Coral bacteria make steroids that transiently reprogram immunity during heat stress

Coral-associated bacteria of the genus Endozoicomonas can synthesize testosterone and progesterone from cholesterol, while laboratory exposure to these steroids temporarily strengthened selected innate immune transcriptional responses in heat-stressed corals. Multi-omics, bacterial culture and coral experiments reveal a previously unrecognized metabolic link between a common coral bacterium, steroid hormones and the host response to acute thermal stress. The separate experiments do not, however, establish that bacterial hormone production improves coral survival or prevents disease in the field.

The study began with field sampling of Acropora pharaonis colonies at Saadiyat Reef in the Arabian Gulf off Abu Dhabi. Colonies were monitored for six months and sampled in June, August and October 2016, when water temperatures were 32 °C, 34 °C and 27 °C, respectively. The 32 °C sampling represented early thermal stress with preliminary signs of white syndrome on some colonies, 34 °C represented severe stress and further disease progression, and 27 °C represented recovery. Researchers collected visibly healthy tissue at all three temperatures, plus white-syndrome lesion tissue and healthy-appearing tissue within two centimetres of lesions at 34 °C. They combined 16S ribosomal RNA gene sequencing, shotgun metagenomics and untargeted metabolomics to characterize the coral holobiont, comprising the animal host, its algal symbionts and associated microorganisms.

At 34 °C, the holobiont metabolome was clearly different from the metabolomes at 32 °C and 27 °C. The latter two clustered together despite being collected four months apart, whereas lesion and adjacent samples showed substantial intercolony variation and significant separation from healthy tissue. The bacterial community was comparatively resistant to temperature alone: lesion samples differed significantly from all healthy samples, but the major compositional change was associated with disease progression rather than increasing temperature. Members of Endozoicomonadaceae represented an average 60% of the bacterial community in healthy samples and persisted at both elevated temperatures. Their relative abundance was only 1.3% at white-syndrome lesions, while Saprospiraceae and Rhodobacteraceae accounted for 39% and 23%, respectively, consistent with a dysbiotic community enriched in potentially opportunistic organisms.

Metagenome-assembled genomes were used to identify metabolic functions associated with these bacteria. An Endozoicomonas genome designated MAG10 was 91% complete and had 1.4% contamination. Its relative abundance in healthy samples ranged from 35% to 43%, before falling to 0.8% in lesion samples. A pangenome assembled from 29 Endozoicomonas genomes and assembled genomes contained 34,846 gene clusters. It confirmed previously proposed capacities for symbiosis-associated functions, vitamin and amino-acid synthesis, antioxidant production and nutrient acquisition. It also revealed cholesterol-binding and transport genes, enzymes involved in steroid degradation and a 17β-hydroxysteroid dehydrogenase capable of converting androstenedione into testosterone. Within the field metagenomes, MAG10 was the only bacterium carrying the testosterone-degradation gene kstD and the 17β-hydroxysteroid dehydrogenase implicated in testosterone synthesis.

Culture experiments then demonstrated steroid-conversion capacities in three Endozoicomonas isolates from different coral hosts and locations: E. acroporae AT381, isolated from Acropora kenti on the Great Barrier Reef; E. acroporae Acr14 from Acropora; and E. montiporae CL-33 from Montipora off southern Taiwan. At 26 °C and 34 °C, all three strains converted androstenedione into testosterone. They also catabolized testosterone into androstenedione and downstream products leading toward the tricarboxylic acid cycle, although Acr14 performed that transformation only at 34 °C. High-resolution mass spectrometry showed that the bacteria could convert cholesterol into terminal steroids. AT381 produced progesterone, testosterone and androstenedione at both temperatures, while the products formed by the other strains changed with temperature. The researchers proposed a pathway in which cholesterol-derived intermediates branch toward progesterone through pregnenolone or toward testosterone through androstenedione, although genomic mining did not identify every reaction in the proposed pathway.

