Parkinson’s Disease (PD) is a neurodegenerative disease, leading to motor and non-motor complications. Autonomic alterations, including gastrointestinal symptoms, precede motor defects and act as early warning signs. Chronic exposure to dietary, environmental heavy metals impacts the gastrointestinal system and host-associated microbiome, eventually affecting the central nervous system. The correlation between dysbiosis and PD suggests a functional and bidirectional communication between the gut and the brain. The bioaccumulation of metals promotes stress mechanisms by increasing reactive oxygen species, likely altering the bidirectional gut–brain link. To better understand the differing molecular mechanisms underlying PD, integrative modeling approaches are necessary to connect multifactorial perturbations in this heterogeneous disorder. By exploring the effects of gut microbiota modulation on dietary heavy metal exposure in relation to PD onset, the modification of the host-associated microbiome to mitigate neurological stress may be a future treatment option against neurodegeneration through bioremediation. The progressive movement towards a systems toxicology framework for precision medicine can uncover molecular mechanisms underlying PD onset such as metal regulation and microbial community interactions by developing predictive models to better understand PD etiology to identify options for novel treatments and beyond. Several methodologies recently addressed the complexity of this interaction from different perspectives; however, to date, a comprehensive review of these approaches is still lacking. Therefore, our main aim through this manuscript is to fill this gap in the scientific literature by reviewing recently published papers to address the surrounding questions regarding the underlying molecular mechanisms between metals, microbiota, and the gut–brain-axis, as well as the regulation of this system to prevent neurodegeneration.

Parkinson’s disease (PD) is a chronic and progressive neurodegenerative disease with the major symptoms comprising loss of movement coordination (motor dysfunction) and non-motor dysfunction, including gastrointestinal symptoms. Alterations in the gut microbiota composition have been reported in PD patients vs. controls. However, it is still unclear how these compositional changes contribute to disease etiology and progression. Furthermore, most of the available studies have focused on European, Asian, and North American cohorts, but the microbiomes of PD patients in Latin America have not been characterized. To address this problem, we obtained fecal samples from Colombian participants (n = 25 controls, n = 25 PD idiopathic cases) to characterize the taxonomical community changes during disease via 16S rRNA gene sequencing. An analysis of differential composition, diversity, and personalized computational modeling was carried out, given the fecal bacterial composition and diet of each participant. We found three metabolites that differed in dietary habits between PD patients and controls: carbohydrates, trans fatty acids, and potassium. We identified six genera that changed significantly in their relative abundance between PD patients and controls, belonging to the families Lachnospiraceae, Lactobacillaceae, Verrucomicrobioaceae, Peptostreptococcaceae, and Streptococcaceae. Furthermore, personalized metabolic modeling of the gut microbiome revealed changes in the predicted production of seven metabolites (Indole, tryptophan, fructose, phenylacetic acid, myristic acid, 3-Methyl-2-oxovaleric acid, and N-Acetylneuraminic acid). These metabolites are associated with the metabolism of aromatic amino acids and their consumption in the diet. Therefore, this research suggests that each individual’s diet and intestinal composition could affect host metabolism. Furthermore, these findings open the door to the study of microbiome–host interactions and allow us to contribute to personalized medicine.

The merozoite surface protein 7 (MSP7) is a Plasmodium protein which is involved in parasite invasion; the gene encoding it belongs to a multigene family. It has been proposed that MSP7 paralogues seem to be functionally redundant; however, recent experiments have suggested that they could have different roles. The msp7 multigene family has been described in newly available Plasmodium genomes; phylogenetic relationships were established in 12 species by using different molecular evolutionary approaches for assessing functional divergence amongst MSP7 members. Gene expansion and contraction rule msp7 family evolution; however, some members could have had concerted evolution. Molecular evolutionary analysis showed that relaxed and/or intensified selection modulated Plasmodium msp7 paralogous evolution. Furthermore, episodic diversifying selection and changes in evolutionary rates suggested that some paralogous proteins have diverged functionally. Even though msp7 has mainly evolved in line with a birth-and-death evolutionary model, gene conversion has taken place between some paralogous genes allowing them to maintain their functional redundancy. On the other hand, the evolutionary rate of some MSP7 paralogs has become altered, as well as undergoing relaxed or intensified (positive) selection, suggesting functional divergence. This could mean that some MSP7s can form different parasite protein complexes and/or recognise different host receptors during parasite invasion. These results highlight the importance of this gene family in the Plasmodium genus.