Effects of glyphosate exposure on intestinal microbiota, metabolism and microstructure: a systematic review.

Glyphosate is the most commercialized herbicide in Brazil and worldwide, and this has become a worrying scenario in recent years. In 2015 glyphosate was classified as potentially carcinogenic by the World Health Organization, which opened avenues for numerous debates about its safe use regarding non-target species' health, including humans. This review aimed to observe the impacts of glyphosate and its formulations on the gut microbiota, as well as on the gut microstructure and animal metabolism. A systematic review was conducted based on the PRISMA recommendations, and the search for original articles was performed in Pubmed/Medline, Scopus and Web of Science databases. The risk of bias in the studies was assessed using the SYRCLE strategy. Our findings revealed that glyphosate and its formulations are able to induce intestinal dysbiosis by altering bacterial metabolism, intestinal permeability, and mucus secretion, as well as causing damage to the microvilli and the intestinal lumen. Additionally, immunological, enzymatic and genetic changes were also observed in the animal models. At the metabolic level, damage was observed in lipid and energy metabolism, the circulatory system, cofactor and vitamin metabolism, and replication, repair, and translation processes. In this context, we pointed out that the studies revealed that these alterations, caused by glyphosate-based herbicides, can lead to intestinal and systemic diseases, such as Crohn's disease and Alzheimer's disease.

Cytokine Networks as Targets for Preventing and Controlling Chagas Heart Disease.

Chagas disease, a neglected disease caused by the protozoan Trypanosoma cruzi, is endemic in 21 Latin American countries, affecting 6-8 million people. Increasing numbers of Chagas disease cases have also been reported in non-endemic countries due to migration, contamination via blood transfusions or organ transplantation, characterizing Chagas as an emerging disease in such regions. While most individuals in the chronic phase of Chagas disease remain in an asymptomatic clinical form named indeterminate, approximately 30% of the patients develop a cardiomyopathy that is amongst the deadliest cardiopathies known. The clinical distinctions between the indeterminate and the cardiac clinical forms are associated with different immune responses mediated by innate and adaptive cells. In this review, we present a collection of studies focusing on the human disease, discussing several aspects that demonstrate the association between chemokines, cytokines, and cytotoxic molecules with the distinct clinical outcomes of human infection with Trypanosoma cruzi. In addition, we discuss the role of gene polymorphisms in the transcriptional control of these immunoregulatory molecules. Finally, we discuss the potential application of cytokine expression and gene polymorphisms as markers of susceptibility to developing the severe form of Chagas disease, and as targets for disease control.

T-cell receptor variable region usage in Chagas disease: A systematic review of experimental and human studies.

T cells recognize their ligand, the peptide major histocompatibility complex (MHC), via the T-cell receptor (TCR), which is composed of covalently linked α and ß or γ and δ chains. This recognition is critical for T-cell ontogeny and controls the selection, activation, and function of T lymphocytes. Specific TCR αß variable regions have been associated with immunopathogenesis of Chagas disease. Here, we present a systematic review that compiles experimental in vivo and human data regarding the preferential expression of variable alpha (Vα) and variable beta (Vß) chain regions in Trypanosoma cruzi infection. The original studies indexed in PubMed/Medline, Scopus, and Web of Science databases were screened according to the PRISMA strategy. The analysis showed that expression of TCR Vα subfamilies were evaluated in one human study, and, unlike TCR Vß, TCR Vα presented a more restricted usage. Despite the great variability in the usage of TCR Vß regions in human Chagas disease, a down-regulation of TCR Vß5 expression by T cells from patients in the acute phase of the disease was shown. Opposingly, this TCR region was found overly expressed in CD4+ T cells from chronic Chagas patients. It was also demonstrated that murine Vß9+ T cells derived from nonlymphoid organs of T. cruzi-infected animals had a modulatory profile, while splenic Vß9+ T cells produced inflammatory cytokines, indicating that although they display the same TCR Vß region usage, these cells are functionally distinct. Despite the limitations of few papers and year of publication of the studies, compiling the data derived from them reveals that further investigation of TCR usage will point to their potential role in protective or pathogenic responses, as biomarkers of disease progression, and in the search for dominant peptides potentially useful for the development of vaccines or therapies.