July 28, 2022 6:05 pm

All About Megasporebiotic

A lot has changed in the last decade.

We can now map the whole microbiome for a minimal cost. This has allowed us to improve our understanding of the gut biome dramatically.

Much of our prior focus and many of our tools have changed.

We are no longer restricted to trying to control symptoms with low histamine probiotics and ever-decreasing elimination diets, many of which cut out the very things we need for gut health.

We are no longer focused on fermented foods or high-dose single or multi-strain probiotics for gut health, which may worsen things.

Instead, we can now focus on restoring our gut function’s health.

Having now tested and worked with hundreds of people, MegaSporeBiotic™ is the next-generation probiotic that works for most people to rebalance the microbiome.

Gram-Negative Bacteria

Every bacterium in the world belongs to one of two categories – gram-negative or gram-positive.

Which category it belongs to depends upon its gram stain.

A gram stain is a way of putting a dye-like stain on the bacterium, which, when absorbed, colors gram-positive bacteria.

The gram-positive bacterium has a cell wall structure that does not absorb the dye.

Gram-negative bacterium only has a cell membrane that consists of lipopolysaccharides (LPS).


Histamine Producing Bacteria

LPS is a very potent endotoxin.

Endotoxins are toxins produced within the gut. It is not a toxin coming into the gastrointestinal tract from outside (such as contaminated or high histamine food)—instead, it’s generated within the gut.

We now know that gram-negative bacteria’s high presence also causes many gut conditions associated with histamine intolerance, such as SIBO, celiac disease, and dysbiosis.

Also, gram-negative bacteria are the biggest driver of leaky gut and chronic inflammation in the gut and the body.

As you start to see a shift towards more gram-negative bacteria, particularly in the small intestine dominated by gram-positive bacteria, you start to see histamine intolerance creep up.

Last Generation Probiotics

A healthy gut biome is a diverse one.

Most last-generation probiotics on the market, and most fermented foods, are high in lactobacillus.

In contrast, lactobacillus makes up around 1% of a healthy gut, so it’s a relatively small player.

So, when we inundate our bodies with one genus of bacteria through fermented foods or probiotics, we can cause dysbiosis.


Next-Generation Probiotics

Before MegaSporeBiotic™, antihistamine strains of probiotics merely alleviated histamine intolerance symptoms.

While this approach helped to suppress symptoms, it did not restore health. Optimal gut health depends on a balanced microbiome.

Physicians Exclusive (the company behind MegaSporeBiotic™) set out to identify specific bacteria strains that could make a big difference to the microbiome.

Their thinking was, and it was a simple but brilliant idea, that it was not about supra-dosing a single strain but whether bacteria could positively impact the hundred trillion population of the microbiome as a whole.

After extensive research, they found that there were microbes that could organize the microbiome into a healthy, homeostatic population even at low doses.

Quorum Sensing

What they discovered was that Bacillus strains had ‘quorum sensing.’

Quorum sensing is microbes’ ability to read other bacteria signatures and figure out who’s there and in what amounts, then methodically go in and affect certain bacteria.

Bacillus is a normal, commensal bacteria studied in hundreds of papers and had a long history of safe use in treating gut infections.

Bacillus sits next to bacteria, bringing dysfunctional bacteria down and beneficial bacteria levels up by influencing keystone bacteria.


Spore-Based Probiotics

Spore-based probiotics are soil-based microorganisms found naturally within dirt and vegetation.

Unlike most probiotics, spore-based probiotics are incredibly stable. They are not rendered ineffective by heat, light, or stomach acid.

Instead, they are naturally encapsulated and remain dormant until they are delivered to the small intestine, where they become active.

They survive within the gastrointestinal tract for around 30 days and exit the body.

Bacillus Strains

MegaSporeBiotic™contains five bacillus strains, including Bacillus subtilis HU58, Bacillus clausii Sc-109, Bacillus coagulans SC-208, Bacillus indicus HU36, and Bacillus licheniformis SL-307.

All five strains were initially isolated from a healthy human gut at the Royal Holloway University of London by Simon Cutting. The “HU” in the strain number represents Holloway University, and the “SC” represents Simon Cutting.

The strains used in MegaSporeBiotic™are these precise strains studied and found to have the following benefits. 

Bacillus indicus HU36 Bacillus indicus HU36 produces high levels of carotenoids (antioxidants) at the absorption site in the gut.

Bacillus clausii SC-109Bacillus clausii SC-109 is a potent immune modulator that enhances cellular immunity and Th1 cell function. It is used in conjunction with antibiotics.

Bacillus subtilis Bacillus subtilis can produce nearly 12 strong antibiotics that fight harmful bacteria. Also, it produces many other vital nutrients in the gut, including nattokinase, the full spectrum of B vitamins, and Vitamin K2. Also, short-chain fatty acids such as butyrate, acetate, and propionate. Butyrate is a mast-cell stabilizer, anti-inflammatory, and has a protective effect on the gastrointestinal tract.

