fiber and, therefore, low in prebiotics. While the FDA recommends consuming 28 g of dietary fiber per day, the average American consumes less than half of that.
Digging into the Research
According to scientific research in animals, prebiotic supplements, by nourishing the beneficial bacteria in our bodies, have shown potential in reducing symptoms of anxiety and stress. Let’s break down the findings in more detail.
What Have We Found in Animal Studies?
Targeting the Microbiota-Gut-Brain Axis: Prebiotics Have Anxiolytic and Antidepressant-like Effects and Reverse the Impact of Chronic Stress in Mice
The Details: In a 2019 study conducted by researchers at University College Cork in Ireland and published in Biological Psychiatry, 69 male mice were divided into three groups and given different prebiotic supplements—either FOS, GOS, or a combination of both. Each mouse received a small daily dose of 0.3 grams of the prebiotic for a duration of three weeks. Mice that received the combined FOS and GOS supplement exhibited a significant decrease in both anxiety-like and depression-like behaviors. Their levels of the stress hormone cortisol dropped, and inflammation decreased, as well. Additionally, there was an increase in SCFAs in their brains. The SCFAs were closely connected to the positive behavioral and physiological changes observed in the mice. Mice that only received one prebiotic (either FOS or GOS) displayed no significant improvement in anxiety-like behavior, depression-like behavior, or physiological measures of stress.
The Takeaway: Feeding mice a variety of prebiotics (both FOS and GOS) showed substantial anxiety and depression reduction, based on both behavioral and physiological measurements.
Prebiotic administration normalizes lipopolysaccharide (LPS)-induced anxiety and cortical 5-HT2A receptor and IL1-β levels in male mice – PMC
The Details: A 2016 study by the University of Oxford in the UK, published in Brain, Behavior, and Immunity, looked at the effects of GOS supplementation in 12 male mice. After three weeks of receiving daily GOS, the mice were exposed to stress. The findings revealed that the mice receiving GOS had significantly lower peaks in cortisol levels and exhibited less anxiety-like behavior compared to the mice that did not receive GOS.
The Takeaway: Feeding mice a single prebiotic source (GOS) substantially reduced their anxiety, based on both behavioral and physiological measurements.
The prebiotics 3’Sialyllactose and 6’Sialyllactose diminish stressor-induced anxiety-like behavior and colonic microbiota alterations: Evidence for effects on the gut-brain axis
The Details: In a 2015 study conducted by the Center for Microbial Pathogenesis in the United States and published in Brain, Behavior, and Immunity, nine male mice were fed a diet containing two types of lactose prebiotics, namely 3′Sialyllactose (3′SL) and 6′Sialyllactose (6′SL), over a two-week period. After the two weeks, the mice were exposed to social stress. The mice that had been supplemented with the lactose prebiotics experienced significantly less stress than their counterparts who did not receive any prebiotic supplementation, as evidenced in their reduced anxiety-like behavior, increased cell growth in the brain, and fewer stress-associated changes in their gut microbiota.
The Takeaway: Feeding mice lactose prebiotics (3’SL and 6’SL) substantially reduced social stress, based on behavioral measurements, and made them more resilient against the physiological changes traditionally associated with stress, both in the gut microbiome and the brain.
In summary, these studies conducted on mice provide promising evidence that taking prebiotic supplements could be a novel approach to alleviate anxiety and stress in humans. Prebiotics essentially act as nourishment for the beneficial bacteria in your body, potentially leading to improved mental well-being.
Does it Apply to Humans?
Using prebiotic supplements to treat anxiety and stress in clinical studies has shown somewhat inconsistent results. Let’s delve into these studies and their findings.
Prebiotic intake reduces the waking cortisol response and alters emotional bias in healthy volunteers
The Details: In a study from 2015 conducted by the University of Oxford in the UK and published in Psychopharmacology, researchers examined the effects of prebiotic supplements on 45 healthy volunteers. These individuals were either given GOS or FOS supplements, with a daily dosage of 5.5 grams for three weeks. To measure anxiety, they used a survey called the State-Trait Anxiety Inventory (STAI), and stress was assessed with the Perceived Stress Reactivity Scale (PSRS). They also checked the volunteers’ cortisol levels in their saliva to understand the physiological stress that their bodies were experiencing. The results showed that people who took the GOS supplement experienced significant decreases in cortisol levels, stress, and anxiety, as indicated by the STAI and PSRS surveys. However, the FOS supplement did not have any effect.
The Takeaway: Health individuals who consumed a single prebiotic source (GOS) had reduced anxiety. This was based on self-reported metrics (participant surveys) and physiological metrics (cortisol). Consuming FOS did not have an effect on stress, either subjectively or physiologically.
