Temporal dynamics of gut microbiomes in non-industrialized urban Amazonia.

Increasing levels of industrialization have been associated with changes in gut microbiome structure and loss of features thought to be crucial for maintaining gut ecological balance. The stability of gut microbial communities over time within individuals seems to be largely affected by these changes but has been overlooked among transitioning populations from low- to middle-income countries. Here, we used metagenomic sequencing to characterize the temporal dynamics in gut microbiomes of 24 individuals living an urban non-industrialized lifestyle in the Brazilian Amazon. We further contextualized our data with 165 matching longitudinal samples from an urban industrialized and a rural non-industrialized population. We show that gut microbiome composition and diversity have greater variability over time among non-industrialized individuals when compared to industrialized counterparts and that taxa may present diverse temporal dynamics across human populations. Enterotype classifications show that community types are generally stable over time despite shifts in microbiome structure. Furthermore, by tracking genomes over time, we show that levels of bacterial population replacements are more frequent among Amazonian individuals and that non-synonymous variants accumulate in genes associated with degradation of host dietary polysaccharides. Taken together, our results suggest that the stability of gut microbiomes is influenced by levels of industrialization and that tracking microbial population dynamics is important to understand how the microbiome will adapt to these transitions.IMPORTANCEThe transition from a rural or non-industrialized lifestyle to urbanization and industrialization has been linked to changes in the structure and function of the human gut microbiome. Understanding how the gut microbiomes changes over time is crucial to define healthy states and to grasp how the gut microbiome interacts with the host environment. Here, we investigate the temporal dynamics of gut microbiomes from an urban and non-industrialized population in the Amazon, as well as metagenomic data sets from urban United States and rural Tanzania. We showed that healthy non-industrialized microbiomes experience greater compositional shifts over time compared to industrialized individuals. Furthermore, bacterial strain populations are more frequently replaced in non-industrialized microbiomes, and most non-synonymous mutations accumulate in genes associated with the degradation of host dietary components. This indicates that microbiome stability is affected by transitions to industrialization, and that strain tracking can elucidate the ecological dynamics behind such transitions.

Effects of Degradation on Microbial Communities of an Amazonian Mangrove.

Mangroves provide a unique ecological environment for complex microbial communities, which play important roles in biogeochemical cycles, such as those for carbon, sulfur, and nitrogen. Microbial diversity analyses of these ecosystems help us understand the changes caused by external influences. Amazonian mangroves occupy an area of 9000 km2, corresponding to 70% of the mangroves in Brazil, on which studies of microbial biodiversity are extremely scarce. The present study aimed to determine changes in microbial community structure along the PA-458 highway, which fragmented a mangrove zone. Mangrove samples were collected from three zones, (i) degraded, (ii) in the process of recovery, and (iii) preserved. Total DNA was extracted and submitted for 16S rDNA amplification and sequencing on an MiSeq platform. Subsequently, reads were processed for quality control and biodiversity analyses. The most abundant phyla were Proteobacteria, Firmicutes, and Bacteroidetes in all three mangrove locations, but in significantly different proportions. We observed a considerable reduction in diversity in the degraded zone. Important genera involved in sulfur, carbon, and nitrogen metabolism were absent or dramatically reduced in this zone. Our results show that human impact in the mangrove areas, caused by the construction of the PA-458 highway, has resulted in a loss of biodiversity.

Mitochondrial Genetics Reinforces Multiple Layers of Interaction in Alzheimer's Disease.

Nuclear DNA has been the main source of genome-wide loci association in neurodegenerative diseases, only partially accounting for the heritability of Alzheimer's Disease (AD). In this context, mitochondrial DNA (mtDNA) is gaining more attention. Here, we investigated mitochondrial genes and genetic variants that may influence mild cognitive impairment and AD, through an integrative analysis including differential gene expression and mitochondrial genome-wide epistasis. We assessed the expression of mitochondrial genes in different brain tissues from two public RNA-Seq databases (GEO and GTEx). Then, we analyzed mtDNA from the ADNI Cohort and investigated epistasis regarding mitochondrial variants and levels of Aß1-42, TAU, and Phosphorylated TAU (PTAU) from cognitively healthy controls, and both mild cognitive impairment (MCI) and AD cases. We identified multiple differentially expressed mitochondrial genes in the comparisons between cognitively healthy individuals and AD patients. We also found increased protein levels in MCI and AD patients when compared to healthy controls, as well as novel candidate networks of mtDNA epistasis, which included variants in all mitochondrially-encoded oxidative phosphorylation complexes, 12S rRNA and MT-DLOOP. Our results highlight layers of potential interactions involving mitochondrial genetics and suggest specific molecular alterations as potential biomarkers for AD.

