Hydrogen sulfide is a toxic compound that can affect various groups of water microorganisms. Photolithotrophic sulfur bacteria including Chromatiaceae and Chlorobiaceae are able to convert inorganic substrate (hydrogen sulfide and carbon dioxide) into organic matter deriving energy from photosynthesis. This process takes place in the absence of molecular oxygen and is referred to as anoxygenic photosynthesis, in which exogenous electron donors are needed. These donors may be reduced sulfur compounds such as hydrogen sulfide. This paper deals with the description of this metabolic process, representatives of the above-mentioned families, and discusses the possibility using anoxygenic phototrophic microorganisms for the detoxification of toxic hydrogen sulfide. Moreover, their general characteristics, morphology, metabolism, and taxonomy are described as well as the conditions for isolation and cultivation of these microorganisms will be presented.

BACKGROUND & AIMS: Inflammatory bowel disease (IBD) is characterized by a dysregulated immune response against the host’s microbiome. Mucosal-associated invariant T (MAIT) cells recognize microbiota-derived riboflavin metabolites and play a crucial role in mucosal homeostasis. However, their specific role in IBD remains enigmatic. MAIT cells express IL-26, a novel IL-10 family cytokine with a controversial role in IBD. We investigated the functions of MAIT cells and IL-26 in IBD using a unique combination of state-of-the-art 3D human intestinal tissue models and clinical samples. METHODS: We analyzed MAIT cells from the peripheral blood and intestinal tissue of Crohn’s disease (CD) patients, using immunofluorescence staining and flow cytometry to describe the phenotype and IL-26 expression of MAIT cells. We used 3D iPSC-derived intestinal organoids as a complex in vitro model of human tissue and RNA sequencing and functional assays such as wound healing assay to study the role of IL-26 in mucosal homeostasis and inflammation. RESULTS: We observed a reduction of MAIT cells in the peripheral blood of CD patients compared to healthy donors (1.5 ± 0.4%; 4.1 ± 1.1%; p < .0065) and a significant decrease of MAIT cells in inflamed compared to non-inflamed ileum of CD patients (0.1 ± 0.03%; 0.17 ± 0.05%; p < .042). MAIT cells were found pathologically activated in inflamed tissue, exhibiting differences in CD8 and CD4 expression and dysregulation of IL-26 expression. Furthermore, we demonstrated a protective role of IL-26 in mucosal homeostasis and inflammation in the iPSC-derived organoid model. CONCLUSION: Our results show a crucial role for IL-26 and MAIT cells in the homeostasis of intestinal tissue and in the pathogenesis of IBD. These cells may therefore represent new therapeutic targets for CD patients.

The intestine houses the largest reservoir of immune cells and is serviced by the largest and most complex peripheral nervous system in the human body. The gut-brain axis orchestrates bidirectional communication between the central and enteric nervous systems, playing a pivotal role in regulating overall body function and intestinal homeostasis. Using a human 3D in vitro model, we investigated the effect of serotonin, a neuromodulator produced in the gut, on immune cell and intestinal tissue interactions. Our findings revealed that serotonin attenuates the tumor-necrosis-factor-alpha-induced pro-inflammatory response, mostly by affecting the expression of chemokines. Serotonin was found to impact tissue-migrating monocytes’ phenotype and distribution, without direct contact with the cells, by remodeling the intestinal tissue. Collectively, using fully human 3D model of intestine, our results show for the first time that serotonin has a crucial role in communication among gut-brain axis components and regulates monocyte migration and plasticity, thereby contributing to gut homeostasis and the progression of intestinal inflammation. In vivo studies focused on role of neuromodulators in gut homeostasis and inflammation have shown controversial results, highlighting importance of development of human experimental models. Moreover, our results emphasize importance of human health research in human-cell-based models and suggests serotonin signaling pathway as new potential therapeutic target for inflammatory bowel disease patients.

Sepsis is a life-threatening condition characterised by an overwhelming immune response and high fatality. While most research has focused on its acute phase, many sepsis survivors remain immunologically weakened leaving them susceptible to serious complications from even mild infections. The mechanisms underlying this prolonged immune dysregulation remain unclear, limiting effective interventions. Here, we analysed whether sepsis induced long-term “training” in hematopoietic stem and progenitor cells (HSPCs), imprinting changes that persist in their myeloid progeny. Peripheral blood analysis of 8 sepsis survivors, 12 patients with septic shock, and 10 healthy donors revealed a significant expansion of CD38+ progenitors in survivors, with increases in megakaryocyte-erythroid and granulocyte-monocyte progenitors, and reduced mature neutrophil counts. This shift suggests impaired granulopoiesis, favouring immature, immunosuppressive granulocytes. Differentiated macrophages from survivors’ HSPCs exhibited impaired metabolic pathways after lipopolysaccharide stimulation, with downregulation of tricarboxylic acid cycle and glycolysis genes, indicating altered immune metabolism. Pathway analysis revealed enhanced type-I interferon (IFN) and JAK-STAT signalling in survivors’ macrophages, reflective of potentially tolerance-prone reprogramming. Finally, exposing healthy donor HSPCs to IFNβ during macrophage differentiation reduced HSPC proliferation, increased apoptosis, and induced a metabolic shift towards glycolysis over mitochondrial respiration. Together, these findings suggest that sepsis induces lasting reprogramming in HSPCs leading to myeloid progeny with altered immune memory that might drive immune dysregulation in survivors. These data open avenues to explore potential targets to better manage long-term immune alterations in sepsis survivors. KEY POINTS: Sepsis induces long-term alterations in HSPCs, leading to the expansion of immature progenitors and metabolic dysregulation of their progeny. Type-I IFN signalling reprograms macrophage differentiation, affecting their metabolic function and reducing cell proliferation.