Patients with ME/CFS, fibromyalgia, and long COVID often struggle with persistent digestive symptoms that are challenging to manage. Among the reasons for these symptoms are poor microbiome diversity, digestive disturbances, and food sensitivities. Research shows that individuals with these conditions tend to have significantly lower gut microbiome diversity compared to healthy individuals, which can exacerbate inflammation, fatigue, and other symptoms.

In an effort to address these imbalances, many patients turn to probiotics. However, probiotics often fall short of expectations, with some patients experiencing little benefit—or even worsening symptoms. This is especially true for those with overlapping conditions like small intestinal bacterial overgrowth (SIBO), irritable bowel syndrome (IBS), and mast cell activation syndrome (MCAS), where introducing the wrong types of probiotics can aggravate underlying issues.

Prebiotics, Probiotics, and Synbiotics: What’s the Difference?

When it comes to gut health, it's important to learn the difference between prebiotics, probiotics, and synbiotics. Differentiating between these terms is essential for tailoring a gut health plan that works for you. Let’s break it down.

What Are Prebiotics?

Prebiotics are non-digestible fibers or compounds that feed the beneficial bacteria already living in your gut. Think of them as the fertilizer that helps your gut flora thrive. Common prebiotics include:

• Inulin: Found in foods like garlic, onions, and chicory root.

• Fructooligosaccharides (FOS): Found in bananas, asparagus, and artichokes.

• Resistant starch: Present in green bananas, cooked and cooled potatoes, and legumes.

By nourishing good bacteria, prebiotics help maintain a balanced gut ecosystem, which can improve digestion and enhance immunity. However, those with gut issues due to post-viral conditions may react poorly to some prebiotics, especially those high in FODMAPS. You may have already guessed that if there are harmful bacteria in the gut (overgrowth), feeding that overgrowth with prebiotics may worsen symptoms.

What Are Probiotics?

Probiotics are either live microorganisms or inactivated microorganisms.

Of the live, viable microorganisms, these are intended to colonize or transiently populate the gut. These are the strains most people associate with probiotics and include well-known types such as:

·        Lactobacillus species (e.g., Lactobacillus rhamnosus)

·        Bifidobacterium species (e.g., Bifidobacterium longum)

·        Saccharomyces boulardii (a beneficial yeast, not a bacterium)

These live probiotics are chosen for their potential to provide health benefits such as enhancing gut barrier integrity, modulating the immune system, and producing beneficial metabolites like short-chain fatty acids (SCFAs).

Some products contain attenuated strains (inactivated), which are microorganisms that have been deliberately inactivated through processes like heat or radiation. These strains are no longer alive but can still exert beneficial effects through their cell wall components or metabolites. For example:

• Immune modulation: Even inactivated strains can interact with the gut-associated lymphoid tissue (GALT), influencing immune responses.

• Barrier support: Non-viable probiotics may strengthen gut lining integrity by interacting with epithelial cells.

This concept is often referred to as "paraprobiotics" or "ghost probiotics," and while these strains are non-viable, they can sometimes be helpful for people who cannot tolerate live microorganisms due to immune or gut sensitivities.

You can also find probiotics in fermented foods like yogurt, kefir, sauerkraut, kimchi, and miso. Alternatively, they’re widely available in supplement form, though it’s crucial to choose high-quality, pharmaceutical-grade products with clinically backed strains from reputable companies.

The Drawbacks of Supplementing with Probiotics

While probiotics are widely praised for their potential health benefits, they aren’t a one-size-fits-all solution. In some cases, supplementing with probiotics can have serious drawbacks that are worth highlighting:

1. Strain-Specific Effects

Probiotics are not all the same. Different strains provide different benefits, and what works for one person might not work for another. For example, a probiotic strain that alleviates irritable bowel syndrome (IBS) symptoms may be ineffective—or even counterproductive—for someone with a different condition. Choosing the wrong strain can lead to wasted money and minimal results.

2. Transient Colonization

Many probiotics don’t permanently colonize the gut. Instead, they pass through the digestive system and require consistent supplementation to maintain their effects. This means that any benefits might only last as long as you keep taking the product.

3. Potential Side Effects

Some people experience side effects when starting probiotics, including:

• Gas and bloating

• Diarrhea or changes in bowel habits

• Abdominal cramping

These effects are often temporary, but they can discourage people from continuing their use. Others will always have side effects with probiotics.