Baker’s yeast beta-glucan supplement reduces upper respiratory symptoms and improves mood state in stressed women
The Details: In 2012, a study conducted by SupplementWatch and published in the Journal of the American College of Nutrition focused on 77 women with a history of moderate stress. For 12 weeks, the researchers gave the participants a 250 mg daily dose of a supplement called Wellmune WGP, which contains the prebiotic beta-glucan. To measure the women’s stress levels, they used a questionnaire called the Profile of Mood States (POMS). The study found that three months of prebiotic supplementation significantly improved the women’s overall mood, stress levels, and energy.
The Takeaway: Women with a history of moderate stress consumed a prebiotic (beta-glucan) for three months and experienced a reduction in stress, improvement in mood, and increase in energy based on self-reports.
These two studies demonstrate that prebiotics have the ability to improve mental health; however, not all studies have been as promising. Multiple studies have found that prebiotic supplementation has no effect on mental health.
Effect of probiotic and prebiotic vs placebo on psychological outcomes in patients with major depressive disorder: A randomized clinical trial
The Details: A 2019 study from Tehran University of Medical Sciences in Iran, published in Clinical Nutrition, included 81 individuals diagnosed with major depressive disorder. Participants were given either a probiotic supplement, a prebiotic supplement (GOS, but the dosage was not disclosed), or a placebo for eight weeks. Researchers used the Beck Depression Inventory to assess mood and, separately, also measured physiological markers of stress. They found that prebiotic supplementation did not seem to change mood based on the Beck Depression Inventory, but it did lead to a decrease in physiological stress markers.
The Takeaway: Individuals diagnosed with major depressive disorder took a prebiotic supplement (GOS); this led to an improvement in physiological markers of stress, but the participants did not self-report a reduction in depression).
Prebiotics and probiotics for depression and anxiety: A systematic review and meta-analysis of controlled clinical trials
The Details: In 2019, a review paper written by researchers from Alpert Medical School at Brown University in the United States and published in Neuroscience Behavioral Review examined the results of six different clinical trials examining the connection between prebiotic supplements and anxiety. These prebiotic supplements were usually either GOS or FOS and were taken for two to eight weeks. Anxiety was assessed using the Hospital Anxiety and Depression Scale (HADS) or the STAI. When the researchers analyzed the data from these trials, they did not find any significant impact of prebiotic supplementation, regardless of the type or duration, on anxiety symptoms.
The Takeaway: Supplementing with GOS or FOS did not improve symptoms of anxiety based on self-reported participant surveys.
Overall, clinical studies using prebiotic supplements to treat anxiety and stress have produced mixed results. Some studies suggest benefits, while others do not show a significant effect. The type of prebiotic and how long it is taken may play a role in these varying outcomes. While studies showed mixed results in terms of efficacy, none of the studies demonstrated negative results, suggesting there is little risk associated with this intervention.
Who Do Prebiotics Help the Most?
One population has shown the greatest benefit from prebiotics: patients with gastrointestinal (GI) tract disorders.
Clinical trial: the effects of a trans-galactooligosaccharide prebiotic on faecal microbiota and symptoms in irritable bowel syndrome
The Details: In 2009, a study from researchers from Imperial College Healthcare NHS Trust in the UK was published in Ailment Pharmacology and Therapeutics. The goal of the study was to see if prebiotic supplementation could help 44 individuals with Irritable Bowel Syndrome (IBS) improve both their GI symptoms and their general mood. The researchersdivided the participants into two groups that received either 3.5 grams or 7 grams of GOS daily for three months. Anxiety levels were measured using the Hospital Anxiety and Depression Scale (HADS). Patients who took the prebiotic scored significantly lower on the anxiety measurements of the HADS after the intervention, suggesting that they experienced fewer symptoms of anxiety. The researchers believed that the prebiotic supplementation achieved this by increasing the levels of Bifidobacterium, one of the “good” bacteria, in the patients’ guts.
The Takeaway: Individuals with diagnosed IBS were given a prebiotic (GOS) for three months. The participants experienced self-reported reductions in anxiety and had increased levels of Bifidobacterium in their gut microbiomes, which was believed to be the cause of reduced anxiety.
Effects of scFOS on the composition of fecal microbiota and anxiety in patients with irritable bowel syndrome: a randomized, double blind, placebo controlled study
The Details: In 2017, a study conducted by multiple institutions in Spain and France and published in Neurogastroenterology and Motility further supported the findings above. This study involved 79 patients also diagnosed with IBS who were given 5 grams of short-chain fructooligosaccharides (scFOS), another type of prebiotic, every day for four weeks. Anxiety levels were assessed using HADS scores. The results were consistent with the 2009 study described above: after four weeks of prebiotic supplementation, participants had significantly lower HADS scores, indicating reduced symptoms of anxiety. Similar to the earlier study, the content of Bifidobacterium in the patients’ gut increased significantly, and the researchers again believed that the improvements in anxiety could be attributed to this change in the gut microbiome.
