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Overgrowth of Hydrogen Sulfide Bacteria - A Gut Imbalance or The Bodies Response To High Oxidative Stress From Chronic Infections

Updated: Jan 15

This article is not intended to be healthcare or medical advice. Seek the advice of your Primary Care Physician or an M.D. before starting any health related regimen.

One of the most common patterns i see in Long Haul and ME CFS folks is overgrowth of hydrogen sulfide bacteria in stool / microbiome results. I have been suspicious why this has been a pattern, and had my own beliefs around it (the body trying to get more access to sulfur due to sulfur transulfuration pathway issues).

I often see upregulations on the CBS gene, mutations in CTH in these folks, low B6, low serine, high taurine or compromised enzymes in other parts of sulfur metabolism like SUOX, SULT1A1, SULT2A1, PAPSS2, etc.

Interestingly, i also see this pattern in older folks (excess H2S bacteria like desulfovibrio [2,3,4]) who deal with neuro degenerative conditions like Parkinson's, AD, various cognitive compromises, etc. There are many papers [2,3,4] that illustrate the interaction of H2S on brain related activities that induce Parkinsons - H2S activates the TRPV receptors which then overstimulate the NMDA receptors (GRIN genes).

One of the most definitive patterns i have seen in Long Haul and ME CFS folks is high levels of oxidative stress, and this is also been reported by a number of ME CFS researchers like Pall, and others over many years.

I recently came across a study [1], although dated does a good job of exploring various ways the body uses H2S. It explores how viral infections (HHV6, HIV, etc) are associated with high levels of oxidative stress, and how H2S is used by the body to counter high levels of oxidative stress. In this process, copper is needed, but copper absorption has been shown to be dramatically reduced in the presence of sulfate. The inference is that the body may run out of what it needs to continue to use H2S as intervention to reduce oxidative stress (copper). Low copper is found in some with Long Haul, and copper is one of the most controversial minerals to assess nutritional status.

H2S: From Neuro Degenerative Gas To An Intelligent Response To Counter Oxidative Stress

"An increasing number of studies have established hydrogen sulfide (H2S) gas as a major cytoprotectant and redox modulator....... Bacterial and viral infections are often accompanied by changes in the redox physiology of both the host and the pathogen. Emerging studies indicate that bacterial-derived H2S constitutes a defense system against antibiotics and oxidative stress. The H2S signaling pathway also seems to interfere with redox-based events affected on infection with viruses. This review aims to summarize recent advances on the emerging role of H2S gas in the bacterial physiology and viral infections."[1]

"In 1960s, co-culture experiments with Desulfovibrio desulfuricans/Pseudomonas aeruginosa and Escherichia coli/Staphylococcus aureus provided the first evidence of a possible “protective” role of H2S in bacteria. H2S produced by D. desulfuricans was demonstrated to be the “diffusible” factor responsible for imparting pseudomonas the ability to resist heavy metal (e.g., mercury) toxicity"[1]

CBS, B6 Involved

"The biogenesis of H2S has been mainly attributed to the transsulfuration pathway. Two enzymes constitute this pathway namely cystathionine beta synthase or CBS and cystathionine gamma lyase or CSE. Both the enzymes uses pyridoxal l- phosphate (PLP-B6) as cofactor and are hence sensitive to common PLP dependent enzyme inhibitors like hydroxylamine......"[1]

B6 Toxic Inhibitors like Hydroxylamines Also Inhibit Important Genes Like G6PD and GSR

"The toxic potency of three industrially used hydroxylamines was studied in human blood cells in vitro. The parent compound hydroxylamine and the O-ethyl derivative gave very similar results. Both compounds induced a high degree of methemoglobin formation and glutathione depletion. Cytotoxicity was visible as Heinz body formation and hemolysis. High levels of lipid peroxidation occurred, in this respect O-ethyl hydroxylamine was more active than hydroxylamine. In contrast H2O2 induced lipid peroxidation was lowered after O-ethyl hydroxylamine or hydroxylamine treatment, this is explained by the ferrohemoglobin dependence of H2O2 induced radical species formation. Glutathione S-transferase (GST) and NADPH methemoglobin reductase (NADPH-HbR) activities were also impaired, probably as a result of the radical stress occurring. The riboflavin availability was decreased. Other enzyme activities glutathione reductase (GSR), glucose 6-phosphate dehydrogenase (G6PDH), glucose phosphate isomerase and NADH methemoglobin reductase, were not or only slightly impaired by hydroxylamine or O-ethyl hydroxylamine treatment. A different scheme of reactivity was found for N,O-dimethyl hydroxylamine. This compound gave much less methemoglobin formation and no hemolysis or Heinz body formation at concentrations up to and including 7 mM. Lipid peroxidase induction was not detectable, but could be induced by subsequent H2O2 treatment. GST and NADPH-HbR activities and riboflavin availability were not decreased. On the other hand GR and G6PDH activities were inhibited. These results combined with literature data indicate the existence of two different routes of hematotoxicity induced by hydroxylamines. Hydroxylamine as well as O-alkylated derivatives primarily induce methemoglobin, a process involving radical formation. The radical stress occurring is probably responsible for most other effects. N-alkylated species like N,O-dimethyl hydroxylamine primarily lead to inhibition of the protective enzymes G6PDH and GSR. Since these enzymes play a key role in the protection of erythrocytes against oxidative stress a risk of potentiation during mixed exposure does exist.


