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Home » Intestinal Sulfide Overproduction (ISO)

Intestinal Sulfide Overproduction (ISO)

Intestinal Sulfide Overproduction (ISO), formally known as Hydrogen Sulfide SIBO, occurs when bacteria from the intestine are overproducing hydrogen sulfide gas. ISO is a rare form of SIBO, a digestive disorder that can cause a number of digestive symptoms that share Irritable Bowel Syndrome symptoms. Hydrogen sulfide (H2S) is a normal gas created by bacteria in the intestines but at elevated levels causes mild to severe inflammation.

Who Can Have ISO

While anyone can have ISO, research has found this to be a rarer form of dysbiosis or bacteria overgrowth in the intestines. Individuals who have been diagnosed with IBS are more likely to have SIBO and ISO.

Research has found that people have higher amounts of Desulffovibrio spp., a bacteria that can produce H2S, if they have ulcerative colitis – a form of Inflammatory Bowel Disease. Anyone can have this strain of bacteria, and in fact, having small amounts of these bacteria is beneficial. At low levels, these bacteria can create ATP, a form of energy. At higher levels – anything about 5 parts per million (ppm) – an overgrowth of the bacteria can develop. And at extremely high levels, Colorectal cancer can develop. Even a type of Yeast called S. cerevisiae, also known as brewer’s yeast, can make highly toxic H2S gas. That being said, ISO is incredibly rare – less than 5% of all SIBO cases.

What ISO Does

High levels of H2S bacteria in the digestive tract can create malabsorption, preventing the body from properly utilizing nutrients. The body could have a number of digestive issues because of food not processing properly. The digestive tract could have rotting food, food not being removed from the body, or a number of other issues listed below. These microorganisms will consume any overabundance of carbohydrates in the intestines that are not absorbed into our body. This leads to the carbohydrates fermenting.

This fermentation of these carbohydrates is going to cause damage to the intestinal tract cells, causing intestinal permeability known as “leaky gut”, or malabsorption syndrome. Some SIBO organisms create hydrogen sulfide (H2S) gas as a byproduct. We now know that Fusobacterium varium and Desulfovibrio piger are the main two products of H2S gas in most SIBO cases. This H2S gas causes damage to cells of the body. Anyone who has ever been near an erupting volcano will know the smell of H2S. This brimstone, sulfur smell is very irritating to the nose but also the rest of the body.

Bacteria and Sugar

Since your blood type is just a carbohydrate – aka sugar – it isn’t limited to just your red blood cells. It can be loaded throughout your body and on the foods that you eat. This sugar is also found in high abundance in 80% of people’s digestive tracts. This is a result of a gene mutation called FUT2. This gene secretes blood-type antigens – aka your blood-type sugar – inside the digestive tract. The normal, commensal bacteria that live in the digestive tract then consume the sugar.

These bacteria, like everyone else, like a free meal. This is why certain probiotics work better (in Dr. Brody’s opinion) than others. If you have a mutation in the FUT2 gene, you don’t secrete your blood type sugars and the bacteria don’t get a regular free meal. When a meal is finally present, the starving bacteria are going to consume it quickly and stuff themselves. This will lead to a lot of flatulence, eructation, and trips to the bathroom as the bacteria break down their meal and expel their byproducts into our digestive systems.

Symptoms of ISO

Patients typically see diarrhea as the classic ISO symptom, but one can see constipation too. These symptoms can appear alongside abdominal pain, flatulence, distention, and heartburn. Other, less frequent symptoms include bladder pain, myalgia, and very rarely, sulfur-smelling gas.

Diagnosis

A diagnosis of ISO takes a couple of steps to procure. First, the patient’s symptoms have to line up with those listed above. Second, the patient needs to take a Lactulose breath test that shows a high reading of H2S gas. The old gold standard of testing SIBO was an endoscopy with a culture. This procedure is both expensive and inaccurate, as the test was limited to the small samples that could be collected and cultured.

This breath test has become the “gold standard” for testing ISO, Classic SIBO, and IMO. However, the key to the breath test lies in the preparation. Beginning 24 hours before the test, the patient needs to switch to a clean diet. Patients can have turkey, chicken, or fish that is only baked or boiled, and seasoned with only salt and pepper. The patient can also have white rice, cooked and seasoned in the same fashion. For the last 12 hours before the test, the patient needs to fast. During this 12-hour period, the patient can only have water and their prescription medications. The test also requires that patients don’t exercise or smoke for at least one hour beforehand.

