H2S Production in Nature, Industry, and the Body

Hydrogen sulfide turns up almost everywhere you look: microbes pump it out of ocean mud, your own cells manufacture it as a signaling molecule, oil wells belch it as a hazardous byproduct, and yeast release it during wine fermentation. Despite its reputation as a foul-smelling poison, H₂S is one of the oldest and most versatile chemicals in biology, with roots stretching back billions of years. Understanding where it comes from and what it does means crossing boundaries between physiology, geology, industrial engineering, and even food science.

An Ancient Molecule With Deep Roots

Earth’s early atmosphere was rich in reduced sulfur compounds, and H₂S likely played a role in the chemistry that gave rise to life roughly 3.8 billion years ago. For the first seven-eighths of evolutionary history, before atmospheric oxygen accumulated, sulfide served as a major energy source for microbial life.¹ When oxygen levels surged around 600 million years ago, most sulfide-dependent organisms either went extinct, retreated into oxygen-poor niches, or repurposed their sulfide-handling biochemistry for new functions. That ancient toolkit was never fully discarded. Much of it persists in modern organisms, including humans, where H₂S now works as a signaling molecule rather than an energy currency.²

How Your Cells Make H₂S

Mammalian tissues produce hydrogen sulfide through three main enzymes. Two of them, cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE), are part of a metabolic route that processes sulfur-containing amino acids. A third enzyme, 3-mercaptopyruvate sulfurtransferase (3-MST), contributes additional production. Together these enzymes keep a low but steady supply of H₂S available throughout the body.³ The gas is made on demand and consumed quickly, so tissue concentrations stay extremely low under normal conditions.

Once released, H₂S acts on its target proteins through a chemical tweak called sulfhydration (sometimes called persulfidation). This modification attaches a sulfur group to specific spots on a protein, changing how that protein behaves. In the cardiovascular system alone, H₂S sulfhydrates enzymes, transcription factors, and ion channels, influencing everything from blood vessel tone to cell survival signals.⁴ One well-studied downstream effect is vasodilation: H₂S activates potassium channels and other proteins in blood vessel walls, causing them to relax and widen.⁵

There is also an intriguing connection to dietary restriction. In mice, cutting back on sulfur amino acids in the diet increased expression of the CSE enzyme, boosted H₂S production, and protected the liver from injury caused by restricted blood flow. When researchers blocked CSE or added the sulfur amino acids back, the protective benefit disappeared.⁶ This finding suggests that some of the health benefits linked to caloric restriction may depend, at least in part, on ramping up H₂S production.

H₂S in the Brain

The brain has its own reasons for making hydrogen sulfide. CBS and 3-MST are both present in brain tissue, and the H₂S they produce appears to participate in memory formation, inflammation control, and blood flow regulation within the brain.⁷ People with Alzheimer’s disease have notably lower H₂S levels compared to age-matched healthy individuals, which has prompted researchers to investigate whether restoring those levels might slow the disease.⁸

Some of the mechanistic details are starting to come into focus. CSE, the enzyme that makes H₂S, normally binds to normal Tau protein, which boosts its activity. In mouse models of Alzheimer’s, a mutant form of Tau fails to bind CSE, and the enzyme itself becomes depleted. Meanwhile, a downstream kinase involved in Tau phosphorylation (the process that leads to the tangles characteristic of Alzheimer’s) is normally kept in check by sulfhydration. When H₂S levels drop, that brake is released, and Tau becomes hyperphosphorylated. In these same mouse models, administering an H₂S-releasing compound improved both motor and cognitive function.⁹ These results are from animal models, not clinical trials in humans, but they outline a plausible therapeutic target.

The Gut’s Double-Edged Sulfide

Your body is not the only source of H₂S inside you. Gut bacteria, particularly sulfate-reducing bacteria, generate hydrogen sulfide as the end product of their metabolism.¹⁰ In a healthy colon, the mucus lining protects the gut wall from this sulfide and from the bacteria that produce it. But sulfide can break down that mucus by attacking the chemical bonds that hold mucin proteins together. When the mucus barrier weakens, bacteria and toxins gain access to the gut lining, which can trigger inflammation.¹¹

The link to ulcerative colitis is particularly striking. Fecal samples from people with the condition released three to four times more H₂S than samples from healthy individuals at every time point measured. Organic sulfur compounds like mucin, cysteine, and taurocholate proved to be more readily used substrates for bacterial H₂S production than inorganic sulfate.¹² Whether this excess sulfide is a cause or consequence of the disease remains debated, but the pattern is consistent and has led researchers to explore whether reducing sulfide-producing bacteria or their substrates could ease symptoms.

