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Implications of Cytolethal Distending Toxins Bring New Perspective on Natural SIBO Treatment
By Vincent Pedre, MD

For the functional medicine practitioner, it is not a rare occurrence when a patient presents to your office with uncomfortable gastrointestinal symptoms such as bloating, abdominal pain, diarrhea and/or constipation. These are common complaints that present across most GI cases. But what happens when the patient doesn’t show improvement, and even small diet changes still present with gas, bloating, diarrhea and food intolerances? Patients like these are frustrating, especially if you have tried numerous approaches, like an elimination diet, with unsuccessful results, and you cannot pinpoint the cause of their symptoms. If this is the case, you may want to consider small intestinal bacterial overgrowth (SIBO).

What is SIBO?

SIBO is an increasingly common condition, where simply put, there’s too high of a concentration of bacteria in the small intestine, which could be due to an overgrowth of naturally occurring flora in the small bowel or translocation of bacteria from the large intestine, where they are found in higher concentration. Sometimes these levels can even approach the levels that we normally find in the colon. Traditionally, this overgrowth was thought to be the result of motility issues, either from inadequate firing of the migrating motor complex due to archaea’s methane production or vagal nerve malfunction. However, there is more to the story.

Dr. Mark Pimentel has suggested that prior food poisoning can lead to irritable bowel syndrome and SIBO. 1

Essentially, food poisoning can introduce pathogenic bacteria into the small intestine. When left unchecked in the environment of the small intestine, they can overgrow and cause devastating chronic symptoms for your patients.

The Link to Cytolethal Distending Toxins

Cytolethal distending toxins (CDTs) are compounds secreted by gram-negative bacteria (e.g., Escherichia coli, Salmonella, Shigella and Campylobacter jejuni), that are also the same type of bacteria often associated with infections of the stomach and small intestine. 2 Cytolethal distending toxin B subtype can damage cytoskeletal proteins within the intestinal epithelial cells without disrupting the tight junction,3 and eventually may lead to increased intestinal permeability and  . This is a novel discovery because leaky gut syndrome was often thought to be associated with just the degradation of tight junction proteins.

The release of cytoskeletal proteins (e.g., α-actinin, talin and vinculin) transcellularly results in IgG, IgM, and IgA antibody production against bacterial cytotoxins along with cytoskeletal proteins and may even lead to an increased risk for autoimmunity due to molecular mimicry. 4

Probiotic Approaches for SIBO

Increased microbial activity from the overgrowth of bacteria undeniably leads to excess fermentation in the small intestine, which is at the core of SIBO-like symptoms. SIBO patients eating the healthiest of diets can still be susceptible to gas, bloating, and an intolerance to certain foods, likes foods high in FODMAPS (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols), as well as experience problems with fermented foods and probiotic supplementation. Although, probiotics can be an effective therapy for dysbiosis, probiotics given to individuals with SIBO may exacerbate the fermentation-based symptoms. I found this conundrum makes a probiotic recommendation difficult for SIBO patients, who are among the most difficult-to-treat GI cases. 

A common treatment approach to SIBO is to start with a low dose probiotic of about 5 billion CFU of a traditional combination of Lactobacillus and Bifidobacterium and gradually increase the dose in a stepwise fashion, while making sure not to worsen symptoms. However, I found that most of the time, symptoms do get worse, even at excessively low doses, making supplementation with traditional Lactobacillus and Bifidobacterium a risky undertaking in the SIBO patient. Doing so leaves both the practitioner and the patient frustrated.

For these challenging cases, I started experimenting with spore-forming probiotic supplements, like Bacillus subtilis. They are particularly helpful, because they remain inactive and dormant until they reach favorable, nutrient-rich environments in the distal gastrointestinal tract where they slowly become active. With a longer life cycle than traditional probiotics, they can be administered in much lower doses to help create microbial diversity without causing irritating symptoms. In fact, certain Bacillus species have been shown to relieve symptoms of bloating. 5  Activated Bacillus species use quorum sensing to group together, communicate, and produce active compounds (e.g., enzymes, bacteriocins) that inhibit and breakdown non-resident species in targeted areas of the small intestine. 6  In other words, they do what antibiotics are meant to do in SIBO, but without all the side-effects and potential for rebound SIBO or SIFO (small intestine fungal overgrowth), as a result of taking antibiotics.

When I started using spore-forming organisms in my SIBO treatment regimen, I immediately noted improved outcomes in patients who had been chronically suffering for months to years. However, I also noted that not every patient did well solely on these spore-based probiotics. They began suffering symptoms consistent with die-off. So, I looked for ways to mitigate these die-off symptoms, while still using the spore-forming organisms to reinstate balance in the gut.  

