Functional prediction of proteins from the human gut archaeome.

The human gastrointestinal tract contains diverse microbial communities, including archaea. Among them, Methanobrevibacter smithii represents a highly active and clinically relevant methanogenic archaeon, being involved in gastrointestinal disorders, such as inflammatory bowel disease and obesity. Herein, we present an integrated approach using sequence and structure information to improve the annotation of M. smithii proteins using advanced protein structure prediction and annotation tools, such as AlphaFold2, trRosetta, ProFunc, and DeepFri. Of an initial set of 873 481 archaeal proteins, we found 707 754 proteins exclusively present in the human gut. Having analysed archaeal proteins together with 87 282 994 bacterial proteins, we identified unique archaeal proteins and archaeal-bacterial homologs. We then predicted and characterized functional domains and structures of 73 unique and homologous archaeal protein clusters linked the human gut and M. smithii. We refined annotations based on the predicted structures, extending existing sequence similarity-based annotations. We identified gut-specific archaeal proteins that may be involved in defense mechanisms, virulence, adhesion, and the degradation of toxic substances. Interestingly, we identified potential glycosyltransferases that could be associated with N-linked and O-glycosylation. Additionally, we found preliminary evidence for interdomain horizontal gene transfer between Clostridia species and M. smithii, which includes sporulation Stage V proteins AE and AD. Our study broadens the understanding of archaeal biology, particularly M. smithii, and highlights the importance of considering both sequence and structure for the prediction of protein function.

The gut microbiome molecular complex in human health and disease.

The human gut microbiome produces a functional complex of biomolecules, including nucleic acids, (poly)peptides, structural molecules, and metabolites. This impacts human physiology in multiple ways, especially by triggering inflammatory pathways in disease. At present, much remains to be learned about the identity of key effectors and their causal roles.

Mesenchymal stem cells with irreversibly arrested proliferation stimulate decidua development in rats.

Stem cell transplantation, which is based on the application of mesenchymal stem/stromal cells (MSCs), is a rapidly developing approach to the regenerative therapy of various degenerative disorders characterized by brain and heart failure, as well as skin lesions. In comparison, the use of stem cell transplantations to treat infertility has received less attention. One of the causes of miscarriages and fetal growth delay is the loss of the decidual reaction of endometrial cells. The present study modeled decidualization processes in pseudopregnant rats. For cell transplantation experiments, the rats were transplanted with MSCs established from endometrial fragments in menstrual blood (eMSCs). These cells express common MSC markers, are multipotent and are able to differentiate into various tissue lineages. Cell therapy frequently requires substantial cell biomass, and cultivation of MSCs may be accompanied by significant changes to their properties, including malignant transformation. In order to minimize the potential for malignant transformation, the proliferation of eMSCs was irreversibly suppressed by irradiation and mitomycin C treatment. Transplantation of the rats with viable, non-proliferating eMSCs stimulated the development of all elements of decidual tissue. Conversely, transplantation of the rats with cells killed using 95% ethanol did not result in the development of decidual tissue. The present study demonstrated the potential for applying eMSCs to the cellular therapy of infertility associated with endometrial disorders characterized by decidualization insufficiency and implantation failure. In addition, the transplantation of viable but non-proliferating cells ensured that their oncogenic potential was limited.