Bacillus licheniformis SL-307 Bacillus licheniformis produces the common antibiotic bacitracin, protease enzymes that digest and absorb proteins, and the full spectrum of B vitamins in the gut, including folate and biotin.

Bacillus coagulans SC-208Bacillus coagulans play a vital role in the digestion and absorption of nutrients, like lactose and dietary fats, producing mast-cell stabilizing butyrate, aiding digestion, and preventing harmful bacteria growth.

Cutting Edge Research

Over and above the substantial research on individual strains, MegaSporeBiotic™ has undertaken studies on the combination of probiotic strains that show that it is one of the most effective probiotics on the market today.

Here is a summary of the research onMegaSporeBiotic™ to date:

Catinean, Adrian, et al. “Bacillus spp. spores—a promising treatment option for patients with irritable bowel syndrome.” Nutrients 11.9 (2019): 1968.

A study of 90 patients with IBS saw patients separated into three groups of 30 and given one of three treatments for 34 days.

The first group was treated with an antibiotic, rifaximin, for ten days, followed by Bifidobacterium longum, prebiotics, and vitamins for 24 days.

The second group was treated with MegaSporeBiotic™ for 34 days.

The third group was treated with rifaximin for ten days, followed by 24 days of a low FODMAP (fermentable oligo-, di, monosaccharides, and polyols)

The study found that treatment with MegaSporeBiotic™ reduced the IBS severity better than other standard treatment options in 34 days.

Duysburgh, Cindy, et al. “A synbiotic concept containing spore-forming Bacillus strains and a prebiotic fiber blend consistently enhanced metabolic activity by modulation of the gut microbiome in vitro.” International journal of pharmaceutics: X 1 (2019): 100021.

This study included a two-week initiation period to establish a stable microbial community, followed by a two-week control period and a four-week treatment period, during whichMegaSporeBiotic™ and MegaPre™ were administered once a day.

At the end of the eight weeks, researchers concluded that the combination of MegaSporeBiotic™ and MegaPre™ significantly increased microbial diversity in the colon, including foundational bacterial strains.

Additionally, this prebiotic and probiotic combination increased by over 150% of all short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate, essential anti-inflammatory mast-cell stabilizers.

Neag, Maria Adriana, et al. “Probiotic bacillus spores protect against acetaminophen-induced acute liver injury in rats.” Nutrients 12.3 (2020): 632.

Acetaminophen use is the #1 cause of liver toxicity in the US and Europe.

An animal study compared  MegaSporeBiotic™ with the well-known hepatoprotective herb – Silymarin.

The use of MegaSporeBiotic™ with Acetaminophen resulted in a significant improvement in liver markers similar to silymarin.

Campbell, Andrew W., et al. “Efficacy of Spore Forming Bacilli Supplementation in Patients with Mild to Moderate Elevation of Triglycerides: A 12 week, Randomized, Double-Blind, Placebo-Controlled Trial.” Integrative Medicine: A Clinician’s Journal 19.2 (2020).

Due to the gut microbiome’s metabolic functions, an imbalance of gut bacteria (gut dysbiosis) can increase serum triglycerides.

A randomized, double-blind, placebo-controlled study with eighty participants with non-fasting triglyceride levels greater than 150 mg/dL was conducted over 90 days.

Compared to the placebo group, participants in the MegaSporeBiotic™  group significantly lowered their triglyceride levels.

Catinean, Adrian, et al. “Probiotic Bacillus Spores Together with Amino Acids and Immunoglobulins Exert Protective Effects on a Rat Model of Ulcerative Colitis.” Nutrients 12.12 (2020): 3607.

This study examined the ability of MegaSporeBiotic™ and MegaMucosa™ to reduce tissue damage and inflammatory responses associated with ulcerative colitis.

The study found that alone and in combination, MegaSporeBiotic™  and MegaMucosa™ significantly lowered inflammation and reduced damage to the colonic mucosa, consistent with methylprednisolone.


Suggested Use

The recommended amount of MegaSporeBiotic™ is 2 capsules with a meal once a day.

The recommended titration schedule is as follows:

Week 1: Take ½ capsule every other day

Week 2: Take ½ capsule daily

Week 3: Take 1 capsule daily

Week 4+: Take 2 capsules daily

If you are particularly sensitive, starting at a lower dose, with a ¼ capsule every other day or even lower, is advisable.

Die-off Symptoms

I recommend using a binder with MegaSporeBiotic™ to adsorb any die-off symptoms.

Die-off symptoms happen when the gram-negative bacteria release endotoxins when they die.

MegaSporeBiotic™ is a potent probiotic that reduces gram-negative bacteria and may result in die-off symptoms.