Patients also need to stop taking any PPIs, antimicrobial medicines, and any substance that can be used to induce a bowel movement such as magnesium, senna, or coffee.

Alternative Testing

The previous standard of diagnosing ISO is a consistently low level of H2 and CH4 gas throughout the entire three-hour breath test. If a patient displays these low levels while having symptoms, it is considered a positive diagnosis for ISO. A doctor can provide this diagnosis when the TrioSmart test is unavailable.

Stool Testing can also help determine if these bacteria are located in the body. The only downfall is that these tests definitely isolate bacteria DNA from the large intestines but not necessarily from the small intestines.

Taking the Test

We recommend that all patients first take a Lactulose breath test that looks for H2 and CH4 gasses. If these are low throughout the three-hour test and the PT is symptomatic, we review labs to rule out SIFO or yeast overgrowth. If this is negative we will then talk to the patient and order the TrioSmart Breath Test. The patient will have to attain a prescription, and the test will be performed at home. We ask all the PTs to take a breath sample every 20 minutes instead of the stated 15 minutes to extend the test into the large intestines. At this point, the Trio Smart Breath Test seems to be (at least ) partially covered by insurance. Insurance usually covers PNM’s in-house SIBO/IMO breath test, but at the moment our test does not test for ISO.

If the H2S level reaches 5ppm or over, then the doctor can safely diagnose ISO. H2S has only recently begun being researched, and there are still plenty of unknowns. However, it currently appears that high levels of two or all three gases can still create a positive ISO diagnosis. The new diagnosis code used for ISO is K63.8212.

DDX

Doctors need to rule out other conditions in order to diagnose ISO including hydrogen SIBO, IMO, and SIFO. A hydrogen breath test can rule out “classic” hydrogen SIBO and a methane breath test can rule out IMO. SIFO is much harder to rule out but Dr. Brody usually ordered Candida Immocomplex and Candida antibodies for this. Further testing for candida can include different chemicals like arabinose but these are usually out of pocket.

About 70% of all IBS cases are actually SIBO/IMO cases, whereas Dr. Brody estimates that 1-5% of SIBO/IMO cases are ISO. Other medical conditions need to be ruled out if the breath test comes back negative, such as inflammatory bowel disease (either ulcerative colitis or Crohn’s disease) but this should have been ruled out before attaining the diagnosis of IBS, collagen-based disorders such as Ehlers Danlos Syndrome, cancer, Celiac’s disease, parasitic infections, Small Intestinal Fungal Overgrowth (SIFO), post-infectious IBS, Helicobacter pylori infection, and more.

Allopathic Treatment

The standard allopathic treatment for ISO is still undergoing research. Most treatment plans include a regime of antibiotics to flush the system. The standard antibiotics used are rifaximin and either neomycin and/or metronidazole as the treatments of choice. Rifaxamin only affects the small intestines, as it requires bile to activate.

Researchers have found that rifaxamin can decrease inflammatory markers in the intestinal tract. Additionally, rifaxamin can even increase certain probiotic species such as bifidobacterium. As such, this antibiotic can be classified as an Eubiotic instead. The other drug that is used with rifaximin is bismuth. This drug helps bind up the H2S gas and can also break up some biofilms.

The thought process is that rifaximin with bismuth remove the cause, and can allow good bacteria to repopulate the vacated space. However, antibiotics function as a nuclear warhead, wiping out everything in the gut. This can lead to the removal of good bacteria as well, taking the gut longer to recover and regulate.

Natural Treatment

Despite being relatively new, Personalized Natural Medicine (PNM) has already created a system of treatment for ISO. It begins with taking a breath test, blood work, and stool tests.

