Metagenomics and Social Inclusion in Peru

Metagenomics is the study of all the genetic material found in an ecosystem. Each part of the human body is an ecosystem with a distinct bacterial profile or microbiota whose metagenomic signature is called a human microbiome. The study of human microbiomes is a promising new area of biomedical research. Certain bacterial species are directly associated to specific diseases, suggesting their potential as biomarkers or even as therapeutic alternatives. As it has happened with genetics and genomics applications, most microbiome research is focused on urban human populations, thus providing a very biased set of study populations, both human and bacterial.The developing world harbors biological phenomena absent in the developed world. The study of traditional communities from developing countries provides unique opportunities for scientific advancement. At the same time, the knowledge obtained might impact public health programs and help to build research capacity in these countries. However, including traditional communities from developing countries in research has proved to be a sensitive matter.Research with indigenous populations carries the stigma of being exploitative, neocolonialist, and imperialist. Engaging communities in research can reduce the risk of exploitation and increase protection for these vulnerable populations. The biggest challenge to establishing meaningful partnerships with indigenous populations is distrust. The history of marginalization and constant friction between indigenous communities and outsiders has eroded any potential predisposition to trust. In absence of trust, any attempt to engage a community will be futile, superficial or pretendcommunity engagements without any real participation from the community. Real community engagement requires open dialog that results in real partnership which is impossible without a relationship of trust.Developing a relationship of trust with indigenous communities and the authorities that represent them is a demanding venture. Some unsuccessful research initiatives in the developing world have been credited to obstacles resulting from inefficient systems of research governance. Barriers that complicate inclusion of indigenous populations in biomedical research will contribute to the existing health disparities.Here, I discuss these topics from my own field experience and my efforts of implementing metagenomic research in Peru. Chapter 1 presents a case- study of the human gut microbiota of a hunter-gatherer community from the Peruvian Amazon region. The findings challenge some of the early conclusions of the study of human gut microbiome, highlighting the need to diversify the populations examined. Chapter 2 discusses distrust as the main barrier to effectively engage indigenous populations from developing countries in biomedical research. Chapter 3 offers the concept of intermediate research organizations as an alternative to overcome some of the barriers related to the implementation of international research with indigenous populations. The necessary process that researchers must undertake can be streamlined, while enhancing protection for human subjects within a system that lacks clear regulations for research

Origins of an Unmarked Georgia Cemetery Using Ancient DNA Analysis

Determining the origins of those buried within undocumented cemeteries is of incredible importance to historical archaeologists and in many cases, the nearby communities. In the case of Avondale Burial Place, a cemetery in Bibb County, Georgia, in use from 1820 to 1950, all written documentation of those interred within it has been lost. Osteological and archaeological evidence alone could not describe, with confidence, the ancestral origins of the 101 individuals buried there. In the present study, we utilize ancient DNA extraction methods to investigate the origins of Avondale Burial Place through the use of well-preserved skeletal fragments from 20 individuals buried in the cemetery. Through examination of hypervariable region I in the mitochondrial genome (HVR1, mtDNA), we determine haplotypes for all 20 of these individuals. A total of 18 of the 20 individuals belong to the L or U haplogroups, suggesting that Avondale Burial Place was most likely used primarily as a resting place for African Americans. After the surrounding Bibb County community expressed interest in investigating potential ancestral relationships to those within the cemetery, a total of eight potential descendants provided saliva in order to obtain mtDNA HVR1 information. This phase of the study revealed that two different individuals from Avondale Burial Place matched two individuals with oral history ties to the cemetery. Using the online tool EMPOP, we calculated the likelihood of these exact matches occurring by chance alone

Subsistence Strategies in Traditional Societies Distinguish Gut Microbiomes

Recent studies suggest that gut microbiomes of urban-industrialized societies are different from those of traditional peoples. Here we examine the relationship between lifeways and gut microbiota through taxonomic and functional potential characterization of faecal samples from hunter-gatherer and traditional agriculturalist communities in Peru and an urban-industrialized community from the US. We find that in addition to taxonomic and metabolic differences between urban and traditional lifestyles, hunter-gatherers form a distinct sub-group among traditional peoples. As observed in previous studies, we find that Treponema are characteristic of traditional gut microbiomes. Moreover, through genome reconstruction (2.2-2.5 MB, coverage depth x26-513) and functional potential characterization, we discover these Treponema are diverse, fall outside of pathogenic clades and are similar to Treponema succinifaciens, a known carbohydrate metabolizer in swine. Gut Treponema are found in non-human primates and all traditional peoples studied to date, suggesting they are symbionts lost in urban-industrialized societies

Analysis of global human gut metagenomes shows that metabolic resilience potential for short-chain fatty acid production is strongly influenced by lifestyle

High taxonomic diversity in non-industrial human gut microbiomes is often interpreted as beneficial; however, it is unclear if taxonomic diversity engenders ecological resilience (i.e. community stability and metabolic continuity). We estimate resilience through genus and species-level richness, phylogenetic diversity, and evenness in short-chain fatty acid (SCFA) production among a global gut metagenome panel of 12 populations (n = 451) representing industrial and non-industrial lifestyles, including novel metagenomic data from Burkina Faso (n = 90). We observe significantly higher genus-level resilience in non-industrial populations, while SCFA production in industrial populations is driven by a few phylogenetically closely related species (belonging to Bacteroides and Clostridium), meaning industrial microbiomes have low resilience potential. Additionally, database bias obfuscates resilience estimates, as we were 2–5 times more likely to identify SCFA-encoding species in industrial microbiomes compared to non-industrial. Overall, we find high phylogenetic diversity, richness, and evenness of bacteria encoding SCFAs in non-industrial gut microbiomes, signaling high potential for resilience in SCFA production, despite database biases that limit metagenomic analysis of non-industrial populations

Possible Positive Selection for an Arsenic-Protective Haplotype in Humans

BACKGROUND: Arsenic in drinking water causes severe health effects. Indigenous people in the South American Andes have likely lived with arsenic-contaminated drinking water for thousands of years. Inhabitants of San Antonio de los Cobres (SAC) in the Argentinean highlands generally carry an AS3MT (the major arsenic-metabolizing gene) haplotype associated with reduced health risks due to rapid arsenic excretion and lower urinary fraction of the monomethylated metabolite. OBJECTIVES: We hypothesized an adaptation to high-arsenic living conditions via a possible positive selection for protective AS3MT variants and compared AS3MT haplotype frequencies among different indigenous groups. METHODS: Indigenous groups we evaluated were a) inhabitants of SAC and villages near Salta in northern Argentina (n = 346), b) three Native American populations from the Human Genome Diversity Project (HGDP; n = 25), and c) five Peruvian populations (n = 97). The last two groups have presumably lower historical exposure to arsenic. RESULTS: We found a significantly higher frequency of the protective AS3MT haplotype in the SAC population (68.7%) compared with the HGDP (14.3%, p < 0.001, Fisher exact test) and Peruvian (50.5%, p < 0.001) populations. Genome-wide micro-satellite (n = 671) analysis showed no detectable level of population structure between SAC and Peruvian populations (measure of population differentiation F-ST = 0.006) and low levels of structure between SAC and HGDP populations (F-ST < 0.055 for all pairs of populations compared). CONCLUSIONS: Because population stratification seems unlikely to explain the differences in AS3MT haplotype frequencies, our data raise the possibility that, during a few thousand years, natural selection for tolerance to the environmental stressor arsenic may have increased the frequency of protective variants of AS3MT. Further studies are needed to investigate this hypothesis