4. Histamine Production

Some probiotic strains, such as certain types of Lactobacillus (Lactobacillus casei & Lactobacillus bulgaricus), can produce histamine as part of their metabolic process. For individuals with mast cell activation syndrome (MCAS) or a high inflammatory load, this can lead to worsened symptoms, including fatigue, headaches, skin reactions, and gastrointestinal discomfort. For these individuals, it’s vital to choose low-histamine probiotic strains, such as Bifidobacterium, which are less likely to exacerbate histamine-related issues.

5. Risk of Overgrowth or Infection

In some cases, probiotics can cause harm by promoting bacterial overgrowth or infections in vulnerable populations like bedridden patients on enteral nutrition. Also, for those with small intestinal bacterial overgrowth (SIBO), taking probiotics can worsen symptoms by adding to an already imbalanced gut environment. This is why probiotics should be used cautiously under medical supervision if you have a compromised immune system.

6. Lack of Regulation and Quality Control

Just like all supplements, the probiotic supplement market isn’t strictly regulated. Some products may contain fewer live organisms than claimed or include strains that haven’t been clinically validated. Contamination and improper storage can also reduce a probiotic's effectiveness. Choosing high-quality, pharmaceutical-grade probiotics is essential to avoid these issues. Products should be tested for contaminants like heavy metals and allergens.

What Are Synbiotics?

Synbiotics combine probiotics and prebiotics in a single product, designed to work synergistically to maximize gut health benefits. Think of them as a team: the prebiotic serves as the fuel, while the probiotic provides the active microorganisms. Together, they’re more effective than either one alone and often they are far better tolerated than their components.

For example, a synbiotic supplement might pair a Lactobacillus strain (probiotic) with inulin (prebiotic). The inulin ensures the Lactobacillus bacteria have a reliable food source, helping them colonize your gut and do their job more effectively.

Synbiotic Are Simply Better

Synbiotics can help overcome some of the limitations of probiotics by enhancing bacterial survival, targeting specific strains, and creating a more balanced gut environment. My favorite option is Seed's DS-01® Daily Synbiotic. Let’s look at how it is different and examine some clinical studies showing its effectiveness.

Key Advantages of DS-01® Daily Synbiotic

1. Enhanced Survival and Delivery:

• A Capsule-in-Capsule Design: DS-01® utilizes a unique nested capsule technology that protects probiotics from stomach acid, bile salts, and digestive enzymes, ensuring that a higher number of viable organisms reach the colon. Standard probiotics typically use single-layer capsules or powders that are not well-protected against stomach acid. As a result, many of the probiotic organisms are destroyed before they can even reach the small intestine, let alone the colon. This results in significantly lower effectiveness.

• How the Capsule-in-Capsule Design Works: The capsule-in-capsule design is precisely what it sounds like: a smaller, inner capsule containing the probiotics is encased within an outer capsule. Each layer serves a specific purpose to protect and deliver the probiotics where they are needed most.

  • Outer Capsule

    • Made from a plant-based, acid-resistant material specifically designed to withstand harsh conditions in the stomach

  • Inner Capsule

    • Contains the probiotics and prebiotics. Once the outer capsule dissolves in the more neutral pH environment of the small intestine, the inner capsule releases its contents.

 2. Comprehensive Formulation:

• 24 Probiotic Strains: Each strain is selected based on robust clinical and mechanistic research, providing a broad spectrum of benefits, including digestive health, cardiovascular health, immune support, and dermatological health. Some examples of bacterial strains found in Seed include:

• Bifidobacterium longum: Known for supporting gut barrier function and immune health.

• Lactiplantibacillus plantarum: Recognized for its role in promoting digestive health and supporting gut immunity.

• Lacticaseibacillus rhamnosus: Associated with benefits to digestive and skin health.

• Bifidobacterium breve: Supports digestive health and may aid in maintaining a healthy gut microbiome.

• Limosilactobacillus reuteri: Involved in micronutrient synthesis, including the natural production of vitamins like B9, B12, and folate.

3. Non-Fermenting Prebiotics: The inclusion of non-fermenting prebiotics ensures that beneficial bacteria are nourished without causing gas or bloating, making it suitable for individuals with sensitive digestive systems.

4. Transparency: Seed tests its products for allergens, heavy metals, pesticides, heat sensitivity, etc. They even have a pediatric version. All of this information can be evaluated here.

Synbiotics Reduce Oxidative Stress

Oxidative stress, caused by an imbalance between free radicals and antioxidants, plays a critical role in many chronic illnesses, including ME/CFS, fibromyalgia, and long COVID. Emerging research suggests that synbiotics may help reduce oxidative stress and improve overall health. Let’s look at some research.

