Search Results (300)

Hydrogen sulfide (H₂S) can be produced from the metabolism of foods containing sulfur in the gastrointestinal tract (GIT). At low doses, H₂S regulates the gut microbial community and supports GIT health, but depending on dose, age, and individual health conditions, it may also contribute to inflammatory responses and gut barrier dysfunction. Controlling H₂S production in the GIT is important for maintaining a healthy gut microbiome. However, research on this subject is limited due to the gaseous nature of the chemical and the difficulty of accessing the GIT in situ. In the present ex vivo experiment, we used a single-dose sodium sulfide preparation (SSP) as a H₂S precursor to test the effect of H₂S on the human gut microbiome across different age groups, including breastfed infants, toddlers, adults, and older adults. Metagenomic sequencing and metabolite measurements revealed that the development of the gut microbial community and the production of short-chain fatty-acids (SCFAs) were age-dependent; that the infant and the older adult groups were more sensitive to SSP exposure; that exogeneous SSP suppressed SCFA production across all age groups, except for butyrate in the older adult group, suggesting that H₂S selectively favors specific gut microbial processes. Full article

The nuclear receptors pregnane X receptor (PXR), constitutive androstane receptor (CAR), and farnesoid X receptor (FXR) regulate the hepatic metabolism of androstenone, a testicular steroid that accumulates in the fat of intact male pigs and causes boar taint. This study evaluated natural product-derived compounds and conventional agonists targeting these nuclear receptors for their effects on androstenone metabolism in primary hepatocytes from slaughter-weight boars, to assess their potential as treatments for boar taint. Cells were incubated with natural products, conventional agonists, or dimethyl sulfoxide (DMSO; control), then being treated with androstenone. Culture media and cells were analyzed to assess changes in androstenone metabolism and gene expression. UGT1A6 was upregulated by treatments targeting both PXR and CAR and downregulated by FXR agonists. Additionally, PGC1α and NR2F1 were downregulated by compounds targeting PXR/CAR, while FXR and NR0B2 were upregulated and HNF4α downregulated by treatments acting on FXR. The natural products diallyl sulfide (DAS) and (Z)-guggulsterone (GUG) increased overall androstenone metabolism (DAS, GUG) and the production of Phase I androstenol metabolites (DAS), but only in hepatocyte culture replicates that responded positively to these treatments. Although gene expression was similar between positive-response and negative/non-responsive replicates following treatments, negative/non-responsive replicates for several treatments had higher basal expression of UGT2B31, UGT2A1, and SIRT1 and lower basal expression of FXR, PXR, and NR0B1 compared to positive-response replicates. These findings suggest that DAS and GUG may be promising treatments for boar taint, specifically in animals with lower basal rates of androstenone metabolism and higher expression of key nuclear receptors. Full article

In recent years, gut microbiota has emerged as a critical regulator of gastrointestinal health and disease, with its role in inflammatory bowel disease (IBD)—including Crohn’s disease and ulcerative colitis—being particularly significant. Among the many factors influencing the gut microbiota, dietary components such as fibers, fats, and polyphenols have received substantial attention. However, nitrogen-containing compounds, such as amino acids, nitrates, urea, and even nucleic acids, such as purines, remain underexplored despite their integral role in shaping microbial ecology, host metabolism, and immune responses. Some of these compounds are metabolized by gut bacteria into bioactive molecules such as short-chain fatty acids, ammonia, and nitric oxide, which exert diverse effects on mucosal integrity and inflammation. IBD pathophysiology is characterized by chronic inflammation, microbial dysbiosis, and compromised epithelial barriers. Nitrogen metabolism contributes significantly to these processes by influencing microbial composition, metabolite production, and host immune pathways. The breakdown of various nitrogen-containing compounds in the body leads to the production of byproducts, such as ammonia and hydrogen sulfide, which have been implicated in mucosal damage and immune dysregulation. At the same time, nitrogen-derived molecules, such as short-chain fatty acids and nitric oxide, exhibit protective effects, underscoring the dual role of dietary nitrogen in health and disease. This narrative review highlights the complex interactions between dietary nitrogen sources, gut microbiota, and IBD pathogenesis. We summarize the mechanisms by which nitrogen compounds influence microbial dynamics, identify their contributions to inflammation and barrier dysfunction, and explore their therapeutic potential. Multidisciplinary approaches integrating clinical, metabolomic, and microbiome research are essential to unravel the full scope of nitrogen’s role in gut health and identify novel therapeutic targets. Full article

