Microbiota and Its Influence on Stem Cells, Intrinsic and Transplanted

The gut microbiota has gained much attention during the last decade due to its participation in the biotransformation of those nutrients that are known substrates of the various enzymes provided by different bacterial taxa, genera, and types. The microbiota represents a larger population of prokaryotic cells that reside within us than all the cells that belong to the human body. The second genome, as has also been said, forces us to address those interactions between the genome, epigenome, and exposome and their consequences. The microbiota participates in the maintenance, proliferation, and differentiation of our intestine’s stem and epithelial cells, favoring these processes when they are healthy or hindering them when altered. Dysbiosis is a term that reflects the alteration in the relationship between good bacteria, such as Bacteroidetes, and unfavorable ones, such as Firmicutes. Dysbiosis is related to proinflammatory, prooxidant, and prothrombotic alterations in the intestinal epithelium in more distant niches. Dysbiosis favors inflammation and the subject’s aging, as has been demonstrated in various models, such as that of D. melanogaster. However, one of the most disruptive effects of this imbalance between commensal and pathogenic bacteria involves the therapeutic outcomes of procedures such as allogeneic stem cell transplants for hematologic malignancies. This is a very relevant issue because this transplant is one of the most successful treatments for the treatment of liquid malignancies which, as is known, can be fatal. This chapter analyzes the relationship between the microbiota and the intestinal epithelium and how it affects their histological and molecular anatomy. The mechanism through which the microbiota modifies the immune response, intestinal permeability, and homeostasis is analyzed. It also focuses on the bystander effect or how those cells that have not been directly affected can influence other naive ones: the metabolome and its impact on damaged receptors, cell cycle regulators, and genetic stability. The role of entero-genotoxins and the evidence for DNA damage, impairment of various DNA repair mechanisms, activation of chromosome number variation, and genetic instability and mutations, which are connected to colorectal cancer, are also reviewed. The adverse effects observed in transplant patients and animal models under dysbiosis are headed by infections such as Clostridium difficile or immunological disorders such as graft-versus-host disease (GVHD). Intervention strategies to avoid these life-threatening complications have targeted the microbiota through different approaches and support the contention that allogeneic stem cell transplantation should include an assessment of the status of the microbiota to improve its clinical success. Also, those approaches utilized to modify microbiota to obtain better therapeutic results are revisited here.