‘Die-off’ symptoms often mimic a person’s primary symptoms.

Typical ‘die-off’ symptoms include fatigue, digestive problems, rashes or skin issues, muscle aches, and a general flu-like feeling.  Looser stools are also common for the first 3 – 4 days.

Die-off symptoms are a sign that MegaSporeBiotic™ is working and not that it is causing the symptoms.

If these die-off symptoms are too intense or last longer than five days, the dosage is likely too high, and you should reduce it and titrate up again more slowly.

Most people notice the benefits of MegaSporeBiotic™  within the first 14-28 days.

However, a typical treatment protocol will be 3 months and up to 6 months after a round of antibiotics or following severe gut infections.


Our gut health depends on eating a broad range of foods and a high diversity of gut bacteria.

MegaSporeBiotic™ is one of the most powerful tools in our arsenal to recondition the gut biome.

The speed at which it works, as little as one month, means that we do not need to limit as many foods or for as long.

It consistently tests exceptionally well for many of my clients.

Additional Reading

Cutting, Simon M. “Bacillus probiotics.” Food Microbiology 28.2 (2011): 214-220.

Dound, Y. A., et al. “The effect of probiotic Bacillus subtilis HU58 on immune function in a healthy human.” The Indian Practitioner 70.9 (2017): 15-20.

Huang, Jen-Min, et al. “Immunostimulatory activity of Bacillus spores.” FEMS Immunology & Medical Microbiology 53.2 (2008): 195-203.

McFarlin, Brian K., et al. “Oral spore-based probiotic supplementation was associated with reduced incidence of post-prandial dietary endotoxin, triglycerides, and disease risk biomarkers.” World journal of gastrointestinal pathophysiology 8.3 (2017): 117.

Khaneja, R., et al. “Carotenoids found in Bacillus.” Journal of applied microbiology 108.6 (2010): 1889-1902.

Perez-Fons, Laura, et al. “Identification and the developmental formation of carotenoid pigments in the yellow/orange Bacillus spore-formers.” Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids 1811.3 (2011): 177-185.

Nista, Enrico Celestino, et al. “Bacillus clausii therapy to reduce side‐effects of anti‐Helicobacter pylori treatment: a randomized, double‐blind, placebo-controlled trial.” Alimentary pharmacology & therapeutics 20.10 (2004): 1181-1188.

Ciprandi, Giorgio, et al. “Cytokines evaluation in nasal lavage of allergic children after Bacillus clausii administration: a pilot study.” Pediatric allergy and immunology 15.2 (2004): 148-151.

Ciprandi, Giorgio, et al. “Bacillus clausii exerts immuno-modulatory activity in allergic subjects: a pilot study.” European annals of allergy and clinical immunology 37.4 (2005): 129-134.

Stein, Torsten. “Bacillus subtilis antibiotics: structures, syntheses, and specific functions.” Molecular Microbiology 56.4 (2005): 845-857.

Cho, Young-Han, et al. “Production of nattokinase by batch and fed-batch culture of Bacillus subtilis.” New Biotechnology 27.4 (2010): 341-346.

Kolchinskaia, I. D., E. I. Kvasnikov, and L. P. Dryndina. “Biosynthesis of vitamins and amino acids of Bacillus subtilis and Bac. mesentericus.” Mikrobiolohichnyi zhurnal 32.4 (1970): 419-423.

Casula, Gabriella, and Simon M. Cutting. “Bacillus probiotics: spore germination in the gastrointestinal tract.” Applied and environmental microbiology 68.5 (2002): 2344-2352.

Possemiers, P. D., and N. Van de Genachte. “Evaluation of the Bacillus subtilis strain HU58 in the SHIME technology platform.” (2013): 1-40.

Vinolo, Marco AR, et al. “Regulation of inflammation by short-chain fatty acids.” Nutrients 3.10 (2011): 858-876.

FRØYSHOV, Øystein, and Søren G. LALAND. “On the biosynthesis of bacitracin by a soluble enzyme complex from Bacillus licheniformis.” European journal of biochemistry 46.2 (1974): 235-242.

Hanlon, G. W., and NORMAN A. Hodges. “Bacitracin and protease production in relation to sporulation during exponential growth of Bacillus licheniformis on poorly utilized carbon and nitrogen sources.” Journal of Bacteriology 147.2 (1981): 427-431.

Bomko, Tatiana V., et al. “Immunotropic aspect of the Bacillus coagulans probiotic action.” Journal of Pharmacy and Pharmacology 69.8 (2017): 1033-1040.

Kim YM, et al. Studies on the production of beta-galactosidase by Bacillus coagulans. Properties and applications of beta-galactosidase. Korean J Applied Microbiol Bioeng. 1985;13:355-360.