H₂S in the Ocean Floor

The largest natural factories for hydrogen sulfide are not living bodies but marine sediments. In the oxygen-free layers beneath the seafloor, sulfate-reducing microorganisms break down organic matter using sulfate instead of oxygen, generating sulfide as a waste product. This process, called dissimilatory sulfate reduction, is one of the dominant ways that organic carbon gets recycled in ocean sediments.¹³ The sulfide produced does not just sit there; it gets chemically or biologically reoxidized through a web of reactions that cycle sulfur back toward sulfate, forming various intermediate sulfur species along the way.

This cycle has been running for an almost incomprehensible span of time. Sulfate-reducing microorganisms have been active for at least 3.5 billion years, and recent work has revealed that their metabolic output is more varied than previously thought. About 9% of the sulfate they reduce gets diverted not to sulfide but to zero-valent sulfur, including elemental sulfur. That sulfur then supports the growth of other microorganisms, tying the sulfur cycle even more tightly into marine ecology.¹⁴

At hydrothermal vents, H₂S takes on a different role entirely. When sulfide-rich vent fluid mixes with cold, oxygenated seawater, the chemical disequilibrium provides energy for microorganisms that oxidize sulfide. These chemosynthetic bacteria form the base of a food web that operates independently of sunlight. Thermodynamic models of vent chemistry show that sulfide oxidation yields the most energy of any available chemosynthetic reaction at these sites.¹⁵ In a real sense, hydrogen sulfide powers entire ecosystems in the deep ocean.

Occasionally, sulfide reaches the surface in dramatic fashion. Off the coast of Namibia, in the Benguela Upwelling System, hydrogen sulfide periodically erupts from sediments into the water column. These events are visible from space as milky plumes of elemental sulfur. The sulfide-rich water even supports unusual photosynthetic bacteria that use sulfide rather than water as an electron source.¹⁶

Animals That Thrive in Sulfide

Most animals treat hydrogen sulfide as a poison because it shuts down the same enzyme in the mitochondria that cyanide targets. Yet some species live permanently in sulfide-rich waters and have evolved multiple strategies for coping. Researchers studying fish adapted to sulfide springs have found changes in genes related to both sulfide detoxification and the mitochondrial targets that sulfide normally poisons, suggesting that these fish defend themselves on two fronts simultaneously.¹⁷

The broader toolkit available to sulfide-adapted animals is surprisingly diverse. Some reduce how much sulfide enters their bodies through behavioral avoidance or physical barriers at their skin and gills. Others tolerate elevated internal sulfide by modifying the proteins that would otherwise be poisoned. Still others ramp up their capacity to detoxify sulfide, converting it to less harmful compounds like thiosulfate. A few species even partner with sulfur-oxidizing bacteria that consume sulfide before it can do damage.¹⁸ In many aquatic species, sulfide oxidation happens directly in the mitochondria and actually produces usable energy in the process, as long as some oxygen is available.¹⁹ These animals have, in a way, retained a version of the ancient sulfide-based energy metabolism that dominated life before the rise of oxygen.

H₂S as a Plant Signaling Molecule

Plants produce hydrogen sulfide too, synthesizing it through their own enzymatic pathways. Like animals, they use it as a gasotransmitter involved in growth, development, and stress responses. H₂S helps plants tolerate drought, high salinity, heavy metals, and temperature extremes, acting through a range of post-translational modifications on key regulatory proteins.²⁰ The fact that H₂S signaling is conserved across such different kingdoms of life underscores how fundamental this molecule is to cellular function.

Industrial Sources and the Problem of Sour Gas

Outside of biology, the biggest headache with hydrogen sulfide comes from the oil and gas industry. Many reservoirs contain “sour” gas or oil that is naturally contaminated with H₂S. The sulfide originates from microbial sulfate reduction by bacteria living in reservoir rock or from thermochemical reactions between organic matter and sulfate minerals at high temperatures deep underground.²¹ For workers, sour gas is dangerous: at low concentrations H₂S is merely foul-smelling, but at high levels it paralyzes the olfactory nerve (eliminating the warning smell) and can kill within minutes by blocking cellular respiration. Countermeasures for acute poisoning focus on binding free sulfide with compounds like hydroxocobalamin, restoring mitochondrial function with agents like methylene blue, or generating nitric oxide to mitigate downstream organ damage.²²

Industrially, the standard method for dealing with H₂S extracted from sour gas is the Claus process, which converts it into elemental sulfur. This is one of the main commercial sources of sulfur worldwide.²³ The process runs in two stages: first a portion of the H₂S is burned to produce sulfur dioxide, then the remaining H₂S reacts with that sulfur dioxide over a catalyst to yield sulfur and water. It is efficient enough to handle acid gases with high sulfide content, turning a dangerous waste stream into a commodity.