Evidence from Parkinson’s Disease Research

A 2022 double-blind, placebo-controlled, randomized controlled trial examined the effects of synbiotic supplementation in patients with Parkinson’s disease (PD) (1):

• Increased Antioxidant Capacity: Synbiotic supplementation significantly increased total antioxidant capacity (TAC), a marker of the body’s ability to neutralize free radicals, compared to the control group.

• Reduced Oxidative Damage: Markers of oxidative damage, such as malondialdehyde (MDA), were significantly reduced, showing the potential of synbiotics to combat oxidative stress.

• Improved Well-Being: Synbiotic supplementation enhanced cognitive function and quality of life as measured by the Parkinson’s Disease Quality of Life (PDQ-39) scale. Depression symptoms also improved in the synbiotic group.

Insights from a 2022 Meta-Analysis

A 2022 meta-analysis of 31 randomized controlled trials involving 1,681 participants provided strong evidence of synbiotics' ability to enhance antioxidant defenses (2):

• Boosted Antioxidant Defenses: Synbiotics significantly increased levels of TAC, glutathione, and nitric oxide, all of which play essential roles in reducing oxidative stress.

• Reduced Oxidative Stress Markers: Levels of MDA were consistently decreased across the studies, further supporting synbiotics’ role in combating oxidative damage.

• Reliable Results: Sensitivity analyses confirmed the consistency and reliability of these findings across the included trials.

Research Supporting Seed's Synbiotic

While the above studies did not specifically test Seed’s DS-01® Daily Synbiotic, the company has published a peer-reviewed study supporting their product (3). The study used a lab-based model of the gut to mimic the environment of the human digestive system. This makeshift human gut microbiome was then disrupted by using either alcohol or antibiotics, both known to harm gut health.

Here’s what they did:

• Caused Gut Disruption: Alcohol and antibiotics reduced the production of important gut molecules called short-chain fatty acids (SCFAs), like butyrate and acetate, which are essential for maintaining a healthy gut and reducing inflammation in the gut.

• Added Seed Synbiotic: Researchers then treated the gut model with the Seed synbiotic to see if it could help the gut recover.

• Measured Recovery: They looked at two key areas:

  • The levels of SCFAs, to see if the synbiotic could bring them back to normal.

  • The balance of bacteria, checking if beneficial gut bacteria increased in number.

This study showed that the synbiotic helped restore the production of SCFAs and promoted the growth of good bacteria.

Conclusion: Synbiotics for Health and Recovery

The evidence is clear: synbiotics, which combine probiotics and prebiotics, offer powerful benefits for improving gut health, enhancing antioxidant defenses, and reducing oxidative stress. For individuals managing chronic conditions like ME/CFS, fibromyalgia, and long COVID synbiotics represent a promising solution supported by solid science.

As numerous research studies in these conditions have shown, patients have low SCFAs and a low abundance of beneficial bacteria. A synbiotic, like Seed, has been shown to effectively counter both. It’s worth a try. I’ve taken Seed for years with great effect. I can’t recommend it enough.

For your convenience, Seed’s DS-01® is available through my FullScript store—ensuring you receive pharmaceutical-grade quality delivered right to your door at a reduced price. If you are outside of the US, you can still order Seed but please do so directly from their website.

 

References

1. Zare S, Mohtashami R, Azadbakht L, Asemi Z. The effects of synbiotic supplementation on oxidative stress markers, mental status, and quality of life in patients with Parkinson’s disease: A double-blind, placebo-controlled, randomized controlled trial. Clin Nutr ESPEN. 2022;49:333-340. doi:10.1016/j.clnesp.2022.07.010.

2. Pourrajab B, Fatahi S, Sohouli MH, Găman MA, Shidfar F. The effects of probiotic/synbiotic supplementation compared to placebo on biomarkers of oxidative stress in adults: a systematic review and meta-analysis of randomized controlled trials. Crit Rev Food Sci Nutr. 2022;62(2):490-507. doi:10.1080/10408398.2020.1821166

3. Tierney BT, Van den Abbeele P, Al-Ghalith GA, et al. Capacity of a Microbial Synbiotic To Rescue the In Vitro Metabolic Activity of the Gut Microbiome following Perturbation with Alcohol or Antibiotics. Appl Environ Microbiol. 2023;89(3):e0188022. doi:10.1128/aem.01880-22