Hydrogen Sulfide: The good, the bad and the misunderstood

What Is Hydrogen Sulfide?

Hydrogen sulfide is a colorless and odorless gas that is produced both endogenously, and, by bacteria in the large intestine. Hydrogen sulfide has emerged as an important ‘gasotransmitter’ that regulates several bodily systems including: the cardiovascular, digestive, immune, hormonal, and nervous systems.

Hydrogen Sulfide Production

The precise locations of its production remain an active area of research.

Hydrogen sulfide is produced endogenously through several key enzymes, including:

  • Cystathionine β-lyase (CBE)
  • Cystathionine γ-lyase (CSE)
  • 3-mercaptopyruvate sulfurtransferase (MST)/cysteine aminotransferase (CAT)

These specific enzymes are expressed accordingly in various organ systems.

From what I understand thus far, when healthy cells are put under stress, such as hypoxic conditions, a hydrogen sulfide-producing enzyme called cystathionine-gamma-lyase (CSE) moves from the cytosol of the cell, to the outer mitochondrial membrane, where it uses cysteine, an amino acid, to generate hydrogen sulfide. The hydrogen sulfide produced actually supports ATP (energy) production. Dr. Nigh puts it well by stating:

The point is that hydrogen sulfide production is vital to the cellular adaptation to physiological stress.

However hydrogen sulfide is also produced by gut bacteria and that is the main topic of today’s post.

The bacteria that reside in our digestive tract aid in the breakdown of nutrients from our food. Certain bacteria, some times called primary fermenters, break down complex carbohydrates (like dietary fibre) into short-chain fatty acids (e.g butyrate), and gases (e.g., hydrogen) that are released or absorbed by the body.

Organisms called ‘hydrogenotrophs’ (essentially hydrogen consuming bacteria and archaea), are essential in keeping gut hydrogen levels low and stabilising the environment for these primary fermenters. Among the groups of hydrogenotrophs are methanogens (producing methane), acetogens (producing acetate), and sulfate reducing bacteria (producing H2S).

The methanogenesis/sulfate reduction ratio is dependent on substrate availability, thermodynamics and pH. In human colon, the ratio is in the favor of methanogenesis, due to neutral pH of stool and low sulfate levels in diet. However, in certain conditions, such as high availability of sulfate substrates in a diet (bread, beer, wine) and hypochlorhydria, sulfate reduction may become the major process

To break this down: bacteria ferment some of our food, they produce hydrogen which we exhale, fart out, or/and absorb. Certain types of bugs (methanogens and sulfate reducing bacteria mainly) compete for the hydrogen as they use it to produce methane and hydrogen sulfide respectively.

Sulfate Reducing Bacteria

The primary hydrogen sulfide producing bacteria include:

  • Bilophila wadsworthii
  • Desulfomonas pigra
  • Desulfovibrio piger

It is thought that the microorganisms have quite a substantial role to play in H2S production based on animal studies demonstrating that:

Microbial produced hydrogen suldife is a significant contributor to the bodies hydrogen sulfide pool, as germ free mice have between 50 and 80% less hydrogen sulfide in their tissues and circulation.

The following quotes summarise the systems and processes hydrogen sulfide may influence and how it may influence them:

Hydrogen Sulfide And Glucose Homeostasis

Hydrogen sulfide (H2S) has emerged as an important regulator of glucose homeostasis. This is achieved through its production and action in several metabolic and hormone producing organs including the pancreas, liver, and adipose.

Hydrogen Sulfide And Cardiovascular Health

Gut bacteria-derived metabolites may cross the gut-blood barrier and target blood vessels, the heart and other organs involved in the regulation of the circulatory system. A number of studies have shown that hydrogen sulfide is an important biological mediator in the circulatory system.

In short, H2S is synthetized in various tissues involved in circulatory system homeostasis, including the heart, blood vessels, kidneys and the brain

changes in colonic hydrogen sulfide homeostasis may be associated with hypertension.

Hydrogen Sulfide And Digestive Health

H2S can damage the gastrointestinal epithelium (cause leaky gut)

Those with constipation-predominant IBS have been found in some studies to have a bacterial imbalance, in particular, a significant increase of sulfate reducing bacteria, and fecal sulfide, indicating a potential role for sulfide in the development of IBS symptoms.

From clinical studies with human volunteers and experimental works with rodents, it appears that hydrogen sulfide can exert mostly pro- but also anti-inflammatory effects on the colonic mucosa [gut lining].

Increased detection of Fusobacterium (a species of bacteria) in colorectal cancer tumors has been reported in two independent studies. Fusobacterium produce hydrogen sulfide through cysteine desulfhydrase activity – a hydrogen sulfide-producing enzyme. As hydrogen sulfide has been demonstrated to be genotoxic, the authors of this paper hypothesised that it may be one causative metabolite in the etiology of colorectal cancer.