Nuclear and Mitochondrial Genome, Epigenome and Gut Microbiome: Emerging Molecular Biomarkers for Parkinson's Disease.

BACKGROUND: Parkinson's disease (PD) is currently the second most common neurodegenerative disorder, burdening about 10 million elderly individuals worldwide. The multifactorial nature of PD poses a difficult obstacle for understanding the mechanisms involved in its onset and progression. Currently, diagnosis depends on the appearance of clinical signs, some of which are shared among various neurologic disorders, hindering early diagnosis. There are no effective tools to prevent PD onset, detect the disease in early stages or accurately report the risk of disease progression. Hence, there is an increasing demand for biomarkers that may identify disease onset and progression, as treatment-based medicine may not be the best approach for PD. Over the last few decades, the search for molecular markers to predict susceptibility, aid in accurate diagnosis and evaluate the progress of PD have intensified, but strategies aimed to improve individualized patient care have not yet been established. CONCLUSIONS: Genomic variation, regulation by epigenomic mechanisms, as well as the influence of the host gut microbiome seem to have a crucial role in the onset and progress of PD, thus are considered potential biomarkers. As such, the human nuclear and mitochondrial genome, epigenome, and the host gut microbiome might be the key elements to the rise of personalized medicine for PD patients.

The structure of Brazilian Amazonian gut microbiomes in the process of urbanisation.

Shifts in subsistence strategy among Native American people of the Amazon may be the cause of typically western diseases previously linked to modifications of gut microbial communities. Here, we used 16S ribosomal RNA sequencing to characterise the gut microbiome of 114 rural individuals, namely Xikrin, Suruí and Tupaiú, and urban individuals from Belém city, in the Brazilian Amazon. Our findings show the degree of potential urbanisation occurring in the gut microbiome of rural Amazonian communities characterised by the gradual loss and substitution of taxa associated with rural lifestyles, such as Treponema. Comparisons to worldwide populations indicated that Native American groups are similar to South American agricultural societies and urban groups are comparable to African urban and semi-urban populations. The transitioning profile observed among traditional populations is concerning in light of increasingly urban lifestyles. Lastly, we propose the term "tropical urban" to classify the microbiome of urban populations living in tropical zones.

New insights on intercontinental origins of paternal lineages in Northeast Brazil.

BACKGROUND: The current Brazilian population is the product of centuries of admixture between intercontinental founding groups. Although previous results have revealed a heterogeneous distribution of mitochondrial lineages in the Northeast region, the most targeted by foreign settlers during the sixteenth century, little is known about the paternal ancestry of this particular population. Considering historical records have documented a series of territorial invasions in the Northeast by various European populations, we aimed to characterize the male lineages found in Brazilian individuals in order to discover to what extent these migrations have influenced the present-day gene pool. Our approach consisted of employing four hierarchical multiplex assays for the investigation of 45 unique event polymorphisms in the non-recombining portion of the Y-chromosome of 280 unrelated men from several Northeast Brazilian states. RESULTS: Primary multiplex results allowed the identification of six major haplogroups, four of which were screened for downstream SNPs and enabled the observation of 19 additional lineages. Results reveal a majority of Western European haplogroups, among which R1b-S116* was the most common (63.9%), corroborating historical records of colonizations by Iberian populations. Nonetheless, FST genetic distances show similarities between Northeast Brazil and several other European populations, indicating multiple origins of settlers. Regarding Native American ancestry, our findings confirm a strong sexual bias against such haplogroups, which represented only 2.5% of individuals, highly contrasting previous results for maternal lineages. Furthermore, we document the presence of several Middle Eastern and African haplogroups, supporting a complex historical formation of this population and highlighting its uniqueness among other Brazilian regions. CONCLUSIONS: We performed a comprehensive analysis of the major Y-chromosome lineages that form the most dynamic migratory region from the Brazilian colonial period. This evidence suggests that the ongoing entry of European, Middle Eastern, and African males in the Brazilian Northeast, since at least 500 years, was significantly responsible for the present-day genetic architecture of this population.

Amazonia Seasons Have an Influence in the Composition of Bacterial Gut Microbiota of Mangrove Oysters (Crassostrea gasar).

