A microbiome–epigenome axis: SRB‐derived H ₂ S suppresses OsHDA710 to activate drought responses in rice

This commentary highlights the recent identification of exogenous application of sodium butyrate, as a histone deacetylase inhibitor that improves rice drought resistance via enriching sulfate-reducing bacteria to elevate rhizosphere-derived H2S production, which in turn represses OsHDA710 expression and activity to activate drought responses. Hydrogen sulfide (H2S) has emerged alongside nitric oxide as a pivotal gaseous signaling molecule in plants, exerting broad influence over growth, development, and adaptive responses to abiotic stresses, including drought, salinity, and heavy-metal toxicity (Zhang et al., 2021). Despite growing mechanistic insight, agricultural use of H2S is limited by delivery challenges: Fast-acting donors such as sodium hydrosulfide (NaHS) generate short-lived spikes and can be phytotoxic at elevated concentrations. Recently, the study by Chen et al. (2025) addresses this limitation by identifying an indirect, microbiome-mediated route for sustained H2S generation in the rhizosphere, thereby linking soil microbiology, gas signaling, and chromatin regulation into a coherent framework for drought resilience (Figure 1). NaB mobilizes rhizosphere SRB to produce sustained H2S that represses OsHDA710 and activates drought-responsive transcription and physiology. NaB application remodels the rhizosphere, enriching SRB and increasing dsrA/dsrB expression and sulfite reductase activity, which drives dissimilatory sulfate reduction and sustained H2S release. Elevated rhizosphere H2S represses the histone deacetylase OsHDA710, thereby increasing H4K5 acetylation at the promoters of drought-responsive genes (e.g., OsAsr2, OsMSr2, OsANN1) and consequently enhancing their transcriptional activation. The resulting physiological responses include reduced stomatal conductance, lower malondialdehyde, and elevated catalase activity, which together enhance drought tolerance while incurring a seedling growth penalty (growth-tolerance trade-off). Experimental evidence this regulatory pathway includes microbial community profiling, sulfate/H₂S soil chemistry analyses, dsr gene expression, CRISPR/Cas9-generated mutants and OsHDA710 overexpression lines, ChIP assays for H4K5ac, and physiological measurements. Rhizosphere microbes and plants engage in close interactions, which can directly influence key physiological processes such as plant growth, development, and resistance to abiotic stresses (Zeng et al., 2025). Chen et al. show that exogenous sodium butyrate (NaB), a short-chain fatty acid salt, remodels rhizosphere microbial communities at the phylum level and, crucially, enriches sulfate-reducing bacteria (SRB). Molecular indicators, upregulated dsrA/dsrB expression, and increased sulfite reductase activity correlate with a prolonged elevation of rhizosphere H2S that substantially outlasts NaHS treatment. Soil chemical analyses further support a microbiological origin of the gas: Declining sulfate (SO42−) parallels rising H2S, consistent with SRB-driven dissimilatory sulfate reduction under hypoxic paddy conditions. Because SRB are obligate anaerobes well adapted to flooded soils, they represent an effective and field-relevant “H2S factory” capable of providing sustained gas release without the toxicity associated with bolus donors (Muyzer and Stams, 2008), promising a strategy for improving rice stress resilience. Functionally, both NaB and NaHS treatments confer enhanced drought tolerance in rice, as evidenced by reduced stomatal conductance, lower malondialdehyde content, and heightened catalase activity, indicators of attenuated oxidative stress, albeit at the cost of inhibited seedling growth (Chen et al., 2025). Transcriptomic profiling reveals substantial overlap in drought-responsive genes induced by both treatments (for example, OsAsr2, OsMSr2, and OsANN1), implicating H2S as a central regulator that shifts plants from growth toward protective stress programs. This trade-off between resource allocation for growth and for defense is a recurring theme in plant adaptation (Zhang et al., 2025), and the SRB-mediated H2S pathway offers a tunable lever that could be exploited to optimize resilience with minimal yield penalty. A particularly compelling contribution of Chen et al. is the mechanistic connection between H2S and chromatin dynamics. Histone acetylation, governed by the antagonistic activities of histone acetyltransferases and deacetylases (HDACs), is a key determinant of stress-responsive transcription (Chang et al., 2020). Among rice HDACs, OsHDA710 was uniquely and consistently downregulated by both NaB and NaHS treatments. Strikingly, OsHDA710 binds directly to the TGACC motif within promoter regions of its target genes, deacetylating H4K5 and thereby repressing transcription. NaB therefore acts through two complementary routes: Directly, by serving as an HDAC inhibitor, and indirectly, by enriching SRB that elevate rhizosphere-derived H2S, which in turn represses OsHDA710 expression and activity. Biochemical assays and chromatin immunoprecipitation confirm increased H4K5 acetylation at promoters of drought-tolerance genes following NaB/H2S exposure, thereby connecting microbial metabolism to targeted epigenetic activation of stress genes. Analogous pathways have been described for nitric oxide, which inhibits HDACs and induces genome-wide hyperacetylation of stress-responsive loci (Mengel et al., 2017; Ageeva-Kieferle et al., 2021). This dual mode of action, chemical inhibition combined with microbiome-driven repression of OsHDA710, constitutes a multilayered regulatory mechanism that enhances transcriptional responsiveness under drought stress. Chen et al.'s work opens several fertile avenues for future research and application. From an agronomic perspective, it is essential to define field-compatible regimes: What NaB dosages and application schedules maximize SRB-mediated H2S production without incurring unacceptable growth suppression? Soil type, baseline microbiome composition, and redox dynamics will likely influence the specificity and efficacy of NaB across agroecosystems. Thus, assessing the universality of SRB enrichment and H2S production across diverse soils and cropping systems is a priority. Mechanistically, the molecular interface between H2S and the acetylation machinery remains to be resolved. In mammals, NO-dependent S-nitrosylation regulates HDACs (Nott et al., 2008; Okuda et al., 2015); in plants, H2S can persulfidate transcription factors such as ABI4 to modulate ABA signaling (Zhou et al., 2021). Does H2S directly persulfidate OsHDA710 or other chromatin regulators to alter their activity, stability, or DNA affinity? Could H2S influence additional histone marks (e.g., methylation) or other epigenetic modifiers, thereby broadening its regulatory reach? Addressing these questions will clarify whether H2S acts primarily as a direct post-translational modifier of chromatin proteins or as a broader redox signal that reshapes epigenomic landscapes. In conclusion, Chen et al. deliver an elegant, multidisciplinary study that connects rhizosphere ecology, gaseous signaling, and epigenetic control to propose a novel strategy for improving drought tolerance in rice. By demonstrating that NaB can mobilize native SRB communities to generate sustained H2S and that this gas modulates histone acetylation via repression of OsHDA710, the work advances both fundamental understanding and translational potential. It suggests new microbiome–epigenome interventions that could complement genetic and management approaches to crop resilience, while highlighting critical questions about dosage, specificity, and mechanistic detail that must be resolved before field implementation. This work is supported by grants from the Natural Science Foundation of China (32470299) and the Jiangsu Natural Science Foundation for Distinguished Young Scholars (BK20220084). The authors declare no conflicts of interest. J.Z., M.Z., and Y.X. wrote the paper. J.Z., M.Z., and Y.X. prepared the figure. All authors read and approved the content.