Recently, a culture-dependent study demonstrated that mucosal biopsies from IBD patients were more often colonized by Fusobacterium spp. than those from matched healthy controls.

A key point here for us folk who are regularly interpreting stool tests is that fusobacteriam species may produce hydrogen sulfide gas via different mechanisms to that of those mentioned above (Bilophila wadsworthii, Desulfomonas pigra, Desulfovibrio piger).

Diet And Hydrogen Sulfide

Magee and colleagues demonstrated that dietary protein intake positively correlates with fecal sulfide concentrations in healthy individuals

The sulfur content of food can be estimated using the sulfur-containing amino acids (methionine and cysteine) as surrogates, but this fails to account for sulfur-containing food modifiers or additives, such as sulfiting agents (e.g., potassium bisulfate, sodium bisulfate), sulfuric acid, or carrageenan.

Dietary input and small intestinal absorption are considered the main determinants of sulfur delivery to the colon. The small intestine has an efficient but saturable dietary sulfate absorptive capacity of ~5–7 mmol/day. Once dietary sulfate intake exceeds ~5–7 mmol/day the amount reaching the colon increases linearly with intake. Therefore, the amount of dietary sulfur that reaches the colon, particularly with increasing levels, can be generally assumed to parallel dietary intake.

A number of additional factors, however, such as food preparation (e.g., cooked versus uncooked, cooking temperature and method, ground versus whole), meal consumption habits (e.g., chewing), and transit time have been shown to influence small intestinal absorption of sulfur-containing molecules and the total amount of sulfur reaching the colon

Not all research aligns however. A paper published this year that looked at short-term changes in dietary sulfur on the relative abundances of intestinal sulfate-reducing bacteria concluded:

These results suggest that the use of dietary interventions alone may be insufficient for rapid therapeutic targeting of sulcate-reducing bacteria.

It should be noted that this study used 10-14 day periods, not very long!

Fibre And Hydrogen Sulfide

Although brassica vegetables are technically considered to be high sulfate foods, they also have a high fiber content. These findings underscore the beneficial role for the latter within the hydrogen sulfide toxin hypothesis and support a clinical approach focusing on plant versus animal-based diets rather than high- and low-sulfur diets.

Production of hydrogen sulfide …. is effectively suppressed by readily fermentable fibers.

The addition of FOS [a prebiotic] to slurries containing cysteine significantly suppressed hydrogen sulfide

Cysteine And Hydrogen Sulfide Production

We have already mentioned the species of bacteria Fusobacterium that can produce hydrogen sulfide via the amino acid cysteine. Other bacteria that can convert cysteine to hydrogen sulfide include:

Several anaerobic bacterial strains (Escherichia coli, Salmonella enterica, Clostridia and Enterobacter aerogenes)

A recent in vitro study that profiled gas production from incubated fecal samples implicated cysteine specifically as a primary driver of H2S production—conversely, the effect of sulfate was small. Cysteine degradation to H2S is catalyzed by enzymes with cysteine desulfhydrase activity

In fact, in vitro modeling using healthy human feces suggests that the contribution of cysteine to H2S production is substantially more than that from sulfate

Escherichia coli possess several enzymes with cysteine desulfhydrase activity

In addition, gut bacteria may produce H2S by sulfite reduction. Sulfite reductase is present in many species such as E. coli, Salmonella, Enterobacter, Klebsiella, Bacillus, Staphylococcus, Corynebacterium, and Rhodococcus

The Importance Of The Liver & Detoxification of H2S

Systemic effects of colon-derived hydrogen sulfide and/or its derivatives may be in part due to some liver-dependent mechanisms

Genetics And Hydrogen Sulfide

Given that most of the colonic disorders for which a potential pathogenic role for sulfide exists are effectively gene-environment disorders, it is straight-forward to envision how common polymorphisms in host genes encoding components of the sulfide oxidation pathway might underlie ineffective epithelial sulfide detoxification and thereby predispose certain individuals to chronic sulfide-generated inflammation or genotoxicity.

Dr. Nigh in his article in NDNR (link at end of this blog under resources) mentions:

Genetics comes into play in this as well, though my clinical experience suggests that outside of polymorphisms in the SUOX gene, the polymorphisms associated with cystathionine-beta-synthase (CBS) and CSE are usually playing a relatively minor role in sulfate production and processing.

These can be tested for via Lifecode GX – I had Emma from Lifecode GX on the podcast (episode 30) for those interested  – a fountain of knowledge on this topic.