The mangrove oysters (Crassostrea gasar) are molluscs native to the Amazonia region and their exploration and farming has increased considerably in recent years. These animals are farmed on beds built in the rivers of the Amazonia estuaries and, therefore, the composition of their microbiome should be directly influenced by environmental conditions. Our work aimed to evaluate the changes in bacterial composition of oyster's microbiota at two different seasons (rainy and dry). For this purpose, we amplified and sequenced the V3-V4 regions of the 16S rRNA gene. Sequencing was performed on the Illumina MiSeq platform. According to the rarefaction curve, the sampling effort was sufficient to describe the bacterial diversity in the samples. Alpha-diversity indexes showed that the bacterial microbiota of oysters is richer during the rainy season. This richness is possibly associated with the diversity at lower taxonomic levels, since the relative abundance of bacterial phyla in the two seasons remained relatively constant. The main phyla found include Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria. Similar results were found for the species Crassostrea gigas, Crassostrea sikamea, and Crassostrea corteziensis. Beta-diversity analysis showed that the bacterial composition of oyster's gut microbiota was quite different in the two seasons. Our data demonstrate the close relationship between the environment and the microbiome of these molluscs, reinforcing the need for conservation and sustainable management of estuaries in the Amazonia.

A Cell's Fate: An Overview of the Molecular Biology and Genetics of Apoptosis.

Apoptosis is one of the main types of regulated cell death, a complex process that can be triggered by external or internal stimuli, which activate the extrinsic or the intrinsic pathway, respectively. Among various factors involved in apoptosis, several genes and their interactive networks are crucial regulators of the outcomes of each apoptotic phase. Furthermore, mitochondria are key players in determining the way by which cells will react to internal stress stimuli, thus being the main contributor of the intrinsic pathway, in addition to providing energy for the whole process. Other factors that have been reported as important players of this intricate molecular network are miRNAs, which regulate the genes involved in the apoptotic process. Imbalance in any of these mechanisms can lead to the development of several illnesses, hence, an overall understanding of these processes is essential for the comprehension of such situations. Although apoptosis has been widely studied, the current literature lacks an updated and more general overview on this subject. Therefore, here, we review and discuss the mechanisms of apoptosis, highlighting the roles of genes, miRNAs, and mitochondria involved in this type of cell death.

mtDNA structure: the women who formed the Brazilian Northeast.

BACKGROUND: The distribution of mitochondrial DNA (mtDNA) lineages in Brazil is heterogeneous due to different regional colonization dynamics. Northeastern Brazil, although being an important region in terms of human imigration and ethnic admixture, has little information regarding its population mtDNA composition. Here, we determine which mitochondrial lineages contributed to the formation of the Northeastern Brazilian population. Our sample consisted of 767 individuals distributed as follows i) 550 individuals from eight Northeastern states (Piauí, Ceará, Rio Grande do Norte, Paraíba, Pernambuco, Alagoas, Sergipe, and Bahia) which were sequenced for mtDNA hypervariable segments I, II, and III; ii) 217 individuals from Alagoas and Pernambuco (previously published data). Data analysis was performed through sequence alignment and Haplogrep 2.0 haplogroup assignment tools. Furthermore, maternal ancestry distribution was contextualized and, when possible, related to historical events to better understand the biological interactions and population dynamics that occurred in this region since the beginning of colonization. RESULTS: Unexpectedly, Amerindian mitochondrial ancestry was the highest in the Northeastern region overall, followed by African, European and non-Amerindian Asian, unlike previous results for this region. Alagoas and Pernambuco states, however, showed a larger African mtDNA frequency. The Northeastern region showed an intraregional heterogeneous distribution regarding ancestral groups, in which states/mesoregions located to the north had a prevalent Amerindian ancestral frequency and those to the south had predominance of African ancestry. Moreover, results showed great diversity of European haplogroups and the presence of non-Amerindian Asian haplogroups. CONCLUSIONS: Our findings are in disagreement with previous investigations that suggest African mitochondrial ancestry is the most prevalent in the Brazilian Northeast. The predominance of Amerindian lineages exemplifies the importance of indigenous women in the formation of the population, despite intense African slave entry and conflicts with European settlers. The variable distribution of ancestral groups observed in the Northeast is in accordance with historical records showing the similarities with colonization dynamics occurred in the Amazon region and the Brazilian Southeast. Moreover, the variety of European haplogroups suggests multiple origins of founding groups, specially those found in Western European populations.