PNM’s standard treatment protocol for ISO includes a high dose of two herbs, Uva Ursi and Hydroxy-Silver. Dr. Brody will also include his Biome Clear and H2S Formula to kill off the bacteria. H2S gas to highly toxic to the body, so we want to reduce the endotoxins created by these bacteria and break up and biofilms they produce. If left unchecked, these endotoxins can create a die-off reaction – a temporary exasperation of the symptoms. To prevent this, Dr. Brody adds a binding agent to each protocol. This can include the mineral MO, or Dr. Paul Anderson’s formula Phase-2 Biofilm. If Dr. Brody deems it medically necessary, he can add NAC and Bismuth.

While H2S eradication is underway Dr. Brody recommends stopping all probiotics and prebiotics. During phase two of treatment, Dr. Brody will usually add different probiotics and prebiotics (GOS) into the treatment plan along with minerals like zinc.

Diet

Diet is one of the key ingredients for preventing and treating any form of internal infection. Despite the evidence on a Low FODMAP diet, SCD Diet, the Biphasic, or a low sulfur diet, Dr. Brody recommends the SWAMI. SWAMI is the only personalized diet out of all the diets listed above. Dr. Brody is able to tailor a diet to you and your unique bacteria based on genetic, personal, family, and lab results.

The SWAMI diet is also the only diet listed that is designed to be used as a long-term option. The other diets are only supposed to be used for a short period of time.

Bacteria Die-Off Reactions

Once the killing phase is completed, then we begin the repopulation, healing, and prevention phase of treatment. Dr. Brody will always ask a patient to perform a follow-up breath test. If a patient has a positive result, then the treatment plan will change accordingly and the patient will undergo another round of treatment. Once the test comes back negative and symptoms have abated, then patients are recommended to perform a follow-up breath test every 3 months to ensure the microorganisms have not returned.

Diet

One of the key components of PNM’s treatment is diet. We use a SWAMI diet, which uses genetic information, lab markers, the SCD and Low FODMOD diets. These combined with other measures create a personalized, digestive-based diet for all of our patients.

Potential Complications

With any form of testing or treatment, potential complications can present themselves. With testing, following the prep diet and fasting for 12 hours can be a challenge. Patients can skew the breath test results if they don’t properly follow the prep diet. Some people will have reactions to the sugary drink that are provided at the start of the test. Depending on the type of sugar used there can be some upset, gas, and diarrhea. Lactulose is an alcohol-based sugar that feeds microorganisms all the way from mouth to anus. This is the sugar needed for ISO diagnosis.

Treatment can yield some symptoms as well. Dieoff reactions can cause your digestive symptoms to become worse for a time. A host of different natural agents can help prevent or manage any digestive symptoms. Other times, patients will have to change treatment plans multiple times to find the right cure. This includes using antibiotics, elemental diets, different rotation of herbs, and finally specific microbiome testing to ensure that there are no other bacteria causing digestive issues.

Related Bacteria

Klebsiella, Citrobacter, E. coli, Proteus, Desulfovibrio piger, and Fusobacterium varium. For a complete workup of these bacteria and to see how they might be involved in your digestive test Dr. Brody might recommend an Ombre Test and/or a GI MAP test.

Related Genes

CBS and SOU. These genes are involved with the sulfur pathway in the body. It may become necessary to investigate these genes are a way of preventing a return of ISO.

Citations

  1. Yarnell, E. (2011). Natural Approach to Gastroenterology. Seattle Wash.: Healing Mountain Pub.
  2. Siebecker, A. (2020, September). Small intestinal bacteria overgrowth Pro Course. SIBO Pro Course. 

Meet Dr. Ferraro

Dr. Shiana “Shi” Ferraro is a licensed Naturopathic Physician and acupuncture specialist. Her areas of practice include pediatrics, obstetrics and gynecology/women’s health, mental/emotional health, neurological health, and all things related to stress and the gut-brain axis. Training … Read more >>

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Personalized Natural Medicine
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Fax: 203-270-0073
Address: 11 Mile Hill Road
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Welcome to the official page of Dr Robert Brody Personalized Natural Medicine LLC. While Dr. Robert Brody is a licensed naturopathic physician in the state of Connecticut, the information on this site is provided for informational purposes only and is not meant to substitute for the advice provided by your physician. Do not use the information on this website for diagnosing or treating a disease, or using any medications discussed. If you have or suspect a medical condition, please seek out a medical professional.

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Personalized Natural Medicine LLC
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Fax: 203-270-0073
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