Advanced Topic: Hydrogen Sulfide SIBO




Hydrogen Sulfide Dysbiosis and SIBO: An Evolving Concept


migraine The trillions of microbial species living and dying at any one moment in the human gastrointestinal (GI) tract produce numerous metabolites and byproducts. Microbes produce fatty acids such as butyrate, sugars such as mannitol, vitamins such as folate and vitamin B12. Microbes also produce a variety of gases.




Overview

The most studied microbial gas product is hydrogen, or H2, gas. Many bacterial species, both helpful and harmful to humans, produce H2 gas as a byproduct of their metabolism, while others consume H2. While there is nothing intrinsically wrong or harmful about H2, gas, we can use the timing of H2, gas release in the breath to map out where in the GI tract H2,-producing organisms dwell. This is the principle used to chart the location of microbes in small intestinal bacterial overgrowth, SIBO, in which bacteria have ascended up into the upper GI tract. Methane gas, or CH4, is produced by a unique class of non-bacterial creatures called Archaea, species such as Methanobrevibacter smithii. Unlike H2, gas that has no known physiologic consequences for humans, methane slows the normal propulsive activity of peristalsis that propels digested food down the length of the GI tract. Because of this effect, overgrowth of methane-producing Archaea is associated with the signature issue of constipation. (It is not clear, however, whether upper GI colonization, not just colonic proliferation, is necessary for methanogenic consequences to be experienced.)

There is a third gas produced by microbes: hydrogen sulfide, or H2S. Unlike H2, H2S can be toxic. “Sewer gas” is H2S with its characteristic unpleasant smell that emits from sewers and large collections of human waste and can cause respiratory illnesses in sewage workers. H2S is also produced by microbes in spoiled meat and rotten eggs in which they are agents of putrefaction—rotting. Other health conditions can also raise breath H2S levels. Chronic obstructive pulmonary disease (COPD), emphysema and bronchitis; emotional stress; laryngopharyngeal reflux; periodontal disease and a coated tongue, even bad breath (halitosis) are associated with increased breath H2S. Dentists use a device called a “Halimeter” to measure H2S in the breath produced by mouth microbes as a cause for bad breath, telling us that even the relatively low levels of H2S are detectable by human smell.

It therefore came as a surprise when it was discovered that H2S is also a critical mediator of numerous physiological processes in the human body. H2S has been labeled “the third biological gas” that mediates bodily processes along with nitric oxide (NO) and carbon monoxide (CO)—also components of car exhaust—with effects that include vasodilation (relaxation of arteries), antioxidation, and anti-inflammation. H2S plays a role in blood pressure regulation and serves an important protective and healing role in the intestinal lining. H2S is being explored as a potential treatment for asthma, a condition in which acute exacerbations have been associated with reduced H2S levels. Administration of H2S can reduce intestinal inflammation, even protect from stomach ulcers caused by use of non-steroidal anti-inflammatory drugs. H2S is the signal that mediates intestinal nociception, signals from gut to brain that keep us aware of internal processes, including discomfort and pain. H2S plays important physiologic roles in many species of animals besides humans, including mediating the marked reduction in metabolic rate in hibernating bears, causing a form of suspended animation. There is an age-related drop in H2S levels as we age, and H2S has been administered in an experimental model that extended longevity. Enhanced levels of intestinal sulfide (via increased taurine intake) have also been shown to increase immunity against intestinal pathogens.

There are two general sources of H2S:

1. Human intestinal conversion of the amino acids cysteine, methionine, and taurine from diet (fish, shellfish, poultry, beef, pork, other protein sources)

2. Bacterial conversion of sulfur-containing compounds from diet (onions, garlic, cruciferous vegetables), as well as bacterial metabolism of human intestinal mucus (sulfated mucin proteins)

In other words, the human body produces H2S and bacteria produce H2S. As with NO and CO, H2S makes numerous physiologic processes possible. Without it, health and life would be seriously impaired, perhaps impossible. Despite its crucial role as a physiologic gas mediator, H2S has paradoxically been associated with unhealthy effects that include:

  • Association with ulcerative colitis and colon cancer, in which excessive H2S-producing bacterial species such as Desulfovibrio are present that results in increased intestinal H2S levels.

  • Suppression of beneficial species such as Lactobacillus

  • Gene damage that may be carcinogenic

  • Disruption of the intestinal mucus barrier
H2S present at low quantities is therefore a critical mediator of multiple physiologic processes. But at higher concentrations, H2S exerts considerable negative effects. We are therefore not so much interested in obtaining zero levels of H2S, but possibly addressing overproduction.

H2S Dysbiosis and SIBO

H2S production by bowel flora is therefore a normal phenomenon important for human health. Incredibly, H2S levels in the colon are normally 50-fold greater than the maximum level of exposure allowed for sewage workers. However, excessive proliferation of H2S-producing species can also occur and, as with other forms of SIBO, H2S-producing species can also ascend up the GI tract. There may also be disruption of the mucus and/or intestinal cell barrier required for the full syndrome of H2S dysbiosis and SIBO to be expressed. Foul smelling flatus with the scent of rotten eggs is a telltale sign of overgrowth of H2S-producing species such as Desulfovibrio, Desulfobulbus, and Atopobium parvulum, though it is not clear whether such a phenomenon is necessary for H2S SIBO to be present. Other sulfur-producing species include Fusobacteria that converts the amino acid cysteine to H2S and Bilophila wadsworthia that converts taurine to H2S.