The Takeaway: Individuals with diagnosed IBS were given a prebiotic (scFOS) for one month. The participants experienced self-reported reductions in anxiety and had increased levels of Bifidobacterium in their gut microbiomes, which was believed to be the cause of reduced anxiety.
It is important to note that prebiotic supplementation also helped alleviate IBS symptoms in both of these studies. Therefore, it is possible that the positive impact on anxiety is connected to the prebiotic supplements’ ability to improve IBS symptoms. Nevertheless, these findings suggest that prebiotics hold promise as a potential treatment for anxiety and stress, especially in individuals with GI tract disorders. Future research will likely delve deeper into this area.
References
- Liu RT, Walsh RFL, Sheehan AE. Prebiotics and probiotics for depression and anxiety: A systematic review and meta-analysis of controlled clinical trials. Neurosci Biobehav Rev. 2019;102:13-23. doi:10.1016/j.neubiorev.2019.03.023
- Slavin J. Fiber and prebiotics: mechanisms and health benefits. Nutrients. 2013;5(4):1417-1435. Published 2013 Apr 22. doi:10.3390/nu5041417
- Simon E, Călinoiu LF, Mitrea L, Vodnar DC. Probiotics, Prebiotics, and Synbiotics: Implications and Beneficial Effects against Irritable Bowel Syndrome. Nutrients. 2021;13(6):2112. Published 2021 Jun 20. doi:10.3390/nu13062112
- Paiva IHR, Duarte-Silva E, Peixoto CA. The role of prebiotics in cognition, anxiety, and depression. Eur Neuropsychopharmacol. 2020;34:1-18. doi:10.1016/j.euroneuro.2020.03.006
- Aurelijus Burokas, Silvia Arboleya, Rachel D. Moloney, Veronica L. Peterson, Kiera Murphy, Gerard Clarke, Catherine Stanton, Timothy G. Dinan, John F. Cryan. Targeting the Microbiota-Gut-Brain Axis: Prebiotics Have Anxiolytic and Antidepressant-like Effects and Reverse the Impact of Chronic Stress in Mice. Biological Psychiatry. 2017;82(7):472-487. https://doi.org/10.1016/j.biopsych.2016.12.031.
- Helene M. Savignac, Yvonne Couch, Michael Stratford, David M. Bannerman, George Tzortzis, Daniel C. Anthony, Philip W.J. Burnet. Prebiotic administration normalizes lipopolysaccharide (LPS)-induced anxiety and cortical 5-HT2A receptor and IL1-β levels in male mice. Brain, Behavior, and Immunity. 2016;52:120-131. https://doi.org/10.1016/j.bbi.2015.10.007.
- Tarr AJ, Galley JD, Fisher SE, Chichlowski M, Berg BM, Bailey MT. The prebiotics 3’Sialyllactose and 6’Sialyllactose diminish stressor-induced anxiety-like behavior and colonic microbiota alterations: Evidence for effects on the gut-brain axis. Brain Behav Immun. 2015;50:166-177. doi:10.1016/j.bbi.2015.06.025
- Schmidt, K., Cowen, P.J., Harmer, C.J. et al. Prebiotic intake reduces the waking cortisol response and alters emotional bias in healthy volunteers. Psychopharmacology 232, 1793–1801 (2015). https://doi.org/10.1007/s00213-014-3810-0
- Talbott SM, Talbott JA. Baker’s yeast beta-glucan supplement reduces upper respiratory symptoms and improves mood state in stressed women. J Am Coll Nutr. 2012;31(4):295-300. doi:10.1080/07315724.2012.10720441
- Kazemi A, Noorbala AA, Azam K, Eskandari MH, Djafarian K. Effect of probiotic and prebiotic vs placebo on psychological outcomes in patients with major depressive disorder: A randomized clinical trial. Clin Nutr. 2019;38(2):522-528. doi:10.1016/j.clnu.2018.04.010
- SILK, D.B.A., DAVIS, A., VULEVIC, J., TZORTZIS, G. and GIBSON, G.R. (2009), Clinical trial: the effects of a trans-galactooligosaccharide prebiotic on faecal microbiota and symptoms in irritable bowel syndrome. Alimentary Pharmacology & Therapeutics, 29: 508-518. https://doi.org/10.1111/j.1365-2036.2008.03911.x
- Azpiroz, F., Dubray, C., Bernalier-Donadille, A., Cardot, J.-.-M., Accarino, A., Serra, J., Wagner, A., Respondek, F. and Dapoigny, M. (2017), Effects of scFOS on the composition of fecal microbiota and anxiety in patients with irritable bowel syndrome: a randomized, double blind, placebo controlled study. Neurogastroenterol. Motil., 29: e12911. https://doi.org/10.1111/nmo.12911