Despite being recognized as toxic in anaerobic systems, sulfide’s potential to enhance hydrogen fermentation via microbial modulation remains underexplored. This study evaluated the combined effects of sulfide concentration (0–800 mg S/L) and heat pretreatment on hydrogen production during dark fermentation (DF). Without pretreatment, hydrogen yield reached 83 ± 2 mL/g COD at 0 mg S/L but declined with increasing sulfide, becoming negligible at 800 mg S/L. In contrast, heat-pretreated inocula showed markedly improved performance: peak cumulative production (4628 ± 17 mL) and yield (231 ± 1 mL/g COD) were attained at 200 mg S/L, while the maximum production rate (1462 ± 64 mL/h) occurred at 400 mg S/L. These enhancements coincided with elevated acetic and butyric acids, indicating a metabolic shift toward hydrogen-producing pathways. The microbial analysis of heat-pretreated samples revealed an enrichment of Clostridium butyricum (from 73.1% to 87.5%) and Clostridium perfringens, which peaked at 13.5% at 400 mg S/L. This species contributed to butyric acid synthesis. At 800 mg S/L, Clostridium perfringens declined sharply to 0.6%, while non-hydrogenogenic Levilinea saccharolytica proliferated, correlating with reduced butyric acid and hydrogen output. These findings indicate that sulfide supplementation, when combined with heat pretreatment, selectively restructures microbial communities and metabolic pathways, enhancing DF performance. Full article

The transsulfuration pathway plays a central role in the regulation of sulfur metabolism and contributes to the maintenance of cellular homeostasis. Starting from homocysteine, a sulfur-containing amino acid derived from methionine via the methionine cycle, this metabolic pathway supports the biosynthesis of cysteine and other downstream products, such as taurine, serine, reduced glutathione and the gasotransmitter hydrogen sulfide (H₂S). The most common disruption of this pathway leads to hyperhomocysteinemia (HHcy), a well-known risk factor for the development of cardiometabolic diseases and other pathological conditions. In this context, identifying effective pharmacological strategies is crucial. Based on both preclinical and clinical evidence, this review provides an updated overview on the role of folates in restoring transsulfuration balance in HHcy and explores the potential effects of downstream products (such as serine, taurine, and precursors of glutathione) under HHcy conditions. Finally, it examines the pharmacological properties of H₂S-donors in cultured cells exposed to HHcy and in animal models of HHcy. This summary of the literature offers new perspectives for the treatment of HHcy and the prevention of its associated multiorgan complications. Full article

This study addresses the microbial corrosion of cement-based materials in coastal urban sewer networks, systematically investigating the kinetic mechanisms of sulfur biogeochemical cycling under seawater infiltration conditions. Through dynamic monitoring of sulfide concentrations and environmental parameter variations in anaerobic pipelines, a multiphase coupled kinetic model integrating liquid-phase, gas-phase, and biofilm metabolic processes was developed. The results demonstrate that moderate salinity enhances the activity of sulfate-reducing bacteria (SRB) and accelerates sulfate reduction rates, whereas excessive sulfide accumulation inhibits SRB activity. At 35 °C, the mathematical model coefficient “a” for sulfate reduction in the reactor with 3 g/L salinity was significantly higher than those in reactors with 19 g/L and 35 g/L salinities, with no significant difference observed between the latter two. Overall, high sulfate concentrations do not act as limiting factors for sulfide oxidation under anaerobic conditions; instead, they enhance the reaction within specific concentration ranges. The refined kinetic model enables prediction of sulfur speciation in tropical coastal urban sewer pipelines, providing a scientific basis for corrosion risk assessment. Full article

