The Landscape of Genetic Content in the Gut and Oral Human Microbiome

Abstract

Highlights d Cross-study meta-analysis of metagenomes covering 3,655 samples from two body sites d Meta-analysis uncovers staggering microbial gene diversity d 50% of all genes in a metagenomic sample are individualspecific or ''singletons'' d Individual's microbiomes can be fingerprinted via rare microbial strains

Gastrointestinal (GI) Tract Microbiome-Derived Neurotoxins—Potent Neuro-Inflammatory Signals From the GI Tract via the Systemic Circulation Into the Brain

“…Together the GI-tract microbiome possesses a remarkable microbiological diversity and staggering genetic complexity of at least 1000 major bacterial species. In the most recent estimate analyses of the GI-tract metagenomes of ∼2100 donors well over 22.3 million nonredundant prokaryotic genes were detected, and at least half of all the genes identified were unique to an individual (Tierney et al, 2019). When compared to the established human genome content of 26.6 thousand protein-encoding transcripts of the human genome sequencing project obtained about ∼18 years ago (Fields et al, 1994;Venter et al, 2001;Hicks et al, 2019) the number of microbial genes in the human GI-tract microbiome alone outnumbers human genes by about 837 to 1 (Tierney et al, 2019).…”

“…In the most recent estimate analyses of the GI-tract metagenomes of ∼2100 donors well over 22.3 million nonredundant prokaryotic genes were detected, and at least half of all the genes identified were unique to an individual (Tierney et al, 2019). When compared to the established human genome content of 26.6 thousand protein-encoding transcripts of the human genome sequencing project obtained about ∼18 years ago (Fields et al, 1994;Venter et al, 2001;Hicks et al, 2019) the number of microbial genes in the human GI-tract microbiome alone outnumbers human genes by about 837 to 1 (Tierney et al, 2019). Another interesting fact is that of the 52 major divisions of bacteria identified to date, only 2 phyla are known to predominate in the human GI-tract microbiomethe Gram-negative Bacteroidetes (representing about ∼20-30% of all GI-tract resident bacteria) and the Gram-positive Firmicutes (representing ∼70-80% of the total) with relatively minor contributions by Actinobacteria (∼3%), Proteobacteria (∼1%), Fusobacteria (∼0.1%) and Verrucomicrobia (0.1%).…”

The predictive power of the microbiome exceeds that of genome-wide association studies in the discrimination of complex human disease

“…. However, there are striking dissimilarities as well, notably in terms of scale (~20,000 human genes vs. tens of millions of microbial genes across thousands of species), the transient nature of human microbiota, and the sensitivity of the microbiome to the host's environment (Rothschild et al 2018;Tierney et al 2019;Moraes and Góes 2016;Theriot et al 2014) We hypothesized that since the microbiome may be viewed as a hub that captures host environmental factors, microbial features may provide sources of variation not captured by static host common variants. Therefore, a natural question arises when reflecting upon our "first" and "second" genomes: how are microbiome and human genome different (or complementary) in their ability to characterize host phenotype, and which one is superior at doing so overall?…”

“…metabolic pathways, individual genes, or even in individual SNPs. The metagenomic space contains millions of genes(Tierney et al 2019) and encompasses complex structural variation on top of simple single nucleotide polymorphisms (SNPs). Host genetic features, on the other hand, are not limited to exclusively the common variants measured on a GWAS chip, which only measures the~0.1% of where the human genome contains variation(1000Genomes Project Consortium et al 2015 .…”

Acquisition of Oral Microbiota is Driven by Environment, Not Host Genetics

“…Only children adopted by a genetically unrelated family were included. The genetic distances between African and northern European populations are among the greatest found in modern humans 18 , and many of our adoptive dyads were composed of white mothers and African-American children, providing maximum genetic distance between unrelated. Only children adopted at birth were included to minimize contact with the birth mother’s microbiota.…”