Symptoms That May Suggest A Hydrogen Sulfide Issue

Hives, hot flashes, dermatitis, brain fog, inflammatory bowel disorders, hypertension, atherosclerosis, heart failure, diabetes, cirrhosis, inflammation, sepsis, neurodegenerative disease, erectile dysfunction, and asthma, to name a few.

Testing For Hydrogen Sulfide

There is not a current validated test for hydrogen sulphide, that I know of, that is accessible at this point in time (June 2019). Please e-mail me if you know of one. One will be available by 2020 which is very exciting. However you can test for levels of sulphate reducing bacteria via stool testing, and thus gain good understanding around whether there is a microbial imbalance contributing to hydrogen sulphide imbalances.

Visit Healthpath – click here – a health tech company providing direct to consumer testing. Your results will include a personalised report, with recommendations. The stool test assesses for almost all of the aforementioned bacteria. Click here to see the bacteria, yeasts, parasites and functional markers (and soon worms) we test for.

Conclusion: What Do We Actually Do?

high colonic H2S levels may be responsible for colonic inflammation and cancer. On the other hand, recent studies suggest that colonic epithelial cells are well-adapted to the H2S-rich environment, and that H2S plays a beneficial role in the protection of the GBB [gut blood barrier]

Microbial H2S has been associated with both maintaining gastric health and being implicated in disease. Several groups have shown that H2S regulates various physiological functions including maintenance of GI barrier function and injury repair

As these quotes demonstrate there is still a lot that we need to learn, and, what to do is very much context dependent. It seems considerations may include:

  • Whether we have a genetic predisposition meaning we may need to be more mindful of sulfur requirements and thus intake.
  • Testing to investigate the underlying causes of our symptoms further.
  • A plant based diet trial.
  • Considering toxin exposure which may increase our requirements for sulfur.
  • Dr. Nigh recommends epsom salt baths, tydroxycobalamin (vitamin B12), molybdenum, Korean ginseng
  • Dr. Nigh also recommends a specific low-sulfur diet that is customized to each patient. In some circumstances we may need to lower our intake, while we seek to restore some health, integrity, balance to the microbiome and gut, before we then re-diversify.
  • Bismuth subsalicylate (sold under the brand name Pepto-Bismol) has been shown to dramatically reduce hydrogen sulfide

Dr. Ruscio has a useful and interesting low sulfur diet handout that can be found by clicking here.

I would like to add this article is for educational purposes only – if you know or suspect you have imbalances in the microbiome, or hydrogen sulfide production/clearance then I highly recommend working with an experienced practitioner to support you through the process of understanding your underlying imbalances and strategies required to restore health.

All in all there is a lot for us to consider and this quote seems apt. to finish with:

The metabolic milieu in the lumen of the colon, however, is the result of a multitude of factors beyond dietary sulfur intake and sulcate-reducing bacteria abundance.

Resources

There is an interesting case study by Dr. Nirola Jacobi you may like to read: click here.

A brilliant article on Hydrogen SUlfide SIBO being an adaptive response: click here.

References

  • Jennifer Pichette and Jeffrey Gagnon (2016) Implications of Hydrogen Sulfide in Glucose Regulation: How H2S Can Alter Glucose Homeostasis through Metabolic Hormones
  • Tomasova et al., (2016) Gut Bacteria and Hydrogen Sulfide: The New Old Players in Circulatory System Homeostasis
  • Teigan et al., (2019) Dietary Factors in Sulfur Metabolism and Pathogenesis of Ulcerative Colitis
  • Carbinero et al., (2012) Microbial pathways in colonic sulfur metabolism and links with health and disease
  • Wallace et al., (2018) Hydrogen sulfide: an agent of stability at the microbiome-mucosa interface
  • Wang R. Physiological implications of hydrogen sulfide: a whiff exploration that blossomed
  • Fu M, Zhang W, Wu L, et al. Hydrogen sulfide (H2S) metabolism in mitochondria and its regulatory role in energy production
  • Yao et al., (2018) Modulation of colonic hydrogen sulfide production by diet and mesalazine utilizing a novel gas-profiling technology
  • Suarez et al., (1998) Bismuth subsalicylate markedly decreases hydrogen sulfide release in the human colon
  • Webster et al., (2019) Influence of short-term changes in dietary sulfur on the relative abundances of intestinal sulfate-reducing bacteria
  • Sing & Lin, (2015) Hydrogen Sulfide in Physiology and Diseases of the Digestive Tract.
  • Linden, (2014) Hydrogen Sulfide Signaling in the Gastrointestinal Tract
  • Huang et al., (2015) A cardioprotective insight of the cystathionine γ-lyase/hydrogen sulfide pathway
Share this post