Biogas, Sewers, and Corrosion

Hydrogen sulfide also causes problems wherever organic waste decomposes under oxygen-free conditions. In anaerobic digesters used to produce biogas from sewage or agricultural waste, sulfate-reducing bacteria convert sulfate in the feedstock into H₂S, while protein-rich organic matter provides additional sulfur through degradation of amino acids.²⁴ The resulting biogas can contain enough H₂S to corrode engines and pipes and to inhibit the methane-producing microbes that make biogas valuable in the first place.²⁵

Sewer systems face a related but distinct version of the problem. H₂S generated in wastewater escapes into the air above the sewage line, where bacteria living on exposed concrete surfaces oxidize it to sulfuric acid. The acid eats away at the concrete, eventually weakening the pipe. This process, called microbially induced corrosion, is a major infrastructure concern for cities around the world.²⁶

One promising approach to cleaning H₂S from biogas is biological scrubbing. Instead of expensive chemical reagents, these systems use sulfur-oxidizing bacteria (such as species in the genus Thiobacillus) that convert dissolved sulfide into sulfate or elemental sulfur. In one system tested at a wastewater treatment facility, a biological scrubber reached steady-state operation within 14 days and consistently removed over 99% of the H₂S from digester biogas.²⁷ These systems pair a gas-liquid contact tower with an aeration tank, cycling sulfide-laden liquid back through aerobic conditions where bacteria break it down.²⁸

Therapeutic H₂S Donors

Given that H₂S relaxes blood vessels, reduces inflammation, and protects against cell death, pharmaceutical researchers have been trying to design compounds that deliver it in a controlled way. Animal and cell-culture experiments have shown that H₂S can prevent harmful changes in blood vessel linings, reduce the stickiness of vessel walls to immune cells, and stabilize the fatty plaques that cause heart attacks.²⁹ The challenge is targeting: a compound that releases H₂S everywhere in the body would cause blood pressure to plummet. Researchers are working on donors that release sulfide only in specific tissues or in response to specific biochemical triggers. None have reached widespread clinical use yet, but the cardiovascular and neurological evidence has kept interest high.

Seeing H₂S in Living Cells

Part of the difficulty in studying H₂S is measuring it. The gas is produced in tiny amounts, consumed rapidly, and reacts with many things in its environment. Traditional detection methods required grinding up tissue samples, which destroyed spatial information. A newer generation of fluorescent probes offers a different approach: small molecules that change their fluorescence when they react with H₂S, allowing researchers to watch sulfide production happen in real time inside living cells.³⁰ One family of these probes was sensitive enough to detect the tiny burst of H₂S produced by human endothelial cells when stimulated with a growth factor, giving researchers a window into signaling events that had previously been invisible.³¹ Better measurement tools have, in turn, refined the field’s understanding of how much H₂S cells actually produce and where, resolving earlier debates that were muddied by crude detection methods.

The Rotten-Egg Problem in Winemaking

For winemakers, hydrogen sulfide is one of the most common and feared off-aromas. Yeast naturally produce H₂S during fermentation, and if concentrations creep above the detection threshold, the wine develops the unmistakable smell of rotten eggs.³² How much H₂S gets made depends heavily on yeast strain and on how much usable nitrogen is available in the grape juice. When nitrogen runs low, yeast ramp up sulfur metabolism, and H₂S production surges. The damage does not stop with the egg smell, either: H₂S reacts with other compounds in the fermenting wine to form additional volatile sulfur molecules that contribute aromas reminiscent of cooked onions and overcooked vegetables, and these secondary products can linger even after the H₂S itself has dissipated.³³ Winemakers manage the problem by selecting low-H₂S yeast strains, supplementing juice with nitrogen, and treating finished wine with copper fining, which binds free sulfide. Getting the balance right is more art than science, and a poorly managed fermentation can leave sulfur faults that no amount of post-treatment fully erases.