Hydroxylamine Can Cause Hemolytic Anemia

"Hydroxylamine acts as a reducing agent when absorbed systemically, producing methemoglobin and the formulation of Heinz bodies in the blood. It can induce hemolytic anemia. It inhibits platelet aggregation and is a nitric oxide vasodilator." [7]

Hydroxylamine used in Photography, Nylons, Chemistry, Soaps, & De Hairing Agents

"Hydroxylamine is used as a reducing agent in photography, in the synthesis of nylons, synthetic and analytical chemistry, as an antioxidant for fatty acids and soaps, and as a dehairing agent for hides. In addition, hydroxylamine is used in the production of cyclohexanone oxime, an isomer of caprolactam, which is an intermediate in the production of nylon-6. In the semiconductor industry, hydroxylamine can be a component of a solution that dissolves a photoresist following lithography. Hydroxylamine can also be used to selectively cleave asparaginyl-glycine peptide bonds (Gross, 1985)"[8]

Serine Can Be Depleted, And Heme is Involved Again To Help Produce H2S

"CBS catalyses the first and committed step of the transsulfuration pathway which canonically, leads to the production of cystathionine from serine and homocysteine. However, when serine is replaced by cysteine, H2S is produced. CBS can generate H2S by additional reactions including β replacement of cysteine by water to form serine and β replacement of cysteine by a second molecule of cysteine to form lanthionine. In addition to PLP, human CBS also contains heme which acts as a redox dependent gas sensor. Apart from this the heme moiety also functions as a “metabolic switch” committing the pathway toward H2S production. Under ER stress, heme oxygenase is induced (HMOX), which catabolises heme in presence of molecular oxygen to produce biliverdin and CO, the later one binds to heme cofactor of CBS and inhibits its activity. This inhibition leads to low levels of cystathionine and increased levels of homocysteine. These metabolites cue the second enzyme, CSE, to increase the production of H2S from cysteine and homocysteine further highlighting the metabolic flexibility of this pathway."[1]

DAO (Copper Dependent) is Involved in H2S Production In the Brain

"...In addition to l-cysteine, H2S production was observed in brain homogenates when d-cysteine was used as a substrate. This led to the discovery of new pathway involving peroxisomal enzyme d-amino oxidase (DAO) in H2S biogenesis. d-cysteine is metabolized by DAO to 3-mercaptopyruvate (3MP), which then translocates to mitochondria where it is converted to H2S and pyruvate. It has been reported that the production of H2S from d-cysteine is ~ 60 times greater in comparison to l-cysteine. Since DAO is only localized to the brain and the kidney, the functionality of the 3MST/DAO pathway for the production of H2S is only relevant to these tissues."[1]

H2S Can Act as a Free Radical Scavenger

"....H2S acts as a cytoprotective molecule and has the ability to directly scavenge free radical species (74). Owing to its nucleophilic properties, H2S has been shown to react with oxygen (O2), ROS, peroxynitrite (ONOOH/ONOO–), and hypochlorite (HOCL/–OCL) (65,75). While these studies indicate a direct scavenging of oxidants by H2S in vitro, the low concentrations of H2S (10 nM to 3 μM) compared to other antioxidants (GSH; 1–10 mM) in vivo raised substantial concerns about its role in remediating ROS/RNS under biologically relevant conditions. Alternatively, H2S has been shown to increase GSH production by enhancing the inward transport of cystine and inducing the expression of GSH-biosynthetic enzyme, GCL (γ-GCS). This increase in intracellular GSH could be another mechanism by which H2S indirectly participates in protection from oxidative stress."[1]