One of the difficulties in discerning whether H2S SIBO is present by breath detection is that people without SIBO produce some amount of H2S in their breath of up to approximately 11 parts per billion (ppb). H2S detected on the breath can also be attributed to H. pylori in the stomach. The “rules” to follow that indicate H2S dysbiosis or SIBO are therefore not yet worked out, nor are timing issues defined after consuming a sugar such as lactulose or a prebiotic fiber.

From Birg 2019. Lactulose 10 grams was administered to participants at time zero. H2 gas levels are in pink, remaining negative for the first 90 minutes and generating the so-called H2 “flatline.” H2S levels are in green; methane levels in purple. Note the early peak for H2S.)
The Birg study (graph above) demonstrated an immediate release of H2S in the breath after participants consumed lactulose, while the Banik study showed a delayed release similar to the timing of H2 release in SIBO:

One of the challenges that emerges when there is proliferation of H2S- and methane-producing microbes is that they consume H2 gas to produce H2S and methane. It means that H2S- and methane-producing microbes can be present at excessive levels but may obscure the concurrent presence of H2-producing microbes. This can be seen as a phenomenon called “flat-lining” of H2 gas, i.e., a low flat curve of H2 during breath testing after lactulose/glucose/prebiotic fiber consumption (as seen in the above two graphs). Most people with H2S-producing species experience diarrhea. But these species can also slow intestinal transit in the small bowel, increasing potential for SIBO. It is not clear whether H2S dysbiotic species must ascend into the small bowel for the full spectrum of problems develop. (The immediate high H2S reading of around 37 parts per billion, ppb, in the Birg study suggests upper GI colonization by H2S-producing species, as does the Banik study, though not as dramatically.)

It is not clear what events, dietary or otherwise, lead to proliferation of H2S-producing species, although limited evidence suggests that this phenomenon occurs in the 7-14 days following a course of antibiotics.

There is no evidence that increased consumption of sulfur-containing foods, such as garlic or onions, or sulfur-containing amino acids cysteine, methionine, and taurine from proteins, contribute to H2S-producing species overgrowth, nor is there evidence that other sulfur-containing compounds such as glucosamine sulfate or chondroitin sulfate, both commonly taken for joint health, stimulate proliferation of these microbes. Although levels of H2S increases in the colon after protein consumption, intestinal cells have a compensatory mechanism to prevent H2S toxicity.

The level of H2S in the breath that suggests SIBO after consuming a sugar such as lactulose or glucose has therefore not yet been determined. There are also the confounding effects of other H2S sources such as mouth microbes producing bad breath, gingivitis, and COPD. Unfortunately, these factors have not been factored into some studies of breath H2S in which any level of H2S has been declared representative of H2S SIBO.

Should you have a stool sample analyzed for microbial composition, then the presence of increased numbers of Desulfovibrio, Desulfobulbus (and other species with “sulfo” in its species designation), Atopobium parvulum, Bilophila wadsworthii, and Fusobacteria should alert you to the possibility of H2S-producing species overgrowth. Eradication of H2S dysbiosis/SIBO

The methods to reduce excessive proliferation of H2S-producing species is virgin territory: there are no clinical trials nor other forms of evidence that help us decide how to best deal with this situation. However, it is likely that the steps we take to eradicate H2-producing microbes, such as Candibactin AR/BR, FC Cidal + Dysbiocide, rifaximin, and perhaps our SIBO yogurt that features bacteriocin-producing and upper GI-colonizing L. gasseri BNR17, may also translate to efficacy in H2S dysbiosis and SIBO. The real advantage in understanding H2S dysbiosis and SIBO is that identification of excessive breath levels of H2S tell us that many more people with complaints such as unexplained diarrhea, irritable bowel syndrome, and other health struggles have this form of dysbiosis/SIBO as the cause. Although unproven, it suggests that many people who tested negative for H2 SIBO do indeed have the condition, pointing the way to potential solutions.

Conclusions

H2S gas is a critical signal transmitter for both the human body and microbes, mediating numerous processes such as immunity and inflammation. However, for unclear reasons, H2S-producing microbial species such as Desulfovibrio, Bilophila, and Fusobacteria can proliferate, then ascend into the upper GI tract, situations in which excessive quantities of H2S can be produced. This typically results in diarrhea or irritable bowel syndrome symptoms with diarrhea. Excessive H2S-producing species can also occur concurrently with methane- and H2-producing species.

While lessons are still being learned on how to interpret H2S breath levels, there are several issues we should bear in mind when testing for H2S:

  • H2S levels of 0-11 ppb (parts per billion) are not necessarily due to intestinal overgrowth of H2S-producing microbes but may be due to breath microbes, asthma, COPD, pancreatic disease or other health conditions.

  • “Flatline” H2 levels on breath testing are highly suggestive of H2S dysbiosis/SIBO due to the H2-consuming behavior of H2S-producing species

  • The timing of H2S measurement on breath testing (after lactulose, glucose, or prebiotic fiber) has not been defined with the limited number of studies demonstrating discrepant results. As with H2 release, early H2S release (within the first 90 minutes) should be tentatively regarded as H2S SIBO.