Ethylmalonic encephalopathy (EE) is a serious metabolic disorder that usually appears in early childhood development and the effects are seen primarily in the brain, gastrointestinal tract, and peripheral vessels. EE is caused by pathogenic variants in the gene that encodes the ETHE1 protein, and its main features are high levels of acidic compounds in body fluids and decreased activity of the mitochondrial complex IV, which limits energy production in tissues that require a large supply of energy. ETHE1 is a mitochondrial sulfur dioxygenase that plays the role of hydrogen sulfide (H₂S) detoxification, and, when altered, it leads to the accumulation of this gaseous molecule due to its deficient elimination. In this article, we characterised the pathophysiology of ETHE1 deficiency in cellular models, fibroblasts, and induced neurons, derived from a patient with a homozygous pathogenic variant in ETHE1. Furthermore, we evaluated the effect of the activation of the mitochondrial unfolded protein response (mtUPR) on the mutant phenotype. Our results suggest that mutant fibroblasts have alterations in ETHE1 protein expression levels, associated with elevated levels of H₂S and protein persulfidation, mitochondrial dysfunction, iron/lipofuscin accumulation, and oxidative stress. We also identified a cocktail of compounds consisting of pterostilbene, nicotinamide, riboflavin, thiamine, biotin, lipoic acid, and L-carnitine that improved the cellular and metabolic alterations. The positive effect of the cocktail was dependent on sirtuin 3 activation (SIRT3) and was also confirmed in induced neurons obtained by direct reprogramming. In conclusion, personalised precision medicine in EE using patient-derived cellular models can be an interesting approach for the screening and evaluation of potential therapies. In addition, the activation of the SIRT3 axe of mtUPR is a promising therapeutic strategy for rescuing ETHE1 pathogenic variants. Full article

Daytime-restricted feeding (TRF) exerts outstanding effects on circadian physiology, nutrient utilization, and energy metabolism. Limiting feeding access to two hours during the daytime (12:00–14:00 h) for three weeks promotes food-anticipatory activity (FAA). FAA encompasses not only behaviors related to meal expectations but also includes diurnal fluctuations in liver metabolic responses, including distinct redox handling. Hepatic microarray profiles of genes associated with redox response processes were analyzed at three crucial time points: at the beginning of the light period or before FAA (08:00 h), during the expression of FAA (11:00 h), and after feeding (14:00 h). Data on fasting and nutrient processing were integrated, whereas circadian implications were extrapolated by comparing the TRF transcriptional output with a one-day fasting group. Transcripts of redox reactions, such as reactive oxygen species (ROS) generation, antioxidant defenses, NAD⁺/NADH equilibrium, and glutathione, hydrogen peroxide (H₂O₂), arginine, nitric oxide (NO), and hydrogen sulfide (H₂S) metabolism, were analyzed. Results showed a decline in antioxidant defenses at 08:00 h, followed by a burst of pro-oxidant reactions, preparation of glutathione metabolism factors, and a tendency to decrease H₂O₂ and increase NO and H₂S during the FAA. Most of the findings observed during the FAA were absent in response to one-day fasting. Hence, TRF involves concerted and sequential responses in liver pro-oxidant and antioxidant reactions, facilitating a redox-related circadian control that optimizes the metabolic utilization of nutrients, which differs from a response to a simple fast-feed cycle. Full article

Peripheral artery disease (PAD) is a chronic progressive accumulation of atherosclerotic lesions with varying degrees of arterial obstruction determining ischemic symptoms of the involved extremities. PAD is associated with decreased bioavailable nitric oxide due to endothelial cell dysfunction and the development and progression of vascular arterial stiffening (VAS). Atherosclerosis also plays an essential role in the development and progression of vascular arterial stiffening (VAS), which is associated with endothelial cell activation and dysfunction that results in a proinflammatory endothelium with a decreased ability to produce bioavailable nitric oxide (NO). NO is one of three gasotransmitters, along with carbon monoxide and hydrogen sulfide, that promotes vasodilation. NO plays a crucial role in the regulation of PAD, and a deficiency in its bioavailability is strongly linked to the development of atherosclerosis, VAS, and PAD. A decreased arterial patency may also occur due to a reduction in the elasticity or diameter of the vessel wall due to the progressive nature of VAS and atherosclerosis in PAD. Progressive atherosclerosis and VAS promote narrowing over time, which leads to impairment of vasorelaxation and extremity blood flow. This narrative review examines how atherosclerosis, aging and hypertension, metabolic syndrome and type 2 diabetes, tobacco smoking, and endothelial cell activation and dysfunction with decreased NO and VAS with its increased damaging pulsatile pulse pressure result in microvessel remodeling. Further, the role of ischemia and ischemia–reperfusion injury is discussed and how it contributes to ischemic skeletal muscle remodeling, ischemic neuropathy, and pain perception in PAD. Full article