Viral Infections Are Associated With Increased Levels Of Oxidative Stress

"Oxidative stress has been linked to vast group of etiological agents that cause acute and chronic diseases such as infection with viruses, bacteria, and parasites. Viral and bacterial infections in particular have been linked to induce ROS/RNS production, alteration in metabolic pathways, and leading to several disease associated complications.....In case of viral infections, induction of oxidative stress inside host is a prerequisite for successful infection and long term viral replication..... A study indicates that the oxidative state of the host cells provides an environment permissive for viral replication. Using mice models, it has been shown that influenza A (RNA virus) infection creates redox imbalance by decreasing the levels of GSH, vitamins C, and vitamin E..... Based on these studies, it has been proposed that antioxidant strategies can be utilized to target viral replication and to decrease viral induced oxidative stress to control pathological manifestations.

The role of oxidative stress has been extensively studied in retroviruses such as HIV-1 (Human Immunodeficiency Virus). Studies have shown that HIV-1 replication induces ROS generation and decreases cellular antioxidants such as GSH and Trx, and modulates immunopathogenesis during AIDS progression . Plasma and peripheral blood mononuclear cells (PBMCs) of AIDS patients show reduction in concentration of other major antioxidants like cysteine, methionine, vitamins C and E, along with elevated levels of lipid peroxidation products."[1]

Copper Absorption Is Dramatically Reduced In The Presence of Sulfur!!!!

"Uptake from buffered saline solutions at neutral pH (but not at lower pH) is inhibited by either d- or l-histidine, unaltered by the removal of sodium ions, and inhibited by ∼90% when chloride ions are replaced by gluconate or sulfate."[5]

The presence of high levels of hydrogen sulfide producing bacteria can now be viewed as a hint of high levels of oxidative stress, rather than just a gut imbalance. There are various way to support the bodies natural systems to combat excess oxidative stress typically done through Super Oxide Dismutase, Thirodoxin, Glutathione, PON1, and Catalase. The excess production of high levels of H2S on an ongoing basis could be another reason why infections and high levels of oxidative stress can lead to neuro degeneration, an intended short term solution by the body causes other issues (NMDA receptor over activation from H2S). Also, interesting, is coppers role to help produce the H2S, as well as the role of heme (which is also copper dependent). It appears if the body is short of copper, heme shortages will result, and then cause an inability to clear oxidative stress. Yet the body is less effective at absorbing copper when sulfate is present in the GI tract from H2S producing bacteria. Likewise, shortages in heme for other reasons could also cause the body to not be able to clear high levels of oxidative stress.

I encourage you to explore the references listed below, and if you would like to discuss strategies, lab results, genetics related to oxidative stress, or hydrogen sulfide production, please schedule an appointment on line or send me a note requesting an appointment.


1. Hydrogen Sulfide in Physiology and Pathogenesis of Bacteria and Viruses. Virender Kumar Pal,# Parijat Bandyopadhyay,# and Amit SinghiD,*IUBMB Life. Author manuscript; available in PMC 2018 Jul 3.

IUBMB Life. 2018 May; 70(5): 393–410. Published online 2018 Mar 30. doi: 10.1002/iub.1740

PMCID: PMC6029659. EMSID: EMS78422. PMID: 29601123

2. Hydrogen Sulfide Produced by Gut Bacteria May Induce Parkinson's Disease. Kari Erik Murros. Cells. 2022 Mar 12;11(6):978. doi: 10.3390/cells11060978. PMID: 35326429. PMCID: PMC8946538.

3. Desulfovibrio Bacteria Are Associated With Parkinson’s Disease. Kari E. Murros1*† Vy A. Huynh. Front. Cell. Infect. Microbiol., 03 May 2021. Sec. Microbiome in Health and Disease. Volume 11 - 2021 |

4. New hope for Parkinson's disease treatment: Targeting gut microbiota. Hong-Xia Fan, Shuo ShengFeng Zhang. First published: 13 July 2022.

5. Acquisition of dietary copper: a role for anion transporters in intestinal apical copper uptake.

Published in American Journal of… 1 March 2011. Biology, Medicine. American journal of physiology. Cell physiology

6. Two mechanisms for toxic effects of hydroxylamines in human erythrocytes: involvement of free radicals and risk of potentiation. C T Evelo, A A Spooren, et. al. Blood Cells Mol Diseases. 1998 Sep;24(3):280-95. doi: 10.1006/bcmd.1998.0194. PMID: 10087986. DOI: 10.1006/bcmd.1998.0194

8. Shayne C. Gad, in Reference Module in Biomedical Sciences, 2023

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