The field metabolome contained a related but not identical pattern. Most steroids decreased as temperature rose, and at 34 °C many were near background levels. Progesterone, testosterone, estradiol-17β and selected bacterial steroid products were exceptions, reaching their highest relative abundances at 34 °C. Because the sampling occurred outside the Arabian Gulf’s March-to-May spawning season, and because progesterone and testosterone precursors were depleted at the highest temperature, the authors considered microbial production a plausible additional source. The cultures establish that Endozoicomonas can make these steroids and that the process is temperature dependent in some strains. The field data, however, do not directly quantify the proportion of measured hormone contributed by Endozoicomonas rather than by the coral or its algal symbionts.

To test whether coral tissue could take up the hormones, researchers exposed fragments of Acropora downingi to carbon-13-labelled testosterone. Corals accumulated labelled hormone at 10 nM, 100 nM and 1 µM, although its relative abundance after 48 hours was much lower in the two higher-concentration treatments, consistent with saturation. Endogenous in situ testosterone levels closely matched the 10 nM exposure, so the investigators used 10 nM for both testosterone and progesterone in the subsequent heat-stress experiment. Daily measurements of the algal symbionts’ maximum photosynthetic efficiency indicated that hormone exposure did not produce measurable photophysiological toxicity over five days. This uptake experiment showed that coral fragments absorbed the hormones; it did not establish that bacteria supplied the effective dose inside a naturally assembled holobiont.

In the immune-response experiment, fragments from five A. downingi colonies were assigned to heat-stress controls, heat stress plus testosterone, or heat stress plus progesterone. Temperature rose from 28 °C to 33 °C over three hours, and hormones were administered before the ramp and again when the corals reached 33 °C. RNA sequencing at three time points identified 39 innate-immunity-related genes with significant expression differences among treatments. At 28 °C, steroid-treated fragments resembled untreated controls, suggesting that the hormones alone did not trigger the measured response. At 33 °C, however, both hormones strengthened the immune transcriptional response induced by heat alone. Compared with heat-stress controls, treated corals showed higher expression of signalling molecules including TNFR1, TRAF2, NF-κB subunits and SYK, together with the cell-survival effectors BIRC2 and BIRC3.

The response was not simply uniform amplification of inflammation. Hormone supplementation reduced expression of TRAF6 relative to the heat-stress-only group, while progesterone increased the negative regulators CISH and SOCS2. The authors interpreted this pattern as a shift toward a survival-oriented state that strengthened selected innate immune pathways while constraining potentially excessive inflammatory signalling. By the final sampling point, 24 hours after heat exposure began, most steroid-associated transcriptional signatures had returned to baseline, indicating transient rather than sustained modulation. The work shows that Endozoicomonas possesses the metabolic capacity to produce host-active steroids and that exogenous steroids can alter coral immune-gene expression during heat stress. Because the bacterial production, coral uptake and immune experiments were conducted separately, the study did not directly demonstrate a complete causal chain from bacterial hormone secretion to immune protection. Whether these natural hormone supplies affect field survival, disease resistance or reef-scale coral resilience remains to be tested across naturally variable environments and microbial communities.

Subject of Research: Microbial steroid metabolism and coral innate immunity during thermal stress

Article Title: Steroid hormones produced by coral-associated Endozoicomonas influence coral immune response during thermal stress

Article References: Mohamed, A. R., Ochsenkühn, M. A., Haydon, T. D., Abdelrazig, S., Coe, L. S. Y., Mochales-Riaño, G., Jo, W. S., Healy, A. R., Abrego, D., Raina, J.-B., Burt, J. A., & Amin, S. A. (2026). Steroid hormones produced by coral-associated Endozoicomonas influence coral immune response during thermal stress. Nature Microbiology. https://doi.org/10.1038/s41564-026-02494-1

Image Credits: AI Generated

DOI: 10.1038/s41564-026-02494-1

Keywords: coral microbiome, Endozoicomonas, thermal stress, steroid hormones, coral immunity, metagenomics, metabolomics, white syndrome, coral holobiont, immune transcription, Steroid, hormones