As arsenopyrite is a typical arsenic-bearing sulfide ore, the biooxidation process of arsenopyrite is of great significance for the extraction of gold from arsenic-bearing gold ores and the generation of arsenic-bearing acid mine drainage. During the biooxidation of arsenopyrite, a large amount of arsenic is produced, which inhibits the growth and metabolism of microorganisms and thus affects the extraction of gold from arsenic-bearing gold ores. Therefore, the screening and enrichment of microorganisms with high arsenic resistance have become important aspects in the study of arsenopyrite biooxidation. As described in this paper, through arsenic acclimation, the maximum arsenic tolerance concentration of Acidithiobacillus ferriphilus QBS 3 isolated from arsenic-containing acid mine drainage was increased to 80 mM As(Ⅲ) and 100 mM As(V). Microorganisms with high arsenic resistance showed better bioleaching performance for arsenopyrite. After 18 days of bioleaching, the leaching rate of arsenopyrite reached 100% at a pulp concentration of 0.5%, and after 30 days of bioleaching, the leaching rate of arsenopyrite was 79.96% at a pulp concentration of 1%. Currently, research on arsenopyrite mainly focuses on the control and optimization of environmental conditions, but there have been few studies on the biooxidation process of arsenopyrite at the protein and gene levels. Therefore, combining the results of a one-month bioleaching experiment on arsenopyrite by A. ferriphilus QBS 3 and the analysis of arsenic resistance genes, a bioleaching model of arsenopyrite was constructed, which laid an experimental basis and theoretical foundation for improving the gold recovery rate from refractory arsenic-bearing ores and exploring the arsenic resistance mechanism of microorganisms during the arsenopyrite leaching process. Full article

Iron overload contributes to proliferative vascular diseases, yet its interplay with hydrogen sulfide (H₂S) in vascular smooth muscle cell (VSMC) proliferation remains poorly understood. This study elucidates H₂S’s role in mitigating iron-overload-induced oxidative stress and cellular damage. Using aortic VSMCs from wildtype (WT) and cystathionine γ-lyase-knockout (CSE-KO) mice treated with ferric ammonium citrate (FAC) at concentrations equivalent to serum levels of iron and citrate, we demonstrate that FAC triggers the integrated stress response (ISR) in WT cells, upregulating CSE to enhance H₂S production. The ISR mediator ATF4 activates caspases but simultaneously induces CSE, which inhibits caspase activity and promotes autophagy via AMPK signaling. In CSE-KO cells, iron overload leads to diminished Ferritin upregulation, unchecked Caspase activation, and impaired autophagy compared to WT cells. Exogenous H₂S restored iron homeostasis by enhancing Ferritin expression, activating NRF2 antioxidant pathways, and restoring apoptosis–autophagy equilibrium in both WT and KO cells. These findings establish H₂S as a critical regulator of iron-induced VSMC dysfunction, highlighting its therapeutic potential in managing vascular pathologies linked to iron dysregulation. Full article

Background: Neurodegenerative diseases (NDDs) are multifactorial disorders frequently associated with gut dysbiosis, oxidative stress, and inflammation; however, the pathophysiological mechanisms remain poorly understood. Methods: Using untargeted mass spectrometry-based metabolomics and 16S sequencing of human stool, we investigated bacterial and metabolic dyshomeostasis in the gut microbiome associated with early disease stages across three NDDs—amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (AD), Parkinson’s disease (PD)—and healthy controls (HC). Results: We discovered a previously unrecognized link between a microbial-derived metabolite with an unknown role in human physiology, 2,3-dihydroxypropane-1-sulfonate (DHPS), and gut dysbiosis in NDDs. DHPS was downregulated in AD, ALS, and PD, while bacteria involved in DHPS metabolism, Eubacterium and Desulfovibrio, were increased in all disease cohorts. Additionally, select taxa within the Clostridia class had strong negative correlations to DHPS, suggesting a potential role in DHPS metabolism. A catabolic product of DHPS is hydrogen sulfide, and when in excess, it is known to promote inflammation, oxidative stress, mitochondrial damage, and gut dysbiosis, known hallmarks of NDDs. Conclusions: These findings suggest that cryptic sulfur metabolism via DHPS is a potential missing link in our current understanding of gut dysbiosis associated with NDD onset and progression. As this was a hypothesis generating study, more work is needed to elucidate the role of DHPS in gut dysbiosis and neurodegenerative diseases. Full article

