Uncovering their global impact on health


Numerous studies have indicated the importance of the gut microbiome in maintaining human health. These microbes are also associated with basic physiological processes, such as aging, response to medication, nutrition, and pathophysiological states (eg, cardiovascular, metabolic, neoplastic, neurological, and autoimmune diseases). To better understand the causal effects between gut microbiota and disease outcomes, careful identification of the human gut microbiota is essential to formulate effective interventions for disease prevention or treatment.

Study: Reconstructing gut microbial species landscapes across 29,000 diverse individuals.  Image credit: SciePro/Shutterstock

Stady: Reconstructing gut microbial species landscapes across 29,000 diverse individuals. Image credit: SciePro/Shutterstock


Whole genome shotgun sequencing (WGS) technology can be used to map microbial species. However, this technique requires deep sequencing coverage and extensive computational work, precluding its application to population-wide samples of tens of thousands of individuals.

The human microbiota can be studied across diverse populations using 16S amplicon sequencing technology. This technique uses PCR to amplify and sequence highly variable regions of bacterial 16S rRNA genes. Amplicon sequence data is processed through popular pipelines, such as Mothur, QIIME2, and DADA2, along with computational reconstruction. Taxonomic assignment is performed by creating a phylogenetic tree using databases such as Greengenes, RDP, and SILVA.

16S sequencing technology helps detect changes in microbial diversity across human phenotypes. Most importantly, it enables identification of vital components of the human genome at the family or genus level. However, this technique fails to distinguish microbes at the microspecies level, which cannot be used for mapping microbial sequences at the species level.

Advances in molecular sequencing technologies have resulted in an exponential increase in the availability of fully sequenced intestinal microbial isolates. More than one 16S gene is present in the genomes of many individual microbial strains, revealing copy number variation of highly variable 16S regions. Given these results, a recent study hypothesized that this microbial difference could be considered to determine the exact differentiation of 16S amplicon data. This will enable stress level mapping, which was not previously possible.

New study

newly Nucleic acid research The study developed the Reference-Based Precision Mapping (RExMap) database of highly variable region 16S variants and their copy numbers. This database was derived from over 170,000 genomes of microbial isolate strains obtained from the NCBI Genome Database. This study used the RExMap database to map microbes at the species level.

Several microbial strains in the RExMap database share highly variable 16S regions and copy numbers. They introduced the term Operational Stress Unit (OSU) for those strains that cannot be distinguished based on highly variable 16S regions alone. Interestingly, OSU contains not only related microbial lineages but also relatively distant microbes, which could be due to horizontal genetic transfer of the 16S gene or incorrect taxonomic assignment.

RExMap correlates sequences from biological samples to accurately match microbial strains and aid in experimental validation. In addition, it can re-analyze existing 16S data through extensive meta-analyses and homologation of sequence data. This approach has enabled the development of a detailed landscape of the human gut microbiome representing tens of thousands of unique microbes.

The current study used RExMap to re-analyze current 16S human gut microbiome data from 29,349 individuals obtained from ten studies conducted in sixteen different regions of the world.


RExMap analysis of 16S microbiome data was able to capture about 75% of species detected using WGS at less than 1% sequencing depth. This approach avoids taxonomic assignments and focuses on exact or close matches to 16S amplicon sequences found in the RExMap database. The current study notes that the human gut microbiota varies across regions of the world. It is worth noting that some gut microbes are abundant in a particular area.

A core group of fifteen microbes has been found to be highly conserved in all humans regardless of their geographic region, host genetics, demographics, diet, environment, and lifestyle. These microbes play a vital role in the metabolic homeostasis of the host. Normally, essential microbes establish themselves in the guts of infants and persist throughout life, in varying abundances. The prevalence and abundance of essential microbes has been validated by whole-genome cataloging-based approaches, such as WGS and Kraken2.

Many microbes belonging to the superfamily Bacteroidetes, e.g Prevotella cobre and Bacteroides species, were not tied to a specific region. rectum Eubacterium And fecal stool; Two basic microbes associated with a particular disease condition. Oscillators s. ER4, Fusicatenibacter saccharivoransAnd Blautia faecisAnd rhombotsia timonensisAnd Hadrous Anrostips They are essential microbes associated with host physiology.


RExMap-based analysis has several limitations, including its low ability to map microbial species present in niches with few lineages, such as aquatic and soil ecosystems. In addition, there are limitations in mapping microbes that lack a full 16S or genomic sequence. However, the RExMap database is constantly updated by end users by adding new microbial genomes as available.

The current study concluded that the human gut microbiome separates western and non-western regions. Distinctive microbial species and strains that are unique to particular geographic regions have been identified. In addition, a set of essential microbes has been detected at species levels common to humans, regardless of lifestyle, environment, or geographic regions. These microbes are usually established at birth and are associated with alimentary metabolism.

Journal reference:

  • Seguta, I et al. (2023) Reconstructing gut microbial species landscapes across 29,000 diverse individuals. Nucleic acid research. JCAD 249. https://doi.org/10.1093/nar/gkad249https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkad249/7127541?login=false


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