Because the resulting die-off can expose the gut to toxins and other harmful compounds, I decided to add serum-derived immunoglobulins (SBI) to my SIBO treatment regimen (with caution in severely constipated SIBO patients, because SBI can aggravate constipation). SBI acts as a targeted and biologically active binder, which can provide remarkable benefits in SIBO cases, as well as provide a dairy-free option for lactose-, whey- and/or casein-sensitive patients. Immunoglobulins have shown broad-spectrum binding capacity, including the ability to prevent bacterial components like LPS and toxins like CDT from damaging gut tissues and eliciting immune responses, 7 , 8  which can then lead to leaky gut syndrome and ongoing symptoms.

This had been the case with my 37-year-old patient, Lauren, who had been suffering from severe, uncomfortable bloating for almost a year. Aside from using a traditional treatment approach to SIBO that included antibiotics, which she had tried several times to no avail, I realized her gut needed the help of a spore-based probiotic plus SBI to reset the microbiome balance in her small bowel. By using this approach, along with targeted nutrition and lifestyle interventions, including stress-reducing strategies, she was finally able to conquer months of SIBO symptoms and resume living a normal life. 

The Bottom Line

The SIBO conversation is changing. Recent findings have suggested prolonged exposure to CDTs from food-borne pathogens have potential to cause tissue damage, possibly leading to leaky gut syndrome, SIBO, and even autoimmunity if left unaddressed.

When treating challenging SIBO patients, practitioners should now consider timely intervention with spore-forming Bacillus sp. probiotics and serum-derived immunoglobulins as a first-line approach to restore the gut terrain and protect the gut lining. 

 

 

References

 

  1. Pimentel M. Update on Irritable Bowel Syndrome Diagnostics and Therapeutics. Gastroenterol Hepatol (N Y). 2016;12(7):442-445.
  2. Vojdani A, Vojdani E. Reaction of antibodies to Campylobacter jejuni and cytolethal distending toxin B with tissues and food antigens. World J Gastroenterol. 2019;25(9):1050-1066. doi:10.3748/wjg.v25.i9.1050.
  3. Eshraghi A, Maldonado-Arocho FJ, Gargi A, Cardwell MM, Prouty MG, Blanke SR, Bradley KA (June 2010). "Cytolethal distending toxin family members are differentially affected by alterations in host glycans and membrane cholesterol". The Journal of Biological Chemistry. 285 (24): 18199–207. doi:10.1074/jbc.m110.112912. PMC 2881744. PMID 20385557.
  4. Izard T, Tran Van Nhieu G, Bois PR. Shigella applies molecular mimicry to subvert vinculin and invade host cells. J Cell Biol. 2006;175:465–475.
  5. Hun L. Bacillus coagulans significantly improved abdominal pain and bloating in patients with IBS. Postgrad Med. 2009 Mar;121(2):119-24. doi: 10.3810/pgm.2009.03.1984. PMID: 19332970.
  6. Dong YH, Wang LH, Xu JL, Zhang HB, Zhang XF, Zhang LH. Quenching quorum-sensing-dependent bacterial infection by an N-acyl homoserine lactonase. Nature. 2001 Jun 14;411(6839):813-7. doi: 10.1038/35081101.
  7. Detzel CJ, Horgan A, Henderson AL, et al.
  8. Bovine immunoglobulin/protein isolate binds pro-inflammatory bacterial compounds and prevents immune activation in an intestinal co-culture model. PLoS One. 2015;10(4):e0120278. Published 2015 Apr 1. doi:10.1371/journal.pone.0120278.
  9. Asmuth DM, Somsouk M, Hunt P, Ma ZM, Miller CL, X.D., Hinkle J, et al. Serum-Derived Bovine Immunoglobulin Protein Isolate Increases Peripheral and Mucosal CD4+ T-cell counts in Patients with HIV Enteropathy. 8th IAS Conference on HIV Pathogenesis, Treatment and Prevention (AIDS 2015); MOAA02; Vancouver, Canada 19-22 July: http://www.ias2015.org/WebContent/File/IAS_2015__MED2.pdf; 2015.

 

 

 

 

Vincent M. Pedre, MD

Dr. Vincent M. Pedre is the Medical Director of Pedre Integrative Health and Founder/CEO of Dr. Pedre Wellness, Chief Medical Officer of United Naturals, and a functional medicine-certified practitioner in private practice in New York City since 2004. He is also certified in yoga and medical acupuncture and part of the mindbodygreen collective of influencers with regular, popular blog posts. In 2017, he joined Lifestyle Matrix Resource Center as the chief Clinical Expert of the Pillars of GI Health Program. In 2018, he joined the faculty for the Institute for Functional Medicine, teaching the first-ever introductory functional medicine courses to practitioners in Lima, Peru, Brisbane, Australia and Mexico City. He believes the gut is the gateway to excellent health and a better brain. As the bestselling author of “Happy Gut: The Cleansing Program To Help You Lose Weight, Gain Energy and Eliminate Pain”, he has helped thousands of people resolve their digestive and gut-related health issues.

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