Sulfur cycling is a fundamental biogeochemical process, yet its microbial underpinnings in environments like the Isinuka sulfur pool remain poorly understood. Using high-throughput Illumina 16S rRNA sequencing and PICRUSt-based functional inference, we analyzed bacterial diversity and metabolic potential in sediment and water samples. Sediments, characterized by high sulfide/sulfate/thiosulfate, salinity, alkalinity, and organic matter content under anoxic conditions, supported diverse sulfur-reducing and organic-degrading bacteria, primarily from the Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria phyla. In contrast, the anoxic water column harbored a less diverse community dominated by α-, γ-, and β-Proteobacteria, including Thiocapsa and Lutimaribacter. Sulfur oxidation genes (soxABCXYZ, sqr) were abundant in water, while sulfate reduction genes (dsrAB, aprAB, and sat/met3) were concentrated in sediments. Core microbiome analysis identified Thiocapsa, Lutimaribacter, and Delftia as functional keystones, integrating sulfur oxidation and nutrient recycling. Sediments supported dissimilatory sulfate-reducing bacteria (unclassified Desulfobacteraceae, Desulfosarcina, Desulfococcus, Desulfotignum, and Desulfobacter), while water samples were enriched in sulfur-oxidizing bacteria like Thiocapsa. Metabolic profiling revealed extensive sulfur, nitrogen, and carbon cycling pathways, with sulfur autotrophic denitrification and anoxygenic photosynthesis coupling sulfur–nitrogen and sulfur–carbon cycles. This study provides key theoretical insights into the microbial dynamics in sulfur-rich environments, highlighting their roles in biogeochemical cycling and potential applications in environmental management. Full article

Cold stress, as an environmental factor that seriously restricts the growth, production and survival of plants, has received extensive attention in recent years. Nitric oxide (NO), as an important bioactive molecule, has emerged as a research focus in the domain of alleviating plant cold damage. In this review, the role of NO in enhancing plant cold tolerance and its underlying mechanisms, including interactions with signaling molecules, are discussed more extensively, and novel research directions and prospects are proposed according to existing research gaps. Interestingly, exogenous NO mitigates cold stress by strengthening antioxidant defense mechanisms, raising proline levels, enhancing photosynthetic capacity, and regulating glucose metabolism. More importantly, NO also interacts with cytoplasmic calcium ions (Ca²⁺), reactive oxygen species (ROS), glutathione (GSH), melatonin (MT), abscisic acid (ABA), ethylene (ETH) and hydrogen sulfide (H₂S). At the same time, in the process of NO alleviating cold stress, it regulates the expression of NO synthesis genes, cold response genes and antioxidant related genes, thereby improving the cold tolerance of plants, which may involve epigenetic reprogramming. This paper also points out the problems existing in the current research and the potential of NO in agricultural practice, and provides relevant theoretical references for future research in this field. Full article

Members of Eubacteriaceae are involved in host health and diseases. Two Gram-stain-positive, strictly anaerobic, non-motile, non-spore-forming, and rod-shaped bacterial strains, HA2171^T and HA2172^T, were isolated from the feces of Chinese healthy donors. Based on 16S rRNA gene sequences, HA2171^T and HA2172^T belonged to the family Eubacteriaceae. Physiological and biochemical characterizations indicated that HA2171^T and HA2172^T were neutrophilic, mesophilic, and tolerant to low-concentration NaCl. The major cellular fatty acids (>10.0%) of HA2171^T were C_16:0, C_14:0, C_18:1ω7c, and C_17:0 2-OH, and those of HA2172^T were C_14:0 and C_16:0. MK-6 was the respiratory quinone in both strains. Phylogenetic and phylogenomic analyses showed that HA2171^T was closest to Anaerofustis stercorihominis ATCC BAA-858^T and that HA2172^T as closest to Pseudoramibacter alactolyticus ATCC 23263^T. Genome annotation revealed that the HA2171^T and HA2172^T were able to metabolize carbohydrates and produce acetate and butyrate. HA2172^T contains genes associated with hydrogen sulfide production, which is a potential risk for diseases. Based on the phylogenetic, phenotypic, and chemotaxonomic characteristics, we propose that HA2171^T and HA2172^T represent two novel species, and the names Anaerofustis butyriciformans sp. nov. and Pseudoramibacter faecis sp. nov. are proposed. Full article