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Metagenomic Analysis of Urban, Rural South African Women Reveals Gut Microbiomes in Transition

NEW YORK — The gut microbiomes of women in two regions of South Africa — urban and rural — fall in between those observed in traditional and industrialized populations, a new study has found, marking a transition of diet and lifestyle in these communities.

Most gut microbiome studies to date have either focused on Western, industrialized populations or traditional populations, including hunter-gatherers and agriculturalists. Populations in transition, on the other hand, are underrepresented in gut microbiome studies, researchers at Stanford University noted, leaving out the majority of the global population.

In a new study appearing Tuesday in Nature Communications, Stanford's Ami Bhatt and colleagues analyzed the gut microbiomes of two South African populations, one rural and one urban. Both fell taxonomically between those of traditional and industrialized populations, they reported.

The researchers further found that the differences in diversity previously reported between traditional and industrialized populations — higher within-sample, or alpha, diversity but lower between-sample, or beta, diversity in non-Western populations — does not always hold and could instead reflect the incompleteness of reference collections for microbiomes more commonly found outside industrialized regions.

"Given that most of the world's microbiome and genomics research has been carried out in a few geographic areas (USA, Western Europe, China, Japan), and that microbiomes vary based on geography, lifestyle, and exposures, it is unsurprising that we can classify sequences from 'Western' microbiomes much more easily than we can classify sequences from 'non-Western' microbiomes," Bhatt said in an email.

She and her colleagues analyzed stool samples from 190 South African women, 118 living in rural Bushbuckridge and 51 in urban Soweto. They sequenced the samples using both short- and long-read approaches, when possible.

Across both groups, the most common bacteria included Prevotella, Bacteroides, and Faecalibacterium. But the groups also contained a number of taxa uncommon among Western microbiomes, including members of the Volatile and/or Associated Negatively with Industrialized Societies of Humans, or VANISH, taxa like Prevotella, Treponema, and Succinatimonas.

At the same time, samples from rural and urban women clustered differently. Samples from rural women had higher alpha diversity than samples from urban women. Bacteroides, Bifidobacterium, and Streptococcus were more abundant among rural individuals.

The researchers also compared the gut microbiomes of the South African populations to publicly available data on two Western cohorts from the US and Sweden and three non-Western cohorts from Burkina Faso, Madagascar, and Tanzania. The South African populations clustered between the Western and non-Western cohorts.

This finding, Bhatt said, was both unsurprising and surprising.

"Given that these populations are in transition from more traditional lifestyles and diets to those more similar to industrialized populations, it seemed reasonable to postulate that their microbiomes would be intermediate in composition," she said. "In other ways, we were quite surprised to find this — I might have expected that microbiome composition would cluster with the lifestyle that people experienced. For example, in Soweto, many of our participants live very similarly to how Americans do. … So to find that their microbiomes were actually quite distinct from those living in Sweden and the United States was a surprise."

The researchers further found, using a k-mer-based analysis, that the previously reported pattern of higher alpha but lower beta diversity among non-Western populations' microbiomes did not always occur. Instead, they suggested that this conclusion stems from the underrepresentation of microbes that are more common among non-Western microbiomes in reference collections and underscores the need for better representation of additional populations in microbiome studies.

"We must help extend research to different populations all over the world," Bhatt said. "By enhancing research infrastructure all over the world and facilitating the development of local research efforts, we will slowly expand the number and different types of individuals and populations who are studied. This will help improve microbiome reference collections."