Adibpour, Nasim, et al. “A review on Bacillus coagulans as a Spore-Forming Probiotic.” Applied Food Biotechnology 6.2 (2019): 91-100.

Jurenka S. Bacillus coagulans: monograph. Altern Med Rev. 2012;17(1):76-81.

Suva MA, Sureja VP, Kheni DB. Novel insight on probiotic Bacillus subtilis: Mechanism of action and clinical applications. J Curr Res Sci Med. 2016;2:65-72.

O’Mahony, Liam. “Short‐chain fatty acids modulate mast cell activation.” (2020): 1848-1849.

Catinean, Adrian, et al. “Probiotic Bacillus spores together with amino acids and immunoglobulins exert protective effects on a rat model of ulcerative colitis.” Nutrients 12.12 (2020): 3607.

Ramezani Kapourchali, Fatemeh, et al. “A Spore‐Forming Probiotic Supplement Improves the Intestinal Immune Response and Protects the Intestinal Health During Recurrent Clostridioides difficile Colonization in Mice.” Journal of Parenteral and Enteral Nutrition 44.8 (2020): 1428-1438.

Campbell, Andrew W., et al. “Efficacy of spore-forming bacilli supplementation in patients with mild to moderate elevation of triglycerides: A 12 week, randomized, double-blind, placebo-controlled trial.” Integrative Medicine: A Clinician’s Journal 19.2 (2020): 22.

Neag MA, Catinean A, Muntean DM, et al. Probiotic Bacillus Spores Protect Against Acetaminophen Induced Acute Liver Injury in Rats. Nutrients. 2020;12(3):632.

Catinean, Adrian, et al. “Bacillus spp. spores—a promising treatment option for patients with irritable bowel syndrome.” Nutrients 11.9 (2019): 1968.

Duysburgh, Cindy, et al. “A synbiotic concept containing spore-forming Bacillus strains and a prebiotic fiber blend consistently enhanced metabolic activity by modulation of the gut microbiome in vitro.” International journal of pharmaceutics: X 1 (2019): 100021.

Marzorati, et al. Treatment with a spore-based probiotic containing five strains of bacillus induced changes in the metabolic activity and community composition of the gut microbiota in a SHIME® model of the human gastrointestinal system. Food Research International. 2021; 149: 110676

Scarpellini, E., et al. “Bacillus clausii treatment of small intestinal bacterial overgrowth in patients with irritable bowel syndrome.” Digestive and Liver Disease 38 (2006): S32.

Rappuoli R. Pathogen elimination by probiotic Bacillus via signaling interference. Nature. 2018;562:532-537.

Marseglia GL, Tosca M, Cirillo I, et al. Efficacy of Bacillus clausii spores in the prevention of recurrent respiratory infections in children: a pilot study. Therapeutics and Clinical Risk Management. 2007;3(1):13-17.

Kosaka T. Effect of Bacillus subtilis spore administration on activation of macrophages and natural killer cells in mice. Veterinary Microbiology. 1998;60(2-4):215-225.

Elshaghabee, Fouad MF, et al. “Bacillus as potential probiotics: status, concerns, and future perspectives.” Frontiers in microbiology (2017): 1490.

Dong T, Van P, Cutting S. Bacillus Probiotics. Nutra Foods. 2009;8(2):7-14.

Suva, Manoj A., Varun P. Sureja, and Dharmesh B. Kheni. “Novel insight on probiotic Bacillus subtilis: mechanism of action and clinical applications.” Journal of Current Research in Scientific Medicine 2.2 (2016): 65.

Hong, Huynh A., Le Hong Duc, and Simon M. Cutting. “The use of bacterial spore formers as probiotics.” FEMS microbiology reviews 29.4 (2005): 813-835.

Campbell, Andrew. “Inflammation and a solution: probiotics.” (2017).

Cutting, Simon M. “Bacillus probiotics.” Food microbiology 28.2 (2011): 214-220.

Hong, Huynh A., et al. “Bacillus subtilis isolated from the human gastrointestinal tract.” Research in microbiology 160.2 (2009): 134-143.

Uyen, Nguyen Q., Huynh A. Hong, and Simon M. Cutting. “Enhanced immunisation and expression strategies using bacterial spores as heat-stable vaccine delivery vehicles.” Vaccine 25.2 (2007): 356-365.

Hong, Huynh A., et al. “Defining the natural habitat of Bacillus spore-formers.” Research in microbiology 160.6 (2009): 375-379.

Hoa, Ngo Thi, et al. “Characterization of Bacillus species used for oral bacteriotherapy and bacterioprophylaxis of gastrointestinal disorders.” Applied and environmental microbiology 66.12 (2000): 5241-5247.

Hong, H. A., et al. “The safety of Bacillus subtilis and Bacillus indicus as food probiotics.” Journal of applied microbiology 105.2 (2008): 510-520.